Thiophosphoric acids as novel organocatalysts and synthetic methods of thiophosphonate derivatives as pharmaceutical agents

Abstract

The present disclosure is concerned with substituted thiophosphoric acids and methods of making and using same as, for example, organocatalysts and fire retardants. Also disclosed are thiophosphonate analogs, including allylic thiophosphonate analogs, and methods of preparing same using the disclosed thiophosphoric acids. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Description

THIOPHOSPHORIC ACIDS AS NOVEL ORGANOCATALYSTS AND SYNTHETIC METHODS OF THIOPHOSPHONATE DERIVATES AS PHARMACEUTICAL AGENTS CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This Application claims the benefit of U.S. Application No.63 / 417,664, filed on October 19, 2022, the contents of which are incorporated herein by reference in their entirety. BACKGROUND

[0002] Organophosphorus chemistry has seen an increased research interest the past few decades as organophosphorus compounds have found widespread use in the fields of medicine, catalysis, agricultural chemistry, and materials chemistry (Demkowicz et al., RSC Adv., 2016, 6, 7101-7112). Specifically, phosphorodithioate compounds bearing the thiophosphoryl bond have useful properties such as being used as insecticides (FIG.1) and as a neurotoxin (Fan et al., Food Control, 2014, 37, 153-157). Thiophosphate compounds bearing the phosphoryl bond also display important biological activity for the treatment of cancer and glaucoma. (Gabled et al., Invest. Ophthalmol. Visual Sci., 2004, 45, 2732-2736). Thiophosphates have been shown to have remarkable antibacterial properties against common strains of bacteria (Mitra et al., Bioorg. Med. Chem. Lett., 2014, 24, 2198-2201).

[0003] Organophosphorous reagents have also been explored as a more environmentally friendly flame retardant (Liang et al., Prog. Org. Coat., 2013, 76, 1642-1665); however, they face threats of leaching out of their substrate if they do not possess a high molecular weight (He et al, Prog. Mat. Sci., 2020, 114, 100687). Therefore, alternative organophosphorous- based flame retardants having additional weight are desired.

[0004] At present, examples of phosphorothioic acids and their applications toward synthetic methodology are few and far between. Wu and co-workers (Wu et al., JACS 2012, 134, 2775- 2780) used phosphorothioic acids as surrogates for H2S to synthesize a chiral tetrahydrothiophenes (THTs). Under metal-free reaction conditions, the Wu group also conducted a two-step process for synthesizing carbon-carbon bonds (Wu et al., JACS, 2010, 132, 4104-4106). The group additionally uncovered that a direct substitution of alcohols with phosphorothioic acids generated sulfur-containing compounds when catalyzed by Ga(OTf)3 (Wu et al., Org. Lett., 2010, 12, 5780-5782). Employing the thionic acids, Togni and co- workers released an electrophilic trifluoromethylation to afford pharmaceutically significantfluorinated phosphorothioates (Togni et al., J. Org. Chem, 2011, 76, 4189-4193). Furthermore, a recent review article reported the synthesis of phosphinothioates, phosphonothioates, phosphorothioates and phosphonodithioates through the usage of phosphorothioic acids as a reagent (O’Sullivan et al., Tetra. Lett., 2018, 59, 4279-4292). Despite a rapidly growing interest in the application of phosphorothioic acids as a powerful synthetic tool, efforts towards the synthesis of chiral phosphorothioic acids and their application as organocatalysts have been remained undeveloped. Accordingly, there remains a need forphosphorothioic acids for use as organocatalysts, as well as their application towards the development of new synthetic methodology under environmentally friendly conditions. SUMMARY

[0005] In accordance with the purpose(s) of the invention, as embodied and broadly described herein, the invention, in one aspect, relates to substituted thiophosphoric acids and methods of making and using same as organocatalysts to prepare, for example, thiophosphonate derivatives. Allylic thiophosphonate derivatives useful as fire retardants are also disclosed.

[0006] Thus, disclosed are compounds having a structure represented by a formula: , wherein A is selected from O and S; wherein Q is selected from O, S, and NR10; wherein R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl,C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6- membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino,or a salt thereof.

[0007] Also disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl, or wherein R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from:;wherein Q, , , , om hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; orwherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R6is selected from C1-C4 alkyl, C1-C4 haloalkyl, ‒CH2Ar4, and Ar4; wherein Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; and wherein each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0008] Also disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl, or wherein R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: ,;wherein Qm hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6- C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R6is selected from C1-C4 alkyl, C1-C4 haloalkyl, ‒CH2Ar4, and Ar4; wherein Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R8is selected from hydrogen, ‒OH, and ‒NHPG; wherein PG is an amine protecting group; and wherein Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 additional groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, provided that when R8is hydrogen, then R6is Ar4and Ar4is a 4-10 membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0009] In one aspect, disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein Q is selected from O, S, and NR10; wherein R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6- membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; and wherein each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0010] Also disclosed are methods of making a disclosed compound such as, for example, a disclosed thiophosphoric acid, a disclosed allylic thiophosphonate, and a disclosed thiophosphonate.

[0011] Also disclosed are methods of using a disclosed thiophosphoric acid compound in, for example, the preparation of allylic thiophosphonate and thiophosphonate compounds as described herein.

[0012] While aspects of the present invention can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present invention can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects and together with the description serve to explain the principles of the invention.

[0014] FIG.1 shows a representative scheme illustrating representative applications of phosphorodithionate and thiophospate analogs.

[0015] FIG.2 shows a representative scheme illustrating S-C bond formation using (EtO)2P(O)SH.

[0016] FIG.3 shows a representative photograph of reaction tubes used for the exemplary reactions detailed herein.

[0017] FIG 4 shows a representative schematic illustrating the scope of the thiophorphorylation reaction towards the preparation of benzylic derivatives. Reaction conditions: 1 (0.1 mmol), 2a (0.15 mmol) in solvent (0.5 mL) for 12 h. Isolated yield is shown.

[0018] FIG.5 shows a representative schematic illustrating the scope of the thiophorphorylation reaction towards the preparation of phenol derivatives. Reactionconditions: 1 (0.1 mmol), 2a (0.15 mmol) in solvent (0.5 mL) for 12 h. Isolated yield is shown.

[0019] FIG.6 shows a representative schematic illustrating the scope of thioacid nucleophiles that can be used. Reaction conditions: 1 (0.1 mmol), 2 (0.15 mmol) in solvent (0.5 mL) for 12 h. Isolated yield is shown.

[0020] FIG.7 shows a representative schematic illustrating the scope of the sulfonamide thiophosphate synthesis. Reaction conditions: 4a (0.1 mmol), 2 (0.2 mmol), and TsOH (10 mol%) in solvent (0.5 mL) for 12 h. Isolated yield is shown.

[0021] FIG.8 is a representative scheme showing the proposed mechanism for the formation thiophosphoric acid analogs.

[0022] FIG.9 shows representative schematics for the control experiments performed.

[0023] FIG.10 shows a representative reaction scheme illustrating the synthesis of a phosphorothioic acid analog having bulky substituents.

[0024] FIG.11 shows representative chiral phorpshorothioic acids useful as fire retardants.

[0025] FIG.12 shows a representative reaction scheme illustrating the synthesis of an allyl phosphorothioate analog.

[0026] FIG.13 shows representative chiral allyl phosphorothioates useful as fire retardants.

[0027] FIG.14 shows a representative reaction scheme illustrating a hurdle in alternative routes to access phosphorothioic acids.

[0028] FIG.15 shows a representative scheme illustrating the modular synthesis of phosphorothioic acid chiral organocatalysts.

[0029] FIG.16 shows a representative reaction scheme illustrating the asymmetric synthesis of allylic thiophosphonates via 3,3-sigmatropic rearrangement.

[0030] FIG.17 shows a representative scheme illustrating the scope of the thiophosphorylation reaction with para-quinone methides.

[0031] FIG.18 shows representative scheme illustrating the scope of the thiophosphorylation reaction between allylic alcohols and phosphorothioic acid.

[0032] FIG.19A-F show representative schemes illustrating the proposed modular synthesis of phosphorothioic acids usefule as chiral organocatalysts.

[0033] FIG.20 shows representative thiophosphoric acid usefule as organocatalysts.

[0034] FIG.21A-C show representative schemes illustrating the synthesis of allyl thiophosphonates, which may be useful as fire retardants.

[0035] Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or can be learned by practiceof the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. DETAILED DESCRIPTION

[0036] The present invention can be understood more readily by reference to the following detailed description of the invention and the Examples included therein.

[0037] Before the present compounds, compositions, articles, systems, devices, and / or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described.

[0038] While aspects of the present invention can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present invention can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

[0039] Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates ofpublication provided herein may be different from the actual publication dates, which can require independent confirmation. A. DEFINITIONS

[0040] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a functional group,” “an alkyl,” or “a residue” includes mixtures of two or more such functional groups, alkyls, or residues, and the like.

[0041] As used in the specification and in the claims, the term “comprising” can include the aspects “consisting of” and “consisting essentially of.”

[0042] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0043] As used herein, the terms “about” and “at or about” mean that the amount or value in question can be the value designated some other value approximately or about the same. It is generally understood, as used herein, that it is the nominal value indicated ±10% variation unless otherwise indicated or inferred. The term is intended to convey that similar values promote equivalent results or effects recited in the claims. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but can be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such. It is understood that where “about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.

[0044] References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound.

[0045] A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included.

[0046] As used herein, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0047] As used herein, the term “derivative” refers to a compound having a structure derived from the structure of a parent compound (e.g., a compound disclosed herein) and whose structure is sufficiently similar to those disclosed herein and based upon that similarity, would be expected by one skilled in the art to exhibit the same or similar activities and utilities as the claimed compounds, or to induce, as a precursor, the same or similar activities and utilities as the claimed compounds. Exemplary derivatives include salts, esters, amides, salts of esters or amides, and N-oxides of a parent compound.

[0048] As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described below. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms, such as nitrogen, can have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This disclosure is not intended to be limited in any manner by the permissible substituents of organic compounds. Also, the terms “substitution” or “substituted with” include the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. It is also contemplated that, in certain aspects,unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted).

[0049] In defining various terms, “A1,” “A2,” “A3,” and “A4” are used herein as generic symbols to represent various specific substituents. These symbols can be any substituent, not limited to those disclosed herein, and when they are defined to be certain substituents in one instance, they can, in another instance, be defined as some other substituents.

[0050] The term “aliphatic” or “aliphatic group,” as used herein, denotes a hydrocarbon moiety that may be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spirofused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1-20 carbon atoms. Aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0051] The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s- butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. The alkyl group can be cyclic or acyclic. The alkyl group can be branched or unbranched. The alkyl group can also be substituted or unsubstituted. For example, the alkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol, as described herein. A “lower alkyl” group is an alkyl group containing from one to six (e.g., from one to four) carbon atoms. The term alkyl group can also be a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like up to and including a C1-C24 alkyl.

[0052] Throughout the specification “alkyl” is generally used to refer to both unsubstituted alkyl groups and substituted alkyl groups; however, substituted alkyl groups are also specifically referred to herein by identifying the specific substituent(s) on the alkyl group. For example, the term “halogenated alkyl” or “haloalkyl” specifically refers to an alkyl group that is substituted with one or more halide, e.g., fluorine, chlorine, bromine, or iodine. Alternatively, the term “monohaloalkyl” specifically refers to an alkyl group that is substituted with a single halide, e.g. fluorine, chlorine, bromine, or iodine. The term “polyhaloalkyl” specifically refers to an alkyl group that is independently substituted with two or more halides, i.e. each halide substituent need not be the same halide as another halidesubstituent, nor do the multiple instances of a halide substituent need to be on the same carbon. The term “alkoxyalkyl” specifically refers to an alkyl group that is substituted with one or more alkoxy groups, as described below. The term “aminoalkyl” specifically refers to an alkyl group that is substituted with one or more amino groups. The term “hydroxyalkyl” specifically refers to an alkyl group that is substituted with one or more hydroxy groups. When “alkyl” is used in one instance and a specific term such as “hydroxyalkyl” is used in another, it is not meant to imply that the term “alkyl” does not also refer to specific terms such as “hydroxyalkyl” and the like.

[0053] This practice is also used for other groups described herein. That is, while a term such as “cycloalkyl” refers to both unsubstituted and substituted cycloalkyl moieties, the substituted moieties can, in addition, be specifically identified herein; for example, a particular substituted cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” Similarly, a substituted alkoxy can be specifically referred to as, e.g., a “halogenated alkoxy,” a particular substituted alkenyl can be, e.g., an “alkenylalcohol,” and the like. Again, the practice of using a general term, such as “cycloalkyl,” and a specific term, such as “alkylcycloalkyl,” is not meant to imply that the general term does not also include the specific term.

[0054] The term “cycloalkyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. The term “heterocycloalkyl” is a type of cycloalkyl group as defined above, and is included within the meaning of the term “cycloalkyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. The cycloalkyl group and heterocycloalkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein.

[0055] The term “polyalkylene group” as used herein is a group having two or more CH2 groups linked to one another. The polyalkylene group can be represented by the formula — (CH2)a—, where “a” is an integer of from 2 to 500.

[0056] The terms “alkoxy” and “alkoxyl” as used herein to refer to an alkyl or cycloalkyl group bonded through an ether linkage; that is, an “alkoxy” group can be defined as —OA1where A1is alkyl or cycloalkyl as defined above. “Alkoxy” also includes polymers of alkoxy groups as just described; that is, an alkoxy can be a polyether such as —OA1—OA2or —OA1—(OA2)a—OA3, where “a” is an integer of from 1 to 200 and A1, A2, and A3are alkyl and / or cycloalkyl groups.

[0057] The term “alkenyl” as used herein is a hydrocarbon group of from 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon double bond. Asymmetric structures such as (A1A2)C=C(A3A4) are intended to include both the E and Z isomers. This can be presumed in structural formulae herein wherein an asymmetric alkene is present, or it can be explicitly indicated by the bond symbol C=C. The alkenyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, as described herein.

[0058] The term “cycloalkenyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms and containing at least one carbon-carbon double bound, i.e., C=C. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, norbornenyl, and the like. The term “heterocycloalkenyl” is a type of cycloalkenyl group as defined above, and is included within the meaning of the term “cycloalkenyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkenyl group and heterocycloalkenyl group can be substituted or unsubstituted. The cycloalkenyl group and heterocycloalkenyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein.

[0059] The term “alkynyl” as used herein is a hydrocarbon group of 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon triple bond. The alkynyl group can be unsubstituted or substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, as described herein.

[0060] The term “cycloalkynyl” as used herein is a non-aromatic carbon-based ring composed of at least seven carbon atoms and containing at least one carbon-carbon triple bound. Examples of cycloalkynyl groups include, but are not limited to, cycloheptynyl, cyclooctynyl, cyclononynyl, and the like. The term “heterocycloalkynyl” is a type ofcycloalkenyl group as defined above, and is included within the meaning of the term “cycloalkynyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkynyl group and heterocycloalkynyl group can be substituted or unsubstituted. The cycloalkynyl group and heterocycloalkynyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein.

[0061] The term “aromatic group” as used herein refers to a ring structure having cyclic clouds of delocalized π electrons above and below the plane of the molecule, where the π clouds contain (4n+2) π electrons. A further discussion of aromaticity is found in Morrison and Boyd, Organic Chemistry, (5th Ed., 1987), Chapter 13, entitled “Aromaticity,” pages 477-497, incorporated herein by reference. The term “aromatic group” is inclusive of both aryl and heteroaryl groups.

[0062] The term “aryl” as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. The aryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, ─NH2, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. The term “biaryl” is a specific type of aryl group and is included in the definition of “aryl.” In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon- carbon bond. For example, biaryl can be two aryl groups that are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl.

[0063] The term “aldehyde” as used herein is represented by the formula —C(O)H. Throughout this specification “C(O)” is a short hand notation for a carbonyl group, i.e., C=O.

[0064] The terms “amine” or “amino” as used herein are represented by the formula — NA1A2, where A1and A2can be, independently, hydrogen or alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. A specific example of amino is ─NH2.

[0065] The term “alkylamino” as used herein is represented by the formula —NH(-alkyl) where alkyl is a described herein. Representative examples include, but are not limited to,methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, (sec-butyl)amino group, (tert-butyl)amino group, pentylamino group, isopentylamino group, (tert-pentyl)amino group, hexylamino group, and the like.

[0066] The term “dialkylamino” as used herein is represented by the formula —N(-alkyl)2 where alkyl is a described herein. Representative examples include, but are not limited to, dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group, diisobutylamino group, di(sec-butyl)amino group, di(tert-butyl)amino group, dipentylamino group, diisopentylamino group, di(tert-pentyl)amino group, dihexylamino group, N-ethyl-N-methylamino group, N-methyl-N-propylamino group, N- ethyl-N-propylamino group and the like.

[0067] The term “carboxylic acid” as used herein is represented by the formula —C(O)OH.

[0068] The term “ester” as used herein is represented by the formula —OC(O)A1or — C(O)OA1, where A1can be alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “polyester” as used herein is represented by the formula —(A1O(O)C-A2-C(O)O)a— or —(A1O(O)C-A2-OC(O))a—, where A1and A2can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer from 1 to 500. “Polyester” is as the term used to describe a group that is produced by the reaction between a compound having at least two carboxylic acid groups with a compound having at least two hydroxyl groups.

[0069] The term “ether” as used herein is represented by the formula A1OA2, where A1and A2can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein. The term “polyether” as used herein is represented by the formula —(A1O-A2O)a—, where A1and A2can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer of from 1 to 500. Examples of polyether groups include polyethylene oxide, polypropylene oxide, and polybutylene oxide.

[0070] The terms “halo,” “halogen,” or “halide” as used herein can be used interchangeably and refer to F, Cl, Br, or I.

[0071] The terms “pseudohalide,” “pseudohalogen,” or “pseudohalo” as used herein can be used interchangeably and refer to functional groups that behave substantially similar to halides. Such functional groups include, by way of example, cyano, thiocyanato, azido, trifluoromethyl, trifluoromethoxy, perfluoroalkyl, and perfluoroalkoxy groups.

[0072] The term “heteroalkyl,” as used herein refers to an alkyl group containing at least one heteroatom. Suitable heteroatoms include, but are not limited to, O, N, Si, P and S, wherein the nitrogen, phosphorous and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. Heteroalkyls can be substituted as defined above for alkyl groups.

[0073] The term “heteroaryl,” as used herein refers to an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, where N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. The heteroaryl group can be substituted or unsubstituted. The heteroaryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. Heteroaryl groups can be monocyclic, or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, thienyl, pyridinyl, pyrrolyl, N-methylpyrrolyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridazinyl, pyrazinyl, benzofuranyl, benzodioxolyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, imidazopyridinyl, pyrazolopyridinyl, and pyrazolopyrimidinyl. Further not limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, pyrazolyl, imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazolyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, and pyrido[2,3-b]pyrazinyl.

[0074] The terms “heterocycle” or “heterocyclyl,” as used herein can be used interchangeably and refer to single and multi-cyclic aromatic or non-aromatic ring systems in which at least one of the ring members is other than carbon. Thus, the term is inclusive of, but not limited to, “heterocycloalkyl”, “heteroaryl”, “bicyclic heterocycle” and “polycyclic heterocycle.” Heterocycle includes pyridine, pyrimidine, furan, thiophene, pyrrole, isoxazole, isothiazole, pyrazole, oxazole, thiazole, imidazole, oxazole, including, 1,2,3- oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole, thiadiazole, including, 1,2,3-thiadiazole, 1,2,5-thiadiazole, and 1,3,4-thiadiazole, triazole, including, 1,2,3-triazole, 1,3,4-triazole, tetrazole, including 1,2,3,4-tetrazole and 1,2,4,5-tetrazole, pyridazine, pyrazine, triazine, including 1,2,4-triazine and 1,3,5-triazine, tetrazine, including 1,2,4,5-tetrazine, pyrrolidine, piperidine, piperazine, morpholine, azetidine, tetrahydropyran, tetrahydrofuran, dioxane, and the like. The term heterocyclyl group can also be a C2 heterocyclyl, C2-C3 heterocyclyl, C2-C4 heterocyclyl, C2-C5 heterocyclyl, C2-C6 heterocyclyl, C2-C7 heterocyclyl, C2-C8 heterocyclyl, C2-C9 heterocyclyl, C2-C10 heterocyclyl, C2-C11 heterocyclyl, and the like up to and including a C2-C18 heterocyclyl. For example, a C2 heterocyclyl comprises a group which has two carbon atoms and at least one heteroatom, including, but not limited to, aziridinyl, diazetidinyl, dihydrodiazetyl, oxiranyl, thiiranyl, and the like. Alternatively, for example, a C5 heterocyclyl comprises a group which has five carbon atoms and at least one heteroatom, including, but not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, diazepanyl, pyridinyl, and the like. It is understood that a heterocyclyl group may be bound either through a heteroatom in the ring, where chemically possible, or one of carbons comprising the heterocyclyl ring.

[0075] The term “bicyclic heterocycle” or “bicyclic heterocyclyl,” as used herein refers to a ring system in which at least one of the ring members is other than carbon. Bicyclic heterocyclyl encompasses ring systems wherein an aromatic ring is fused with another aromatic ring, or wherein an aromatic ring is fused with a non-aromatic ring. Bicyclic heterocyclyl encompasses ring systems wherein a benzene ring is fused to a 5- or a 6- membered ring containing 1, 2 or 3 ring heteroatoms or wherein a pyridine ring is fused to a 5- or a 6-membered ring containing 1, 2 or 3 ring heteroatoms. Bicyclic heterocyclic groups include, but are not limited to, indolyl, indazolyl, pyrazolo[1,5-a]pyridinyl, benzofuranyl, quinolinyl, quinoxalinyl, 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, 3,4-dihydro-2H- chromenyl, 1H-pyrazolo[4,3-c]pyridin-3-yl; 1H-pyrrolo[3,2-b]pyridin-3-yl; and 1H- pyrazolo[3,2-b]pyridin-3-yl.

[0076] The term “heterocycloalkyl” as used herein refers to an aliphatic, partially unsaturated or fully saturated, 3- to 14-membered ring system, including single rings of 3 to 8 atoms and bi- and tricyclic ring systems. The heterocycloalkyl ring-systems include one to four heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein a nitrogen and sulfur heteroatom optionally can be oxidized and a nitrogen heteroatom optionally can be substituted. Representative heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl.

[0077] The term “hydroxyl” or “hydroxyl” as used herein is represented by the formula — OH.

[0078] The term “ketone” as used herein is represented by the formula A1C(O)A2, where A1and A2can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein.

[0079] The term “azide” or “azido” as used herein is represented by the formula —N3.

[0080] The term “nitro” as used herein is represented by the formula —NO2.

[0081] The term “nitrile” or “cyano” as used herein is represented by the formula —CN.

[0082] The term “silyl” as used herein is represented by the formula —SiA1A2A3, where A1, A2, and A3can be, independently, hydrogen or an alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein.

[0083] The term “sulfo-oxo” as used herein is represented by the formulas —S(O)A1, — S(O)2A1, —OS(O)2A1, or —OS(O)2OA1, where A1can be hydrogen or an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. Throughout this specification “S(O)” is a short hand notation for S=O. The term “sulfonyl” is used herein to refer to the sulfo-oxo group represented by the formula —S(O)2A1, where A1can be hydrogen or an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfone” as used herein is represented by the formula A1S(O)2A2, where A1and A2can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfoxide” as used herein is represented by the formula A1S(O)A2, where A1and A2can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein.

[0084] The term “thiol” as used herein is represented by the formula —SH.

[0085] “R1,” “R2,” “R3,” “Rn,” where n is an integer, as used herein can, independently, possess one or more of the groups listed above. For example, if R1is a straight chain alkyl group, one of the hydrogen atoms of the alkyl group can optionally be substituted with a hydroxyl group, an alkoxy group, an alkyl group, a halide, and the like. Depending upon the groups that are selected, a first group can be incorporated within second group or, alternatively, the first group can be pendant (i.e., attached) to the second group. For example, with the phrase “an alkyl group comprising an amino group,” the amino group can be incorporated within the backbone of the alkyl group. Alternatively, the amino group can be attached to the backbone of the alkyl group. The nature of the group(s) that is (are) selected will determine if the first group is embedded or attached to the second group.

[0086] As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” ornot, means that one or more hydrogen of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. In is also contemplated that, in certain aspects, unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted).

[0087] The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain aspects, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0088] Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; –(CH2)0–4R ^; –(CH2)0–4OR ^; -O(CH2)0-4Ro, – O–(CH2)0–4C(O)OR°; –(CH2)0–4CH(OR ^)2; –(CH2)0–4SR ^; –(CH2)0–4Ph, which may be substituted with R°; –(CH2)0–4O(CH2)0–1Ph which may be substituted with R°; –CH=CHPh, which may be substituted with R°; –(CH2)0–4O(CH2)0–1-pyridyl which may be substituted with R°; –NO2; –CN; –N3; -(CH2)0–4N(R ^)2; –(CH2)0–4N(R ^)C(O)R ^; –N(R ^)C(S)R ^; – (CH2)0–4N(R ^)C(O)NR ^2; -N(R ^)C(S)NR ^2; –(CH2)0–4N(R ^)C(O)OR ^; –N(R ^)N(R ^)C(O)R ^; -N(R ^)N(R ^)C(O)NR ^2; -N(R ^)N(R ^)C(O)OR ^; –(CH2)0–4C(O)R ^; –C(S)R ^; –(CH2)0–4C(O)OR ^; –(CH2)0–4C(O)SR ^; -(CH2)0–4C(O)OSiR ^3; –(CH2)0–4OC(O)R ^; –OC(O)(CH2)0– 4SR–, SC(S)SR°; –(CH2)0–4SC(O)R ^; –(CH2)0–4C(O)NR ^2; –C(S)NR ^2; –C(S)SR°; -(CH2)0– 4OC(O)NR ^2; -C(O)N(OR ^)R ^; –C(O)C(O)R ^; –C(O)CH2C(O)R ^; –C(NOR ^)R ^; -(CH2)0–4SSR ^; –(CH2)0–4S(O)2R ^; –(CH2)0–4S(O)2OR ^; –(CH2)0–4OS(O)2R ^; –S(O)2NR ^2; -(CH2)0–4S(O)R ^; -N(R ^)S(O)2NR ^2; –N(R ^)S(O)2R ^; –N(OR ^)R ^; –C(NH)NR ^2; –P(O)2R ^; -P(O)R ^2; -OP(O)R ^2; –OP(O)(OR ^)2; SiR ^3; –(C1–4 straight or branched alkylene)O–N(R ^)2; or –(C1–4 straight or branched alkylene)C(O)O–N(R ^)2, wherein each R ^ may be substituted as defined below and is independently hydrogen, C1–6aliphatic, –CH2Ph, –O(CH2)0–1Ph, - CH2-(5-6 membered heteroaryl ring), or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R ^, taken together with their intervening atom(s), form a 3–12–membered saturated, partially unsaturated, or arylmono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0089] Suitable monovalent substituents on R ^ (or the ring formed by taking two independent occurrences of R ^ together with their intervening atoms), are independently halogen, – (CH2)0–2R^, –(haloR^), –(CH2)0–2OH, –(CH2)0–2OR^, –(CH2)0–2CH(OR^)2; -O(haloR^), –CN, –N3, –(CH2)0–2C(O)R^, –(CH2)0–2C(O)OH, –(CH2)0–2C(O)OR^, –(CH2)0–2SR^, –(CH2)0–2SH, –(CH2)0–2NH2, –(CH2)0–2NHR^, –(CH2)0–2NR^2, –NO2, –SiR^3, –OSiR^3, -C(O)SR^,–(C1–4straight or branched alkylene)C(O)OR^, or –SSR^wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R ^ include =O and =S.

[0090] Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =O, =S, =NNR*2, =NNHC(O)R*, =NNHC(O)OR*, =NNHS(O)2R*, =NR*, =NOR*, –O(C(R*2))2–3O–, or –S(C(R*2))2–3S–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: –O(CR*2)2–3O–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0091] Suitable substituents on the aliphatic group of R*include halogen, –R^, -(haloR^), -OH, –OR^, –O(haloR^), –CN, –C(O)OH, –C(O)OR^, –NH2, –NHR^, –NR^2, or –NO2, wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6– membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0092] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include –R†, –NR†2, –C(O)R†, –C(O)OR†, –C(O)C(O)R†, –C(O)CH2C(O)R†, –S(O)2R†,-S(O)2NR†2, –C(S)NR†2, –C(NH)NR†2, or –N(R†)S(O)2R†; wherein each R†is independently hydrogen, C1–6aliphatic which may be substituted as defined below, unsubstituted –OPh, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R†, taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0093] Suitable substituents on the aliphatic group of R†are independently halogen, –R^, -(haloR^), –OH, –OR^, –O(haloR^), –CN, –C(O)OH, –C(O)OR^, –NH2, –NHR^, –NR^2, or –NO2, wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6– membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0094] The term “leaving group” refers to an atom (or a group of atoms) with electron withdrawing ability that can be displaced as a stable species, taking with it the bonding electrons. Examples of suitable leaving groups include halides and sulfonate esters, including, but not limited to, triflate, mesylate, tosylate, and brosylate.

[0095] The terms “hydrolysable group” and “hydrolysable moiety” refer to a functional group capable of undergoing hydrolysis, e.g., under basic or acidic conditions. Examples of hydrolysable residues include, without limitation, acid halides, activated carboxylic acids, and various protecting groups known in the art (see, for example, “Protective Groups in Organic Synthesis,” T. W. Greene, P. G. M. Wuts, Wiley-Interscience, 1999).

[0096] The term “organic residue” defines a carbon-containing residue, i.e., a residue comprising at least one carbon atom, and includes but is not limited to the carbon-containing groups, residues, or radicals defined hereinabove. Organic residues can contain various heteroatoms, or be bonded to another molecule through a heteroatom, including oxygen, nitrogen, sulfur, phosphorus, or the like. Examples of organic residues include but are not limited alkyl or substituted alkyls, alkoxy or substituted alkoxy, mono or di-substituted amino, amide groups, etc. Organic residues can preferably comprise 1 to 18 carbon atoms, 1 to 15, carbon atoms, 1 to 12 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. In a further aspect, an organic residue can comprise 2 to 18 carbon atoms, 2 to 15, carbon atoms, 2 to 12 carbon atoms, 2 to 8 carbon atoms, 2 to 4 carbon atoms, or 2 to 4 carbon atoms.

[0097] A very close synonym of the term “residue” is the term “radical,” which as used in the specification and concluding claims, refers to a fragment, group, or substructure of a molecule described herein, regardless of how the molecule is prepared. For example, a 2,4- thiazolidinedione radical in a particular compound has the structure: , regardless of whether thiazolidinediones use o prepare the compound. In some embodiments the radical (for example an alkyl) can be further modified (i.e., substituted alkyl) by having bonded thereto one or more “substituent radicals.” The number of atoms in a given radical is not critical to the present invention unless it is indicated to the contrary elsewhere herein.

[0098] “Organic radicals,” as the term is defined and used herein, contain one or more carbon atoms. An organic radical can have, for example, 1-26 carbon atoms, 1-18 carbon atoms, 1- 12 carbon atoms, 1-8 carbon atoms, 1-6 carbon atoms, or 1-4 carbon atoms. In a further aspect, an organic radical can have 2-26 carbon atoms, 2-18 carbon atoms, 2-12 carbon atoms, 2-8 carbon atoms, 2-6 carbon atoms, or 2-4 carbon atoms. Organic radicals often have hydrogen bound to at least some of the carbon atoms of the organic radical. One example, of an organic radical that comprises no inorganic atoms is a 5, 6, 7, 8-tetrahydro-2-naphthyl radical. In some embodiments, an organic radical can contain 1-10 inorganic heteroatoms bound thereto or therein, including halogens, oxygen, sulfur, nitrogen, phosphorus, and the like. Examples of organic radicals include but are not limited to an alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, mono-substituted amino, di-substituted amino, acyloxy, cyano, carboxy, carboalkoxy, alkylcarboxamide, substituted alkylcarboxamide, dialkylcarboxamide, substituted dialkylcarboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, thiohaloalkyl, alkoxy, substituted alkoxy, haloalkyl, haloalkoxy, aryl, substituted aryl, heteroaryl, heterocyclic, or substituted heterocyclic radicals, wherein the terms are defined elsewhere herein. A few non-limiting examples of organic radicals that include heteroatoms include alkoxy radicals, trifluoromethoxy radicals, acetoxy radicals, dimethylamino radicals and the like.

[0099] Compounds described herein can contain one or more double bonds and, thus, potentially give rise to cis / trans (E / Z) isomers, as well as other conformational isomers.Unless stated to the contrary, the invention includes all such possible isomers, as well as mixtures of such isomers.

[0100] Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer and diastereomer, and a mixture of isomers, such as a racemic or scalemic mixture. Compounds described herein can contain one or more asymmetric centers and, thus, potentially give rise to diastereomers and optical isomers. Unless stated to the contrary, the present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof. Mixtures of stereoisomers, as well as isolated specific stereoisomers, are also included. During the course of the synthetic procedures used to prepare such compounds, or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers.

[0101] Many organic compounds exist in optically active forms having the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are non-superimposable mirror images of one another. A specific stereoisomer can also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture. Many of the compounds described herein can have one or more chiral centers and therefore can exist in different enantiomeric forms. If desired, a chiral carbon can be designated with an asterisk (*). When bonds to the chiral carbon are depicted as straight lines in the disclosed formulas, it is understood that both the (R) and (S) configurations of the chiral carbon, and hence both enantiomers and mixtures thereof, are embraced within the formula. As is used in the art, when it is desired to specify the absolute configuration about a chiral carbon, one of the bonds to the chiral carbon can be depicted as a wedge (bonds to atoms above the plane) and the other can be depicted as a series or wedge of short parallel lines is (bonds to atoms below the plane). The Cahn-Ingold-Prelog system can be used to assign the (R) or (S) configuration to a chiral carbon.

[0102] When the disclosed compounds contain one chiral center, the compounds exist in two enantiomeric forms. Unless specifically stated to the contrary, a disclosed compound includes both enantiomers and mixtures of enantiomers, such as the specific 50:50 mixture referred to as a racemic mixture. The enantiomers can be resolved by methods known to those skilled in the art, such as formation of diastereoisomeric salts which may be separated, for example, by crystallization (see, CRC Handbook of Optical Resolutions via Diastereomeric Salt Formation by David Kozma (CRC Press, 2001)); formation of diastereoisomeric derivatives or complexes which may be separated, for example, by crystallization, gas-liquid or liquid chromatography; selective reaction of one enantiomer with an enantiomer-specific reagent, for example enzymatic esterification; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support for example silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that where the desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step can liberate the desired enantiomeric form. Alternatively, specific enantiomers can be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer into the other by asymmetric transformation.

[0103] Designation of a specific absolute configuration at a chiral carbon in a disclosed compound is understood to mean that the designated enantiomeric form of the compounds can be provided in enantiomeric excess (e.e.). Enantiomeric excess, as used herein, is the presence of a particular enantiomer at greater than 50%, for example, greater than 60%, greater than 70%, greater than 75%, greater than 80%, greater than 85%, greater than 90%, greater than 95%, greater than 98%, or greater than 99%. In one aspect, the designated enantiomer is substantially free from the other enantiomer. For example, the “R” forms of the compounds can be substantially free from the “S” forms of the compounds and are, thus, in enantiomeric excess of the “S” forms. Conversely, “S” forms of the compounds can be substantially free of “R” forms of the compounds and are, thus, in enantiomeric excess of the “R” forms.

[0104] When a disclosed compound has two or more chiral carbons, it can have more than two optical isomers and can exist in diastereoisomeric forms. For example, when there are two chiral carbons, the compound can have up to four optical isomers and two pairs of enantiomers ((S,S) / (R,R) and (R,S) / (S,R)). The pairs of enantiomers (e.g., (S,S) / (R,R)) are mirror image stereoisomers of one another. The stereoisomers that are not mirror-images (e.g., (S,S) and (R,S)) are diastereomers. The diastereoisomeric pairs can be separated bymethods known to those skilled in the art, for example chromatography or crystallization and the individual enantiomers within each pair may be separated as described above. Unless otherwise specifically excluded, a disclosed compound includes each diastereoisomer of such compounds and mixtures thereof.

[0105] The compounds according to this disclosure may form prodrugs at hydroxyl or amino functionalities using alkoxy, amino acids, etc., groups as the prodrug forming moieties. For instance, the hydroxymethyl position may form mono-, di-, or triphosphates and again these phosphates can form prodrugs. Preparations of such prodrug derivatives are discussed in various literature sources (examples are: Alexander et al., J. Med. Chem.1988, 31, 318; Aligas-Martin et al., PCT WO 2000 / 041531, p.30). The nitrogen function converted in preparing these derivatives is one (or more) of the nitrogen atoms of a compound of the disclosure.

[0106] “Derivatives” of the compounds disclosed herein are pharmaceutically acceptable salts, prodrugs, deuterated forms, radio-actively labeled forms, isomers, solvates and combinations thereof. The “combinations” mentioned in this context refer to derivatives falling within at least two of the groups: pharmaceutically acceptable salts, prodrugs, deuterated forms, radio-actively labeled forms, isomers, and solvates. Examples of radio- actively labeled forms include compounds labeled with tritium, phosphorous-32, iodine-129, carbon-11, fluorine-18, and the like.

[0107] Compounds described herein comprise atoms in both their natural isotopic abundance and in non-natural abundance. The disclosed compounds can be isotopically- labeled or isotopically-substituted compounds identical to those described, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as2H,3H,13C,14C,15N,18O,17O,35S,18F and36Cl, respectively. Compounds further comprise prodrugs thereof, and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds of the present invention, for example those into which radioactive isotopes such as3H and14C are incorporated, are useful in drug and / or substrate tissue distribution assays. Tritiated, i.e.,3H, and carbon-14, i.e.,14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e.,2H, canafford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labeled compounds of the present invention and prodrugs thereof can generally be prepared by carrying out the procedures below, by substituting a readily available isotopically labeled reagent for a non- isotopically labeled reagent.

[0108] The compounds described in the invention can be present as a solvate. In some cases, the solvent used to prepare the solvate is an aqueous solution, and the solvate is then often referred to as a hydrate. The compounds can be present as a hydrate, which can be obtained, for example, by crystallization from a solvent or from aqueous solution. In this connection, one, two, three or any arbitrary number of solvent or water molecules can combine with the compounds according to the invention to form solvates and hydrates. Unless stated to the contrary, the invention includes all such possible solvates.

[0109] The term “co-crystal” means a physical association of two or more molecules which owe their stability through non-covalent interaction. One or more components of this molecular complex provide a stable framework in the crystalline lattice. In certain instances, the guest molecules are incorporated in the crystalline lattice as anhydrates or solvates, see e.g. “Crystal Engineering of the Composition of Pharmaceutical Phases. Do Pharmaceutical Co-crystals Represent a New Path to Improved Medicines?” Almarasson, O., et. al., The Royal Society of Chemistry, 1889-1896, 2004. Examples of co-crystals include p- toluenesulfonic acid and benzenesulfonic acid.

[0110] It is also appreciated that certain compounds described herein can be present as an equilibrium of tautomers. For example, ketones with an α-hydrogen can exist in an equilibrium of the keto form and the enol form.

[0111] Likewise, amides with an N-hydrogen can exist in an equilibrium of the amide form and the imidic acid form. As another example, pyrazoles can exist in two tautomeric forms, N1-unsubstituted, 3-A3and N1-unsubstituted, 5-A3as shown below.Unless stated to the contible tautomers.

[0112] It is known that chemical substances form solids, which are present in different states of order which are termed polymorphic forms or modifications. The different modifications of a polymorphic substance can differ greatly in their physical properties. The compounds according to the invention can be present in different polymorphic forms, with it being possible for particular modifications to be metastable. Unless stated to the contrary, the invention includes all such possible polymorphic forms.

[0113] In some aspects, a structure of a compound can be represented by a formula: , which is understood to be equivalent toa formula: ,wherein n is typically an integer. That is, Rnis understood to represent five independent substituents, Rn(a), Rn(b), Rn(c), Rn(d), Rn(e). By “independent substituents,” it is meant that each R substituent can be independently defined. For example, if in one instance Rn(a)is halogen, then Rn(b)is not necessarily halogen in that instance.

[0114] Certain materials, compounds, compositions, and components disclosed herein can be obtained commercially or readily synthesized using techniques generally known to those of skill in the art. For example, the starting materials and reagents used in preparing the disclosed compounds and compositions are either available from commercial suppliers such as Aldrich Chemical Co., (Milwaukee, Wis.), Acros Organics (Morris Plains, N.J.), Strem Chemicals (Newburyport, MA), Fisher Scientific (Pittsburgh, Pa.), or Sigma (St. Louis, Mo.) or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser’s Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd’s Chemistry of Carbon Compounds, Volumes 1-5 andsupplemental volumes (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991); March’s Advanced Organic Chemistry, (John Wiley and Sons, 4th Edition); and Larock’s Comprehensive Organic Transformations (VCH Publishers Inc., 1989).

[0115] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps or operational flow; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification.

[0116] Disclosed are the components to be used to prepare the compositions of the invention as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the invention. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the methods of the invention.

[0117] It is understood that the compounds and compositions disclosed herein have certain functions. Disclosed herein are certain structural requirements for performing the disclosed functions, and it is understood that there are a variety of structures that can perform the same function that are related to the disclosed structures, and that these structures will typically achieve the same result. B. THIOPHOSPHORIC ACIDS

[0118] In one aspect, the invention relates to substituted thiophosphoric acids useful in organocatalyst applications. The disclosed thiophosphoric acids can also be useful as fire retardants, as further described herein .

[0119] It is contemplated that each disclosed derivative can be optionally further substituted. It is also contemplated that any one or more derivative can be optionally omitted from the invention. It is understood that a disclosed compound can be provided by the disclosed methods. It is also understood that the disclosed compounds can be employed in the disclosed methods of using. 1. STRUCTURE

[0120] In one aspect, disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein Q is selected from O, S, and NR10; wherein R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6- membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino,or a salt thereof.

[0121] In various aspects, the compound has a structure represented by a formula: ,or a salt thereof.

[0122] In various aspects, the compound has a structure represented by a formula: R1aR10O SH ,or a salt thereof.

[0123] In various aspects, the compound has a structure represented by a formula: , or a salt thereof.

[0124] In various aspects, the compound has a structure represented by a formula: , ach of R20a, R20bwherein e , R20c, R20d, and R20eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R20a, R20b, R20c, R20d, and R20eis hydrogen; and wherein each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R21a, R21b, R21c, R21d, and R21eis hydrogen, or a salt thereof.

[0125] In various aspects, the compound has a structure represented by a formula:, or a salt thereof.

[0126] In various aspects, the compound has a structure represented by a formula: ,or a salt thereof. In a further aspect, each of R1band R2is independently selected from hydrogen, C1-C4 alkyl, and unsubstituted phenyl. In a still further aspect, each of R20a, R20c, R20e, R21a, R21c, and R21eis independently selected from C1-C4 alkyl and unsubstituted phenyl.

[0127] In various aspects, compound is selected from: , ,, or a salt thereof.

[0128] In various aspects, the compound is selected from: , , or a salt t ereo .

[0129] In various aspects, the compound is selected from: Ph Ph H Ph ,,,or a salt thereof.

[0130] In various aspects, the compound is selected from:Ph Ph H h , , ,, or a sa

[0131] In various aspects, Q is NR10. In a further aspect, R10is C1-C4 alkyl. In a still further aspect, R10is selected from methyl, ethyl, n-propyl, and isopropyl. In yet a further aspect, R10is methyl. In an even further aspect, R10is Ar1. In a still further aspect, Ar1is C6 aryl substituted with 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar1is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl. In an even further aspect, Ar1is unsubstituted C6 aryl.

[0132] In various aspects, each of R1aand R1bis independently selected from hydrogen and Ar2. In a further aspect, each of R1aand R1bis hydrogen. In a still further aspect, each of R1aand R1bis Ar2. In yet a further aspect, one of R1aand R1bis hydrogen and one of R1aand R1bis Ar2. In an even further aspect, Ar2is unsubstituted C6 aryl.

[0133] In various aspects, R2is selected from ‒CH2Ar1and Ar2. In a further aspect, Ar2is unsubstituted C6 aryl.

[0134] In various aspects, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- to 6-membered cycloalkyl.

[0135] In various aspects, R3is selected from hydrogen, C1-C4 alkyl, and Ar3. In a further aspect, R3is C1-C4 alkyl. In a still further aspect, R3is methyl. In yet a further aspect, R3is Ar3. In an even further aspect, Ar3is C6 aryl substituted with 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar3is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl. In yet a further aspect, Ar3is unsubstituted C6 aryl.

[0136] In various aspects, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- to 6-membered cycloalkyl. a. A GROUPS

[0137] In one aspect, A is selected from O and S. In a further aspect, A is O. In a still further aspect, A is S. b. Q GROUPS

[0138] In one aspect, Q is selected from O, S, and NR10. In a further aspect, Q is selected from O and S. In a still further aspect, Q is selected from O and NR10. In yet a further aspect, Q is selected from S and NR10. In an even further aspect, Q is O. In a still further aspect, Q is S. In yet a further aspect, Q is NR10. c. R1A, R1B, AND R2GROUPS

[0139] In one aspect, each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, or R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0140] In various aspects, each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2. In a further aspect, each of R1a, R1b, and R2is independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, ‒CH2Ar1, and Ar2. In a still further aspect, each of R1a, R1b, and R2is independently selected from hydrogen, methyl, ethyl, ‒CH2Ar1, and Ar2. In yet a further aspect, each of R1a, R1b, and R2is independently selected from hydrogen, methyl, ‒CH2Ar1, and Ar2.

[0141] In various aspects, each of R1a, R1b, and R2is independently selected from hydrogen and C1-C4 alkyl. In a further aspect, each of R1a, R1b, and R2is independently selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, each of R1a, R1b, and R2is independently selected from hydrogen, methyl, and ethyl. In yet a further aspect, each of R1a, R1b, and R2is independently selected from hydrogen and methyl.

[0142] In various aspects, each of R1a, R1b, and R2is independently C1-C4 alkyl. In a further aspect, each of R1a, R1b, and R2is independently selected from methyl, ethyl, n- propyl, and isopropyl. In a still further aspect, each of R1a, R1b, and R2is independently selected from methyl and ethyl. In yet a further aspect, each of R1a, R1b, and R2is methyl.

[0143] In various aspects, each of R1a, R1b, and R2is independently selected from hydrogen, ‒CH2Ar1, and Ar2. In a further aspect, each of R1a, R1b, and R2is independently selected from hydrogen and ‒CH2Ar1. In a still further aspect, each of R1a, R1b, and R2is independently selected from hydrogen and Ar2.

[0144] In various aspects, each of R1a, R1b, and R2is hydrogen.

[0145] In various aspects, R1ais hydrogen and each of R1band R2is C1-C4 alkyl.

[0146] In various aspects, R2is C1-C4 alkyl. In a further aspect, R2is selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R2is selected from methyl and ethyl. In yet a further aspect, R2is methyl.

[0147] In various aspects, R2is selected from hydrogen, ‒CH2Ar1, and Ar2. In a further aspect, R2is selected from hydrogen and ‒CH2Ar1. In a still further aspect, R2is selected from hydrogen and Ar2. In yet a further aspect, R2is selected from ‒CH2Ar1and Ar2. In an even further aspect, R2is hydrogen.

[0148] In various aspects, R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0149] In various aspects, R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2. In a further aspect, R1ais selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, ‒CH2Ar1, and Ar2. In a still further aspect, R1ais selected from hydrogen, methyl, ethyl, ‒CH2Ar1, and Ar2. In yet a further aspect, R1ais selected from hydrogen, methyl, ‒CH2Ar1, and Ar2.

[0150] In various aspects, R1ais selected from hydrogen and C1-C4 alkyl. In a further aspect, R1ais selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R1ais selected from hydrogen, methyl, and ethyl. In yet a further aspect, R1ais selected from hydrogen and methyl.

[0151] In various aspects, R1ais C1-C4 alkyl. In a further aspect, R1ais selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R1ais selected from methyl and ethyl. In yet a further aspect, R1ais ethyl. In an even further aspect, R1ais methyl.

[0152] In various aspects, R1ais selected from ‒CH2Ar1and Ar2. In a further aspect, R1ais ‒CH2Ar1. In a still further aspect, R1ais Ar2.

[0153] In various aspects, R1ais hydrogen.

[0154] In various aspects, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- to 6-membered cycloalkyl.

[0155] In various aspects, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, – SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycloalkyl substituted with 0 or 1 group selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycloalkyl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5-membered cycloalkyl.

[0156] In various aspects, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, – SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl substituted with 0 or 1 group selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl monosubstituted with a group selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6-membered cycloalkyl.

[0157] In various aspects, each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0158] In various aspects, each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2. In a further aspect, each of R1aand R1bis independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, ‒CH2Ar1, and Ar2. In a still further aspect, each of R1aand R1bis independently selected from hydrogen, methyl, ethyl, ‒CH2Ar1, and Ar2. In yet a further aspect, each of R1aand R1bis independently selected from hydrogen, methyl, ‒CH2Ar1, and Ar2.

[0159] In various aspects, each of R1aand R1bis independently selected from hydrogen and C1-C4 alkyl. In a further aspect, each of R1aand R1bis independently selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, each of R1aand R1bis independently selected from hydrogen, methyl, and ethyl. In yet a further aspect, each of R1aand R1bis independently selected from hydrogen and methyl.

[0160] In various aspects, each of R1aand R1bis independently C1-C4 alkyl. In a further aspect, each of R1aand R1bis independently selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, each of R1aand R1bis independently selected from methyl and ethyl. In yet a further aspect, each of R1aand R1bis ethyl. In an even further aspect, each of R1aand R1bis ethyl.

[0161] In various aspects, each of R1aand R1bis independently selected from hydrogen, ‒CH2Ar1, and Ar2. In a further aspect, each of R1aand R1bis independently selected from hydrogen and ‒CH2Ar1. In a still further aspect, each of R1aand R1bis independently selected from hydrogen and Ar2. In yet a further aspect, one of R1aand R1bis hydrogen and one of R1aand R1bis Ar2.

[0162] In various aspects, each of R1aand R1bis independently selected from ‒CH2Ar1and Ar2. In a further aspect, each of R1aand R1bis ‒CH2Ar1. In a still further aspect, each of R1aand R1bis Ar2.

[0163] In various aspects, each of R1aand R1bis hydrogen.

[0164] In various aspects, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-memberedcycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- to 6-membered cycloalkyl.

[0165] In various aspects, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, – SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycloalkyl ubstituted with 0 or 1 group selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms,comprise a 5-membered cycloalkyl monosubstituted with a group selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5-membered cycloalkyl.

[0166] In various aspects, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, – SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl ubstituted with 0 or 1 group selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 6-membered cycloalkyl monosubstituted with a group selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6-membered cycloalkyl. d. R3GROUPS

[0167] In one aspect, R3is selected from hydrogen, C1-C4 alkyl, and Ar3. In a further aspect, R3is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, and Ar3. In astill further aspect, R3is selected from hydrogen, methyl, ethyl, and Ar3. In yet a further aspect, R3is selected from hydrogen, methyl, and Ar3.

[0168] In various aspects, R3is selected from hydrogen and C1-C4 alkyl. In a further aspect, R3is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R3is selected from hydrogen, methyl, and ethyl. In yet a further aspect, R3is selected from hydrogen and ethyl. In an even further aspect, R3is selected from hydrogen and methyl.

[0169] In various aspects, R3is C1-C4 alkyl. In a further aspect, R3is selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R3is selected from methyl and ethyl. In yet a further aspect, R3is ethyl. In an even further aspect, R3is methyl.

[0170] In various aspects, R3is Ar3.

[0171] In various aspects, R3is hydrogen. e. R10GROUPS

[0172] In one aspect, R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1. In a further aspect, R10, when present, is selected from hydrogen, methyl, ethyl, n- propyl, isopropyl, and Ar1. In a still further aspect, R10, when present, is selected from hydrogen, methyl, ethyl, and Ar1. In yet a further aspect, R10, when present, is selected from hydrogen, methyl, and Ar1.

[0173] In various aspects, R10, when present, is selected from hydrogen and C1-C4 alkyl. In a further aspect, R10, when present, is selected from hydrogen, methyl, ethyl, n- propyl, and isopropyl. In a still further aspect, R10, when present, is selected from hydrogen, methyl, and ethyl. In yet a further aspect, R10, when present, is selected from hydrogen and ethyl. In an even further aspect, R10, when present, is selected from hydrogen and methyl.

[0174] In various aspect, R10, when present, is hydrogen.

[0175] In various aspects, R10, when present, is C1-C4 alkyl. In a further aspect, R10, when present, is selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R10, when present, is selected from methyl and ethyl. In yet a further aspect, R10, when present, is ethyl. In an even further aspect, R10, when present, is methyl.

[0176] In various aspects, R10, when present, is Ar1. f. R20A, R20B, R20C, R20D, AND R20EGROUPS

[0177] In one aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R20a, R20b, R20c, R20d, and R20eis hydrogen. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, −CH(CH3)CH2NH2, and unsubstituted phenyl. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, −CH2CH2NH2, and unsubstituted phenyl. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH3, −NHCH3, −N(CH3)2, −CH2NH2, and unsubstituted phenyl.

[0178] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, and unsubstituted phenyl. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, −CH(CH3)CH2NH2, and unsubstituted phenyl. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen,–NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, −CH2CH2NH2, and unsubstituted phenyl. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, – NO2, –CN, –OH, –SH, –NH2, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, −CH2NH2, and unsubstituted phenyl.

[0179] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, – NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0180] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eisindependently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0181] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0182] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl,−CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0183] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0184] In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis selected from the group consisting of hydrogen and halogen. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis selected from the group consisting of hydrogen, ‒F, ‒Cl, and ‒Br. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis selected from the group consisting of hydrogen, ‒F, and ‒Cl. In an even further aspect, each of R20a, R20b, R20c, R20d, and R20eis selected from the group consisting of hydrogen and ‒Cl. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis selected from the group consisting of hydrogen and ‒F.

[0185] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, halogen, and C1-C4 haloalkyl. In a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, and −CH(CH3)CH2Cl. In a still further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2Cl, and−CH2CH2Cl. In yet a further aspect, each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, and −CH2Cl.

[0186] In various aspects, each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen and unsubstituted phenyl.

[0187] In various aspects, at least two of R20a, R20b, R20c, R20d, and R20eis hydrogen. In a still further aspect, at least three of R20a, R20b, R20c, R20d, and R20eis hydrogen. In yet a further aspect, at least four of R20a, R20b, R20c, R20d, and R20eis hydrogen. In an even further aspect, each of R20a, R20b, R20c, R20d, and R20eis hydrogen. g. R21A, R21B, R21C, R21D,ANDR21EGROUPS

[0188] In one aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R21a, R21b, R21c, R21d, and R21eis hydrogen. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, −CH(CH3)CH2NH2, and unsubstituted phenyl. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, −CH2CH2NH2, and unsubstituted phenyl. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH3, −NHCH3, −N(CH3)2, −CH2NH2, and unsubstituted phenyl.

[0189] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, and unsubstituted phenyl. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, −CH(CH3)CH2NH2, and unsubstituted phenyl. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, −CH2CH2NH2, and unsubstituted phenyl. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, – NO2, –CN, –OH, –SH, –NH2, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, −CH2NH2, and unsubstituted phenyl.

[0190] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, – NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0191] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0192] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R21a, R21b,R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0193] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0194] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0195] In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis selected from the group consisting of hydrogen and halogen. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis selected from the group consisting of hydrogen, ‒F, ‒Cl, and ‒Br. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis selected from the group consisting of hydrogen, ‒F, and ‒Cl. In an even further aspect, each of R21a, R21b, R21c, R21d, and R21eis selected from the group consisting of hydrogen and ‒Cl. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis selected from the group consisting of hydrogen and ‒F.

[0196] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, halogen, and C1-C4 haloalkyl. In a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, and −CH(CH3)CH2Cl. In a still further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2Cl, and −CH2CH2Cl. In yet a further aspect, each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, and −CH2Cl.

[0197] In various aspects, each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen and unsubstituted phenyl.

[0198] In various aspects, at least two of R21a, R21b, R21c, R21d, and R21eis hydrogen. In a still further aspect, at least three of R21a, R21b, R21c, R21d, and R21eis hydrogen. In yet a further aspect, at least four of R21a, R21b, R21c, R21d, and R21eis hydrogen. In an even further aspect, each of R21a, R21b, R21c, R21d, and R21eis hydrogen. h. AR1GROUPS

[0199] In one aspect, Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a further aspect, Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar1, when present, isselected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is unsubstituted.

[0200] In various aspect, Ar1, when present, is C6-C14 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. Examples of C6- C14 aryls include, but are not limited to, phenyl, naphthyl, anthracenyl, and phenanthrenyl. In a further aspect, Ar1, when present, is C6-C14 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar1, when present, is C6-C14 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar1, when present, is C6-C14 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar1, when present, is unsubstituted C6-C14 aryl.

[0201] In various aspect, Ar1, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a further aspect, Ar1, when present, is C6 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar1, when present, is C6 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar1, when present, is C6 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar1, when present, is unsubstituted C6 aryl.

[0202] In various aspects, Ar1is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl.

[0203] In various aspects, Ar1, when present, is C2-C10 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. Examples of C2-C10 heteroaryls include, but are not limited to, furan, pyrrole, thiophene, oxazole, isothiazole, pyridine, triazine, quinoline, and isoquinoline. In a further aspect, Ar1, when present, is C2-C10 heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar1, when present, is C2-C10 heteroaryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar1, when present, is C2-C10 heteroaryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar1, when present, is unsubstituted C2-C10 heteroaryl. i. AR2GROUPS

[0204] In one aspect, each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even furtheraspect, each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is unsubstituted.

[0205] In various aspects, each occurrence of Ar2, when present, is C6-C14 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. Examples of C6-C14 aryls include, but are not limited to, phenyl, naphthyl, anthracenyl, and phenanthrenyl. In a further aspect, each occurrence of Ar2, when present, is C6-C14 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, – SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, each occurrence of Ar2, when present, is C6-C14 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, each occurrence of Ar2, when present, is C6-C14 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, each occurrence of Ar2, when present, is unsubstituted C6-C14 aryl.

[0206] In various aspects, each occurrence of Ar2, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, each occurrence of Ar2, when present, is C6 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, each occurrence of Ar2, when present, is C6 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, each occurrence of Ar2, when present, is C6 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, each occurrence of Ar2, when present, is unsubstituted C6 aryl.

[0207] In one aspect, each occurrence of Ar2, when present, is C2-C10 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. Examples of C2-C10 heteroaryls include, but are not limited to, furan, pyrrole, thiophene, oxazole, isothiazole, pyridine, triazine, quinoline, and isoquinoline. In a further aspect, each occurrence of Ar2, when present, is C2-C10 heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, each occurrence of Ar2, when present, is C2-C10 heteroaryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, each occurrence of Ar2, when present, is C2-C10 heteroaryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, – NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, each occurrence of Ar2, when present, is unsubstituted C2-C10 heteroaryl.j. AR3GROUPS

[0208] In one aspect, Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a further aspect, Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is unsubstituted.

[0209] In various aspects, Ar3, when present, is C6-C14 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. Examples of C6-C14 aryls include, but are not limited to, phenyl, naphthyl, anthracenyl, and phenanthrenyl. In a further aspect, Ar3, when present, is C6-C14 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl,C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar3, when present, is C6-C14 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar3, when present, is C6-C14 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar3, when present, is unsubstituted C6-C14 aryl.

[0210] In various aspects, Ar3, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a further aspect, Ar3, when present, is C6 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar3, when present, is C6 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar3, when present, is C6 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar3, when present, is unsubstituted C6 aryl.

[0211] In various aspects, Ar3is C6 aryl substituted with 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a further aspect, Ar3is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl.

[0212] In various aspects, Ar3, when present, is C2-C10 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. Examples of C2-C10 heteroaryls include, but are not limited to, furan, pyrrole, thiophene, oxazole, isothiazole, pyridine, triazine, quinoline, and isoquinoline. In a further aspect, Ar3, when present, is C2-C10 heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In a still further aspect, Ar3, when present, is C2- C10 heteroaryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar3, when present, is C2-C10 heteroaryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar3, when present, is unsubstituted C2-C10 heteroaryl. 2. EXEMPLARY THIOSPHORIC ACIDS

[0213] In one aspect, a compound can be present as:, or a salt thereof.3. PROPHETIC THIOSPHORIC ACID EXAMPLES

[0214] The following compound examples are prophetic, and can be prepared using the synthesis methods described herein above and other general methods as needed as would be known to one skilled in the art. It is anticipated that the prophetic compounds would be useful as organocatalysts and fire retardants, and such utility can be determined using the methods described herein.

[0215] In one aspect, a compound can be selected from: , ,or a salt thereof.

[0216] In one aspect, a compound can be selected from:,, or a sa.

[0217] In one aspect, a compound can be selected from: Ph ,,, or a salt tereo.

[0218] In one aspect, a compound can be selected from: Ph Ph H Ph ,Ph , ,or a salt thereof. C. ALLYLIC THIOPHOSPHONATES

[0219] In one aspect, the invention relates to substituted allylic thiophosphonates, which can be prepared using a thiophosphoric acid as further described herein. Without wishing to be bound by theory, the disclosed allylic thiophosphonates can be useful as fire retardants.

[0220] It is contemplated that each disclosed derivative can be optionally further substituted. It is also contemplated that any one or more derivative can be optionally omitted from the invention. It is understood that a disclosed compound can be provided by the disclosed methods. It is also understood that the disclosed compounds can be employed in the disclosed methods of using. 1. STRUCTURE

[0221] In one aspect, disclosed are compounds having a structure represented by a formula: , wherein A is selected from O and S; wherein each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl, or wherein R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: ;wherein Q is selected from O, S, and NR10; wherein R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R6is selected from C1-C4 alkyl, C1-C4 haloalkyl, ‒CH2Ar4, and Ar4; wherein Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; and wherein each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0222] In various aspects, the compound has a structure represented by a formula selected from: , or a salt

[0223] In various aspects, the compound has a structure represented by a formula: ,or a salt thereof.

[0224] In various aspects, the compound has a structure represented by a formula selected from: , ,, or a salt thereof.

[0225] In various aspects, the compound has a structure represented by a formula: , or a salt thereof.

[0226] In various aspects, the compound has a structure represented by a formula: ,wherein each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R20a, R20b, R20c, R20d, and R20eis hydrogen; and wherein each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R21a, R21b, R21c, R21d, and R21eis hydrogen, or a salt thereof.

[0227] In various aspects, the compound has a structure represented by a formula: , or a salt thereof.In various aspects, the compound has a structure represented by a formula: ,or a salt thereof. In a further aspect, each of R1band R2is independently selected from hydrogen, C1-C4 alkyl, and unsubstituted phenyl. In a still further aspect, each of R20a, R20c, R20e, R21a, R21c, and R21eis independently selected from C1-C4 alkyl and unsubstituted phenyl.

[0228] In various aspects, the compound is selected from: ,, ,or a salt thereof.

[0229] In various aspects, the compound is selected from:,, ,, or a salt thereof.

[0230] In various aspects, the compound is selected from: , ,,or a saltthereof.

[0231] In various aspects, each of R4and R5is independently selected from C1-C4 alkyl, C1-C4 alkoxy, and unsubstituted phenyl. In a further aspect, each of R4and R5is C1- C4 alkoxy. In a still further aspect, each of R4and R5is ethoxy. In yet a further aspect, each of R4and R5is independently selected from C1-C4 alkyl and unsubstituted phenyl. In an even further aspect, each of R4and R5is independently selected from methyl and unsubstituted phenyl.

[0232] In various aspects, R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: ,.In a further, , ate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: nd . In a still further aspec , an are cova en y on e an , oge er w h the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: .In yet a further aspect, R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula: .In an even further aspect, Q is O. In a still further aspect, Q is NR10. In yet a further aspect, R10is C1-C4 alkyl. In an even further aspect, R10is methyl. In a still further aspect, R10is Ar1. In yet a further aspect, Ar1is C6 aryl substituted with 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino, and unsubstituted phenyl. In an even further aspect, Ar1is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl. In a still further aspect, Ar1is unsubstituted C6 aryl.

[0233] In various aspects, each of R1aand R1bis independently selected from hydrogen and Ar2. In an even further aspect, each of R1aand R1bis hydrogen. In a still further aspect, each of R1aand R1bis Ar2. In yet a further aspect, one of R1aand R1bis hydrogen and one of R1aand R1bis Ar2. In an even further aspect, Ar2is unsubstituted C6 aryl. In a still further aspect, each of R1aand R1bis independently selected from hydrogen and C1-C4 alkyl.

[0234] In various aspects, R2is hydrogen. In an even further aspect, R2is selected from ‒CH2Ar1and Ar2. In a still further aspect, Ar2is unsubstituted C6 aryl. In yet a further aspect, R2is C1-C4 alkyl.

[0235] In various aspects, each of R1a, R1b, and R2is hydrogen. In a still further aspect, R1ais hydrogen and each of R1band R2is C1-C4 alkyl. In yet a further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6- membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, R1band R2are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- to 6-membered cycloalkyl.

[0236] In various aspects, R3is selected from hydrogen, C1-C4 alkyl, and Ar3. In a still further aspect, R3is C1-C4 alkyl. In yet a further aspect, R3is methyl. In an even further aspect, R3is Ar3. In a still further aspect, Ar3is C6 aryl substituted with 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl. In yet a further aspect, Ar3is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl. In an even further aspect, Ar3is unsubstituted C6 aryl.

[0237] In various aspects, R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl,C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, R2and R3are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- to 6-membered cycloalkyl.

[0238] In various aspects, R6is C1-C4 alkyl. In a further aspect, R6is methyl. In a still further aspect, R6is Ar4. In yet a further aspect, Ar4is C6-C14 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar4is C6-C14 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar4is C6-C14 aryl monosubstituted with a group selected from halogen and C1-C4 haloalkyl. In yet a further aspect, Ar4is unsubstituted C6-C14 aryl. a. R4 ANDR5GROUPS

[0239] In one aspect, each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl, or wherein R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: .

[0240] In various aspects, each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl. In a further aspect, each of R4and R5is independently selected from methyl, ethyl, n-propyl, isopropyl, ethenyl, n-propenyl, isopropenyl, methoxy, ethoxy, n-propoxy, isopropoxy, ‒OC6H5, and unsubstituted phenyl. In a still further aspect, each of R4and R5is independently selected from methyl, ethyl, ethenyl, methoxy, ethoxy, ‒OC6H5, and unsubstituted phenyl. In yet a further aspect, each of R4and R5is independently selected from methyl, methoxy, ‒OC6H5, and unsubstituted phenyl.

[0241] In various aspects, each of R4and R5is independently selected from C1-C4 alkyl, C1-C4 alkoxy, and unsubstituted phenyl. In a further aspect, each of R4and R5is independently selected from methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, and unsubstituted phenyl. In a still further aspect, each of R4and R5is independently selected from methyl, ethyl, methoxy, ethoxy, and unsubstituted phenyl. In yet a further aspect, each of R4and R5is independently selected from methyl, methoxy, and unsubstituted phenyl.

[0242] In various aspects, each of R4and R5is independently selected from C1-C4 alkyl and unsubstituted phenyl. In a further aspect, each of R4and R5is independently selected from methyl, ethyl, n-propyl, isopropyl, and unsubstituted phenyl. In a still further aspect, each of R4and R5is independently selected from methyl, ethyl, and unsubstituted phenyl. In yet a further aspect, each of R4and R5is independently selected from methyl and unsubstituted phenyl.

[0243] In various aspects, each of R4and R5is independently C1-C4 alkyl. In a further aspect, each of R4and R5is independently selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, each of R4and R5is independently selected from methyl and ethyl. In yet a further aspect, each of R4and R5is ethyl. In an even further aspect, each of R4and R5is methyl.

[0244] In various aspects, each of R4and R5is independently C2-C4 alkenyl. In a further aspect, each of R4and R5is independently selected from ethenyl, n-propenyl, and isopropenyl, . In a still further aspect, each of R4and R5is ethenyl.

[0245] In various aspects, each of R4and R5is independently C1-C4 alkoxy. In a further aspect, each of R4and R5is independently selected from methoxy, ethoxy, n-propoxy, and isopropoxy. In a still further aspect, each of R4and R5is independently selected from methoxy and ethoxy. In yet a further aspect, each of R4and R5is ethoxy. In an even further aspect, each of R4and R5is methoxy.

[0246] In various aspects, each of R4and R5is independently selected from ‒OC6H5 and unsubstituted phenyl.

[0247] In various aspects, R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: .

[0248] In var ous aspects, R and R are cova ent y bonded and, toget er w th the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: .

[0249] In various aspects, R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from: .

[0250] In various aspects, R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula:.

[0251] In various further aspects, embered ring has a structure represented by a formula selected from: .

[0252] Inp , g e represented by a formula: .

[0253] In various further aspects, the 5-membered ring has a structure represented by a formula: ,wherein each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R20a, R20b, R20c, R20d,and R20eis hydrogen; and wherein each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R21a, R21b, R21c, R21d, and R21eis hydrogen.

[0254] In various further aspects, the 5-membered ring has a structure represented by a formula: .

[0255] In various further aspects, the 5-membered ring has a structure represented by a formula: .In a still further aspect, each of R1band R2is independently selected from hydrogen, C1-C4 alkyl, and unsubstituted phenyl. In a yet further aspect, each of R20a, R20c, R20e, R21a, R21c, and R21eis independently selected from C1-C4 alkyl and unsubstituted phenyl.

[0256] In various further aspects, the 5-membered ring has a structure represented by a formula:,,

[0257] In various further aspects, the 5-membered ring has a structure represented by a formula: , ,

[0258] In various further aspects, the 5-membered ring has a structure represented by a formula:Ph Ph H h , , ,. [00259ted by a formula: Ph Ph SH Ph , ,,.b. R6GROUPS

[0260] In one aspect, R6is selected from C1-C4 alkyl, C1-C4 haloalkyl, ‒CH2Ar4, and Ar4. In a further aspect, R6is selected from methyl, ethyl, n-propyl, isopropyl, ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, ‒CH2Cl, ‒CH2CH2F, ‒CH2CH2Cl, ‒CH2CH2CH2F, ‒CH2CH2CH2Cl, ‒CH(CH2F)CH3, ‒CH(CH2Cl)CH3, ‒CH2Ar4, and Ar4. In a still further aspect, R6is selected from methyl, ethyl, ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, ‒CH2Cl, ‒CH2CH2F, ‒CH2CH2Cl, ‒CH2Ar4, and Ar4. In yet a further aspect, R6is selected from methyl, ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, ‒CH2Cl, ‒CH2Ar4, and Ar4.

[0261] In various aspects, R6is C1-C4 alkyl. In a further aspect, R6is selected from methyl, ethyl, n-propyl, and isopropyl. In a still further aspect, R6is selected from methyl and ethyl. In yet a further aspect, R6is methyl.

[0262] In various aspects, R6is C1-C4 haloalkyl. In a further aspect, R6is selected from ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, ‒CH2Cl, ‒CH2CH2F, ‒CH2CH2Cl, ‒CH2CH2CH2F, ‒CH2CH2CH2Cl, ‒CH(CH2F)CH3, and ‒CH(CH2Cl)CH3. In a still further aspect, R6is selected from ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, ‒CH2Cl, ‒CH2CH2F, and‒CH2CH2Cl. In yet a further aspect, R6is selected from ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, and ‒CH2Cl.

[0263] In various aspects, R6is selected from ‒CH2Ar4and Ar4. In a further aspect, R6is ‒CH2Ar4. In a still further aspect, R6is Ar4. c. R7A, R7B, R7C, R7D,ANDR7EGROUPS

[0264] In one aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0265] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH,−CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0266] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0267] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl,−CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0268] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0269] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2,−CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0270] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0271] In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis selected from the group consisting of hydrogen and halogen. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis selected from the group consisting of hydrogen, ‒F, ‒Cl, and ‒Br. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis selected from the group consisting of hydrogen, ‒F, and ‒Cl. In an even further aspect, each of R7a, R7b, R7c, R7d, and R7eis selected from the group consisting of hydrogen and ‒Cl. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis selected from the group consisting of hydrogen and ‒F.

[0272] In various aspects, each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, halogen, and C1-C4 haloalkyl. In a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, and−CH(CH3)CH2Cl. In a still further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2Cl, and −CH2CH2Cl. In yet a further aspect, each of R7a, R7b, R7c, R7d, and R7eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, and −CH2Cl.

[0273] In various aspects, at least one of R7a, R7b, R7c, R7d, and R7eis hydrogen. In a further aspect, at least two of R7a, R7b, R7c, R7d, and R7eis hydrogen. In a still further aspect, at least three of R7a, R7b, R7c, R7d, and R7eis hydrogen. In yet a further aspect, at least four of R7a, R7b, R7c, R7d, and R7eis hydrogen. In an even further aspect, each of R7a, R7b, R7c, R7d, and R7eis hydrogen. d. AR4GROUPS

[0274] In one aspect, Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1- C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is monosubstituted with a group selected from halogen, –NO2, –CN, –OH, – SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0275] In various aspects, Ar4, when present, is C6-C14 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. Examples of C6-C14 aryls include, but are not limited to, phenyl, naphthyl, anthracenyl, and phenanthrenyl. In a further aspect, Ar4, when present, is C6-C14 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar4, when present, is C6-C14 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, – NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar4, when present, is C6-C14 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar4, when present, is unsubstituted C6-C14 aryl.

[0276] In various aspects, Ar4, when present, is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, Ar4, when present, is C6 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar4, when present, is C6 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar4, when present, is C6 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar4, when present, is unsubstituted C6 aryl.

[0277] In various aspects, Ar4, when present, is 4-10 membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. Examples of 4-10 membered heteroaryls include, but are not limited to, furan, pyrrole, thiophene, imidazole, oxazole, isothiazole, pyridine, triazine, quinoline, indole, and isoquinoline. In a further aspect, Ar4, when present, is 4-10 membered heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar4, when present, is 4-10 membered heteroaryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar4, when present, is 4-10 membered heteroaryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar4, when present, is unsubstituted 4-10 membered heteroaryl.

[0278] In various aspects, Ar4is selected from furanyl, pyrrolyl, indolyl, imidazolyl, and thiophenyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0279] In various aspects, Ar4, when present, is C6-C14 aryl monosubstituted with a group selected from halogen and C1-C4 haloalkyl. In a further aspect, Ar4, when present, is C6-C14 aryl monosubstituted with a group selected from ‒F, ‒Cl, ‒CF3, ‒CHF2, ‒CH2F, ‒CH2CH2F, ‒CH2CH2CH2F, ‒CH(CH2F)CH3, ‒CCl3, ‒CHCl2, ‒CH2Cl, ‒CH2CH2Cl,‒CH2CH2CH2Cl, and ‒CH(CH2Cl)CH3. In a still further aspect, Ar4, when present, is C6- C14 aryl monosubstituted with a group selected from ‒F, ‒Cl, ‒CF3, ‒CHF2, ‒CH2F, ‒CH2CH2F, ‒CCl3, ‒CHCl2, ‒CH2Cl, and ‒CH2CH2Cl. In yet a further aspect, Ar4, when present, is C6-C14 aryl monosubstituted with a group selected from ‒F, ‒Cl, ‒CF3, ‒CHF2, ‒CH2F, ‒CCl3, ‒CHCl2, and ‒CH2Cl. 2. EXEMPLARY ALLYLIC THIOPHOSPHONATES

[0280] In one aspect, a compound can be present as: , or a salt thereof.3. PROPHETIC ALLYLIC THIOPHOSPHONATE EXAMPLES

[0281] The following compound examples are prophetic, and can be prepared using the synthesis methods described herein above and other general methods as needed as would be known to one skilled in the art. It is anticipated that the prophetic compounds would be useful as fire retardants, and such utility can be determined using the methods described herein.

[0282] In one aspect, a compound can be selected from: , ,, , , , or a salt thereof.

[0283] In one aspect, a compound can be selected from: ,, ,or a salt thereof.

[0284] In one aspect, a compound can be selected from:,, ,, or a salt thereof.D. ADDITIONALTHIOPHOSPHONATEANALOGS

[0285] In one aspect, the invention relates to substituted thiophosphonates, which can be prepared using a thiophosphoric acid as further described herein. Without wishing to be bound by theory, the disclosed thiophosphonate analogs may be useful in a variety of different applications, including in the fields of medicine, catalysis, agricultural chemistry, and materials chemistry.

[0286] It is contemplated that each disclosed derivative can be optionally further substituted. It is also contemplated that any one or more derivative can be optionally omitted from the invention. It is understood that a disclosed compound can be provided by the disclosed methods. It is also understood that the disclosed compounds can be employed in the disclosed methods of using. 1. STRUCTURE

[0287] In one aspect, disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl, or wherein R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from:;wherein Q, , , , om hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6- C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R6is selected from C1-C4 alkyl, C1-C4 haloalkyl, ‒CH2Ar4, and Ar4; wherein Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R8is selected from ‒OH and ‒NHPG; wherein PG is an amine protecting group; and wherein Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 additional groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0288] In one aspect, disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein each of R4and R5is independently selected from C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, ‒OC6H5, and unsubstituted phenyl, or wherein R4and R5are covalently bonded and, together with the intermediate atoms, comprise a 5-membered ring having a structure represented by a formula selected from:;wherein Q, , , , om hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6- C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R6is selected from C1-C4 alkyl, C1-C4 haloalkyl, ‒CH2Ar4, and Ar4; wherein Ar4, when present, is selected from C6-C14 aryl and 4-10 membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R8is selected from hydrogen, ‒OH, and ‒NHPG; wherein PG is an amine protecting group; and wherein Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 additional groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, provided that when R8is hydrogen, then R6is Ar4and Ar4is a 4-10 membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0289] In one aspect, disclosed are compounds having a structure represented by a formula: ,wherein A is selected from O and S; wherein Q is selected from O, S, and NR10; wherein R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6- membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; and wherein each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

[0290] In various aspects, the compound has a structure represented by a formula selected from: , wherein ea, , , , alogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0291] In various aspects, the compound has a structure represented by a formula selected from: , or a salt th

[0292] In various aspects, the compound has a structure represented by a formula selected from: , ,, or a s

[0293] In various aspects, the compound has a structure represented by a formula selected from: ,wherein Ar4is a 4-10 membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, Ar4is selected from furanyl, pyrrolyl, indolyl, imidazolyl, and thiophenyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1- C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

[0294] In various aspects, the compound is selected from:,or a py p .

[0295] In various aspects, the compound has a structure represented by a formula selected from: R9cR1bR9d 9bR10R , or a salt.

[0296] In various aspects, the compound has a structure represented by a formula selected from: ,wherein each of R20a, R20b, R20c, R20d, and R20eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R20a, R20b, R20c, R20d, and R20eis hydrogen; and wherein each of R21a, R21b, R21c, R21d, and R21eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl, provided that at least two of R21a, R21b, R21c, R21d, and R21eis hydrogen, or a salt thereof.

[0297] In various aspects, the compound has a structure represented by a formula selected from: , or a salt

[0298] In various aspects, the compound has a structure represented by a formula selected from: , or a saltthereof. In a further aspect, each of R and R is independently selected from hydrogen, C1-C4 alkyl, and unsubstituted phenyl. In a still further aspect, each of R20a, R20c, R20e, R21a, R21c, and R21eis independently selected from C1-C4 alkyl and unsubstituted phenyl.

[0299] In various aspects, the compound has a structure selected from: OEt OEt EtO S EtO S P P H , H , , , ,,, , , or asalt thereof.

[0300] In various aspects, the compound has a structure selected from: ,, , , ,or a salt thereof.

[0301] In various aspects, PG is an amine protecting group. Examples of amine protecting groups include, but are not limited to, carbobenzyloxy, p-methoxybenzyl carbonyl, t-butyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, acetyl, benzoyl, benzyl, carbamate, p- methoxybenzyl, 3,4-dimethoxybenzyl, p-methoxyphenyl, tosyl, and 4-nitrobenzenesulfonyl.

[0302] In various aspects, the compound has a structure represented by a formula: , or a salt thereof.

[0303] In various aspects, the compound has a structure represented by a formula: ,or a salt thereof.

[0304] In various aspects, the compound has a structure represented by a formula: ,or a salt thereof.

[0305] In various aspects, the compound has a structure represented by a formula:, or a salt thereof.

[0306] In various aspects, the compound has a structure represented by a formula: , or a salt thereof.

[0307] In various aspects, the compound is selected from: ,,, or a salt thereof.

[0308] In various aspects, the compound is selected from: ,,or a salt thereof.

[0309] In various aspects, the compound is selected from: ,,or a salt thereof.

[0310] In various aspects, the compound is selected from: ,,or a sat t ereo . a. R8GROUPS

[0311] In one aspect, R8is selected from hydrogen, ‒OH, and ‒NHPG. In a further aspect, R8is hydrogen.

[0312] In one aspect, R8is selected from ‒OH and ‒NHPG. In a further aspect, R8is ‒OH. In a still further aspect, R8is ‒NHPG. b. R9A, R9B, R9C, AND R9DGROUPS

[0313] In one aspect, each of R9a, R9b, R9c, and R9dis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3,−OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, – CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0314] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, – CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0315] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl,−CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0316] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0317] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3,−NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0318] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0319] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen,methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0320] In a further aspect, each of R9a, R9b, R9c, and R9dis selected from the group consisting of hydrogen and halogen. In a still further aspect, each of R9a, R9b, R9c, and R9dis selected from the group consisting of hydrogen, ‒F, ‒Cl, and ‒Br. In yet a further aspect, each of R9a, R9b, R9c, and R9dis selected from the group consisting of hydrogen, ‒F, and ‒Cl. In an even further aspect, each of R9a, R9b, R9c, and R9dis selected from the group consisting of hydrogen and ‒Cl. In a still further aspect, each of R9a, R9b, R9c, and R9dis selected from the group consisting of hydrogen and ‒F.

[0321] In various aspects, each of R9a, R9b, R9c, and R9dis independently selected from hydrogen, halogen, and C1-C4 haloalkyl. In a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, and −CH(CH3)CH2Cl. In a still further aspect, each of R9a, R9b, R9c, and R9dis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2Cl, and −CH2CH2Cl. In yet a further aspect, each of R9a, R9b, R9c, and R9dis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, and −CH2Cl.

[0322] In various aspects, at least one of R9a, R9b, R9c, and R9dis hydrogen. In a further aspect, at least two of R9a, R9b, R9c, and R9dis hydrogen. In a still further aspect, at least three of R9a, R9b, R9c, and R9dis hydrogen. In yet a further aspect, each of R9a, R9b, R9c, and R9dis hydrogen. c. R12A, R12B, R12C, R12D, AND R12E

[0323] In one aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH,−CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, – NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0324] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0325] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R12a, R12b,R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, – NO2, –CN, –OH, –SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0326] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, –SH, –NH2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, –NO2, –CN, –OH, – SH, –NH2, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0327] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4aminoalkyl. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCH3, −OCH2CH3, −OCH2CH2CH3, −OCH(CH3)2, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2OH, −CH2CH2OH, −OCH3, −OCH2CH3, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2OH, −OCH3, −NHCH3, −N(CH3)2, and −CH2NH2.

[0328] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −NHCH3, −NHCH2CH3, −NHCH2CH2CH3, −NHCH(CH3)2, −N(CH3)2, −N(CH3)CH2CH3, −N(CH3)CH2CH2CH3, −N(CH3)CH(CH3)2, −CH2NH2, −CH2CH2NH2, −CH2CH2CH2NH2, and −CH(CH3)CH2NH2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −NHCH3, −NHCH2CH3, −N(CH3)2, −N(CH3)CH2CH3, −CH2NH2, and −CH2CH2NH2. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −NHCH3, −N(CH3)2, and −CH2NH2.

[0329] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, isopropenyl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl,−CH2CH2CH2Cl, −CH(CH3)CH2Cl, −CH2CN, −CH2CH2CN, −CH2CH2CH2CN, −CH(CH3)CH2CN, −CH2OH, −CH2CH2OH, −CH2CH2CH2OH, −CH(CH3)CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH2CH2CH2F, −OCH(CH3)CH2F, −OCH3, −OCH2CH3, −OCH2CH2CH3, and −OCH(CH3)2. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, ethyl, ethenyl, −CH2F, −CH2CH2F, −CH2Cl, −CH2CH2Cl, −CH2CN, −CH2CH2CN, −CH2OH, −CH2CH2OH, −OCF3, −OCHF3, −OCH2F, −OCH2CH2F, −OCH3, and −OCH2CH3. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from the group consisting of hydrogen, halogen, methyl, −CH2F, −CH2Cl, −CH2CN, −CH2OH, −OCF3, −OCHF3, −OCH2F, and −OCH3.

[0330] In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis selected from the group consisting of hydrogen and halogen. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis selected from the group consisting of hydrogen, ‒F, ‒Cl, and ‒Br. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis selected from the group consisting of hydrogen, ‒F, and ‒Cl. In an even further aspect, each of R12a, R12b, R12c, R12d, and R12eis selected from the group consisting of hydrogen and ‒Cl. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis selected from the group consisting of hydrogen and ‒F.

[0331] In various aspects, each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, halogen, and C1-C4 haloalkyl. In a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2CH2CH2F, −CH(CH3)CH2F, −CH2Cl, −CH2CH2Cl, −CH2CH2CH2Cl, and −CH(CH3)CH2Cl. In a still further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, −CH2CH2F, −CH2Cl, and −CH2CH2Cl. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis independently selected from hydrogen, ‒F, ‒Cl, −CH2F, and −CH2Cl.

[0332] In various aspects, at least one of R12a, R12b, R12c, R12d, and R12eis hydrogen. In a further aspect, at least two of R12a, R12b, R12c, R12d, and R12eis hydrogen. In a still further aspect, at least three of R12a, R12b, R12c, R12d, and R12eis hydrogen. In yet a further aspect, each of R12a, R12b, R12c, R12d, and R12eis hydrogen. d. AR5GROUPS

[0333] In one aspect, Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 additional groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar5is selected from C6-C14 aryl and C2-C10 heteroaryl, and is unsubstituted.

[0334] In various aspects, Ar5is C6-C14 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. Examples of C6-C14 aryls include, but are not limited to, phenyl, naphthyl, anthracenyl, and phenanthrenyl. In a further aspect, Ar5is C6-C14 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, – CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar5is C6-C14 aryl substituted with 0 or 1 group selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar5is C6-C14 aryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar5is unsubstituted C6-C14 aryl.

[0335] In various aspects, Ar5is C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a further aspect, Ar5is C6 aryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar5is C6 aryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, –OH, –SH, – NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1- C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1- C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar5is C6 aryl monosubstituted with a group selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar5is unsubstituted C6 aryl.

[0336] In one aspect, Ar5is C2-C10 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. Examples of C2-C10 heteroaryls include, but are not limited to, furan, pyrrole, thiophene, oxazole, isothiazole, pyridine, triazine, quinoline, and isoquinoline. In a further aspect, Ar5is C2-C10 heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In a still further aspect, Ar5is C2-C10 heteroaryl substituted with 0 or 1 group selected from halogen, –NO2, –CN, – OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In yet a further aspect, Ar5is C2-C10 heteroaryl monosubstituted with a group selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino. In an even further aspect, Ar5is unsubstituted C2-C10 heteroaryl. 2. EXEMPLARY THIOPHOSPHONATE ANALOGS

[0337] In one aspect, a compound can be present as: OEt OEt EtO S EtO S OH , OH , , ,O OEt , , , , , or a.

[0338] In one aspect, a compound can be present as: ,or a salt thereof. 3. PROPHETIC THIOPHOSPHONATE EXAMPLES

[0339] The following compound examples are prophetic, and can be prepared using the synthesis methods described herein above and other general methods as needed as would be known to one skilled in the art.

[0340] In one aspect, a compound can be selected from: , , , ,tBu OH Ph , or

[0341] In one aspect, a compound can be selected from: ,,or a salt thereof.

[0342] In one aspect, a compound can be selected from:,,or a sa

[0343] In one aspect, a compound can be selected from: , ,or a salt thereof.E. METHODS OF MAKING AN THIOPHOSPHORIC ACIDS

[0344] The thiophosphoric acid compounds of this invention can be prepared by employing reactions as shown in the following schemes, in addition to other standard manipulations that are known in the literature, exemplified in the experimental sections or clear to one skilled in the art. For clarity, examples having a single substituent are shown where multiple substituents are allowed under the definitions disclosed herein.

[0345] Reactions used to generate the thiophosphoric acid compounds of this invention are prepared by employing reactions as shown in the following Reaction Schemes, as described and exemplified below. In certain specific examples, the disclosed compounds can be prepared by Route I, as described and exemplified below. The following examples are provided so that the invention might be more fully understood, are illustrative only, and should not be construed as limiting. 1. ROUTE I

[0346] In one aspect, substituted thiophosphoric acids can be prepared as shown below. SCHEME1A.

[0347] Compounds are represented in generic form, with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 1B.

[0348] In one aspect, the synthesis of thiophosphoric acids can begin with a bi- functional amine, e.g., 1.4 as shown above. Bi-functional amine derivatives are commercially available or readily prepared by one skilled in the art. Thus, compounds of type 1.6, and similar compounds, can be prepared according to reaction Scheme 1B above. Compounds of type 1.5 can be prepared via cyclization of an appropriate bi-functional amine, e.g., 1.4 as shown above. The cyclization is carried out in the presence of an appropriate phosphorous reagent, e.g., phosphorous trichloride, and an appropriate amine, e.g., triethylamine, in an appropriate solvent, e.g., dichloromethane. Compounds of type 1.6 can be prepared by oxidation of an appropriate phosphite analog, e.g., 1.5 as shown above. The oxidation is carried out in the presence of an appropriate sulphur reagent, e.g., octasulfur, and an appropriate base, e.g., triethylamine, in an appropriate solvent system, e.g., ether and ethyl acetate. As can be appreciated by one skilled in the art, the above reaction provides an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 1.1 and 1.2), can be substituted in the reaction to provide substituted thiophosphoric acid analogs similar to Formula 1.3. F. METHODS OF MAKING ALLYLIC THIOPHOSPHONATES

[0349] The allylic thiophosphonate compounds of this invention can be prepared by employing reactions as shown in the following schemes, in addition to other standard manipulations that are known in the literature, exemplified in the experimental sections or clear to one skilled in the art. For clarity, examples having a single substituent are shown where multiple substituents are allowed under the definitions disclosed herein.

[0350] Reactions used to generate the allylic thiophosphonate compounds of this invention are prepared by employing reactions as shown in the following Reaction Schemes, as described and exemplified below. In certain specific examples, the disclosed compounds can be prepared by Route I, as described and exemplified below. The following examples are provided so that the invention might be more fully understood, are illustrative only, and should not be construed as limiting. 2. ROUTE I

[0351] In one aspect, substituted allylic thiophosphonates can be prepared as shown below.SCHEME 2A.

[00352] Compounds are represented n gener c orm, w t subst tuents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 2B.

[0353] In one aspect, the synthesis of allylic thiophosphonates can begin with an allylic alcohol, e.g., 2.4 as shown above, and a phosphorothioic acid analog, e.g., 2.5 as shown above. Allylic alcohols and phosphorothioic acid analogs are commercially available or readily prepared by one skilled in the art. Thus, compounds of type 2.6, and similar compounds, can be prepared according to reaction Scheme 2B above. Compounds of type 2.6 can be prepared by a substitution reaction between an allylic alcohol, e.g., 2.4 as shown above, and a phosphorothioic acid analog, e.g., 2.5 as shown above. The substitution reaction is carried out in the presence of an appropriate solvent, e.g., dichloromethane, at an appropriate temperature, e.g., room temperature, for an appropriate period of time, e.g., 30 minutes. As can be appreciated by one skilled in the art, the above reaction provides an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 2.1 and 2.2), can be substituted in the reaction to provide substituted allylic thiophosphonate analogs similar to Formula 2.3. G. ADDITIONAL METHODS OF MAKING THIOPHOSPHATES

[0354] The thiophosphonate compounds of this invention can be prepared by employing reactions as shown in the following schemes, in addition to other standard manipulations that are known in the literature, exemplified in the experimental sections orclear to one skilled in the art. For clarity, examples having a single substituent are shown where multiple substituents are allowed under the definitions disclosed herein.

[0355] Reactions used to generate the thiophosphonate compounds of this invention are prepared by employing reactions as shown in the following Reaction Schemes, as described and exemplified below. In certain specific examples, the disclosed compounds can be prepared by Routes I-III, as described and exemplified below. The following examples are provided so that the invention might be more fully understood, are illustrative only, and should not be construed as limiting. 3. ROUTE I

[0356] In one aspect, substituted thiophosphonates can be prepared as shown below. SCHEME3A.

[0357] Compounds are represented in generic form, with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 3B.

[0358] In one aspect, the synthesis of thiophosphonates can begin with a phenol, e.g., 3.4 as shown above, or an aniline, e.g., 3.7 as shown above, and a thiophosphoric acid analog,e.g., 3.5 and 3.8 as shown above. Phenol and aniline derivatives are commercially available or readily prepared by one skilled in the art. Thiophosphoric acid analogs are commercially available or can be prepared as disclosed herein. Thus, compounds of type 3.6 and 3.7, and similar compounds, can be prepared according to reaction Scheme 3B and Scheme 3C above. Compounds of type 3.6 and 3.7 can be prepared by a substitution reaction between an appropriate phenol derivative or an appropriate aniline derivative, e.g., 3.4 and 3.7, respectively, as shown above. The substitution reaction is carried out in the presence of an appropriate solvent, e.g., dichloromethane, at an appropriate temperature, e.g., room temperature, for an appropriate period of time, e.g., 12 hours. In the case of aniline derivatives, the substitution reaction is also carried out in the presence of an appropriate acid, e.g., p-toluenesulfonic acid (TsOH) as shown above. As can be appreciated by one skilled in the art, the above reaction provides an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 3.1 and 3.2), can be substituted in the reaction to provide substituted thiophosphonate analogs similar to Formula 3.3. 4. ROUTE II

[0359] In one aspect, substituted thiophosphonates can be prepared as shown below. SCHEME 4A.

[0360] Compounds are represented in generic form, with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 4B.

[0361] In one aspect, the synthesis of thiophosphonates can begin with a para- quinone methide, e.g., 4.1 as shown above, and a thiophosphoric acid analog, e.g., 4.4 as shown above. Para-quinone methide derivatives are commercially available or readily prepared by one skilled in the art. Thiophosphoric acid analogs are commercially available or can be prepared as disclosed herein. Thus, compounds of type 4.6, and similar compounds, can be prepared according to reaction Scheme 4B above. Compounds of type 4.6 can be prepared by a substitution reaction between an appropriate para-quinone methide derivative, e.g., 4.4 as shown above, and a thiophosphoric acid analog, e.g., 4.5 as shown above. The substitution reaction is carried out in the presence of an appropriate solvent, e.g., dichloromethane, at an appropriate temperature, e.g., room temperature, for an appropriate period of time, e.g., 12 hours. As can be appreciated by one skilled in the art, the above reaction provides an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 4.1 and 4.2), can be substituted in the reaction to provide substituted thiophosphonate analogs similar to Formula 4.3. 5. ROUTE III

[0362] In one aspect, substituted thiophosphonates can be prepared as shown below. SCHEME 5A.

[0363] Compounds are represented in generic form, with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below.SCHEME 5B.

[0364] o e aspec , e sy es s o op osp o a es ca eg w a allylic alcohol, e.g., 5.1 as shown above, and a thiophosphoric acid analog, e.g., 5.2 as shown above. Allylic alcohols are commercially available or readily prepared by one skilled in the art. Thiophosphoric acid analogs are commercially available or can be prepared as disclosed herein. Thus, compounds of type 5.6, and similar compounds, can be prepared according to reaction Scheme 5B above. Compounds of type 5.6 can be prepared by a substitution reaction followed by a 3,3-sigmatropic rearrangement of an appropriate allylic alcohol derivative, e.g., 5.4 as shown above, and a thiophosphoric acid analog, e.g., 5.5 as shown above. The rearrangement is carried out in the presence of an appropriate solvent, e.g., toluene. As can be appreciated by one skilled in the art, the above reaction provides an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 5.1 and 5.2), can be substituted in the reaction to provide substituted thiophosphonate analogs similar to Formula 5.3.

[0365] The foregoing description illustrates and describes the disclosure. Additionally, the disclosure shows and describes only the preferred embodiments but, as mentioned above, it is to be understood that it is capable to use in various other combinations, modifications, and environments and is capable of changes or modifications within the scope of the invention concepts as expressed herein, commensurate with the above teachings and / or the skill or knowledge of the relevant art. The embodiments described herein above are further intended to explain best modes known by applicant and to enable others skilled in the art to utilize the disclosure in such, or other, embodiments and with the various modifications required by the particular applications or uses thereof. Accordingly, the description is not intended to limit the invention to the form disclosed herein. Also, it is intended to the appended claims be construed to include alternative embodiments.

[0366] All publications and patent applications cited in this specification are herein incorporated by reference, and for any and all purposes, as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. In the event of an inconsistency between the present disclosure and any publications or patent application incorporated herein by reference, the present disclosure controls. H. EXAMPLES

[0367] The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and / or methods claimed herein are made and evaluated, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric.

[0368] The Examples are provided herein to illustrate the invention, and should not be construed as limiting the invention in any way. Examples are provided herein to illustrate the invention and should not be construed as limiting the invention in any way. 1. EXPERIMENTAL i. GENERALINFORMATION

[0369] All reactions were carried out under air atmosphere in oven-dried glassware with magnetic stirring bar. Dry solvents (THF, toluene, and DCM) were obtained by solvent purification system under argon. All commercially available reagents were used as received without further purification. The tubes used for the reaction are shown in FIG.3. Purification of reaction products was carried out by flash column chromatography using silica gel 60 (230-400 mesh). Analytical thin layer chromatography was performed on 0.25 mm aluminum-backed silica gel 60-F plates. Visualization was accompanied with UV light and KMnO4solution. Concentration under reduced pressure refers to the removal of volatiles using a rotary evaporator attached to a dry diaphragm pump (10-15 mm Hg) followed by pumping to a constant weight with an oil pump (<300 mTorr). Infrared (IR) spectra were recorded on an IR spectrometer with KBr wafers or a film on KBr plate. High-resolution mass spectra (HRMS) were recorded on LCMS-IT-TOF mass spectrometer using ESI(electrospray ionization) or APCI (Atmospheric Pressure Chemical Ionization).1H NMR spectra were recorded in CDCl3on 400 MHz NMR spectrometer. The1H chemical shifts are referenced to residual solvent signals at δ 7.26 (CHCl3) or δ 0.00 (TMS).1H NMR coupling constants (J) are reported in Hertz (Hz) and multiplicities are indicated as follows: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), dt (doublet of triplets), td (triplet of doublets), tt (triplet of triplets).13C NMR spectra were proton decoupled and recorded in CDCl3 on 100.5 MHz NMR spectrometer. The13C chemical shifts are referenced to solvent signals at δ 77.16 (CDCl3).31P NMR spectra were proton decoupled and recorded in CDCl3 on 162 MHz NMR spectrometer.31P chemical shifts are reported relative to 85% H3PO4(0.00 ppm) as an external standard. ii. GENERAL PROCEDURE FOR THE SYNTHESIS OF DIARYL ALCOHOL 2

[0370] Diaryl alcohol starting materials 1a-1p were synthesized via Grignard reaction according procedure in Huang et al., Org. Lett., 2017, 19, 5988-5991. To a suspension of Mg (10.0 mmol) in THF (8.0 mL) was added a crystal of iodine followed by drop wise addition of halide (10.0 mmol) dissolved in THF (3.0 mL), the solution was then refluxed for 1 h. Grignard Reagent (10.0 mmol, 3.3 equiv) was cooled to 0 °C and aldehyde (3.33 mmol, 1.0 equiv) in THF (3.0 mL) was added dropwise, the solution was stirred for 1 h. The solution was then quenched with NH4Cl and extracted with dichloromethane (3X). The organic layer was washed with brine, dried over sodium sulfate, and then directly purified by column chromatography. iii. GENERALPROCEDURE FOR THESYNTHESIS OFTHIOPHOSPHATE3

[0371] O,O-diethyl S-hydrogen phosphorothioate (.15 mmol, 1.5 equiv) was dissolved in dichloromethane (0.5 mL), diaryl phenol (.10 mmol, 1.0 equiv) was then added and the solution was stirred for 12 h. The crude reaction was then directly purified by column chromatography. iv. GENERALPROCEDURE FOR THESYNTHESIS OFTHIOPHOSPHATE4

[0372] Thiophosphoric acid (0.15 mmol, 1.5 equiv) was dissolved in dichloromethane (0.5 mL).2-(hydroxy(phenyl)methyl)-4-methylphenol (.10 mmol, 1.0 equiv) was then added and the solution was stirred for 12 h. The crude reaction was then directly purified by column chromatography. v. GENERALPROCEDURE FOR THESYNTHESIS OFTHIOPHOSPHORICACID2

[0373] Step 1: Alkoxyphosphites were prepared by a modified version of the following procedure (Fakhraian et al., Org. Process Res. Dev., 2004, 8, 401-404). Phosphorous trichloride (3.0 mmol, 1.0 equiv) was dissolved in DCM (200 microliter) under inert atmosphere and cooled to 0 °C. Alkyl alcohol (9.0 mmol, 3.0 equiv) was added dropwise, and the reaction was allowed to warm to room temperature and was stirred for 15 minutes. The reaction was then concentrated and dried under high vacuum to give alkoxyphosphite in quantitative yield.

[0374] Step 2: Thiophosphoric acids were prepared according to the following procedure (Guo et al., Org. Lett., 2021, 23, 6729-6734). Alkoxy phosphite (10.0 mmol, 1.0 equiv) and sulfur was dissolved in ether. Triethylamine was then added and the reaction was allowed to stir for 12 h. Upon completion of the reaction as indicated by TLC, the crude reaction was diluted with ether and transferred to a separatory funnel and the organic layerwas washed three times with 1 M HCl until acidic. The organic layer was the dried with sodium sulfate and concentrated to give thiophosphoric acid. vi. GENERALPROCEDURE FOR THESYNTHESIS OFSULFONAMIDOTHIOPHOSPHATES6

[00375] op osp or c ac (. mmo, .0 equ v) was sso ve n c oromet ane (0.5 mL), amino alcohol (.1 mmol, 1.0 equiv), and para-toulene sulfonic acid catalyst (0.01 mmol, 0.1 equiv) was then added and the solution was stirred for 12 h. The crude reaction was then directly purified by column chromatography. vii. GENERALPROCEDURE FOR THESYNTHESIS OFDIARYLSULFONAMIDOALCOHOLS5

[0376] Step 1: 2-amino benzyaldehyde was prepared according to the following procedure.42-nitrobenzyladehyde (8.5 mmol, 1.0 equiv) was dissolved in ethanol (50 mL), iron powder (51 mmol, 6.0 equiv) was then added, followed by the addition of concentrated HCl (0.5 mL). The solution was refluxed for 1 h. The iron was removed by filtration over celite. The crude yellow mixture was then rotovapped to dryness and dissolved in water. The solution was then extracted with ethyl acetate three times and washed with brine, followed by drying with sodium sulfate. The dried organic extract was then conentrated and the crude amine was used for the following step without further purification.

[0377] Step 2: 2-aminobenzaldehyde (2.15 mmol, 1.0 equiv) was dissolved in dichloromethane (5.8 mL). Tosyl chloride (2.36 mmol, 1.1 equiv) was added, followed by the addition of pyridine (4.73 mmol, 2.2 equiv). The reaction was allowed to stir for 12 h. The reaction was then diluted with water, and extracted with DCM three times. The organic layerwas washed with brine, and dried over sodium sulfate. The dried organic layer was directly purified by column chromatography.

[0378] Step 3: To a suspension of Mg (3.0 mmol) in THF (2.0 mL) was added a crystal of iodine followed by drop wise addition of halide (3.0 mmol) dissolved in THF (1.0 mL), the solution was then refluxed for 1 h. Grignard Reagent (3.0 mmol, 3.3 equiv) was cooled to 0 °C and aldehyde (1.0 mmol, 1.0 equiv) in THF (1.0 mL) was added dropwise, the solution was stirred for 1 h. The solution was then quenched with NH4Cl and extracted with dichloromethane three times. The organic layer was washed with brine, dried over sodium sulfate, and then directly purified by column chromatography. viii. PROCEDURE FOR THE SYNTHESIS OF 5G

[0379] Step 1: (2-aminophenyl)(phenyl)methanone (1.0 mmol, 1.0 equiv) was dissolved in dichloromethane (5.0 mL), benzoyl chloride (1.5 mmol, 1.5 equiv) was added, followed by addition of triethyl amine (1.5 mmol, 1.5 equiv). The reaction stirred for 2 h and then was directly purififed by column chromatography.

[0380] Step 2: N-(2-benzoylphenyl)benzamide (.63 mmol, 1.0 equiv) was dissolved in methanol (3.0 mL) and was cooled to 0 °C. Sodium borohydride (1.55 mmol, 2.5 equiv) was added slowly. The reaction was stirred for an hour and was quenched by addition of water and extraction with DCM three times. The organic layer was washed with brine and dried over sodium sulfate. The dried organic extract was concentrated to give N-(2- (hydroxy(phenyl)methyl)phenyl)benzamide. ix. SCALE UPEXPERIMENT

[0381] Thiophosphoric acid (4.5 mmol, 1.5 equiv) was dissolved in dichloromethane (15 mL), Diaryl phenol (3.0 mmol, 1.0 equiv) was then added and the solution was stirred for 12 h. The crude reaction was then directly purified by column chromatography.922.8 mg of 3a, 87% yield. 2. CHARACTERIZATIONDATA FORFINALCOMPOUNDSi. O,O-DIETHYLS-((2-HYDROXYPHENYL)(PHENYL)METHYL) PHOSPHOROTHIOATE(3A)

[0382] 31.5 mg, 91%; as an oil; IR ^ (thin film, cm-1); 3322, 2986, 1597, 1480, 1450, 1226, 1018, 972, 756, 702;1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.0 Hz, 2H), 7.32-7.28 (m, 2H), 7.24-7.21 (m, 2H), 7.11-7.07 (m, 1H), 6.92 (d, J = 4.0 Hz, 1H), 6.83 (t, J = 7.2 Hz, 1H), 6.14 (d, J = 12.4 Hz, 1H).4.07-3.91 (m, 3H), 3.90- 3.83 (m, 1H), 1.22-1.13 (dt, J = 18.8 Hz, J = 7.2 Hz, 6H).13C NMR (100.5 MHz, CDCl3) δ 153.8, 140.7 (d, J = 5.2 Hz), 129.0, 128.8, 128.5 (d, J = 5.2 Hz), 128.4, 128.3, 127.3, 120.4, 117.2, 64.0 (dd, J = 11.2 Hz, J = 5.9 Hz), 48.1 (d, J = 3.0 Hz), 15.7 (d, J = 7.4 Hz);31P NMR (162 MHz, CDCl3): δ 28.62; HRMS (ESI): m / z calcd. for C17H21O4PS ([M+Na]+): 375.0790; Found: 375.0769. ii. O,O-DIETHYLS-((4-FLUOROPHENYL)(2- HYDROXYPHENYL)METHYL)PHOSPHOROTHIOATE(3B)

[0383] 28.2 mg, 76%; as an oil; IR ^ (thin film, cm-1); 3140, 2985, 1597, 1504, 1411, 1342, 1234, 1157, 1095, 702; 78%;1H NMR (400 MHz, CDCl3) δ 8.18 (br s, 1H), 7.45-7.42 (m, 2H), 7.20 (dd, J = 7.6 Hz, J =1.6 Hz, 1H), 7.13-7.08 (m, 1H), 6.99-6.95 (m, 2H), 6.91 (dd, J = 8.4 Hz, J =1.2 Hz, 1H), 6.91 (td, J = 8.4 Hz, J =1.2 Hz, 1H), 4.05-3.94 (m, 3H), 3.93- 3.86 (m, 1H) 1.22-1.14 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 161.8 (d, J = 246.0 Hz), 153.7, 136.8, 136.7 (d, J = 5.9 Hz), 129.9 (d, J = 8.2 Hz), 128.8 (d, J = 16.4 Hz), 128.3 (d, J = 5.2 Hz), 120.2, 117.1, 115.2 (d, J = 20.8 Hz), 64.1 (ap t, J = 5.9 Hz), 47.3 (d, J = 12.0 Hz) 15.7 (d, J = 7.5 Hz);31P NMR (162 MHz, CDCl3): δ 28.03; HRMS (ESI): m / z calcd. for C17H20O4FPS ([M+Na]+): 393.0696; Found: 393.0688. iii. S-((4-CHLOROPHENYL)(2-HYDROXYPHENYL)METHYL) O,O- DIETHYL PHOSPHOROTHIOATE(3C)

[0384] 24.2 mg, 63%; as an oil; IR ^ (thin film, cm-1); 3224, 1597, 1489, 1226, 1018, 756;1H NMR (400 MHz, CDCl3) δ 8.14 (br s, 1H), 7.42-7.38 (m, 2H), 7.28-7.25 (m, 2H), 7.21 (dd, J = 7.6 Hz, J =1.2 Hz, 1H), 7.13-7.09 (m, 1H), 6.90 (dd, J = 8.4 Hz, J =1.2 Hz, 1H), 6.84 (td, J = 8.4 Hz, J = 1.2 Hz, 1H), 6.12 (d, J = 12.8 Hz, 1H), 4.06-3.95 (m, 3H), 3.93-3.86(m, 1H), 1.23-1.48 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.7, 139.5 (d, J = 5.2 Hz), 133.1, 129.6, 128.9, 128.7, 128.5, 128.1 (d, J = 5.2 Hz), 120.3, 117.2, 64.1 (ap t, J = 5.9 Hz), 47.4 (d, J = 2.9 Hz), 15.7 (d, J = 7.4Hz);31P NMR (162 MHz, CDCl3): δ 28.00; HRMS (ESI): m / z calcd. for C17H20O4ClPS ([M+Na]+): 409.0401; Found: 409.0378. iv. S-((3,4-DICHLOROPHENYL)(2-HYDROXYPHENYL)METHYL) O,O-DIETHYL PHOSPHOROTHIOATE(3D)

[0385] 33.2 mg, 82%; as a white solid; mp 118-120 °C IR ^ (thin film, cm-1) 3224, 2985, 1597, 1458, 1226, 1018, 756;1H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.35-7.24 (m, 3H), 7.14-7.10 (m, 1H), 6.91-6.84 (m, 2H), 6.12 (d, J = 12.4 Hz, 1H), 4.07-4.00 (m, 3H), 3.99-3.89 (m, 1H), 1.25-1.16 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.7, 141.5 (d, J = 5.3 Hz), 132.3, 131.3, 130.2 (J = 7.4 Hz), 129.1, 128.6, 127.7, 127.3, 127.2, 120.3, 116.8, 64.2 (ap t, J = 5.9 Hz), 46.8 (d, J = 3.0 Hz), 15.8 (d, J = 7.5 Hz);31P NMR (162 MHz, CDCl3): δ 27.34; HRMS (ESI): m / z calcd. for C17H19O4PSCl2 ([M+Na]+ ): 443.0011; Found: 443.0075. v. O,O-DIETHYL S-((2-HYDROXYPHENYL)(P-TOLYL)METHYL) PHOSPHOROTHIOATE (3E)

[0386] 28.7 mg, 80%; as an oil; IR ^ (thin film, cm-1); 3232, 2985, 2924, 1597, 1504, 1450, 1219, 1018, 756; 80%;1H NMR (400 MHz, CDCl3) δ 7.93 (br s, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.18 (dd, J = 8.0 Hz, J =1.2 Hz, 1H), 7.13-7.09 (m, 2H), 7.08 (d, J = 1.6 Hz, 1H), 6.92 (dd, J = 8.0 Hz, J =1.2 Hz, 1H), 6.82 (td, J = 6.8 Hz, J =1.2 Hz, 1H), 6.07 (d, J = 12.4 Hz, 1H), 4.09-3.94 (m, 3H), 3.89-3.82 (m, 1H), 2.32 (s, 3H), 1.23-1.12 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.6, 137.5 (d, J = 6.0 Hz), 137.1, 129.2, 129.1, 129.0, 128.7, 128.1, 120.5, 117.7, 64.1 (d, J = 6.7 Hz), 64.0 (d, J = 5.9 Hz), 48.0 (d, J = 3.0 Hz), 21.0, 15.8 (dd, J = 7.4 Hz, J = 3.0 Hz);31P NMR (162 MHz, CDCl3): δ 28.88; HRMS (ESI): m / z calcd. for C18H23O4PS ([M+Na]+): 389.0947; Found: 389.0926. vi. O,O-DIETHYL S-(1-(2-HYDROXYPHENYL)PENTYL) PHOSPHOROTHIOATE (3F)

[0387] 11.1 mg, 37%; as an oil; IR ^ (thin film, cm-1); 3224, 2954, 1597, 1458, 1219, 1018, 972, 756;1H NMR (400 MHz, CDCl3) δ 8.10 (br s, 1H), 7.27-7.25 (m, 2H), 7.16-7.11 (m, 1H), 6.96-6.91 (m, 2H), 4.73-4.66 (m, 1H), 4.23-4.10 (m, 2H), 3.83-3.67 (m, 2H), 2.08- 2.00 (m, 2H), 1.44-1.24 (m, 6H), 1.12-1.07 (m, 3H), 0.90-0.85 (m, 3H);13C NMR (100.5 MHz, CDCl3) δ 153.7, 130.6, 128.6, 126.9, 121.2, 119.1, 64.1 (d, J = 6.7 Hz), 64.0 (d, J = 6.0Hz), 44.9 (d, J = 3.7 Hz), 36.3 (d, J = 9.7 Hz), 29.8, 22.0, 15.9 (d, J = 7.4 Hz), 15.6 (dd, J = 31.2 Hz, J = 7.4 Hz), 13.8;31P NMR (162 MHz, CDCl3): δ 30.85; HRMS (ESI): m / z calcd. for C15H25O4PS ([M+Na]+): 355.1103; Found: 355.1087. vii. S-([1,1'-BIPHENYL]-4-YL(2-HYDROXYPHENYL)METHYL) O,O- DIETHYL PHOSPHOROTHIOATE (3G)

[0388] 32.5 mg, 78%; as a white solid; mp 128-130 °C; IR ^ (thin film, cm-1); 3209, 2978, 1597, 1481, 1220,1018, 750;1H NMR (400 MHz, CDCl3) δ 8.0 (br s, 1H), 7.77-7.51 (m, 6H), 7.44-7.39 (m, 2H), 7.35-7.31 (m, 1H), 7.27-7.15 (m, 1H), 7.14-7.11 (m, 1H), 6.94 (dd, J = 8.0 Hz, J =1.2 Hz, 1H), 6.86 (td, J = 7.6 Hz, J = 1.2 Hz, 1H), 6.17 (d, J = 12.8 Hz, 1H), 4.10-3.97 (m, 3H), 3.92-3.86 (m, 1H), 1.23-1.14 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.7, 140.4, 140.2, 139.6 (d, J = 5.9 Hz), 129.0, 128.9, 128.8 (d, J = 4.4 Hz), 128.76, 128.7, 127.3, 127.1, 127.0, 120.5, 117.6, 64.2 (d, J = 6.7 Hz), 64.1 (d, J = 6.0 Hz), 47.9 (d, J = 2.3 Hz), 15.8 (ap t, J = 2.2 Hz);31P NMR (162 MHz, CDCl3): δ 28.56; HRMS (ESI): m / z calcd. for C23H25O4PS ([M+Na]+): 451.1103; Found: 451.1097. viii. O,O-DIETHYL S-((2-HYDROXYPHENYL)(2- METHOXYPHENYL)METHYL) PHOSPHOROTHIOATE (3H)

[0389] 29.5 mg, 81%; as a white solid; mp 123-125 °C; IR ^ (thin film, cm-1); 3232, 2985, 1597, 1489, 1018, 756;1H NMR (400 MHz, CDCl3) δ 7.82 (br s, 1H), 7.60 (dd, J = 7.6, 1.6 Hz, 1H), 7.28-7.24 (m, 1H), 7.17 (dd, J = 8.0, J = 2.0 Hz, 1H), 7.11-7.07 (m, 1H), 6.99 (td, J = 8.0 Hz, J = 1.2 Hz, 1H), 6.91 (dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 6.86 (dd, J = 8.4 Hz, J = 0.8 Hz, 1H), 6.78 (td, J = 7.6 Hz, J = 1.2 Hz, 1H), 6.27 (d, J = 14.0 Hz, 1H), 4.08- 3.94 (m, 3H), 3.93-3.86 (m, 1H), 3.78 (s, 3H), 1.20-1.15 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 155.8, 155.3, 129.4, 129.0, 128.94, 128.90, 128.7, 128.6, 128.3, 128.2, 117.7, 111.0, 63.9 (ap t, J = 5.9 Hz), 42.8 (d, J = 3.0 Hz), 15.8 (dd, J = 7.5, 4.4 Hz);31P NMR (162 MHz, CDCl3): δ 29.40; HRMS (ESI): m / z calcd. for C18H23O5PS ([M+Na]+ ): 405.0896; Found: 405.0885. ix. O,O-DIETHYL S-((2-HYDROXYPHENYL)(4- (METHYLTHIO)PHENYL)METHYL) PHOSPHOROTHIOATE (3I)

[0390] 46.4 mg, 69% as a white solid; mp 142-145 °C IR ^ (thin film, cm-1) 3224, 2962, 1597, 1458, 1226, 1018, 756;1H NMR (400 MHz, CDCl3) δ 7.30 (s, 3H), 7.18-7.16 (m, 1H), 7.11-7.07 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.81 (t, J = 8.0 Hz, 1H), 6.05 (d, J = 12.8 Hz, 1H), 4.04-3.93 (m, 3H), 3.86- 3.82 (m, 1H), 1.29 (s, 18H), 1.18-1.09 (m, 6H);13CNMR (100.5 MHz, CDCl3) δ 153.7, 150.8, 139.3 (d, J = 5.9 Hz), 129.1 (d, J = 4.5 Hz), 129.0, 128.7, 122.7, 121.3, 120.4, 117.7, 64.0 (dd, J = 17.1, 5.9 Hz), 49.0 (d, J = 2.9 Hz), 34.8, 31.4, 15.7 (d, J = 7.4 Hz);31P NMR (162 MHz, CDCl3): δ 29.35; HRMS (ESI): m / z calcd. for C25H37NO5PS ([M+Na]+ ): 487.2042; Found: 487.2024. x. S-((3,5-DI-TERT-BUTYLPHENYL)(2- HYDROXYPHENYL)METHYL) O,O-DIETHYLPHOSPHOROTHIOATE (3J)

[0391] 35.9 mg, 92%; as an oil; IR ^ (thin film, cm-1) 3217, 2985, 1597, 1458, 1219, 1018, 756;1H NMR (400 MHz, CDCl3) δ 8.52 (br s, 1H), 8.08-8.06 (m, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.84-7.79 (m, 2H), 7.53-7.49 (m, 1H), 7.44-7.40 (m, 2H), 7.12-7.05 (m, 2H), 7.0 (dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 6.83 (d, J = 12.4 Hz, 1H), 6.75-6.71 (m, 1H), 4.14-3.81 (m, 4H), 1.21-1.09 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.2, 136.4 (d, J = 6.7 Hz), 133.7, 130.6, 129.4, 129.3, 129.0, 128.9, 128.6, 128.5, 126.7, 125.9, 124.8, 123.7, 120.7, 118.3, 64.3 (d, J = 6.7 Hz), 64.1 (d, J = 6.0 Hz), 45.7 (d, J = 2.3 Hz), 15.7 (ap t, J = 7.4 Hz);31P NMR (162 MHz, CDCl3): δ 29.29 ; HRMS (ESI): m / z calcd. for C21H23O4PS ([M+Na]+ ): 425.0947; Found: 425.0927. xi. O,O-DIETHYLS-((2-HYDROXYPHENYL)(NAPHTHALEN-1- YL)METHYL)PHOSPHOROTHIOATE(3K)

[0392] 24.7 mg, 67%; as an oil; IR ^ (thin film, cm-1) 3248, 2985, 1597, 1450, 1226, 1018, 756;1H NMR (400 MHz, CDCl3) δ 7.35-7.33 (m, 1H), 7.30-7.25 (m, 5H), 7.16-7.12 (m, 1H), 6.95-6.91 (m, 2H), 4.96-4.89 (m, 1H), 3.89-3.83 (m, 1H), 3.82-3.68 (m, 2H), 3.67- 3.57 (m, 1H), 3.35-3.26 (m, 2H), 1.13-1.09 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.5, 138.3, 130.2 (d, J = 1.5 Hz), 129.4, 128.9, 128.3, 127.2, 126.7, 121.0, 118.8, 63.7 (ap t, J = 5.6 Hz), 42.5 (d, J = 8.9 Hz), 15.7 (ap t, J = 7.4 Hz);31P NMR (162 MHz, CDCl3): δ 29.92. xii. O,O-DIETHYL S-(1-(2-HYDROXYPHENYL)-2-PHENYLETHYL) PHOSPHOROTHIOATE(3L)

[0393] 34.3 mg, 90%; as a white solid; mp 119-121°C IR ^ (thin film, cm-1) 3248, 2985, 1597, 1435, 1103, 720;1H NMR (400 MHz, CDCl3) δ 7.47-7.45 (m, 2H), 7.34-7.30 (m, 2H), 7.27-7.25 (m, 1H), 6.88 (d, J = 8.4 Hz, 1H), 6.73 (d, J = 2.8 Hz, 1H), 6.73 (dd, J = 8.8 Hz, J = 3.2 Hz, 1H), 6.07 (d, J = 12.0 Hz, 1H), 4.10-3.95 (m, 3H), 3.87-3.81 (m, 1H), 3.62 (s, 3H), 1.25-1.31 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.5, 147.4, 140.2 (d, J = 6.7 Hz), 130.4 (d, J = 3.7 Hz), 128.4, 128.1, 127.4, 118.9, 114.5, 114.0, 64.5 (d, J = 6.0 Hz),64.2 (d, J = 6.7 Hz), 55.6, 48.2 (d, J = 3.0 Hz), 15.8 (d, J = 7.5 Hz), 15.7 (d, J = 7.5 Hz);31P NMR (162 MHz, CDCl3): δ 28.73; HRMS (ESI): m / z calcd. for C18H23O5PS ([M+Na]+): 405.0896; Found: 405.0886. xiii. O,O-DIETHYL S-((2-HYDROXY-5- METHOXYPHENYL)(PHENYL)METHYL) PHOSPHOROTHIOATE (3M)

[0394] 27.4 mg, 78%; as an oil; IR ^ (thin film, cm-1) 3232, 2985, 1504, 1226, 1018, 810;1H NMR (400 MHz, CDCl3) δ 7.48-7.45 (m, 2H), 7.34-7.29 (m, 2H), 7.27-7.23 (m, 2H), 6.96-6.89 (m, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.06 (d, J = 12.8 Hz, 1H); 4.07-3.95 (m, 3H), 3.90-3.81 (m, 1H), 2.19 (s, 3H), 1.23-1.12 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 151.2, 140.5 (d, J = 6.0 Hz), 129.8, 129.5, 129.3, 128.8 (d, J = 3.7 Hz), 128.4, 128.2, 127.3, 117.7, 64.1 (dd, J = 17.9, J = 6.7 Hz), 48.2 (d, J = 3.0 Hz), 20.6, 15.7 (dd, J = 7.5, J = 4.5 Hz);31P NMR (162 MHz, CDCl3): δ 28.76; HRMS (ESI): m / z calcd. for C18H23O4PS ([M+Na]+): 389.0947; Found: 389.0935. xiv. O,O-DIETHYLS-((2-HYDROXY-5- METHYLPHENYL)(PHENYL)METHYL)PHOSPHOROTHIOATE(3N)

[0395] 31.0 mg, 84%; as an oil; IR ^ (thin film, cm-1) 3201, 2985, 1597, 1489, 1219, 1018;1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.6 Hz, 2H), 7.31 (t, J = 8.0 Hz, 2H), 7.28- 7.25 (m, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.03 (dd, J = 8.8 Hz, J = 2.8 Hz, 1H), 6.84 (d, J = 8.8 Hz, 1H), 6.09 (d, J = 12.4 Hz, 1H), 4.06-3.98 (m, 3H), 3.96-3.91 (m, 1H), 1.20 (q, J = 6.8 Hz, 6H);13C NMR (100.5 MHz, CDCl3) δ 152.6, 139.9 (d, J = 6.7 Hz), 130.5, 130.4, 128.7, 128.6, 128.1, 127.6, 124.7, 118.7, 64.3 (ap t, J = 6.7 Hz), 47.7 (d, J = 2.2 Hz), 15.7 (d, J = 7.5 Hz);31P NMR (162 MHz, CDCl3): δ 27.91; HRMS (ESI): m / z calcd. for C17H20NO4PSCl ([M+Na]+ ): 409.0401; Found: 409.0377. xv. S-((5-CHLORO-2-HYDROXYPHENYL)(PHENYL)METHYL) O,O- DIETHYL PHOSPHOROTHIOATE (3O)

[0396] 31.1 mg, 72%; as an oil; IR ^ (thin film, cm-1) 3170, 2985, 1589, 1489, 1219, 1018, 748;1H NMR (400 MHz, CDCl3) δ 7.43-7.41 (m, 2H), 7.39-7.25 (m, 4H), 7.16 (dd, J = 8.4 Hz, J = 2.4 Hz, 1H), 6.77 (d, J = 8.4 Hz, 1H), 6.11 (d, J = 12.4 Hz, 1H), 4.07-4.0 (m, 3H), 3.97-3.90 (m, 1H), 1.22-1.17 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.2, 140.0 (d, J = 6.7 Hz), 131.4, 130.72, 130.68, 128.6, 128.2, 127.6, 118.8, 111.7, 64.3 (ap t, J = 6.0 Hz), 47.6(d, J = 3.0 Hz), 15.7 (d, J = 7.5 Hz);31P NMR (162 MHz, CDCl3): δ 28.01; HRMS (ESI): m / z calcd. for C17H20O4BrPS ([M+Na]+): 452.9895; Found: 452.9882. xvi. S-((5-BROMO-2-HYDROXYPHENYL)(PHENYL)METHYL) O,O- DIETHYL PHOSPHOROTHIOATE(3P)

[0397] 31.1 mg, 72%; as an oil; IR v (thin film, cm-1) 3170, 2985, 1589, 1489, 1219, 1018, 748;1H NMR (400 MHz, CDCl3) δ 8.62 (br s, 1H), 7.43-7.39 (m, 2H), 7.33-7.29 (m, 2H), 7.27-7.23 (m, 1H) 7.16 (dd, J = 8.4 Hz, J = 2.4 Hz, 1H), 6.77 (d, J = 8.4 Hz, 1H), 6.11(d, J = 12.4 Hz), 4.07-4.0 (m, 3H), 3.97-3.90 (m, 1H), 1.22-1.17 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 153.2, 140.0 (d, J = 6.7 Hz), 131.4, 130.72, 130.68, 128.6, 128.2, 127.6, 118.8, 111.7, 64.31 (ap t, J = 6.0 Hz), 64.5 (J = 3.0 Hz), 47.6 (d, J = 3.0 Hz), 15.7 (ap t, J = 7.5 Hz);31P NMR (162 MHz, CDCl3): δ 28.01; HRMS (ESI): m / z calcd. for C17H20O4BrPS ([M+Na]+ ): 452.9895; xvii. O,O-DIETHYL S-((2-HYDROXYPHENYL)(PHENYL)METHYL) PHOSPHORODITHIOATE (4A)

[0398] 33.4 mg, 82%; as an oil; IR ^ (thin film, cm-1) 3224, 2962, 1597, 1458, 1219, 1018, 748;1H NMR (400 MHz, CDCl3) δ 7.47-7.45 (m, 2H), 7.33-7.30 (m, 2H), 7.27-7.23 (m, 1H), 7.16 (dd, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.12-7.09 (m, 1H), 6.93 (dd, J = 8.0 Hz, J = 0.8 Hz, 1H), 6.82 (td, J = 7.6 Hz, J = 1.2 Hz, 1H), 6.11 (d, J = 12.8 Hz, 1H), 3.99-3.87 (m, 3H), 3.82-3.76 (m, 1H), 1.58-1.44 (m, 4H), 1.30-1.21 (m, 4H), 0.86-0.82 (m, 6H),13C NMR (100.5 MHz, CDCl3) δ 153.7, 140.5 (d, J = 6.0 Hz), 129.2, 129.1, 129.0, 128.8, 128.4, 128.2, 127.3, 126.8, 67.9 (d, J = 6.7 Hz), 67.7 (d, J = 6.0 Hz), 48.2 (d, J = 3.0 Hz), 31.9 (d, J = 2.2 Hz), 31.8 (d, J = 1.5 Hz), 18.5 (d, J = 3.0 Hz), 13.4;31P NMR (162 MHz, CDCl3): δ 29.29 ; HRMS (ESI): m / z calcd. for C21H29O4PS ([M+Na]+): 431.1416; Found: 431.1404. xviii. O,O-DIBUTYL S-((2-HYDROXYPHENYL)(PHENYL)METHYL) PHOSPHOROTHIOATE (4B)

[0399] 35.7 mg, 93%; as an oil; IR ^ (thin film, cm-1) 3217, 2978, 1597, 1458, 1219, 987, 748;1H NMR (400 MHz, CDCl3) δ 8.39 (br s, 1H), 7.46 (d, J = 7.2 Hz, 2H) 7.31 (t, J = 7.2 Hz, 2H), 7.24 (d, J = 5.6 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.12-7.07 (m, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 7.2 Hz, 1H), 6.14 (d, J = 13.2 Hz, 1H), 4.61-4.48 (m, 2H), 1.21- 1.19 (m, 9H), 1.12 (d, J = 6.0 Hz, 3H);13C NMR (100.5 MHz, CDCl3) δ 153.9, 140.7 (d, J = 6.7 Hz), 129.3 (d, J = 3.8 Hz), 129.0, 128.7, 128.4, 128.3, 127.2, 120.3, 117.9, 73.5 (ap t, J = 6.7 Hz), 48.3 (d, J = 2.3 Hz); 23.6 (dd, J = 8.9, J = 3.7 Hz), 23.3 (dd, J = 5.2, J = 2.2 Hz);31PNMR (162 MHz, CDCl3): δ 26.76; HRMS (ESI): m / z calcd. for C19H25O4PS ([M+Na]+): 403.1103; Found: 403.1091. xix. S-((2-HYDROXYPHENYL)(PHENYL)METHYL) O,O-DIMETHYLPHOSPHOROTHIOATE(4C)

[0400] 24.3 mg, 75%; as an oil; IR v (thin film, cm-1) 3248, 2947, 1597, 1489, 1226, 1033, 756;1H NMR (400 MHz, CDCl3) δ 7.48-7.46 (m, 2H), 7.34-7.30 (m, 2H), 7.27-7.21 (m, 1H), 7.13-7.09 (m, 1H), 6.92 (dd, J = 8.4 Hz, J = 0.8 Hz, 1H), 6.84 (td, J = 7.6 Hz, J =1.2 Hz, 1H), 6.11 (d, J = 12.4 Hz, 1H), 3.64 (d, J = 13.2 Hz, 3H), 3.54 (d, J = 13.2 Hz, 3H);13C NMR (100.5 MHz, CDCl3) δ 153.6, 140.4 (d, J = 6.7 Hz), 129.1, 128.9, 128.7 (d, J = 4.4 Hz), 128.4, 128.2, 127.4, 54.1 (d, J = 5.2 Hz), 53.9 (J = 5.3 Hz), 48.2 (J = 3.0 Hz);31P NMR (162 MHz, CDCl3): δ 32.23; xx. S-((2-HYDROXYPHENYL)(PHENYL)METHYL) O,O- DIISOPROPYL PHOSPHOROTHIOATE (4D)

[0401] 35.7 mg, 93%; IR v (thin film, cm-1) 3217, 2978, 1597, 1458, 1219, 987, 748;1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.2 Hz, 2H) 7.31 (t, J = 7.2 Hz, 2H), 7.24 (d, J = 5.6 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.12-7.07 (m, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 7.2 Hz, 1H), 6.14 (d, J = 13.2 Hz, 1H), 4.61-4.48 (m, 2H), 1.21-1.19 (m, 9H), 1.12 (d, J = 6.0 Hz, 3H);13C NMR (100.5 MHz, CDCl3) δ 153.9, 140.7 (d, J = 6.7 Hz), 129.3 (d, J = 3.8 Hz), 129.0, 128.7, 128.4, 128.3, 127.2, 120.3, 117.9, 73.5 (ap t, J = 6.7 Hz), 48.3 (d, J = 2.3 Hz);31P NMR (162 MHz, CDCl3): δ 26.76; HRMS (ESI): m / z calcd. for C19H25O4PS ([M+Na]+ ): 403.1103; Found: 403.1091. xxi. O,O-DIETHYL S-((2-((4- METHYLPHENYL)SULFONAMIDO)PHENYL)(PHENYL)METHYL) PHOSPHOROTHIOATE (6A)

[0402] 45.3 mg, 90%; as a white solid; mp 139-141°C ; IR ^ (thin film, cm-1) 3116, 2985, 1597, 1489, 1334, 1226, 1165, 1018, 748, 563;1H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.24-7.17 (m, 4H), 7.17-7.12 (m, 2H), 7.08 (td, J = 8.4, J = 1.2 Hz, 1H), 7.03 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 6.80 (dd, J = 8.4 Hz, J = 1.6 Hz, 2H), 5.59 (d, J = 12.8 Hz, 1H), 4.13-4.01 (m, 2H), 3.97-3.93 (m, 1H), 3.83-3.77 (m, 1H), 2.33 (s, 3H), 1.22-1.11 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 143.2, 139.1, 139.0, 137.6, 136.6, 136.5, 133.8, 129.6, 128.4, 128.2, 127.3, 127.2, 126.8, 126.5, 64.5 (d, J = 6.0 Hz), 64.2 (d, J = 6.7 Hz), 48.4 (d, J = 3.0 Hz), 21.4, 15.8 (d, J = 6.7 Hz), 15.7 (d, J = 7.5Hz);31P NMR (162 MHz, CDCl3): δ 27.72; HRMS (ESI): m / z calcd. for C24H28NO5PS2 ([M+Na]+): 528.1039; Found: 528.1037. xxii. O,O-DIETHYLS-((2-((4- METHYLPHENYL)SULFONAMIDO)PHENYL)(P-TOLYL)METHYL) PHOSPHOROTHIOATE (6B)

[0403] 46.4 mg, 90%; as a white solid; mp 135-137 °C; IR ^ (thin film, cm-1) 3132, 2985, 1597, 1473, 1342, 1234, 1157, 1018, 756, 563;1H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 2.0 Hz, 1H), 7.16-7.12 (m, 5H), 7.10-7.02 (m, 4H), 5.48 (d, J = 12.0 Hz, 1H), 4.01-3.95 (m, 2H), 3.87-3.77 (m, 2H), 2.34 (s, 3H), 2.31 (s, 3H), 1.15-1.08 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 143.5, 142.7 (d, J = 5.2 Hz), 137.9 (d, J = 5.9 Hz), 137.3, 137.2, 136.1, 129.5, 129.3, 129.2, 127.9, 127.3, 124.4, 120.4, 119.8, 63.6 (d, J = 6.0 Hz), 53.5 (d, J = 2.9 Hz), 21.5, 21.0, 15.8 (dd, J = 7.5, J = 2.9 Hz);31P NMR (162 MHz, CDCl3): δ 25.64; HRMS (ESI): m / z calcd. for C25H30NO5PS2 ([M+Na]+): 542.1195; Found: 542.1200. xxiii. O,O-DIETHYLS-((4-METHOXYPHENYL)(2-((4- METHYLPHENYL)SULFONAMIDO)PHENYL)METHYL) PHOSPHOROTHIOATE(6C)

[0404] 42.4 mg, 82% as a white solid; mp 145-148 °C IR ^ (thin film, cm-1) 3248, 2985, 1604, 1512, 1473, 1334, 1249, 1165, 1018;1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.4 Hz, 2H), 7.39 (br s, 1H), 7.20-7.14 (m, 6H), 7.10 (d, J = 8.0 Hz, 1H), 7.02 (dt, J = 8.0 Hz, J = .8 Hz, 1H), 6.80 (d, J = 8.8 Hz, 2H), 5.50 (d, J = 11.2 Hz, 1H), 4.01-3.96 (m, 2H), 3.95- 3.80 (m, 2H).3.78 (s, 3H), 2.38 (s, 3H), 1.16-1.10 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 158.8, 143.6, 142.9 (d, J = 5.2 Hz), 137.1, 136.0, 132.9 (d, J = 6.0 Hz), 129.5, 129.4, 129.2, 127.3, 124.5, 120.5, 119.3, 113.8, 63.5 (d, J = 5.9 Hz), 55.2, 53.3 (d, J = 3.0 Hz), 21.5, 15.8 (dd, J = 7.5, 3.7 Hz);31P NMR (162 MHz, CDCl3): δ 29.29 ; HRMS (ESI): m / z calcd. for C25H30NO6PS2 ([M+Na]+): 558.1144; Found: 558.1117. xxiv. O,O-DIETHYL S-((4-FLUOROPHENYL)(2-((4- METHYLPHENYL)SULFONAMIDO)PHENYL)METHYL) PHOSPHOROTHIOATE (6D)

[0405] 42.7 mg, 81%; as an oil; IR ^ (thin film, cm-1) 3140, 2985, 1597, 1505, 1411, 1342, 1157, 702, 633 %;1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H).7.27-7.24 (m, 2H), 7.16 (d, J = 8.0 Hz, 4H), 7.09 (d, J = 6.8 Hz, 1H), 7.04-7.01 (m, 1H), 6.97-6.93 (m, 2H), 5.53 (d, J = 11.6 Hz, 1H), 4.01-3.95 (m, 2H), 3.89-3.82 (m, 2H), 2.35 (s,3H), 1.16-1.15 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 161.9 (d, J = 245.6 Hz), 143.7, 142.3 (d, J = 6.0 Hz), 137.4, 136.8 (dd, J = 5.9 Hz, 3.7 Hz), 136.0, 129.8 (d, J = 8.2 Hz), 129.5 (d, J = 2.2 Hz), 127.9, 124.3, 120.3, 120.0, 115.4, 115.2, 63.8 (d, J = 3.0 Hz), 63.7 (d, J = 3.0 Hz), 52.9 (d, J = 2.9 Hz), 21.4, 15.7 (dd, J = 7.5 Hz, d, J = 2.2 Hz);31P NMR (162 MHz, CDCl3): δ 25.17; HRMS (ESI): m / z calcd. for C24H27NO5FPS2 ([M+Na]+): 546.0944; Found: 546.0944. xxv. S-((4-CHLOROPHENYL)(2-((4- METHYLPHENYL)SULFONAMIDO)PHENYL)METHYL) O,O- DIETHYL PHOSPHOROTHIOATE (6E)

[0406] 42.3 mg, 78% as a white solid; mp 131-133 °C; IR ^ (thin film, cm-1) 3140, 2985, 1597, 1489, 1404, 1342, 1234, 1157, 1095, 1018;1H NMR (400 MHz, CDCl3) δ 7.63- 7.60 (m, 2H), 7.54 (s, 1H), 7.25-7.20 (m, 4H), 7.15-7.13 (m, 4H), 7.08 (d, J = 8.0 Hz, 1H), 7.04-7.001 (m, 1H), 5.51 (d, J = 11.6 Hz, 1H), 4.02-3.96 (m, 2H), 3.89-3.83 (m, 2H), 2.36 (s, 3H), 1.17-1.12 (m, 6H);13C NMR (100.5 MHz, CDCl3) δ 143.7, 142.1 (d, J = 5.9 Hz), 139.6, 139.5, 137.3, 136.0, 133.3, 129.6, 129.5, 128.6, 127.2, 124.3, 120.2, 120.1, 63.8 (dd, J = 6.0, 2.2 Hz), 52.9 (d, J = 3.0 Hz), 21.4, 15.7 (ap t, J = 6.0 Hz);31P NMR (162 MHz, CDCl3): δ 25.01; HRMS (ESI): m / z calcd. for C24H27NO5PS2Cl ([M+Na]+): 562.0649; Found: 562.0640. xxvi. O,O-DIETHYLS-((2-((4- METHYLPHENYL)SULFONAMIDO)PHENYL)(NAPHTHALEN-1- YL)METHYL)PHOSPHOROTHIOATE(6F)

[0407] 41.3 mg, 74% as a white solid; mp 175-178 °C; IR ^ (thin film, cm-1) 3140, 2985, 1597, 1473, 1334, 1234, 1165, 1018, 786;1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.49- 7.42 (m, 4H), 7.41-7.39 (m, 1H), 7.28 (br s, 1H), 7.19-7.12 (m, 2H), 7.04-7.00 (m, 3H), 6.32 (d, J = 12.4 Hz, 1H), 4.03-3.96 (m, 2H), 3.95-3.82 (m, 2H), 2.29 (s, 3H), 1.13-1.07 (m.6H);13C NMR (100.5 MHz, CDCl3) δ 143.5, 142.3 (d, J = 3.8 Hz), 137.2, 136.1 (d, J = 5.9 Hz), 135.9, 133.9, 130.3, 129.5, 129.4, 128.8, 128.6, 127.2, 126.8, 126.4, 125.8, 125.0, 124.8, 123.6, 120.8, 119.9, 63.8 (ap t, J = 6.0 Hz), 50.5, 21.4, 15.8 (d, J = 5.2 Hz), 15.7 (d, J = 6.0 Hz);31P NMR (162 MHz, CDCl3): δ 25.64; HRMS (ESI): m / z calcd. for C28H30NO5PS2 ([M+Na]+): 578.1195; Found: 578.1157. xxvii. S-((2-BENZAMIDOPHENYL)(PHENYL)METHYL) O,O-DIETHYL PHOSPHOROTHIOATE (6G)

[0408] 15.3 mg, 34%; as an oil; IR ^ (thin film, cm-1) 3278, 2985, 1674, 1581, 1519, 1450, 1296, 1018, 748;1H NMR (400 MHz, CDCl3) δ 9.64 (br s, 1H), 8.09-8.07 (m, 2H), 7. 77 (d, J = 8.8 Hz, 1H), 7.56-7.44 (m, 3H), 7.42-7.34 (m, 3H), 7.30-7.23 (m, 3H), 7.21-7.17 (m, 2H), 6.08 (d, J = 10.4, 1H), 4.20-4.03 (m, 2H), 3.76-3.61 (m, 2H), 1.30-1.26 (m, 3H), 1.05-1.00 (m, 3H),13C NMR (100.5 MHz, CDCl3) δ 166.1, 139.4 (d, J = 8.9 Hz), 139.1 (d, J = 2.3 Hz), 134.7, 134.2, 131.7, 129.9, 128.6, 128.5, 128.2, 127.8, 127.7, 127.6, 126.9, 126.3, 64.3 (d, J = 6.0 Hz), 63.6 (d, J = 6.7 Hz), 48.8 (d, J = 3.0 Hz), 15.9 (d, J = 7.4 Hz), 15.6 (d, J = 8.2 Hz);31P NMR (162 MHz, CDCl3): δ 26.96 ; HRMS (ESI): m / z calcd. for C24H26NO4PS ([M+Na]+): 478.1212; Found: 478.1209. 3. OPTIMIZATION OF REACTION CONDITIONS

[0409] To develop an operationally simple and atom economical synthesis of thiophosphate compounds that avoids the need for a metal catalyst, moisture sensitive chloride reagents, and base, it was hypothesized that reactive o-QM intermediates can be formed in situ from aryl alcohols and reacted with (EtO)2P(O)SH to synthesize functionalized diaryl thiophosphate. To test the hypothesis, 2-(hydroxy(phenyl)methyl)phenol 1a and (EtO)2P(O)SH 2a were used as a model substrate for reaction optimization (Table 1). The reaction was first tested using a 1:1 molar equivalence of 1a:2a and the product 3a was generated in 37% yield (Table 1, Entry 1). Increasing the molar equivalence of 1a:2a to 1:1.5 gave the desired product 3a in 91% yield (Table 1, Entry 2). Solvent effects were then tested and other solvents (THF, DCE, toluene, ACN, and ether) were inferior to DCM (table 1, Entries 3-7). TABLE 1.Entry 1a:2a Solvent Yield (%)bEntry 1a:2a Solvent Yield (%)b4. INVESTIGATION OF REACTION SCOPE

[0410] With the optimized conditions in hand, the scope of the reaction was tested to see the steric and electronic effect on reaction outcome (FIG.4). First, diverse substituents on the benzylic carbon of the diaryl phenol substrate were screened. Halogenated diaryl phenols 1b-1d (4-F, 4-Cl, and 3,4-di-Cl) were well-tolerated to give the desired products 3b- 3d in moderate to high yields of 63-82%. Diaryl phenols containing electron donating groups 1e, 1h, and 1l (4-Me, 2-OMe, and 4-SMe) furnished products 3e, 3h, and 3l in high yields of 72-81%. Phenols with aliphatic substituents 1f and 1l (n-Bu and Bn) gave products 3f and 3l in moderate yields of 37% and 54%; presumably due to less hyperconjugation effect and stabilization of o-QM intermediate. Bulky aromatic groups 1g and 1k (biphenyl and naphthyl) generated products 3j and 3k with high yields of 78% and 92%, respectively. Sterically hindered phenol 1j (3,5-di-tertbutyl) gave the product 3j in a yield of 69%.

[0411] Next the scope of the reaction was further broadened by varying the phenolic substituents (FIG.5). Electron donating substrates 1m and 1n, (5-OMe and 5-Me) provided the correspond products 3m, and 3n, in high yields of 90% and 78%. Halogenated substrates 1o and 1p (5-Br and 5-Cl) afforded the desired products 3o and 3p in high yields of 84% and 72%, respectively. 5. EVALUATION OFNUCLEOPHILESCOPE

[0412] Other thioacids such as phosphorodithioates and different alkoxy substituted thiophosphoric acids were evaluated to test their effect on reaction outcome. (FIG.6) (EtO)2P(S)SH 2b was used to generate 4a in 94% yield, the slight increase in yield is presumably attributed to 2b being a presumably more favourable soft nucleophile whencompared with 2a. Other alkoxy substituted thioacids 2c-2e (n-butyl, methyl, and isopropyl) gave the target compounds 4b-d in high yields of 75-93%.

[0413] With promising results with o-QM addition, the reaction was broaded to apply to aza o-QM intermediates (FIG.7). In the preliminary screening it was found that the acid 2a was not a strong enough acid to dehydrate sulfonamido alcohol 4a. However, with the addition of catalytic TsOH, the reaction proceeded smoothly giving 5a in a high yield of 90%. With the optimized reaction conditions for aza o-QM, the scope was tested with benzylic aryl substituents. Sulfonamindo alcohols bearing electron donating groups 4b and 4c (4-Me, 4-OMe) gave the target products 5b and 5c in high yields of 90% and 82%, respectively. Next, halogenated sulfonamido alcohols 4d and 4e (4-F, 4-Cl) were tested and gave the products 5d and 5e in high yields of 81% and 78%, respectively. Naphthyl sulfonamido thiophosphate 5f was formed from 4f in a high yield of 74%. Furthermore, a different protecting group on nitrogen atom was tested 4g (benzoyl), which gave rather a low yield of 5g presumably due to a weak polarizability of the reactive intermediate compared to a tosyl protected nitrogen atom. 6. PROPOSED MECHANISM

[0414] Mechanistically, diaryl phenol 1a is protonated by 2a and water is released to form a reactive o-QM intermediate and O,O-diethyl phosphorothioate. Subsequent Michael addition reaction of o-QM and O,O-diethyl phosphorothioate provides product 3a. (FIG.8)

[0415] Control experiments were performed to gain mechanistic insight for this synthetic transformation (FIG.9).1a was treated with 2a (20 mol%) and diphenylphosphinic acid 2aa and gave 3a in 13% yield. This result indicates that the 2a serves as both Brønsted acid and nucleophile. An additional reaction of 2a with benzyl alcohol 1aa did not generate the target thiophosphate, which suggests that a direct dehydrothiophosporylation reaction is limited. The reaction of diphenylphosphinic acid 2aa with 1a did not generate the desired product which implies that hard phosphinic acid nucleophiles are unsuitable under these reaction conditions.

[0416] A metal, catalyst-, chloride reagent-, and base-free thiophosphorylation reaction of o-QM to synthesize functionalized thiophosphates has been developed. The reaction tolerates a wide variety of functional groups. Future experiments involving cascade and multicomponent reactions of O,O-diethyl S-hydrogen phosphorothioate are currently underway as well as development of an enantioselective version of this reaction.I. PROPHETIC EXAMPLES 1. SYNTHESIS OFPHOSPHOROUS, SULFUR-CONTAININGFIRERETARDANTS

[0417] Fire retardants play an essential role in NASA’s Standard for Fire Protection, which was created to protect human life, property, as well as the environment from the risks of fire (Jomaas et al. (2015) Acta Astronautica 109: 208-216; Fujita, O., (2015) Proceedings of the Combustion Institute 35(3): 2487-2502). Moreover, NASA’s approach towards fire protection in manned missions centers around the HARPP objective: a program with the primary goal to supply safe, efficient non-halon fire protection (Collins, M. M. In Fire protection in manned missions: current and planned, Halon Options Technical Working Conference, 2001; pp 3-6). The synthesis of a less environmentally harmful, efficient phosphorus-sulfur based fire retardant would aid in this mission goal.

[0418] It is no secret that flame retardants can pose the risk of toxicity for the environment (Liu, et al. (2021) Environmental Science & Technology 55(21): 14477-14479). However, in contrast to other fire-retardants, phosphorus-based fire retardants have been found to be more environmentally friendly (Liang, et al. (2013) Progress in Organic Coatings 76(11): 1642-1665). However, phosphorus and phosphorus / nitrogen containing polymeric flame retardants face an issue with leaching out of their substrate if they do not possess a high molecular weight (He, et al. (2020) Progress in Materials Science 114: 100687). Therefore, an alternative phosphorothioic acid-based flame retardant could solve this issue because of the additional sulfur molecule that will add more weight to the entire compound. This more favorable flame retardant would also possess a phosphorus characteristic, thus reducing the risk of toxicity for the environment.

[0419] Phosphorus-based monomer flame retardants work by acting in the gas phase (Schartel, B., (2010) Materials 3(10): 4710-4745). Phosphorus-oxygen radicals use radical recombination to render hydrogen and hydroxy radicals harmless, which decreases heat release (Schartel, B., (2010) Materials 3(10): 4710-4745). In terms of sulfur’s role in the flame retardant, there has been discovery of sulfur containing polymer flame retardants exhibiting excellent thermal stability, enhanced mechanical properties, and outstanding corrosion resistance (Dai, et al. (2012) Industrial & engineering chemistry research 51(49): 15918-15926). Without wishing to be bound by theory, these traits should help bolster the phosphorothioic acid flame retardant monomer described herein to be used as a polymeric fire retardant.

[0420] As noted above, major obstacle in synthesizing a phosphorus based polymeric fire retardant is the possible leaching of the fire retardant if the molecular weight is inadequately large while maintaining the radical scavenger properties. To address this issue, phosphorothioic acid-based flame retardants will be tested. The following is hypothesized: hypothesis 1: prevention of leaching can be achieved by using a phosphorus-sulfur based flame retardant for increasing weight (FIG.10 and FIG.11); hypothesis 2: bulky derivatives of phosphorothioic acid flame retardants can accomplish increased stabilization of the compound or stabilized radical intermediates (FIG.12 and FIG.13). Rationally designed testable experiments will be used to test these hypotheses.

[0421] The hypothesis will be tested by synthesizing phosphorothioic flame retardants to prevent leaching, as the addition of sulfur to the compound will contribute further weight. Preliminary data uncovered a synthesis methodolgy for a phosphorothioic acid 9. This methodology will be incorporated to synthesize various novel phosphorothioic fire retardants (FIG.10 and FIG.11). In the previous study, synthesis of these phosphorothioic acids 9 were enhanced with a bulky subtituent (mesityl ethylenediamine) 7 on the phosphorus center 8, as it prevented hydrolysis of the structure (FIG.10 and FIG. 11). With these results, theattention will be turned towards synthesizing novel phosphorothioic fire retardants (10-13) with the incorporation of bulky substitutents on phosphorus center in the hopes to accomplish increased stabilization. FIG.12 provides a proposed synthesis pathway for construction of allyl phosphorothioate as alternative fire retardants with an alkene functional group for the polymerization process. The preliminary study in a new reaction discovery unearthed a 99% product yield of the allyl phosphorothioate 16 from a phosphorothioic acid 15 and an allylic alcohol 14 (FIG.12). With this preliminary data, the efforts will be centered on synthesizing novel allyl phosphorothioates (17-19, FIG.13) as potential fire retardants and acessing whether these bulky derviatives can increase stability of radical intermediates. This will be done through incorporation of the phosphorothioic fire retardants from FIG.11 as the starting material for FIG.12. FIG.21A-C shows proposed synthesis of allylic thiophosphates as potential fire retardants. 2. SYNTHESIS OF NOVEL CHIRAL PHOSPHOROTHIOC ACID ORGANOCATALYSTS

[0422] One of the major hurdles in the synthesis of phosphorothioic acids is the prone hydrolysis of phosphine oxide intermediates, which hinder the accessibility to novel phosphorus organocatalysts (FIG.14). To address this issue, bulky substituents to prevent thehydrolysis of the phosphine oxide intermediates and chiral amino acid derivatives to install the chirality will be tested. The following is hypothesized: hypothesis 1: A highly tunable synthetic approach toward novel phosphorothioic acid organocatalysts can be achieved by phosphonylation and thionylation; hypothesis 2: Tunability of the phosphorothioic acid organocatalysts can be accomplished by a modular synthetic approach with chiral pool synthesis which is a strategy that aims to improve the efficiency of chiral synthesis (FIG.15). To test these hypothesizes, rationally designed testable experiments will be carried out.

[0423] The hypothesis will be tested by employing a bulky substituent on the phosphorus center for the synthesis of phosphorothioic acid to prevent the hydrolysis. Preliminary data revealed that when a less bulky diphenylethylendiamine 20a was employed for the synthesis of phosphine oxide intermediates 20b, the hydrolysis of phosphorus compounds 20b was unavoidable (FIG.14). A previous study also unearthed a favorable effect on the synthesis of phosphorothioic acid 9 with a bulky substituent (mesityl ethylenediamine) 7 on the phosphorus center (FIG.10). With these results, the synthesis of chiral phosphorothioic acids as highly tunable organocatalysts will be explored, which is a significant factor for the development of new catalysts over the conventional organocatalysts. FIG.15 shows the proposed synthetic routes for chiral phosphorothioic acids. Chiral amino alcohol derivates will be used to synthesize chiral phosphorothioic acids. For example, prolinols (21a, 21b), chiral diamines (21c, 21d), and chiral amino alcohols 21e will be employed for the synthesis of chiral phosphorothioic acids. Secondary amines (21a-21d) are expected to provide higher product yields due to a higher nucleophilicity. However, if primary amines (21e) are challenging to synthesize the target products, they will be converted into the secondary amines via a reductive amination. This reductive amination should resolve the challenges associated with the primary amine substrates. This modular approach using chiral pool synthesis will generate the desired phosphorothioic acids (21aaa-21eee). These phosphorothioic acids will be utilized for new synthetic transformation. A preliminary study of new reaction discovery de...

Claims

CLAIMS What is claimed is:

1. A compound having a structure represented by a formula: , wherein A is selected from O and; wherein Q is selected from O, S, and NR10; wherein R10, when present, is selected from hydrogen, C1-C4 alkyl, and Ar1; wherein Ar1, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1- C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl; wherein each of R1a, R1b, and R2is independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2; wherein each occurrence of Ar2, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; or wherein R1ais selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R1band R2are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6- membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; wherein R3is selected from hydrogen, C1-C4 alkyl, and Ar3; and wherein Ar3, when present, is selected from C6-C14 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, – NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and unsubstituted phenyl; or wherein each of R1aand R1bis independently selected from hydrogen, C1-C4 alkyl, ‒CH2Ar1, and Ar2, and R2and R3are covalently bonded and, together with the intermediate atoms, comprise a 5- to 6-membered cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino, or a salt thereof.

2. The compound of claim 1, wherein A is O.

3. The compound of claim 1 or claim 2, wherein Q is NR10.

4. The compound of claim 3, wherein R10is Ar1.

5. The compound of any one of claims 1 to 4, wherein each of R1aand R1bis independently selected from hydrogen and Ar2.

6. The compound of claim 5, wherein Ar2is unsubstituted C6 aryl.

7. The compound of any one of claims 1 to 4, wherein each of R1aand R1bis independently selected from hydrogen and C1-C4 alkyl.

8. The compound of any one of claims 1 to 4, wherein each of R1a, R1b, and R2is hydrogen.

9. The compound of any one of claims Error! Reference source not found. to 8, wherein R3is Ar3.

10. The compound of claim 9, wherein Ar3is C6 aryl substituted with 3 groups independently selected from halogen, –NO2, –CN, –OH, –SH, –NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 thioalkyl, C1-C4 alkylthiol, C1-C4 aminoalkyl, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and unsubstituted phenyl.

11. The compound of claim 9, wherein Ar3is C6 aryl substituted with 3 groups independently selected from C1-C4 alkyl and unsubstituted phenyl.

12. The compound of claim 9, wherein Ar3is unsubstituted C6 aryl.

13. The compound of claim 1, wherein the compound is selected from: , ,or a salt thereof.

14. The compound of claim 1, wherein the compound is selected from:,, or.

15. The compound of claim 1, wherein the compound is selected from: Ph Ph SH Ph , ,,, or asa ereo.

16. The compound of claim 1, wherein the compound is selected from: Ph Ph H Ph ,Ph , ,or a salt thereof.

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