Sulfinate salts and their applications

Abstract

Described are sulfinate salts and methods of using the same in synthesis. The sulfinate salt may be a salt of formula (I): wherein: a is 1 or 2; X+a is a cation having a +a charge; R1 is hydrogen, -NO2, -OC1-4alkyl, C1-4alkyl, F, or Cl; and R2 is hydrogen, -OC1-4alkyl, C1-4alkyl, or -NO2; with the proviso that at least one of R1 and R2 is not hydrogen.

Description

[0001] SULFINATE SALTS AND THEIR APPLICATIONS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No.63 / 552,325, filed on February 12, 2025, which is incorporated by reference herein in its entirety. TECHNICAL FIELD The present disclosure relates to sulfinate salts and methods of using the same in synthesis. In various instances, the sulfinate salts described herein may be used to prepare various sulfonyl fluoride compounds. INTRODUCTION Over the past decade, sulfonyl fluoride exchange (SuFEx) chemistry has seen an increase in popularity owing to its use as a biocompatible “click” reaction. First introduced in 2014, sulfur (VI) fluoride exchange (SuFEx) chemistry, illustrated below, relies upon the exchange of an incoming nucleophile with fluoride on a hexavalent sulfur forming an irreversible, covalent bond. This both the sulfonyl group and departing fluoride group are stabilized by hydrogen bonding. This imparts a degree of stability and selectivity on sulfonyl fluorides (SFs) not seen with other electrophilic groups such as sulfonyl chlorides, epoxides, and acrylamides. When placed in the context of an enzyme active site, this catalytic condition is the hydrogen bonding associated with donor residues surrounding the nucleophilic residue of interest. This quiescent affinity model requires that the sulfonyl fluoride first establishes noncovalent interactions before undergoing nucleophilic attack. This selectivity and click-like reactivity of sulfonyl fluorides has led to their incorporation into pharmaceutically active drug molecules and biochemical probes. Although sulfonyl fluorides contain enhanced stability under physiological conditions, their use is often complicated by their incompatibility to various common synthetic conditions such as nucleophiles, base, and high temperature. This results in sulfonyl fluorides being incorporated onto a core scaffold late in the synthetic route and limits structural diversity. What is needed are methods and reagents for achieving more diverse sulfonyl fluoride compounds. SUMMARY In some aspects, the present disclosure provides salts of formula (I): , wherein: a is 1 or 2; X+ais a cation having a +a charge; R1is hydrogen, –NO2, –OC1-4alkyl, C1-4alkyl, F, or Cl; and R2is hydrogen, –OC1-4alkyl, C1-4alkyl, or –NO2; with the proviso that at least one of R1and R2is not hydrogen. In some instances, a is 1. In other instances, a is 2. X+amay be Na+1, K+1, Li+1, Mg+2, Zn+2, or Bu4N+1. R1may be hydrogen. R1may be –NO2. R1may be –OC1-4alkyl. R1may be C1-4alkyl. R2may be hydrogen. R2may be –OC1-4alkyl. R2may be C1-4alkyl. R2may be –NO2. The salt of formula (I) may be a salt of any one of formulae (I-a)-(I-j): b) d) f) -h) -j) In other aspects, the present disclosure provides methods of synthesizing a sulfinate compound, the method comprising reacting the salt of any one of claims 1-13 with a compound of formula (II): X1–Y1(II), to provide a compound of formula (III): , wherein: X1is a leaving group; Y1is G1, –C1-6alkylene–G1, C1-10alkyl, C2-10alkenyl, or C2-10alkynyl; G1, at each occurrence, is independently a 6- to 12-membered aryl, a 4- to 12-membered heterocyclyl, a 3- to 12-membered carbocyclyl, or a 5- to 12-membered heteroaryl, wherein the heteroaryl and heterocyclyl each contain 1-4 heteroatoms independently selected from the group consisting of O, N, and S, and G1is optionally substituted with a first substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, oxo, –OR1x, –N(R1x)2, –SR1x, –SO2R1x, –C(O)R1x, –C(O)OR1x, –C(O)N(R1x)2, G1a, –C1-6alkylene–OR1x, –C1-6alkylene–SR1x, –C1-6alkylene–N(R1x)2, –C1-6alkylene–SO2R1x, –C1-6alkylene–C(O)R1x, – C1-6alkylene–C(O)OR1x, –C1-6alkylene–C(O)N(R1x)2, and –C1-6alkylene–G1a, and optionally further substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, and –OR1x; R1x, at each occurrence, is independently hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, –C1-3alkylene–C3-6cycloalkyl, phenyl, or –C1-3alkylene–phenyl, wherein each cycloalkyl or phenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C1-4alkyl, and C1-4haloalkyl; and G1ais a phenyl, a 5- to 6-membered heteroaryl containing 1-3 heteroatoms, a 4- to 8- membered heterocyclyl containing 1-2 heteroatoms, or a 3- to 8-membered carbocyclyl, wherein the heteroatoms are independently selected from the group consisting of O, N, and S, and G1a, at each occurrence, is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, –C1-6alkylene–OH, oxo, OH, –OC1-4alkyl, –OC1-4haloalkyl, C3-4cycloalkyl, and –C1-3alkylene–C3-4cycloalkyl. X1may be I, Br, Cl, or –SH. Y1may be G1or –C1-3alkylene–G1. The method may further comprise reacting the compound of formula (III) with a compound containing –Y2to provide a compound of formula (IV): , wherein: Y2is G2or –C1- or C2-10alkynyl; G2, at each occurrence, is independently a 6- to 12-membered aryl, a 4- to 12-membered heterocyclyl, a 3- to 12-membered carbocyclyl, or a 5- to 12-membered heteroaryl, wherein the heteroaryl and heterocyclyl each contain 1-4 heteroatoms independently selected from the group consisting of O, N, and S, and G2is optionally substituted with a first substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, oxo, –OR2x, –N(R2x)2, –SR2x, –SO2R2x, –C(O)R2x, –C(O)OR2x, –C(O)N(R2x)2, G2a, –C1-6alkylene–OR2x, –C1-6alkylene–SR2x, –C1-6alkylene–N(R2x)2, –C1-6alkylene–SO2R2x, –C1-6alkylene–C(O)R2x, – C1-6alkylene–C(O)OR2x, –C1-6alkylene–C(O)N(R2x)2, and –C1-6alkylene–G2a, and optionally further substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, and –OR2x; R2x, at each occurrence, is independently hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, –C1-3alkylene–C3-6cycloalkyl, phenyl, or –C1-3alkylene–phenyl, wherein each cycloalkyl or phenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C1-4alkyl, and C1-4haloalkyl; and G2ais a phenyl, a 5- to 6-membered heteroaryl containing 1-3 heteroatoms, a 4- to 8- membered heterocyclyl containing 1-2 heteroatoms, or a 3- to 8-membered carbocyclyl, wherein the heteroatoms are independently selected from the group consisting of O, N, and S, and G2a, at each occurrence, is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, –C1-6alkylene–OH, oxo, OH, –OC1-4alkyl, –OC1-4haloalkyl, C3-4cycloalkyl, and –C1-3alkylene–C3-4cycloalkyl. The method may further comprise reacting the compound of formula (III) or formula (IV) with a fluorinating agent in the presence of light.The fluorinating agent . BRIEF DESCRIPTION OF THE DRAWINGS FIG.1A schematically illustrates the quiescent binding model for sulfur fluoride exchange (SuFEx). FIG.1B schematically illustrates late-stage pendant –SO2F coupling. FIG.1C schematically illustrates late-stage direct –SO2F functionalization. FIG.1D schematically illustrates sulfinate protecting group building blocks. FIG.1E shows sulfinate protecting groups used to date. FIG. 1F shows exemplary sulfinate protecting groups, described herein, that may be converted to sulfonyl fluorides using blue light and Selectfluor™. FIG.2 schematically illustrates an exemplary method for preparing a library of compounds using an exemplary sulfinate salt described herein. FIG. 3A shows the model sulfinate protecting groups (SPG) substrates used in the synthesis and stability studies. FIG.3B shows the isolated yields for the synthesis of the model SPG substrates of FIG. 3A via copper coupling. Copper coupling conditions: 4-fluoroiodobenzene (0.23 mmol, 1 equiv), NaO2SPG (1.5-3 equiv), CuI (6-10 mol %), (2S,4R)-4-hydroxy-N-(2-methylnaphthalen-1- yl)pyrrolidine-2-carboxamide (HMNPC, 6-10 mol %), K3PO4(1 equiv), DMSO, 50 °C, 24 h. FIG.3C shows the isolated yields for the synthesis of the model SPG substrates of FIG. 3A via dual photocatalysis. Dual photocatalysis conditions: 4-fluoroiodobenzene (0.1 mmol, 1 equiv), NaO2SPG (2 equiv), NiBr2DME (5 mol %), 4CzIPN (0.2 mol %), DABCO (2.2 equiv), Et3N (0.5 equiv), DMA, blue LED, 24 h. FIG.3D shows the isolated yields for the synthesis of the model SPG substrates of FIG. 3A via thio-etherification (step 2) followed by oxidation (step 2). Thio-etherification conditions are described in the experimental examples. Oxidation conditions (step 2): m-CPBA (3 equiv), CH2Cl2, 23 °C, 12 h, or Na2WO4(0.5 equiv), H2O2(5 equiv), MeOH, 23 °C, 24 h. Alkylation Conditions: BnBr (0.29 mmol, 1 equiv), NaO2SPG (1.5 equiv), DMSO, 23 °C, 24 h. FIG.3E shows the isolated yields for the synthesis of the model SPG substrates of FIG. 3A via alkylation. Alkylation conditions: BnBr (0.29 mmol, 1 equiv), NaO2SPG (1.5 equiv), DMSO, 23 °C, 24 h. FIG.4 shows the scope of deprotection / fluorination. FIG. 5 shows a schematic for the one-pot synthesis of sulfonamides. Conditions for amination of 15a: Et3N (5 equiv), piperidine (3 equiv), 85 °C, 16 h; for amination of 15b: Et3N (5 equiv), piperidine (3 equiv), 40 °C, 16 h. FIG.6A shows SPG Suzuki building blocks. Reagents and conditions: 1. CuI (10 mol%), HMNPC (10 mol%), PMB-R-Na (1.5 equiv), and K3PO4 (1 equiv), DMSO, 40 °C, 24 h; 2. B2Pin2 (1.5 equiv), Pd(dppf)Cl2(5 mol%), KOAc (3 equiv), DMSO, 100 °C, 1 h; 3. Aryl halide (1.5 equiv), Pd(PPh3)4(5 mol%), Na2CO3(3 equiv), DME: H2O, 100 °C, 3 h; 4. Selectfluor™ (3 equiv), MeCN: H2O,Blue LEDs, 16 h. FIG.6B shows the synthesis of AZD2858. FIG. 6C shows the synthesis of non-commercial analogs. Reagents and conditions: 1. CuI (10 mol%), HMNPC (10 mol%), PMB-R-Na (1.5 equiv), and K3PO4(1 equiv), DMSO, 40 °C, 24 h; 2. Selectfluor™ (3 equiv), MeCN: H2O,Blue LEDs, 16 h, then Et3N (5 equiv), piperidine (3 equiv), 40 °C, 16 h. FIG.7A shows the synthesis of BCl-6 inhibitor TMX-2164. FIG.7B schematically illustrates the late stage diversification of BCL-6 inhibitor analog. Reagents and conditions: 1. CuI (10 mol%), HMNPC (10 mol%), oNB-R-Na (3 equiv), and K3PO4(1 equiv), DMSO, 40 °C, 24 h; 2.33 (1.2 equiv), DIPEA (1.2 equiv), dioxane, 100 °C, 16 h, then POCl3(3 equiv), 100 °C, 2 h; 3. aniline (2 equiv), Pd(OAc)2(9 mol%), XantPhos (10 mol%), Cs2CO3(1.4 equiv), dioxane, 110 °C, 24 h; Selectfluor™ (5 equiv), MeCN: H2O,Blue LEDs, 36 h. DETAILED DESCRIPTION Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various way. Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein may be used in practice or testing of the present invention. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting. The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not. The modifier “about” used in connection with a quantity is inclusive of the stated value and has the meaning dictated by the context (for example, it includes at least the degree of error associated with the measurement of the particular quantity). The modifier “about” should also be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the expression “from about 2 to about 4” also discloses the range “from 2 to 4.” The term “about” may refer to plus or minus 10% of the indicated number. For example, “about 10%” may indicate a range of 9% to 11%, and “about 1” may mean from 0.9–1.1. Other meanings of “about” may be apparent from the context, such as rounding off, so, for example “about 1” may also mean from 0.5 to 1.4. Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March’s Advanced Organic Chemistry, 5thEdition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3rdEdition, Cambridge University Press, Cambridge, 1987; the entire contents of each of which are incorporated herein by reference. The term “alkoxy,” as used herein, refers to a group –O–alkyl. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy and tert- butoxy. The term “alkyl,” as used herein, means a straight or branched, saturated hydrocarbon chain. The term “lower alkyl” or “C1-6alkyl” means a straight or branched chain hydrocarbon containing from 1 to 6 carbon atoms. The term “C1-4alkyl” means a straight or branched chain hydrocarbon containing from 1 to 4 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n- pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n- heptyl, n-octyl, n-nonyl, and n-decyl. The term “alkenyl,” as used herein, means a straight or branched, hydrocarbon chain containing at least one carbon-carbon double bond. The term “alkoxyalkyl,” as used herein, refers to an alkoxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The term “alkylamino,” as used herein, means at least one alkyl group, as defined herein, is appended to the parent molecular moiety through an amino group, as defined herein. The term “amide,” as used herein, means –C(O)NR– or –NRC(O)–, wherein R may be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl. The term “aminoalkyl” as used herein, means at least one amino group, as defined herein, is appended to the parent molecular moiety through an alkylene group, as defined herein. The term “amino,” as used herein, means –NRxRy, wherein Rxand Rymay be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl. In the case of an aminoalkyl group or any other moiety where amino appends together two other moieties, amino may be –NRx–, wherein Rxmay be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, alkenyl, or heteroalkyl. The term “aryl,” as used herein, refers to a phenyl or a phenyl appended to the parent molecular moiety and fused to a cycloalkane group (e.g., the aryl may be indan-4-yl), fused to a 6-membered arene group (i.e., the aryl is naphthyl), or fused to a non-aromatic heterocycle (e.g., the aryl may be benzo[d][1,3]dioxol-5-yl). The term “phenyl” is used when referring to a substituent and the term 6-membered arene is used when referring to a fused ring. The 6- membered arene is monocyclic (e.g., benzene or benzo). The aryl may be monocyclic (phenyl) or bicyclic (e.g., a 9- to 12-membered fused bicyclic system). The term “cyanoalkyl,” as used herein, means at least one –CN group, is appended to the parent molecular moiety through an alkylene group, as defined herein. The term “cycloalkoxy,” as used herein, refers to a cycloalkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. The term “cycloalkyl” or “cycloalkane,” as used herein, refers to a saturated ring system containing all carbon atoms as ring members and zero double bonds. The term “cycloalkyl” is used herein to refer to a cycloalkane when present as a substituent. A cycloalkyl may be a monocyclic cycloalkyl (e.g., cyclopropyl), a fused bicyclic cycloalkyl (e.g., decahydronaphthalenyl), or a bridged cycloalkyl in which two non-adjacent atoms of a ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms (e.g., bicyclo[2.2.1]heptanyl). Representative examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, adamantyl, and bicyclo[1.1.1]pentanyl. The term “cycloalkenyl” or “cycloalkene,” as used herein, means a non-aromatic monocyclic or multicyclic ring system containing all carbon atoms as ring members and at least one carbon-carbon double bond and preferably having from 5-10 carbon atoms per ring. The term “cycloalkenyl” is used herein to refer to a cycloalkene when present as a substituent. A cycloalkenyl may be a monocyclic cycloalkenyl (e.g., cyclopentenyl), a fused bicyclic cycloalkenyl (e.g., octahydronaphthalenyl), or a bridged cycloalkenyl in which two non-adjacent atoms of a ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms (e.g., bicyclo[2.2.1]heptenyl). Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl. Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl. The term “carbocyclyl” means a “cycloalkyl” or a “cycloalkenyl.” The term “carbocycle” means a “cycloalkane” or a “cycloalkene.” The term “carbocyclyl” refers to a “carbocycle” when present as a substituent. The terms cycloalkylene and heterocyclylene refer to divalent groups derived from the base ring, i.e., cycloalkane, heterocycle. For purposes of illustration, examples of cycloalkylene and heterocyclylene include, . Cycloalkylene and heterocyclylene include a geminal divalent groups such as 1,1-C3-6cycloalkylene ). A further example is 1,1-cyclopropylene (i.e., ). The term “halogen” or “halo,” as means Cl, Br, I, or F. The term “haloalkyl,” as used an alkyl group, as defined herein, in which one, two, three, four, five, six, seven or eight hydrogen atoms are replaced by a halogen. The term “haloalkoxy,” as used herein, means at least one haloalkyl group, as defined herein, is appended to the parent molecular moiety through an oxygen atom. The term “halocycloalkyl,” as used herein, means a cycloalkyl group, as defined herein, in which one or more hydrogen atoms are replaced by a halogen. The term “heteroalkyl,” as used herein, means an alkyl group, as defined herein, in which one or more of the carbon atoms has been replaced by a heteroatom selected from S, O, P and N. Representative examples of heteroalkyls include, but are not limited to, alkyl ethers, secondary and tertiary alkyl amines, amides, and alkyl sulfides. The term “heteroaryl,” as used herein, refers to an aromatic monocyclic heteroatom- containing ring (monocyclic heteroaryl) or a bicyclic ring system containing at least one monocyclic heteroaromatic ring (bicyclic heteroaryl). The term “heteroaryl” is used herein to refer to a heteroarene when present as a substituent. The monocyclic heteroaryl are five or six membered rings containing at least one heteroatom independently selected from the group consisting of N, O and S (e.g., 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N). The five membered aromatic monocyclic rings have two double bonds, and the six membered aromatic monocyclic rings have three double bonds. The bicyclic heteroaryl is an 8- to 12- membered ring system and includes a fused bicyclic heteroaromatic ring system (i.e., 10 π electron system) such as a monocyclic heteroaryl ring fused to a 6-membered arene (e.g., quinolin-4-yl, indol-1-yl), a monocyclic heteroaryl ring fused to a monocyclic heteroarene (e.g., naphthyridinyl), and a phenyl fused to a monocyclic heteroarene (e.g., quinolin-5-yl, indol-4-yl). A bicyclic heteroaryl / heteroarene group includes a 9-membered fused bicyclic heteroaromatic ring system having four double bonds and at least one heteroatom contributing a lone electron pair to a fully aromatic 10 π electron system, such as ring systems with a nitrogen atom at the ring junction (e.g., imidazopyridine) or a benzoxadiazolyl. A bicyclic heteroaryl also includes a fused bicyclic ring system composed of one heteroaromatic ring and one non-aromatic ring such as a monocyclic heteroaryl ring fused to a monocyclic carbocyclic ring (e.g., 6,7-dihydro-5H- cyclopenta[b]pyridinyl), or a monocyclic heteroaryl ring fused to a monocyclic heterocycle (e.g., 2,3-dihydrofuro[3,2-b]pyridinyl). The bicyclic heteroaryl is attached to the parent molecular moiety at an aromatic ring atom. Other representative examples of heteroaryl include, but are not limited to, indolyl (e.g., indol-1-yl, indol-2-yl, indol-4-yl), pyridinyl (including pyridin-2-yl, pyridin-3-yl, pyridin-4-yl), pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl (e.g., pyrazol-4-yl), pyrrolyl, benzopyrazolyl, 1,2,3-triazolyl (e.g., triazol-4-yl), 1,3,4-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4- oxadiazolyl, 1,2,4-oxadiazolyl, imidazolyl, thiazolyl (e.g., thiazol-4-yl), isothiazolyl, thienyl, benzimidazolyl (e.g., benzimidazol-5-yl), benzothiazolyl, benzoxazolyl, benzoxadiazolyl, benzothienyl, benzofuranyl, isobenzofuranyl, furanyl, oxazolyl, isoxazolyl, purinyl, isoindolyl, quinoxalinyl, indazolyl (e.g., indazol-4-yl, indazol-5-yl), quinazolinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, isoquinolinyl, quinolinyl, imidazo[1,2-a]pyridinyl (e.g., imidazo[1,2-a]pyridin-6-yl), naphthyridinyl, pyridoimidazolyl, thiazolo[5,4-b]pyridin-2-yl, and thiazolo[5,4-d]pyrimidin-2-yl. The term “heterocycle” or “heterocyclic,” as used herein, means a monocyclic heterocycle, a bicyclic heterocycle, or a tricyclic heterocycle. The term “heterocyclyl” is used herein to refer to a heterocycle when present as a substituent. The monocyclic heterocycle is a three-, four-, five- , six-, seven-, or eight-membered ring containing at least one heteroatom independently selected from the group consisting of O, N, and S. The three- or four-membered ring contains zero or one double bond, and one heteroatom selected from the group consisting of O, N, and S. The five- membered ring contains zero or one double bond and one, two or three heteroatoms selected from the group consisting of O, N and S. The six-membered ring contains zero, one or two double bonds and one, two, or three heteroatoms selected from the group consisting of O, N, and S. The seven- and eight-membered rings contains zero, one, two, or three double bonds and one, two, or three heteroatoms selected from the group consisting of O, N, and S. Representative examples of monocyclic heterocyclyls include, but are not limited to, azetidinyl, azepanyl, aziridinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, 2-oxo-3-piperidinyl, 2- oxoazepan-3-yl, oxadiazolinyl, oxadiazolidinyl, oxazolinyl, oxazolidinyl, oxetanyl, oxepanyl, oxocanyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl, 1,2-thiazinanyl, 1,3-thiazinanyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1- dioxidothiomorpholinyl (thiomorpholine sulfone), thiopyranyl, and trithianyl. The bicyclic heterocycle is a monocyclic heterocycle fused to a 6-membered arene, or a monocyclic heterocycle fused to a monocyclic cycloalkane, or a monocyclic heterocycle fused to a monocyclic cycloalkene, or a monocyclic heterocycle fused to a monocyclic heterocycle, or a monocyclic heterocycle fused to a monocyclic heteroarene, or a spiro heterocycle group, or a bridged monocyclic heterocycle ring system in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, or an alkenylene bridge of two, three, or four carbon atoms. The bicyclic heterocyclyl is attached to the parent molecular moiety at a non-aromatic ring atom (e.g., indolin-1-yl). Representative examples of bicyclic heterocyclyls include, but are not limited to, chroman-4-yl, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzothien-2-yl, 1,2,3,4- tetrahydroisoquinolin-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, azabicyclo[2.2.1]heptyl (including 2-azabicyclo[2.2.1]hept-2-yl), azabicyclo[3.1.0]hexanyl (including 3-azabicyclo[3.1.0]hexan-3-yl), 2,3-dihydro-1H-indol-1-yl, isoindolin-2-yl, octahydrocyclopenta[c]pyrrolyl, octahydropyrrolopyridinyl, tetrahydroisoquinolinyl, 7- oxabicyclo[2.2.1]heptanyl, hexahydro-2H-cyclopenta[b]furanyl, 2-oxaspiro[3.3]heptanyl, 3- oxaspiro[5.5]undecanyl, 6-oxaspiro[2.5]octan-1-yl, and 3-oxabicyclo[3.1.0]hexan-6-yl. Tricyclic heterocycles are exemplified by a bicyclic heterocycle fused to a 6-membered arene, or a bicyclic heterocycle fused to a monocyclic cycloalkane, or a bicyclic heterocycle fused to a monocyclic cycloalkene, or a bicyclic heterocycle fused to a monocyclic heterocycle, or a bicyclic heterocycle in which two non-adjacent atoms of the bicyclic ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, or an alkenylene bridge of two, three, or four carbon atoms. Examples of tricyclic heterocycles include, but are not limited to, octahydro-2,5-epoxypentalene, hexahydro-2H-2,5- methanocyclopenta[b]furan, hexahydro-1H-1,4-methanocyclopenta[c]furan, aza-adamantane (1- azatricyclo[3.3.1.13,7]decane), and oxa-adamantane (2-oxatricyclo[3.3.1.13,7]decane). The monocyclic, bicyclic, and tricyclic heterocyclyls are connected to the parent molecular moiety at a non-aromatic ring atom. The term “hydroxyl” or “hydroxy,” as used herein, means an -OH group. The term “hydroxyalkyl,” as used herein, means at least one -OH group, is appended to the parent molecular moiety through an alkylene group, as defined herein. Terms such as “alkyl,” “cycloalkyl,” “alkylene,” etc. may be preceded by a designation indicating the number of atoms present in the group in a particular instance (e.g., “C1-4alkyl,” “C3-6cycloalkyl,” “C1-4alkylene”). These designations are used as generally understood by those skilled in the art. For example, the representation “C” followed by a subscripted number indicates the number of carbon atoms present in the group that follows. Thus, “C3alkyl” is an alkyl group with three carbon atoms (i.e., n-propyl, isopropyl). Where a range is given, as in “C1-4,” the members of the group that follows may have any number of carbon atoms falling within the recited range. A “C1-4alkyl,” for example, is an alkyl group having from 1 to 4 carbon atoms, however arranged (i.e., straight chain or branched). The term “substituted” refers to a group that may be further substituted with one or more non-hydrogen substituent groups. Substituent groups include, but are not limited to, halogen, =O (oxo), =S (thioxo), cyano, nitro, fluoroalkyl, alkoxyfluoroalkyl, fluoroalkoxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, heteroalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, heteroarylalkyl, arylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylene, aryloxy, phenoxy, benzyloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, sulfonylamino, sulfinylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl,sulfinyl, –COOH, ketone, amide, carbamate, and acyl. The term “leaving group” refers to an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction. Sulfinate Salts Exemplary sulfinate salts of the present disclosure are set forth in the following numbered embodiments. The first embodiment is denoted E1, another embodiment is denoted E2 and so forth. E1. A salt of formula (I): , wherein: a is 1 or 2; X+ais a cation having a +a charge; R1is hydrogen, –NO2, –OC1-4alkyl, C1-4alkyl, F, or Cl; and R2is hydrogen, –OC1-4alkyl, C1-4alkyl, or –NO2; with the proviso that at least one of R1and R2is not hydrogen. E2. The salt of E1, wherein a is 1. E3. The salt of E1, wherein a is 2. E4. The salt of E2 or E3, wherein X+ais Na+1, K+1, Li+1, Mg+2, Zn+2, or Bu4N+1. E5. The salt of any one of E1-E4, wherein R1is hydrogen. E6. The salt of any one of E1-E4, wherein R1is –NO2. E7. The salt of any one of E1-E4, wherein R1is –OC1-4alkyl. E8. The salt of any one of E1-E4, wherein R1is C1-4alkyl. E9. The salt of any one of E1-E4 or E6-E8, wherein R2is hydrogen. E10. The salt of any one of E1-E8, wherein R2is –OC1-4alkyl. E11. The salt of any one of E1-E8, wherein R2is C1-4alkyl. E12. The salt of any one of E1-E8, wherein R2is –NO2. E13. The salt of any one of E1-E8, wherein the salt of formula (I) is a salt of any one of formulae (I-a)-(I-j): b) d) f) h) j) Preparation of Sulfinate Salts and their Synthetic Applications The following schemes illustrate exemplary methods for preparing and applying the sulfinate salts described herein. 1. Preparation General Scheme 1, below, illustrates an exemplary method for preparing salts of formula (I) wherein X+ais Na+1. General Scheme 1 R1GXSH R1B GX K+1, or Li+1) may be prepared by reacting a ((chloromethoxy)methyl)benzyl compound of formula A with a thiol of formula B under suitable thioestiferication reaction conditions to provide an intermediate of formula C. Intermediates of formula C may then be subjected to suitable oxidation conditions, followed by reaction with NaBH4or a compound of formula [X+][OH−] (e.g., NaOH, LiOH, KOH), to provide exemplary salts of formula (I) wherein X+ais X+1. 2. Applications Exemplary salts of formula (I) may be used to prepare various compounds comprising sulfonyl moieties. For example, as shown in General Schemes 2-4, below, the salts of formula (I) may be used to prepare various sulfinates. General Scheme 2 As shown in General Scheme 2 above, salts of formula (I) may be reacted with a compound of formula (II) under suitable conditions, such as coupling conditions, to provide compounds of formula (III), where: X1is a leaving group; Y1is G1, –C1-6alkylene–G1, C1-10alkyl, C2-10alkenyl, or C2-10alkynyl; G1, at each occurrence, is independently a 6- to 12-membered aryl, a 4- to 12-membered heterocyclyl, a 3- to 12-membered carbocyclyl, or a 5- to 12-membered heteroaryl, wherein the heteroaryl and heterocyclyl each contain 1-4 heteroatoms independently selected from the group consisting of O, N, and S, and G1is optionally substituted with a first substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, oxo, –OR1x, –N(R1x)2, –SR1x, –SO2R1x, –C(O)R1x, –C(O)OR1x, –C(O)N(R1x)2, G1a, –C1-6alkylene–OR1x, –C1-6alkylene–SR1x, –C1-6alkylene–N(R1x)2, –C1-6alkylene–SO2R1x, –C1-6alkylene–C(O)R1x, –C1-6alkylene–C(O)OR1x, –C1-6alkylene–C(O)N(R1x)2, and –C1-6alkylene–G1a, and optionally further substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, and –OR1x; R1x, at each occurrence, is independently hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, –C1-3alkylene–C3-6cycloalkyl, phenyl, or –C1-3alkylene–phenyl, wherein each cycloalkyl or phenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C1-4alkyl, and C1-4haloalkyl; and G1ais a phenyl, a 5- to 6-membered heteroaryl containing 1-3 heteroatoms, a 4- to 8-membered heterocyclyl containing 1-2 heteroatoms, or a 3- to 8-membered carbocyclyl, wherein the heteroatoms are independently selected from the group consisting of O, N, and S, and G1a, at each occurrence, is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, –C1-6alkylene–OH, oxo, OH, –OC1-4alkyl, –OC1-4haloalkyl, C3-4cycloalkyl, and –C1-3alkylene–C3-4cycloalkyl. General Scheme 3 As may be further modified. For example, the compound of formula (III) may be reacted with a compound of formula H–Y2under suitable reaction conditions to provide compounds of formula (IV): , wherein: Y2is G2or –C1-6alkylene–G2, C1-10alkyl, C2-10alkenyl, or C2-10alkynyl; G2, at each occurrence, is independently a 6- to 12-membered aryl, a 4- to 12-membered heterocyclyl, a 3- to 12-membered carbocyclyl, or a 5- to 12-membered heteroaryl, wherein the heteroaryl and heterocyclyl each contain 1-4 heteroatoms independently selected from the group consisting of O, N, and S, and G2is optionally substituted with a first substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, oxo, –OR2x, –N(R2x)2, –SR2x, –SO2R2x, –C(O)R2x, –C(O)OR2x, –C(O)N(R2x)2, G2a, –C1-6alkylene–OR2x, –C1-6alkylene–SR2x, –C1-6alkylene–N(R2x)2, –C1-6alkylene–SO2R2x, –C1-6alkylene–C(O)R2x, –C1-6alkylene–C(O)OR2x, –C1-6alkylene– C(O)N(R2x)2, and –C1-6alkylene–G2a, and optionally further substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, and –OR2x; R2x, at each occurrence, is independently hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, –C1-3alkylene–C3-6cycloalkyl, phenyl, or –C1-3alkylene–phenyl, wherein each cycloalkyl or phenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C1-4alkyl, and C1-4haloalkyl; and G2ais a phenyl, a 5- to 6-membered heteroaryl containing 1-3 heteroatoms, a 4- to 8- membered heterocyclyl containing 1-2 heteroatoms, or a 3- to 8-membered carbocyclyl, wherein the heteroatoms are independently selected from the group consisting of O, N, and S, and G2a, at each occurrence, is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, –C1-6alkylene–OH, oxo, OH, –OC1-4alkyl, –OC1-4haloalkyl, C3-4cycloalkyl, and –C1-3alkylene–C3-4cycloalkyl. General Scheme 4. As shown in General Scheme 4 above, a compound of formula (III) or a compound of formula (IV) may be converted to the corresponding sulfonyl fluoride by reacting the compound of formula (III) or (IV) with a fluorinating agent in the presence of blue light, (e.g., Blue LEDs).The fluorinating agent ma .e.,N-Fluorobenzenesulfonimide (NF The compounds and inter e aes ay e soae a pu e y e o s e - own to those skilled in the art of organic synthesis. Examples of conventional methods for isolating and purifying compounds can include, but are not limited to, chromatography on solid supports such as silica gel, alumina, or silica derivatized with alkylsilane groups, by recrystallization at high or low temperature with an optional pretreatment with activated carbon, thin-layer chromatography, distillation at various pressures, sublimation under vacuum, and trituration, as described for instance in “Vogel’s Textbook of Practical Organic Chemistry”, 5th edition (1989), by Furniss, Hannaford, Smith, and Tatchell, pub. Longman Scientific & Technical, Essex CM20 2JE, England. A disclosed compound may have at least one basic nitrogen whereby the compound can be treated with an acid to form a desired salt. For example, a compound may be reacted with an acid at or above room temperature to provide the desired salt, which is deposited, and collected by filtration after cooling. Examples of acids suitable for the reaction include, but are not limited to tartaric acid, lactic acid, succinic acid, as well as mandelic, atrolactic, methanesulfonic, ethanesulfonic, toluenesulfonic, naphthalenesulfonic, benzenesulfonic, carbonic, fumaric, maleic, gluconic, acetic, propionic, salicylic, hydrochloric, hydrobromic, phosphoric, sulfuric, citric, hydroxybutyric, camphorsulfonic, malic, phenylacetic, aspartic, or glutamic acid, and the like. Optimum reaction conditions and reaction times for each individual step can vary depending on the reactants employed and substituents present in the reactants used. Specific procedures are provided in the Examples section. Reactions may be worked up in the conventional manner, e.g., by eliminating the solvent from the residue and further purified according to methodologies generally known in the art such as, but not limited to, crystallization, distillation, extraction, trituration, and chromatography. Unless otherwise described, the starting materials and reagents are either commercially available or may be prepared by one skilled in the art from commercially available materials using methods described in the chemical literature. Starting materials, if not commercially available, may be prepared by procedures selected from standard organic chemical techniques, techniques that are analogous to the synthesis of known, structurally similar compounds, or techniques that are analogous to the above-described schemes or the procedures described in the synthetic examples section. Routine experimentations, including appropriate manipulation of the reaction conditions, reagents and sequence of the synthetic route, protection of any chemical functionality that cannot be compatible with the reaction conditions, and deprotection at a suitable point in the reaction sequence of the method are included in the scope of the invention. Suitable protecting groups and the methods for protecting and deprotecting different substituents using such suitable protecting groups are well known to those skilled in the art; examples of which may be found in PGM Wuts and TW Greene, in Greene’s book titled Protective Groups in Organic Synthesis (4thed.), John Wiley & Sons, NY (2006), which is incorporated herein by reference in its entirety. Synthesis of the compounds of the invention may be accomplished by methods analogous to those described in the synthetic schemes described hereinabove and in specific examples. When an optically active form of a disclosed compound is required, it may be obtained by carrying out one of the procedures described herein using an optically active starting material (prepared, for example, by asymmetric induction of a suitable reaction step), or by resolution of a mixture of the stereoisomers of the compound or intermediates using a standard procedure (such as chromatographic separation, recrystallization, or enzymatic resolution). Similarly, when a pure geometric isomer of a compound is required, it may be obtained by carrying out one of the above procedures using a pure geometric isomer as a starting material, or by resolution of a mixture of the geometric isomers of the compound or intermediates using a standard procedure such as chromatographic separation. It may be appreciated that the synthetic schemes and specific examples as described are illustrative and are not to be read as limiting the scope of the invention as it is defined in the appended claims. All alternatives, modifications, and equivalents of the synthetic methods and specific examples are included within the scope of the claims. It will be apparent to one of ordinary skill in the relevant art that suitable modifications and adaptations to the compositions, formulations, methods, processes, and applications described herein can be made without departing from the scope of any embodiments or aspects thereof. The compositions and methods provided are exemplary and are not intended to limit the scope of any of the specified embodiments. All of the various embodiments, aspects, and options disclosed herein can be combined in any variations or iterations. The scope of the compositions, formulations, methods, and processes described herein include all actual or potential combinations of embodiments, aspects, options, examples, and preferences herein described. The exemplary compositions and formulations described herein may omit any component, substitute any component disclosed herein, or include any component disclosed elsewhere herein. The ratios of the mass of any component of any of the compositions or formulations disclosed herein to the mass of any other component in the formulation or to the total mass of the other components in the formulation are hereby disclosed as if they were expressly disclosed. Should the meaning of any terms in any of the patents or publications incorporated by reference conflict with the meaning of the terms used in this disclosure, the meanings of the terms or phrases in this disclosure are controlling. Furthermore, the foregoing discussion discloses and describes merely exemplary embodiments. All patents and publications cited herein are incorporated by reference herein for the specific teachings thereof. EXAMPLES Sulfonyl fluorides (SFs) are one of the rare electrophilic warheads known to react with both lysine and tyrosine residues and thus are often used as covalent inhibitors and biochemical probes. Sulfonyl fluoride exchange (SuFEx), first introduced in 2014, relies upon the exchange of an incoming nucleophile with fluoride on a hexavalent sulfur forming an irreversible, covalent bond (FIG. 1A). This exchange, however, must occur under catalytic conditions whereby both the sulfonyl group and departing fluoride group are stabilized by hydrogen bonding. This imparts a degree of stability and selectivity on SFs not seen with other electrophilic groups. Increased electron density and steric hinderance results in an increase in overall stability of the SF as shown in both aqueous solutions and in rat serum. Although both electron density and steric hinderance decrease reactivity of the SF toward exogenous nucleophiles, reactivity with a targeted nucleophilic residue should not be as adversely affected due to the rate enhancement of the catalytic microenvironment of the binding site and the quiescent affinity (two-step) binding model for a SF inhibitor. The use of SFs has been restricted by the methods by which they are synthesized and their overall instability to basic and nucleophilic synthetic conditions. Ultimately most SF containing small molecules are formed by coupling a pendant preformed SF to a core structure at the end of a synthetic sequence through alkylation or amide bond formation (FIG.1B). This ultimately restricts the diversity of the structures that are obtainable. In general, SFs are installed on the outer periphery of a core structure and reach out to a nucleophilic residue outside of the binding pocket. This leaves the SF exposed and more likely to be reactive to exogenous nucleophiles. As steric hinderance influences stability, a more internalized SF would be valuable. Ideally, this is done through late stage coupling or C-H activation to directly yield the SF (FIG. 1C). These protocols, although often elegant, have limitations in scope, specifically with ortho- functionalization and must still be done at the end of a synthetic endeavor. Conversely, if a SF’s reactivity may be masked and protected, then it may be installed anywhere in a synthetic route (FIG.1D) and can expand the reactions that are amenable to late- stage functionalization. This would ultimately allow for greater diversity in structure and a more combinatorial approach to building SF libraires. To protect the reactivity of a SF, it is best to protect the parent sulfinate as a sulfone. Sulfinates may be converted to the SF by oxidation with Selectfluor™. Sulfinate protecting groups (SPGs) can therefore mask the reactivity of a SF and be controllably deprotected. It was recently discovered two novel SPGs possessing a para- methoxybenzyl and ortho-nitrobenzyl protected methyloxy sulfone (PMB-R and oNB-R, respectively) that may be converted to sulfonyl fluorides using blue light and Selectfluor™ (FIG. 1F). These two protecting groups have broad stability across the 10 most common synthetic transformations including withstanding C-N and C-C bond forming conditions. The overall stability of the SPGs would allow for sulfur incorporation anywhere in a synthetic route (as in FIG.1D). Conversely, this stability would also allow for late-stage incorporation of sulfur onto structures that can then undergo harsh C-N and C-C bond couplings. Furthermore, these aryl-containing SPGs may be synthesized through copper coupling or photocatalysis from the corresponding sulfinate salt and aryl halide. Given their stability, ease of synthesis, and facile deprotection / fluorination, they are ideally suited to be used in the construction of libraries of sulfonyl fluorides precursors (FIG.2). The overall goal therefore is to synthesize a wide library of at least 60+ aryl scaffolds containing nitrogen coupling partner and a PMB-R or oNB-R protected sulfinate (FIG.2, step 1). This library can then be coupled using either C-C and C-N cross coupling, amide bond formation, or alkylation to form more complex intermediates (step 2), and then deprotected and fluorinated to yield sulfonyl fluorides (step 3). Ideally, two SPG libraries would be developed for complex molecule synthesis: a C-N coupling library and a C-C coupling library. Each library would consist of an aryl core and possess either the oNB-R or PMB-R sulfinate protecting group and functionality for further coupling (an amine, halide or boronic ester). The SPG may be coupled to the aryl core through aryl halide coupling to the sulfinate using copper or dual nickel photocatalysis (FIG.2, Step 1). For the C-N coupling library, the aryl core can include heterocycles, anilines, benzyl amines, or amides. For the SPG C-C coupling library, aryl cores containing either an aryl halide or boronic ester may be made. These two libraries could therefore serve as starting point for more complex molecule development and drug discovery applications. General Information All chemicals were purchased from Ambeed, Sigma Aldrich or ThermoFisher Scientific and used without purification. Anhydrous solvents (THF, CH2Cl2, DMF, CH3CN) were purified before use by passing through a column composed of activated alumina and a supported copper redox catalyst. ACS grade MeCN was purchased from Fisher Chemicals and used without purification. Yields refer to chromatographically and spectroscopically (1H NMR) homogeneous material unless otherwise noted. Analytical thin-layer chromatography (TLC) was performed using Merck Silica Gel 60 Å F-254 precoated plates (0.25 mm thickness), and components were visualized by ultraviolet light (254 nm) and / or by staining with KMnO4 or phosphomolybdic acid. Flash column chromatography was performed on a Teledyne CombiFlash NextGen 300 automated flash purification system with various Teledyne cartridges (4-80 g, 40-63 µm, 60 Å). Purifications were performed with hexanes and ethyl acetate unless otherwise noted.1H and13C NMR spectra were recorded on a Bruker Advance-III spectrometer at 400 MHz and 101 MHz, respectively, in CDCl3, MeOD or DMSO-d6. Chemical shifts were reported in ppm; multiplicities are indicated by s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, sep = septet, dd = doublet of doublet, dt = doublet of triplet, dp = doublet of pentet, m = multiplet, br = broad resonance. Coupling constants ‘J’ were reported in Hz. High-resolution mass spectral data were obtained on a Waters SYNAPT XS (TOF) high resolution mass spectrometer using electron spray ionization (ESI) in the positive ion mode. All photoredox reactions were performed using a Kessil PR160L-Blue LED lamp (30 W, λmax= 440 nm, 100% intensity, 5 cm from the wall of vial) with continuous air flow for cooling. Synthesis of Reagents Abbreviations: Me is methyl; Et is ethyl; Ph is phenyl; Ac is acetyl; Bn is benzyl; MeOH is methanol; EtOAc is ethyl acetate; MeCN is acetonitrile; THF is tetrahydrofuran; DMSO is dimethylsulfoxide; DCM is dichloromethane; DMF is N,N-dimethylformamide; DMA is dimethylacetamide; NiBr2DME is nickel(II) bromide ethylene glycol dimethyl ether complex; DABCO is 1,4-diazabicyclo[2.2.2]octane; dba is dibenzylideneacetone; HATU is hexafluorophosphate azabenzotriazole tetramethyl uranium; NaOMe is sodium methoxide; NaOtBu is sodium tertbutoxide; Boc is tert-butyloxycarbonyl; SMOPS is sodium 3-methoxy-3-oxopropane-1-sulfinate; TBS is tert-butyl(dimethyl)silyl; TBSOMS is silyloxymethanesulfinate; oNB is o-nitrobenzyl; PMB is p-methoxybenzyl; DIPEA is N,N-diisopropylethylamine; Selectfluor™ is 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium ditetrafluoroborate; PC is photocatalyst; 4CzIPN is 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene; HMNPC is ((2S,4R)-4-Hydroxy-N-(2-methylnaphthalen-1-yl)pyrrolidine-2-carboxamide; PPh3is triphenylphosphine; TLC is thin layer chromatography; LED is light emitting diode; Molar is M; min or min. is minute(s); h or hr. is hour(s); rt, RT, or r.t. is room temperature; sat. is saturated; eq, eq., or equiv is equivalent(s); wt% or wt.% is weight %; NMR is nuclear magnetic resonance; LCMS is liquid chromatography mass spectrometry; and ESI is electrospray ionization; and TOF is time-of-flight. EXAMPLE 1 2-((((4-Methoxybenzyl)oxy)methyl)thio)pyrimidine (S1). A 250 mL round-bottom flask was charged with 2-mercaptopyrimidine (3.85 g, 34.33 mmol) and dry DMF (170 mL). Sodium hydride (NaH) (1.65 g, 41.19 mmol, 60% dispersion in oil, 1.2 equiv) was added to the reaction mixture portion wise at 0 °C under N2atmosphere. After one hour, 1-((chloromethoxy)methyl)-4- methoxybenzene (6.41 g, 34.33 mmol) was added dropwise to the mixture over 10 minutes. The reaction mixture was then warmed to room temperature and stirred overnight. After reaction completion, ammonium chloride was added to quench the reaction at 0 °C. The organic layer was extracted with ethyl acetate (3 times) and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified by flash chromatography to obtain the desired product as a yellow solid (8.55 g, 95% yield).1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.8 Hz, 2H), 7.30–7.26 (m, 2H), 7.02 (t, J = 4.8 Hz, 1H), 6.87 (d, J = 8.7 Hz, 2H), 5.42 (s, 2H), 4.63 (s, 2H), 3.80 (s, 3H);13C NMR (101 MHz, CDCl3) δ 170.9, 159.4, 157.5, 129.9, 129.2, 117.2, 113.8, 70.9, 70.4, 55.3. 2-((((4-Methoxybenzyl)oxy)me S2). To a solution of 2-((((4- methoxybenzyl)oxy)methyl)thio)pyrimidine (4.40 g, 16.77 mmol) and Na2WO4(2.80 g, 8.39 mmol, 0.5 equiv) in MeOH (160 mL), was added aq. H2O2(14.37 mL, 0.25 mol, 50% v / v, 15 equiv) dropwise at 0 °C under N2atmosphere. After reaction completion, a solution of Na2S2O5(8.8 grams) in 90 mL water was added to the reaction mixture at 0 °C. The organic layer was extracted with dichloromethane (3 times), and the combined organic layers were washed with brine and then dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was then washed with diethyl ether (3 times) to obtain 2-((((4- methoxybenzyl)oxy)methyl)sulfonyl)pyrimidine as a white solid (4.54 g, 92% yield).1H NMR (400 MHz, CDCl3) δ 8.97 (d, J = 4.8 Hz, 2H), 7.57 (t, J = 4.9 Hz, 1H), 7.25 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 5.04 (s, 2H), 4.88 (s, 2H), 3.80 (s, 3H);13C NMR (101 MHz, CDCl3) δ 165.1, 159.9, 158.8, 130.5, 127.7, 124.0, 114.1, 80.8, 74.3, 55.3. Sodium ((4-methoxybenzyl) R-Na”). To a solution of 2-((((4- methoxybenzyl)oxy)methyl)sulfonyl)pyrimidine (4.00 g, 13.59 mmol) in MeOH (40 mL), NaOMe (3.02 mL, 13.59 mmol, 1 equiv) was added at 0 °C. The reaction mixture was then warmed to room temperature and stirred for one hour. After reaction completion, the solvent was removed under reduced pressure, and the resulting residue was then washed with diethyl ether three times, to obtain the desired product as a white solid (3.14 g, 97% yield).1H NMR (400 MHz, DMSO) δ 7.23 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.58 (s, 2H), 3.74 (s, 3H), 3.30 (s, 2H).13C NMR (101 MHz, DMSO) δ 158.6, 130.5, 129.3, 113.5, 93.5, 72.1, 55.0. Lithium ((4-methoxybenzyl) R-Li”). To a solution of 2-((((4- methoxybenzyl)oxy)methyl)sulfonyl)pyrimidine (20 mg, 0.07 mmol) in MeOH:H2O (1:1, 0.2 mL), LiOH (1.63 mg, 0.07 mmol, 1 equiv) was added at 0 °C. The reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred overnight at 50 °C. After the reaction was complete, the solvent was removed under reduced pressure. The residue was washed with diethyl ether three times, to obtain the desired product as a white solid (14 mg, 93% yield).1H NMR (400 MHz, DMSO) δ 7.23 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.58 (s, 2H), 3.74 (s, 3H), 3.34 (s, 2H).13C NMR (101 MHz, DMSO) δ 158.6, 130.5, 129.3, 113.5, 93.1, 72.1, 55.0. Potassium ((4-methoxybenzyl) R-K”). To a solution of 2-((((4- methoxybenzyl)oxy)methyl) mg, mmol) in MeOH (0.2 mL), KOH (3.93 mg, 0.07 mmol, 1 equiv) was added at 0 °C. The reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred for one hour at rt. After the reaction was complete, the solvent was removed under reduced pressure. The residue was washed with diethyl ether three times, to obtain the desired product as a white solid (17 mg, 96% yield).1H NMR (400 MHz, DMSO) δ 7.22 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 4.58 (s, 2H), 3.74 (s, 3H), 3.29 (s, 2H).13C NMR (101 MHz, DMSO) δ 158.5, 130.6, 129.2, 113.5, 93.6, 72.0, 55.0. EXAMPLE 2

[0002] 2-((((2-Nitrobenzyl)oxy)methyl)thio)benzo[d]thiazole (S3). A 100 mL round-bottom flask was charged with 2-mercaptobenzothiazole (1.69 g, 10.09 mmol) and dry DMF (40 mL). NaH (483 mg, 12.12 mmol, 60% dispersion in oil, 1.2 equiv) was added to the reaction mixture portion wise at 0 °C under N2atmosphere. After one hour, 1-((chloromethoxy)methyl)-2-nitrobenzene (2.03 g, 10.09 mmol) was added dropwise to the mixture over 10 minutes. The reaction mixture was then warmed to room temperature and stirred overnight. After reaction completion, ammonium chloride was added to quench the reaction at 0 °C. The organic layer was extracted with ethyl acetate (3 times) and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified by flash chromatography to obtain the desired product as a light-yellow solid (2.68 g, 80% yield).1H NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 8.2, 1.4 Hz, 1H), 7.96–7.89 (m, 1H), 7.78 (d, J = 1.3 Hz, 2H), 7.62 (td, J = 7.6, 1.3 Hz, 1H), 7.44 (ddd, J = 8.3, 7.3, 1.3 Hz, 2H), 7.33 (ddd, J = 8.3, 7.3, 1.2 Hz, 1H), 5.61 (s, 2H), 5.18 (s, 2H);13C NMR (101 MHz, CDCl3) δ 164.7, 153.0, 147.3, 135.7, 133.8, 129.0, 128.3, 126.3, 124.8, 124.7, 122.1, 121.1, 74.8, 68.4. 2-((((2-Nitrobenzyl)oxy)methyl) (S4). To a solution of 2-((((2- nitrobenzyl)oxy)methyl)thio)benzo[d]thiazole (2.60 g, 7.82 mmol) and Na2WO4(1.30 g, 3.91 mmol, 0.5 equiv) in MeOH (80 mL), was added aq. H2O2(2.2 mL, 39.1 mmol, 50% v / v, 5 equiv) dropwise at 0 °C under N2atmosphere. After reaction completion, a solution of Na2S2O5(5.2grams) in 40 mL water was added to the reaction mixture at 0̊ C. The organic layer was extractedwith dichloromethane (3 times), and the combined organic layers were washed with brine and then dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was then washed with diethyl ether (3 times) to obtain the desired sulfone as a white solid (2.56 g, 90% yield).1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 7.4 Hz, 1H), 8.04 (ddd, J = 17.1, 7.7, 1.2 Hz, 2H), 7.70–7.53 (m, 4H), 7.45 (ddd, J = 8.7, 7.0, 2.0 Hz, 1H), 5.35 (s, 2H), 5.16 (s, 2H);13C NMR (101 MHz, CDCl3) δ 164.3, 152.9, 147.2, 137.3, 133.9, 132.4, 129.2, 129.0, 128.4, 127.9, 125.8, 125.1, 122.4, 85.5, 72.3. Sodium ((2-nitrobenzyl)oxy)meth B-R-Na”). To a solution of 2-((((2- nitrobenzyl)oxy)methyl)sulfonyl)benzo[d]thiazole (1.60 g, 4.39 mmol) in EtOH (45 mL), NaBH4(830.5 mg, 21.95 mmol, 5 equiv) was added at 0 ˚C. The reaction mixture was then warmed to room temperature and stirred for one hour. After reaction completion, the solvent was removed under reduced pressure, and the resulting residue was then washed with diethyl ether three times, to obtain the desired product as a white solid (1.07 g, 96% yield).1H NMR (400 MHz, DMSO) δ 8.05 (dd, J = 8.1, 1.2 Hz, 1H), 7.83–7.70 (m, 2H), 7.61–7.51 (m, 1H), 5.06 (s, 2H), 3.45 (s, 2H);13C NMR (101 MHz, DMSO) δ 147.1, 134.6, 133.8, 128.9, 128.4, 124.4, 93.9, 69.1. of 2-((((2- nitrobenzyl)oxy)methyl)sulfonyl)benzo[d]thiazole (20 mg, 0.05 mmol) in MeOH: H2O (1:1, 0.2 mL), KOH (2.80 mg, 0.05 mmol, 1 equiv) was added at 0 °C. The reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred overnight at 50 °C. After the reaction was complete, the solvent was removed under reduced pressure. The residue was washed with diethyl ether three times, to obtain the desired product as a light-yellow solid (11.23 mg, 87% yield).1H NMR (400 MHz, DMSO) δ 8.06 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 5.11 (s, 2H), 4.05 (s, 2H);13C NMR (101 MHz, DMSO) δ 147.1, 134.5, 133.8, 128.9, 128.4, 124.4, 81.6, 68.9. Sulfone Synthesis Aryl Iodides to Aryl Sulfones General Procedure A1: A sealed microwave vial was charged with CuI (6 mol%), L (6 mol%), R”-SO2Na (2 equiv), aryl iodide (if solid), and K3PO4(1 equiv). The vial was then evacuated and backfilled with argon, and aryl iodide (if liquid) and DMSO were then added into the tube via syringe. The reaction mixture was stirred at 35 °C in an oil bath for 24 h. After cooling to room temperature, the crude product was diluted with ethyl acetate and filtrated through silica gel. Then the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with ethyl acetate / hexanes) to afford the corresponding aryl sulfone. General Procedure A2: A sealed microwave vial was charged with CuI (6 mol%), L (6 mol%), R”-SO2Na (1.5 equiv), aryl iodide (if solid), and K3PO4(1 equiv). The vial was then evacuated and backfilled with argon, and aryl iodide (if liquid) and DMSO were then added into the tube via syringe. The reaction mixture was stirred at 50 °C in an oil bath for 24 h. After cooling to room temperature, the crude product was diluted with ethyl acetate and filtrated through silica gel. Then the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with ethyl acetate / hexanes) to afford the corresponding aryl sulfone. General Procedure A3: A sealed microwave vial was charged with CuI (6 mol%), L (6 mol%), R”-SO2Na (1.5 equiv), aryl iodide (if solid), and K3PO4(1 equiv). The vial was then evacuated and backfilled with argon, and aryl iodide (if liquid) and DMSO were then added into the tube via syringe. The reaction mixture was stirred at 35 °C in an oil bath for 24 h. After cooling to room temperature, the crude product was diluted with ethyl acetate and filtrated through silica gel. Then the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with ethyl acetate / hexanes) to afford the corresponding aryl sulfone. General Procedure A4: A sealed microwave vial was charged with CuI (10 mol%), L (10 mol%), R”-SO2Na (3 equiv), aryl iodide (if solid), and K3PO4(1 equiv). The vial was then evacuated and backfilled with argon, and aryl iodide (if liquid) and DMSO were then added into the tube via syringe. The reaction mixture was stirred at 50 °C in an oil bath for 24 h. After cooling to room temperature, the crude product was diluted with ethyl acetate and filtrated through silica gel. Then the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with ethyl acetate / hexanes) to afford the corresponding aryl sulfone. Notes: When HMNPC was used as a ligand, trace amount of product was obtained. TBSOMS-Na (16.26 mg, 0.07 mmol), ((2S,4R)-N-(2,6-dimethylphenyl)-4-hydroxypyrrolidine-2-carboxamide (10 mol %), CuI (10 mol%), and 1-fluoro-4-iodobenzene (16.14 µL, 0.15 mmol, 2 equiv) yielded 3 as a white solid (15.34 mg, 72 % yield). 1-Fluoro-4-((((4-methoxybenzyl) (4). According to general procedure A2, 1-fluoro-4-iodobenzene (8.6 µL, 0.07 mmol), PMB-R-Na (26.80 mg, 0.10 mmol), and K3PO4(16 mg, 0.01 mmol) in 0.2 mL DMSO yielded 4 as a white solid (21.00 mg, 92 % yield).1H NMR (400 MHz, CDCl3) δ 8.01–7.89 (m, 2H), 7.25–7.18 (m, 4H), 6.88 (d, J = 8.6 Hz, 2H), 4.84 (s, 2H), 4.52 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 256.6 Hz), 160.1, 133.6 (d, J = 3.1 Hz), 131.9 (d, J = 9.6 Hz), 130.3, 127.8, 116.7 (d, J = 22.5 Hz), 114.2, 84.5, 74.4, 55.4;19F NMR (376 MHz, CDCl3) δ −103.0. 1-((((4-Fluorophenyl)sulfonyl) (5). According to general procedure A4, 1-fluoro-4-iodobenzene (8.6 µL, 0.07 mmol), oNB-R-Na (50.84 mg, 0.22 mmol), and K3PO4(16 mg, 0.01 mmol) in 0.4 mL DMSO yielded 5 as a yellow solid (17.81 mg, 73 % yield).1H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.1, 1.3 Hz, 1H), 7.99–7.92 (m, 2H), 7.63 (ddd, J = 14.8, 8.8, 7.3 Hz, 2H), 7.50 (td, J = 7.6, 7.0, 1.7 Hz, 1H), 7.31–7.21 (m, 2H), 5.28 (s, 2H), 4.69 (s, 2H);13C NMR (101 MHz, CDCl3) δ 166.4 (d, J = 257.3 Hz), 147.5, 133.9, 133.4 (d, J = 3.1 Hz), 132.6, 131.9 (d, J = 9.8 Hz), 129.2 (d, J = 10.8 Hz), 125.2, 116.9 (d, J = 22.7 Hz), 86.2, 72.1;19F NMR (376 MHz, CDCl3) δ −102.4. Aryl Bromides to Aryl Sulfones General Procedure B: A sealed vial was charged with R”-SO2Na (0.2 mmol, 2 equiv), NiBr2.glyme (5 mol%), 4CzIPN (0.2 mol%), DABCO (25 mg, 0.22 mmol. 2.2 equiv) and NEt3(7 µL, 0.06 mmol, 0.6 equiv). The vial was then evacuated and backfilled with argon (3 times), and 1-bromo-4-(trifluoromethyl) benzene (14 µL, 0.1 mmol) and degassed DMA (0.4 mL) were then added into the vial via syringe. The reaction mixture was stirred at 60 °C under Blue LED irradiation for 4 h. After cooling to room temperature, the crude product was extracted with ethyl acetate and washed with brine. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with ethyl acetate / hexanes) to afford the corresponding aryl sulfone. 1-Methoxy-4-((((4- methyl)benzene (4c). The general procedure B with PMB-R-Na (48 mg, 0.2 equiv) was adopted to afford the desired product as a light-yellow solid (36.03 mg, 82% yield).1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.2 Hz, 2H), 7.83 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.86 (s, 2H), 4.56 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 160.1, 141.1, 135.7 (q, J = 33.0 Hz), 130.3, 129.6, 128.7, 127.6, 126.4 (q, J = 3.7 Hz), 114.2, 84.2, 74.5, 55.4;19F NMR (376 MHz, CDCl3) δ −63.2. Aryl Thiols to Aryl Sulfones

[0003] (4-Fluorophen ound-bottom flask was charged with 4-fluorobenzenethiol (0.27 mL, 2.52 mmol) and dry DMF (10 mL). NaH (120 mg, 3 mmol, 60% dispersion in oil, 1.2 equiv) was added to the reaction mixture portion wise at 0 °C under N2atmosphere. After one hour, 1-((chloromethoxy)methyl)-4-methoxybenzene (470.32 mg, 2.52 mmol) was added dropwise to the mixture over 10 minutes. The reaction mixture was then warmed to room temperature and stirred overnight. After reaction completion, ammonium chloride was added to quench the reaction at 0 °C. The organic layer was extracted with ethyl acetate (3 times) and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified by flash chromatography to obtain the desired product as a yellow solid (610.23 mg, 87% yield).1H NMR (400 MHz, CDCl3) δ 7.58–7.44 (m, 2H), 7.31–7.23 (m, 2H), 7.02 (t, J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 4.97 (s, 2H), 4.66 (s, 2H), 3.83 (s, 3H);13C NMR (101 MHz, CDCl3) δ 163.5, 161.0, 159.5, 133.0 (d, J = 8.1 Hz), 130.9 (d, J = 3.4 Hz), 129.9, 129.1, 116.1 (d, J = 21.8 Hz), 114.0, 75.6, 69.5, 55.3;19F NMR (376 MHz, CDCl3) δ −115.0. 1-Fluoro-4-((((4-methoxybenzyl)oxy)methyl)sulfonyl)benzene (4). To a solution of (4- fluorophenyl)(((4-methoxybenzyl)oxy)methyl)sulfane (270 mg, 0.97 mmol) and Na2WO4(161.93 mg, 0.48 mmol, 0.5 equiv) in MeOH (10 mL), was added aq. H2O2(0.28 mL, 4.85 mol, 50% v / v, 5 equiv) dropwise at 0 °C under N2atmosphere. After reaction completion, a solution of Na2S2O5(500 mg) in 5 mL water was added to the reaction mixture at 0 °C. The organic layer was extracted with dichloromethane (3 times), and the combined organic layers were washed with brine and then dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified by flash chromatography to obtain 4 as a white solid (280 mg, 93% yield).1H NMR (400 MHz, CDCl3) δ 8.01–7.89 (m, 2H), 7.25–7.18 (m, 4H), 6.88 (d, J = 8.6 Hz, 2H), 4.84 (s, 2H), 4.52 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 256.6 Hz), 160.1, 133.6 (d, J = 3.1 Hz), 131.9 (d, J = 9.6 Hz), 130.3, 127.8, 116.7 (d, J = 22.5 Hz), 114.2, 84.5, 74.4, 55.4;19F NMR (376 MHz, CDCl3) δ −103.0. charged with 4-fluorobenzenethiol (0.27 mL, 2.52 mmol) and dry DMF (10 mL). NaH (120 mg, 3 mmol, 60% dispersion in oil, 1.2 equiv) was added to the reaction mixture portion wise at 0 °C under N2atmosphere. After one hour, 1-((chloromethoxy)methyl)-2-nitrobenzene (508.05 mg, 2.52 mmol) was added dropwise to the mixture over 10 minutes. The reaction mixture was then warmed to room temperature and stirred overnight. After reaction completion, ammonium chloride was added to quench the reaction at 0 °C. The organic layer was extracted with ethyl acetate (3 times) and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified by flash chromatography to obtain the desired product as a yellow solid (606.10 mg, 82% yield).1H NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 8.2, 1.4 Hz, 1H), 7.70 (dd, J = 7.8, 1.4 Hz, 1H), 7.64–7.59 (m, 1H), 7.50–7.38 (m, 3H), 7.01 (t, J = 8.7 Hz, 2H), 5.07 (s, 4H);13C NMR (101 MHz, CDCl3) δ 163.90, 161.45, 147.69, 134.29, 133.94, 133.61 (d, J = 8.2 Hz), 130.57 (d, J = 3.4 Hz), 129.16, 128.51, 125.08, 116.40 (d, J = 21.9 Hz), 77.35, 67.35;19F NMR (376 MHz, CDCl3) δ −114.5. 1-((((4-Fluorophenyl)sulfonyl) (5). To a solution of (4- fluorophenyl)(((2-nitrobenzyl)oxy) 0.88 mmol) and Na2WO4(147.98 mg, 0.44 mmol, 0.5 equiv) in MeOH (8 mL), was added aq. H2O2(0.25 mL, 4.4 mol, 50% v / v, 5 equiv) dropwise at 0 °C under N2atmosphere. After reaction completion, a solution of Na2S2O5(500 mg) in 5 mL water was added to the reaction mixture at 0 °C. The organic layer was extracted with dichloromethane (3 times), and the combined organic layers were washed with brine and then dried over Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified by flash chromatography to obtain 5 as a yellow solid (263.37 mg, 92% yield).1H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.1, 1.3 Hz, 1H), 7.99–7.92 (m, 2H), 7.63 (ddd, J = 14.8, 8.8, 7.3 Hz, 2H), 7.50 (td, J = 7.6, 7.0, 1.7 Hz, 1H), 7.31–7.21 (m, 2H), 5.28 (s, 2H), 4.69 (s, 2H);13C NMR (101 MHz, CDCl3) δ 166.4 (d, J = 257.3 Hz), 147.5, 133.9, 133.4 (d, J = 3.1 Hz), 132.6, 131.9 (d, J = 9.8 Hz), 129.2 (d, J = 10.8 Hz), 125.2, 116.9 (d, J = 22.7 Hz), 86.2, 72.1;19F NMR (376 MHz, CDCl3) δ −102.4. Alkyl Halides to Alkyl Sulfones General Procedure C: A mixture of benzyl bromide and R”-SO2Na (1.5 equiv, unless otherwise noted) in anhydrous DMSO was stirred under N2atmosphere at room temperature for 12 h. Upon completion, the reaction mixture was diluted in diethyl ether and washed twice with H2O. The organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluting with ethyl acetate / hexanes) to afford the desired alkyl sulfone product. 1-(((Benzylsulfonyl)methoxy)meth ene (4a). According to the general procedure C, benzyl bromide (33 µL, 0.28 mmol), PMB-R-Na (100 mg, 0.42 mmol, 1.5 equiv) in 1.2 mL DMSO yielded 4b as a white solid (83.21 mg, 97% yield).1H NMR (400 MHz, CDCl3) δ 7.41–7.35 (m, 5H), 7.31 (d, J = 8.6 Hz, 2H), 6.92 (d, J = 8.7 Hz, 2H), 4.88 (s, 2H), 4.32 (s, 2H), 4.28 (s, 2H), 3.83 (s, 3H);13C NMR (101 MHz, CDCl3) δ 160.1, 130.9, 130.5, 129.1, 129.1, 127.9, 127.8, 114.2, 79.5, 74.3, 56.5, 55.5. 1-(((Benzylsulfonyl)methoxy) (5a). According to the general procedure C, benzyl bromide (0.14 mL, 1.16 mmol), oNB-R-Na (393 mg, 1.74 mmol, 1.5 equiv) in 5 mL DMSO yielded 5b as a light-yellow solid (328 mg, 88% yield).1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.7 Hz, 1H), 7.75–7.63 (m, 2H), 7.57–7.49 (m, 1H), 7.43–7.38 (m, 5H), 5.32 (s, 2H), 4.43 (s, 2H), 4.35 (s, 2H);13C NMR (101 MHz, CDCl3) δ 147.8, 133.9, 132.3, 130.9, 129.6, 129.3, 129.3, 127.6, 125.2, 81.3, 72.1, 56.9. Stability Assessment for SPGs 1. Amide Coupling Conditions To added DIPEA (0.60 mL, 3.45 mmol, 3 equiv) and HATU (524 mg, 1.38 mmol, 1.2 equiv). The resulting mixture was stirred at room temperature for 1 hour, after which aniline (0.11 mL, 1.27 mmol, 1.1 equiv) was added and stirred overnight. Upon completion, the product was extracted with ethyl acetate and washed with brine. The organic extracts were dried over anhydrous NaaSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain (S)-2-acetamido-4-methyl-N- phenylpentanamide as a white solid (206 mg, 72% yield).1H NMR (400 MHz, DMSO) δ 10.04 (s, 1H), 8.13 (d, J = 7.9 Hz, 1H), 7.61 (d, J = 7.4 Hz, 2H), 7.36–7.24 (m, 2H), 7.11–6.92 (m, 1H), 4.45 (td, J = 8.9, 5.9 Hz, 1H), 1.86 (s, 3H), 1.72–1.57 (m, 1H), 1.58–1.43 (m, 2H), 0.90 (dd, J = 13.3, 6.5 Hz, 6H);13C NMR (101 MHz, DMSO) δ 171.35, 169.23, 138.99, 128.62, 123.23, 119.29, 51.88, 40.93, 24.33, 22.92, 22.39, 21.70. An example for the setup of stability testing of 1: To the solution of acetyl-L-leucine (17.3 mg, 0.1 mmol) and 1 (25 mg, 0.1 mmol, 1 equiv) in 0.5 mL DMF, was added DIPEA (0.05 mL, 0.3 mmol, 3 equiv) and HATU (45.6 mg, 0.12 mmol, 1.2 equiv). The resulting mixture was stirred at room temperature for 1 hour, after which aniline (10 µL, 0.11 mmol, 1.1 equiv) was added and stirred overnight. Upon completion, the product was extracted with ethyl acetate and washed with brine. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. To the crude residue was added 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 2. SNArConditions An In a sealed vial were combined 2-chloroquinoline (16.4 mg, 0.1 mmol), benzylamine (13 µL, 0.12 mmol, 1.2 equiv), 1 (25 mg, 0.1 mmol, 1 equiv), and DIPEA (35 µL, 0.2 mmol, 2 equiv). The solution was stirred at 110 °C for 16 h. The reaction was cooled to room temperature and 4- fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 3. Boc Deprotection Conditions An example for the To the solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (20 mg, 0.1 mmol) and 1 (25 mg, 0.1 mmol, 1 equiv) in 0.5 mL DCM, was added 0.5 mL trifluoroacetic acid. The resulting mixture was stirred at room temperature for 12 h. Upon completion, the solvent was removed under reduced pressure and 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 4. Ester Hydrolysis Conditions CO2Et NaOH CO2H An To the solution of ethyl 2-(4-methoxyphenyl)acetate (18 µL, 0.1 mmol) and 1 (25 mg, 0.1 mmol, 1 equiv) in 0.2 mL H2O: Dioxane (1:1), was added sodium hydroxide (12 mg, 0.3 mmol, 3 equiv). The resulting mixture was stirred at room temperature for 12 h. Upon completion, 4- fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 5. Suzuki-Miyaura Coupling Conditions An A sealed vial was charged with 1-iodo-4-methylbenzene (22 mg, 0.1 mmol), phenyl boronic acid (16 mg, 0.13 mmol, 1.3 equiv), 1 (25 mg, 0.1 mmol, 1 equiv), Pd(PPh3)4(12 mg, 10 mol%), and K3PO4(32 mg, 0.15 mmol.1.5 equiv). The vial was then evacuated and backfilled with argon (3 times), and degassed 0.48 mL H2O: Dioxane (1:5) were then added into the vial via syringe. The resulting mixture was stirred at 110 °C for 12 h. The reaction was cooled to room temperature and 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 6. Amine SN2Conditions An To a suspension of morpholine (8.6 µL, 0.1 mmol), 1 (25 mg, 0.1 mmol, 1 equiv), and K2CO3(18 mg, 0.13 mmol.1.3 equiv) in 0.12 mL CH3CN, was added benzyl bromide (13 µL, 0.11 mmol, 1.1 equiv). The resulting mixture was stirred at room temperature for 2 h. Upon completion, 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 7. Reductive Amination Conditions An example To the , amine (18.1 mg, 0.12 mmol, 1.2 equiv), and 1 (25 mg, 0.1 mmol, 1 equiv) in 0.4 mL MeOH, was added sodium cyanoborohydride (18.85 mg, 0.3 mmol, 3 equiv). The resulting mixture was stirred at room temperature for 12 h. Upon completion, 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after the 8. Hydrogenation Conditions An example To a solution of methyl cinnamate (16.2 mg, 0.1 mmol) and 1 (25 mg, 0.1 mmol, 1 equiv) in 0.3 mL MeOH, was added Pd / C (10 mol%). The resulting mixture was stirred under H2atmosphere for 12 h. Upon completion, 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. 9. Buchwald-Hartwig Coupling An ex A sealed vial was charged with 1-iodo-4-methylbenzene (22 mg, 0.1 mmol), morpholine (20 µL, 0.24 mmol, 2.4 equiv), 1 (25 mg, 0.1 mmol, 1 equiv), NaOtBu (27 mg, 0.28 mmol, 2.8 equiv), Pd2(dba)3(1 mol%) and p(o-tolyl)3(1 mol%). The vial was then evacuated and backfilled with argon (3 times), and degassed 0.4 mL dioxane was then added into the vial via syringe. The resulting mixture was stirred at 100 °C for 24 h. The reaction was cooled to room temperature and 4-fluoro-acetophenone (12 µL, 0.1 mmol, 1 equiv) was added as an internal standard. The NMR yield was calculated as the percentage of 1 recovered after reaction completion. Synthesis of Sulfones 1-Nitro-2-(((phenylsulfonyl)methoxy)methyl)benzene (13a). According to general procedure A4, iodobenzene (8.4 µL, 0.07 mmol), oNB-R-Na (50.80 mg, 0.22 mmol), L (2.02 mg), CuI (1.4 mg), and K3PO4(16 mg, 0.07 mmol) in 0.4 mL DMSO yielded 8 as a yellow solid (9.70 mg, 42 % yield).1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.7 Hz, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.70 (t, J = 7.5 Hz, 1H), 7.66–7.55 (m, 4H), 7.48 (ddd, J = 8.7, 6.4, 2.5 Hz, 1H), 5.25 (s, 2H), 4.71 (s, 2H);13C NMR (101 MHz, CDCl3) δ 147.3, 137.3, 134.4, 133.9, 132.8, 129.4, 129.0, 128.9, 128.9, 125.0, 86.1, 71.9. 1-Methoxy-4-(((phenylsulfonyl)methoxy)methyl)benzene (13b). According to general procedure A2, iodobenzene (8.4 µL, 0.07 mmol), PMB-R-Na (26.80 mg, 0.11 mmol), L (1.2 mg), CuI (0.8 mg), and K3PO4(16 mg, 0.07 mmol) in 0.2 mL DMSO yielded 13b as a white solid (15.6 mg, 71 % yield).1H NMR (400 MHz, CDCl3) δ 7.98–7.89 (m, 2H), 7.70–7.65 (m, 1H), 7.61–7.53 (m, 2H), 7.22 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.83 (s, 2H), 4.54 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 159.9, 137.6, 134.1, 130.2, 129.3, 128.9, 127.9, 114.1, 84.4, 74.2, 55.3. 1-((((4-Methoxyphenyl)sulfonyl) (14a). According to general procedure A4, 1-iodo-4- mg, 0.23 mmol), oNB-R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded 14a as a light yellow solid (64 mg, 83 % yield).1H NMR (400 MHz, CDCl3) δ 8.10–8.02 (m, 1H), 7.85 (d, J = 8.9 Hz, 2H), 7.68–7.54 (m, 2H), 7.53–7.40 (m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 5.23 (s, 2H), 4.66 (s, 2H), 3.89 (s, 3H);13C NMR (101 MHz, CDCl3) δ 164.4, 147.4, 133.9, 133.0, 131.2, 129.2, 128.9, 128.7, 125.1, 114.7, 86.3, 71.9, 55.9. 1-Methoxy-4-((((4- benzene (14b). According to general procedure A2, 1-iodo-4-methoxybenzene (54 mg, 0.23 mmol), PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4(49 mg, 0.23 mmol) in 0.6 mL DMSO yielded 14b as a white solid (64 mg, 92 % yield).1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.82 (s, 2H), 4.50 (s, 2H), 3.88 (s, 3H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 164.2, 159.9, 131.1, 130.2, 129.0, 128.1, 114.6, 114.1, 84.6, 74.2, 55.8, 55.4. Methyl 4-((((2-nitrobenzyl)oxy)methyl)sulfonyl)benzoate (15a). According to general procedure A4, methyl 4-iodobenzoate (60.2 mg, 0.23 mmol), oNB-R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded 15a as a light orange solid (53 mg, 63 % yield).1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.5 Hz, 2H), 8.09 (dd, J = 8.2, 1.3 Hz, 1H), 8.06–7.97 (m, 2H), 7.73–7.55 (m, 2H), 7.50 (ddd, J = 8.9, 7.3, 1.7 Hz, 1H), 5.29 (s, 2H), 4.74 (s, 2H), 3.98 (s, 3H);13C NMR (101 MHz, CDCl3) δ 165.5, 147.3, 141.1, 135.4, 133.9, 132.5, 130.5, 129.0, 125.1, 86.0, 72.1, 52.9. Methyl 4-((((4-methoxybenzyl) (15b). According to general procedure A2, methyl 4- mg, , PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4(49 mg, 0.23 mmol) in 0.6 mL DMSO yielded 15b as a white solid (70 mg, 87 % yield).1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.5 Hz, 2H), 8.01 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.84 (s, 2H), 4.56 (s, 2H), 3.97 (s, 3H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 165.6, 160.0, 141.4, 135.1, 130.3, 130.3, 129.0, 127.6, 114.1, 84.3, 74.4, 55.4, 52.8. 1-(4-((((2-Nitrobenzyl)oxy) 1-ol (16a). According to general procedure A4, 1-(4-iodophenyl)ethan-1-ol (57 mg, 0.23 mmol), oNB-R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded 16a as yellow oil (53 mg, 66 % yield).1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.2 Hz, 1H), 7.94–7.84 (d, J = 6.9 Hz, 2H), 7.64 (d, J = 5.4 Hz, 2H), 7.58 (d, J = 7.9 Hz, 2H), 7.53–7.48 (m, 1H), 5.21 (s, 2H), 5.07–4.97 (m, 1H), 4.71 (s, 2H), 1.98 (s, 1H), 1.54 (d, J = 6.5 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 153.1, 147.3, 135.9, 134.0, 132.8, 129.2, 128.9, 126.4, 125.1, 86.2, 71.9, 69.7, 25.5.OOS OPMB 1-(4-((((4-Methoxybenzyl)oxy) 1-ol (16b). According to general procedure A2, 1-(4-iodophenyl) , PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4 (49 mg, 0.23 mmol) in 0.6 mL DMSO yielded 16b as a white solid (68 mg, 88 % yield).1H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 8.3, 1.5 Hz, 2H), 7.57 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 7.3 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 5.00 (q, J = 6.5 Hz, 1H), 4.84 (s, 2H), 4.53 (s, 2H), 3.81 (s, 3H) 1.94 (s, 1H), 1.52 (d, J = 6.5 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 159.9, 152.8, 136.1, 130.3, 129.1, 127.9, 126.2, 114.1, 84.4, 74.3, 69.6, 55.4, 25.5. 1-Nitro-2-((((4-(trifluoromethyl) methyl)benzene (17a). According to general procedure A4, 1-iodo-4-(trifluoromethyl)benzene (33.4 µL, 0.23 mmol), oNB-R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded the corresponding sulfone as a yellow solid (63 mg, 73 % yield).1H NMR (400 MHz, CDCl3) δ 8.16–8.04 (m, 3H), 7.85 (d, J = 8.2 Hz, 2H), 7.65 (td, J = 7.5, 1.3 Hz, 1H), 7.58 (d, J = 6.3 Hz, 1H), 7.51 (td, J = 7.7, 1.7 Hz, 1H), 5.32 (s, 2H), 4.74 (s, 2H);13C NMR (101 MHz, CDCl3) δ 147.5, 140.9, 136.0 (q, J = 33.2 Hz), 133.9, 132.3, 129.6, 129.2 (d, J = 3.2 Hz), 126.6 (q, J = 3.7 Hz), 125.2, 86.0, 72.2;19F NMR (376 MHz, CDCl3) δ -63.2. 1-Methoxy-4-((((4- methyl)benzene (17b). According to general procedure A2, 1-iodo-4-(trifluoromethyl)benzene (33.4 µL, 0.23 mmol), PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4(49 mg, 0.23 mmol) in 0.6 mL DMSO yielded the corresponding sulfone as a light yellow solid (72 mg, 87 % yield).1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.2 Hz, 2H), 7.83 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.86 (s, 2H), 4.56 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 160.1, 141.1, 135.7 (q, J = 33.0 Hz), 130.3, 129.6, 128.7, 127.6, 126.4 (q, J = 3.7 Hz), 114.2, 84.2, 74.5, 55.4;19F NMR (376 MHz, CDCl3) δ -63.2. (3-Iodophenyl) acid (1 g, 4.03 mmol) in 20 was 12.09 mmol, 3 equiv) and 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxide hexafluorophosphate (HATU) (1.8 g, 4.83 mmol, 1.2 equiv). The resulting mixture was stirred at room temperature for 1 hour, after which piperidine (0.43 mL, 4.43 mmol, 1.1 equiv) was added and stirred overnight. Upon completion, the product was extracted with ethyl acetate and washed with brine. The organic extracts were dried over anhydrous NaaSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the title compound as a yellow solid (1.12 g, 88% yield).1H NMR (400 MHz, CDCl3) δ 7.73 (dh, J = 4.6, 1.3 Hz, 2H), 7.34 (dt, J = 7.6, 1.3 Hz, 1H), 7.17–7.10 (m, 1H), 3.68 (s, 2H), 3.32 (s, 2H), 1.69–1.59 (m, 4H), 1.52 (s, 2H);13C NMR (101 MHz, CDCl3) δ 168.0, 138.3, 138.0, 135.4, 129.9, 125.6, 94.0, 48.5, 42.9, 26.3, 25.3, 24.3. (3-((((2-Nitrobenzyl)oxy)methyl)sulfonyl)phenyl)(piperidin-1-yl)methanone (18a). According to general procedure A4, (3-iodophenyl)(piperidin-1-yl)methanone (72.48 mg, 0.23 mmol), oNB- R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded 18a as a white solid (73 mg, 76 % yield).1H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.1, 1.3 Hz, 1H), 8.02–7.91 (m, 2H), 7.73 (d, J = 7.7 Hz, 1H), 7.71–7.56 (m, 3H), 7.58–7.42 (m, 1H), 5.30 (s, 2H), 4.72 (s, 2H), 3.71 (s, 2H), 3.28 (s, 2H), 1.68 (s, 4H), 1.50 (s, 2H);13C NMR (101 MHz, CDCl3) δ 168.0, 147.3, 138.0, 137.7, 134.0, 132.8, 132.7, 129.8 (d, J = 6.7 Hz), 129.1, 128.9, 127.3, 125.1, 86.0, 72.0, 48.9, 43.4, 26.6, 25.6, 24.5. (3-((((4-Methoxybenzyl)oxy)methyl)sulfonyl)phenyl)(piperidin-1-yl)methanone (18b). According to general procedure A2, (3-iodophenyl)(piperidin-1-yl)methanone (72.48 mg, 0.23 mmol), PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4(49 mg, 0.23 mmol) in 0.6 mL DMSO yielded 18b as a white solid (83 mg, 89 % yield).1H NMR (400 MHz, CDCl3) δ 8.00–7.89 (m, 2H), 7.71 (dt, J = 7.7, 1.4 Hz, 1H), 7.62 (t, J = 7.7 Hz, 1H), 7.23 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.84 (s, 2H), 4.53 (s, 2H), 3.81 (s, 3H), 3.71 (s, 2H), 3.25 (s, 2H), 1.67 (s, 4H), 1.48 (s, 2H);13C NMR (101 MHz, CDCl3) δ 168.0, 159.9, 137.8, 137.7, 132.6, 130.2, 129.6 (d, J = 2.1 Hz), 127.7, 127.2, 114.1, 84.3, 74.3, 55.3, 48.8, 43.3, 26.5, 25.5, 24.4. 2-((((2-Nitrobenzyl)oxy)methyl)sulfonyl)pyridine (19a). According to general procedure A4, 2- iodopyridine (25 µL, 0.23 mmol), oNB-R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded 19a as a yellow solid (29 mg, 41 % yield).1H NMR (400 MHz, CDCl3δ 8.77 (dd, J = 4.7, 0.8 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 8.04 (dd, J = 8.2, 1.2 Hz, 1H), 7.97 (td, J = 7.8, 1.7 Hz, 1H), 7.63–7.53 (m, 3H), 7.44 (ddd, J = 8.6, 6.8, 2.1 Hz, 1H), 5.20 (s, 2H), 5.07 (s, 2H);13C NMR (101 MHz, CDCl3) δ 156.0, 150.5, 147.2, 138.2, 133.8, 132.7, 129.0, 128.7, 127.7, 124.9, 123.5, 82.8, 71.8. 2-((((4-Methoxybenzyl) oxy)methyl)sulfonyl)pyridine (19b). According to general procedure A2, 2-iodopyridine (25 µL, 0.23 mmol), PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4(49 mg, 0.23 mmol) in 0.6 mL DMSO yielded 26 as a clear oil (59 mg, 88 % yield).1H NMR (400 MHz, CDCl3) δ 8.76 (ddd, J = 4.7, 1.8, 1.0 Hz, 1H), 8.16 (dt, J = 7.9, 1.0 Hz, 1H), 7.98 (td, J = 7.8, 1.7 Hz, 1H), 7.56 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.19 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.89 (s, 2H), 4.78 (s, 2H), 3.79 (s, 3H);13C NMR (101 MHz, CDCl3) δ 160.0, 156.2, 150.6, 138.2, 130.3, 127.9, 127.6, 123.7, 114.1, 81.2, 74.2, 55.4. 2-((((2-Nitrobenzyl)oxy)methyl)sulfonyl)thiophene (20a). According to general procedure A4, 2-iodothiophene (23.4 µL, 0.23 mmol), oNB-R-Na (156 mg, 0.69 mmol), L (6.2 mg), CuI (4.4 mg), and K3PO4(49 mg, 0.23 mmol) in 1.3 mL DMSO yielded 20a as a yellow solid (49 mg, 68 % yield).1H NMR (400 MHz, CDCl3δ 8.77 (dd, J = 4.7, 0.8 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 8.04 (dd, J = 8.2, 1.2 Hz, 1H), 7.97 (td, J = 7.8, 1.7 Hz, 1H), 7.63–7.53 (m, 3H), 7.44 (ddd, J = 8.6, 6.8, 2.1 Hz, 1H), 5.20 (s, 2H), 5.07 (s, 2H);13C NMR (101 MHz, CDCl3) δ 156.0, 150.5, 147.2, 138.2, 133.8, 132.7, 129.0, 128.7, 127.7, 124.9, 123.5, 82.8, 71.8. 2-((((4-Methoxybenzyl)oxy)methyl)sulfonyl)thiophene (20b). According to general procedure A2, 2-iodothiophene (23.4 µL, 0.23 mmol), PMB-R-Na (82 mg, 0.34 mmol), L (3.7 mg), CuI (2.6 mg), and K3PO4(49 mg, 0.23 mmol) in 0.6 mL DMSO yielded 20b as a white solid (60 mg, 89 % yield).1H NMR (400 MHz, CDCl3) δ 8.76 (ddd, J = 4.7, 1.8, 1.0 Hz, 1H), 8.16 (dt, J = 7.9, 1.0 Hz, 1H), 7.98 (td, J = 7.8, 1.7 Hz, 1H), 7.56 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.19 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.89 (s, 2H), 4.78 (s, 2H), 3.79 (s, 3H);13C NMR (101 MHz, CDCl3) δ 7.82–7.69 (m, 2H), 7.28–7.24 (m, 2H), 7.18 (dd, J = 5.0, 3.8 Hz, 1H), 6.89 (d, J = 8.7 Hz, 2H), 4.87 (s, 2H), 4.60 (s, 2H), 3.81 (s, 3H). Deprotection / Fluorination of SPGs General Procedure D: A 1-dram (90.9 mg, 0.25 mmol, 3 equiv). The vial was then evacuated and backfilled with argon (3 times), and degassed MeCN:H2O (1.28:0.32 mL, 4:1) were then added into the vial via syringe. The reaction was irradiated at 40-50 °C at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 16 h. Upon completion, the reaction mixture was diluted with water and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous NaaSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the corresponding sulfonyl fluoride. Note: Presence of air in the reaction mixture results in the formation of the oxidized benzoyl side product. General Procedure E: A 1-dram vial was charged with sulfone (0.08 mmol) and Selectfluor™ (142 mg, 0.4 mmol, 5 equiv). The vial was then evacuated and backfilled with argon (3 times), and degassed MeCN:H2O (1.28:0.32 mL, 4:1) were then added into the vial via syringe. The reaction was irradiated at 40-50 °C at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 36 h. Upon completion, the reaction mixture was diluted with water and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous NaaSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the corresponding sulfonyl fluoride. Note: Presence of air in the reaction mixture results in the formation of the oxidized benzoyl side product. Benzenesulfonyl fluoride (13c). Follow l procedure E, 13a (25 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a cooress oil (11 mg, 87% yield). Following general procedure D, 13b (24 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (11.50 mg, 89% yield). The spectral data matched that of literature. 4-Fluorobenzenesulfonyl fluoride (7) procedure E, 5 (26 mg, 0.08 mmol) gave the corresponding sulfonyl as a oil (12 mg, 84% yield). Following general procedure D, 4 (25 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (12.30 mg, 86% yield). The spectral data matched that of literature. 4-Methoxybenzenesulfonyl general procedure E, 14a (14 mg, 0.04 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (5.55 mg, 73% yield). Following general procedure D, 14b (26 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (9 mg, 59% yield). The spectral data matched that of literature. Methyl 4-(fluorosulfonyl) procedure E, 15a (29 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a white solid (15.50 mg, 89% yield). Following general procedure D, 15b (28 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a white solid (16 mg, 92% yield). The spectral data matched that of literature. 4-(1-Hydroxyethyl)benzenesulfonyl Following general procedure E, 16a (28 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a white solid (14.2 mg, 82% yield). Following general procedure D, 16b (27 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a white solid (14 mg, 87% yield).1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 5.04 (q, J = 6.6 Hz, 1H), 2.15–1.92 (m, 1H), 1.53 (d, J = 6.6 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 154.4, 131.9 (d, J = 24.5 Hz), 128.9, 126.7, 69.6, 25.7;19F NMR (376 MHz, CDCl3) δ 66.1. 4-(Trifluoromethyl)benzenesulfonyl Following general procedure E, 17a (18 mg, 0.05 mmol) gave the corresponding sulfonyl fluoride as a white solid (8.6 mg, 84% yield). Following general procedure D, sulfone 17b (29 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a white solid (14 mg, 86% yield). The spectral data matched that of literature. 3-(Piperidine-1-carbonyl) (18c). Following general procedure E, 18a (14 mg, 0.03 mmol) gave the corresponding sulfonyl fluoride as a white solid (7.2 mg, 89% yield). Following general procedure D, 18b (32.3 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a white solid (21 mg, 97% yield).1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 7.7 Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 3.72 (s, 2H), 3.31 (s, 2H), 1.70 (s, 4H), 1.55 (s, 2H);13C NMR (101 MHz, CDCl3) δ 167.4, 138.5, 134.0, 133.7 (d, J = 25.2 Hz), 130.2, 129.2, 127.0, 49.0, 43.6, 26.6, 25.6, 24.5;19F NMR (376 MHz, CDCl3) δ 66.0. Pyridine-2-sulfonyl fluoride (19c). Fo neral procedure E, 19a (25 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a coorless oil (11.62 mg, 90% yield). Following general procedure D, 19b (15 mg, 0.05 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (7 mg, 88% yield). The spectral data matched that of literature. Thiophene-2-sulfonyl fluoride (20c). procedure E, 20a (11.3 mg, 0.08 mmol) gave the corresponding sulfonyl oil (11.62 mg, 85% yield). Following general procedure D, 20b (24 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (10.62 mg, 80% yield). The spectral data matched that of literature. Phenylmethanesulfonyl fluoride procedure E, sulfone 5a (26 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (11 mg, 79% yield). Following general procedure D, sulfone 4a (25 mg, 0.08 mmol) gave the corresponding sulfonyl fluoride as a colorless oil (11.2 mg, 80% yield). The spectral data matched that of literature. Sulfinate Applications 1. C-4 Sulfonylation of pyridine General procedure G. A dried and nitrogen flushed round-bottom flask, equipped with a rubber septum and a magnetic stirring bar was charged with pyridine (24 μL, 0.3 mmol, 1.0 equiv.) and dry CHCl3(3.0 mL). After cooling to −30 °C a solution of Tf2O (55 μL, 0.33 mmol, 1.1 equiv.) in dry CHCl3(1.2 mL) was added dropwise over 10 min. resulting in a colourless suspension. After complete addition the suspension was stirred for another 30 min. at −30 °C. N-methylpiperidine (0.12 mL, 0.96 mmol, 3.2 equiv.) was added and after 10 min. a solution of the R”-SO2Na (0.39 mmol, 1.3 equiv) in DMF (3 mL, 0.1 M) was added. The resulting solution was stirred at −30 °C for another 2 h and slowly warmed to ambient temperature overnight. Then the reaction mixture was diluted with DCM and transferred in a separation funnel. Aqueous saturated NaHCO3was added, the organic layer was separated, and the aqueous phase was extracted with DCM. The combined organic extracts were dried over Na2SO4and evaporated under reduced pressure. Purification of the crude product by flash column chromatography (n-hexane / EtOAc) furnishing the desired sulfone. 4-((((2-Nitrobenzyl)oxy)methyl) . Following general procedure G, oNB- R-Na (88 mg, 0.39 mmol) yielded the as a yellow solid (45 mg, 49% yield).1H NMR (400 MHz, CDCl3) δ 8.93 (d, J = 6.0 Hz, 2H), 8.10 (dd, J = 8.1, 1.3 Hz, 1H), 7.79 (d, J = 6.1 Hz, 2H), 7.65 (td, J = 7.5, 1.3 Hz, 1H), 7.61–7.40 (m, 2H), 5.32 (s, 2H), 4.75 (s, 2H);13C NMR (101 MHz, CDCl3) δ 151.4, 147.5, 145.5, 134.0, 132.2, 129.2 (d, J = 4.6 Hz), 125.3, 121.9, 81.6 (d, J = 838.2 Hz), 72.3. 4-((((4-Methoxybenzyl)oxy)methyl) (23). Following general procedure G, PMB-R-Na (93 mg, 0.39 mmol) yielded the corresponding sulfone as a yellow oil (51 mg, 58% yield).1H NMR (400 MHz, CDCl3) δ 8.90 (d, J = 5.0 Hz, 2H), 7.78 (d, J = 4.0 Hz, 2H), 7.21 (d, J = 6.9 Hz, 2H), 6.88 (d, J = 6.7 Hz, 2H), 4.85 (s, 2H), 4.57 (d, J = 1.6 Hz, 2H), 3.81 (d, J = 1.7 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 160.0, 151.1, 145.6, 130.3, 127.3, 114.2, 83.9, 74.4, 55.3. One-pot Synthesis of Sulfonamides A vial was mol, 5 equiv). The vial was then evacuated and backfilled with argon (X3), and degassed MeCN:H2O (1.6 mL, 4:1) was then added into the vial via syringe. The reaction was irradiated at 40-50 °C (radiant heating) at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 36 h. Et3N (55.6 µL, 0.4 mmol, 5 equiv) and piperidine (23.7 µL, 0.24 mmol, 3 equiv) were added to the reaction mixture and stirred at 85 °C for 16 h. Upon completion, the reaction mixture was diluted with water, and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the corresponding sulfonamide as a white solid (15 mg, 65% yield).1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 3.03 (t, J = 5.5 Hz, 4H), 1.66 (p, J = 5.7 Hz, 4H), 1.45 (tq, J = 8.8, 5.6, 4.5 Hz, 2H);13C NMR (101 MHz, CDCl3) δ 140.5, 134.4 (q, J = 33.1 Hz), 128.2, 126.3 (q, J = 3.7 Hz), 123.4 (d, J = 273.0 Hz), 47.0, 25.3, 23.6;19F NMR (376 MHz, CDCl3) δ −63.1. Synthesis of SPG Suzuki Building Blocks 1-Bromo-4-((((4-methoxybenzyl)o enzene (21). According to general procedure A2, 1-bromo-4-iodobenzene (1.50 g, 5.30 mmol), PMB-R-Na (1.893 g, 7.95 mmol), L (143.3 mg), CuI (100.9 mg), and K3PO4(1.125 g, 5.3 mmol) in 13.25 mL DMSO yielded 21 as a off-white solid (1.55 g, 79 % yield).1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.6 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 4.83 (s, 2H), 4.52 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 159.7, 136.4, 132.3, 130.2, 130.0, 129.2, 127.6, 113.9, 84.3, 74.2, 55.1; HRMS (ESI-TOF) m / z: [M+Na]+calc’d for C15H15BrNaO4S 392.9772; found: 392.9771. 2-(4-((((4-Methoxybenzyl)oxy) tetramethyl-1,3,2- dioxaborolane (22). A sealed microwave vial was charged with 21 (300 mg, 0.81 mmol), Pd(dppf)Cl2.DCM (33.07 mg, 5 mol%), B2Pin2(307 mg, 1.21 mmol, 1.5 equiv), and KOAc (238.49 mg, 2.43 mmol, 3 equiv). The vial was then evacuated and backfilled with argon (X3) and degassed DMSO (8 mL) was then added into the vial via syringe. The reaction mixture was microwaved at 100 °C for 60 min. After cooling to room temperature, the mixture was filtered to remove excess salts. The reaction mixture was diluted with water and the product was extracted with DCM. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was used in the next step without further purification. 6-(4-((((4-Methoxybenzyl) (S16a). A sealed microwave vial was charged with 22 (167.32 mg, 0.4 mmol), 7-bromisoquinoline (124.83 mg, 0.6 mmol, 1.5 equiv), Pd(PPh3)4(23.11 mg, 5 mol%), and Na2CO3(127.19 mg, 1.2 mmol, 3 equiv). The vial was then evacuated and backfilled with argon (X3) and degassed DME: H2O (4 Ml, 3:1) was then added into the vial via syringe. The reaction mixture was microwaved at 100 °C for 3 hours. After cooling to room temperature, the mixture was filtered hot to remove excess salts. The reaction mixture was diluted with water and the product was extracted with DCM. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by high-performance liquid chromatography with a C18 column (Agilent 50 mm x 150 mm) and a gradient of acetonitrile / water to obtain S16a ( 154 mg, 92% yield).1H NMR (400 MHz, CDCl3) δ 9.81 (s, 1H), 8.66 (d, J = 6.4 Hz, 1H), 8.46 (d, J = 8.6 Hz, 1H), 8.29 (s, 1H), 8.23 (d, J = 6.4 Hz, 1H), 8.17 (d, J = 8.6 Hz, 1H), 8.14 (d, J = 8.1 Hz, 2H), 7.93 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 7.7 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 4.91 (s, 2H), 4.62 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 160.1, 147.2, 146.9, 144.0, 138.9, 138.5, 133.2, 131.3, 130.4, 130.4, 130.0, 128.8, 127.7, 127.2, 125.7, 125.2, 114.2, 84.5, 74.5, 55.4; HRMS (ESI-TOF) m / z: [M+H]+calc’d for C24H22NO4S 420.1270; found: 420.1272. 4-(Isoquinolin-6-yl) was charged with S16a (40 mg, 0.09 mmol) and Selectfluor™ (101.34 mg, 0.29 mmol, 3 equiv). The vial was then evacuated and backfilled with argon (X3), and degassed MeCN:H2O (1.8 mL, 4:1) was then added into the vial via syringe. The reaction was irradiated at 40-50 °C (radiant heating) at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 16 h. Upon completion, the reaction mixture was diluted with water, and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the corresponding sulfonyl fluoride as a yellow solid (20 mg, 76% yield);1H NMR (400 MHz, CD3CN) δ 9.57 (bs, 1H), 8.77 (bs, 1H), 8.48 (s, 1H), 8.45 – 8.38 (m, 3H), 8.30 (d, J = 8.3 Hz, 2H), 8.21 (dd, J = 8.6, 1.8 Hz, 1H), 8.08 (d, J = 5.5 Hz, 1H);13C NMR (101 MHz, CD3CN) zδ 152.9, 148.6, 143.9, 141.4, 137.1, 132.8 (d, J = 24.6 Hz), 130.2, 130.1, 129.9, 129.4*, 127.9, 126.8, 122.2*; HRMS (ESI-TOF) m / z: [M+H]+calc’d for C15H11FNO2S 288.0495; found: 288.0509. Note: Carbons 4 and 5 (*) of the isoquinoline do not show up in the standard13C spectrum due to broadening; they are however visible in the HSQC and HMBC and are in agreement with the shifts for those carbons in the literature13C of isoquinoline. 4-(4-((((4-Methoxybenzyl)oxy) phene-2-carbaldehyde (S16b). A sealed microwave vial was charged with 22 (167.32 mg, 0.4 mmol), 4-bromothiophene-2- carbaldehyde (114.63 mg, 0.6 mmol, 1.5 equiv), Pd(PPh3)4 (23.11 mg, 5 mol%), and Na2CO3(127.19 mg, 1.2 mmol,3 equiv). The vial was then evacuated and backfilled with argon (X3) and degassed DME: H2O (4 Ml, 3:1) was then added into the vial via syringe. The reaction mixture was microwaved at 100 °C for 3 hours. After cooling to room temperature, the mixture was filtered hot to remove excess salts. The reaction mixture was diluted with water and the product was extracted with DCM. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by high- performance liquid chromatography with a C18 column (Agilent 50 mm x 150 mm) and a gradient of acetonitrile / water to obtain (S16b) as a yellow solid ( 143 mg, 89% yield).1H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H), 8.07 (d, J = 1.5 Hz, 1H), 8.00 (d, J = 8.2 Hz, 3H), 7.24 (d, J = 9.7 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 4.87 (s, 2H), 4.57 (s, 2H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 183.0, 160.0, 145.1, 141.6, 139.9, 136.6, 134.5, 131.7, 130.3, 129.8, 127.8, 127.0, 114.2, 84.5, 74.4, 55.4. HRMS (ESI-TOF) m / z: [M+NH4]+calc’d for C20H22NO5S2420.1270; found: 420.1272. 4-(5-Formylthiophen-3-yl) . A vial was charged with S16b (38 mg, 0.09 mmol) and Selectfluor™ (101.34 mg, 0.29 mmol, 3 equiv). The vial was then evacuated and backfilled with argon (X3), and degassed MeCN:H2O (1.8 mL, 4:1) was then added into the vial via syringe. The reaction was irradiated at 40-50 °C (radiant heating) at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 16 h. Upon completion, the reaction mixture was diluted with water, and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the corresponding sulfonyl fluoride 23b as a white solid (20 mg, 83% yield).1H NMR (400 MHz, CDCl3) δ 10.01 (d, J = 1.3 Hz, 1H), 8.19 – 8.06 (m, 3H), 8.03 (t, J = 1.5 Hz, 1H), 7.84 (d, J = 8.3 Hz, 2H);13C NMR (101 MHz, CDCl3) δ 182.7, 145.5, 141.2 (d, J = 55.6 Hz), 134.0, 132.3, 132.1, 132.0, 129.5, 127.4;19F NMR (376 MHz, CDCl3) δ 66.4; HRMS (ESI-TOF) m / z: [M+CH3CN+H]+ calc’d for C12H11FNO3S2312.0164; found: 312.0171. Synthesis of Sulfonamide Building Block for AZD2858 Analog 1. selectfluorPMB-R-SOMe2Na OPMB MeCN: H O N Br IHMNPCO2(4:1) O N to general procedure A2, methyl 3-bromo-5-iodobenzoate (267 mg, 0.78 mmol), PMB-R-Na (279.85 mg, 1.17 mmol), L (21.08 mg), CuI (14.85 mg), and K3PO4(165.57 mg, 0.78 mmol) in 2 mL DMSO yielded 27 as a clear oil (245 mg, 73 % yield).1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 8.44 (s, 1H), 8.22 (s, 1H), 7.22 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.85 (s, 2H), 4.57 (s, 2H), 3.96 (s, 3H), 3.81 (s, 3H);13C NMR (101 MHz, CDCl3) δ 164.1, 160.0, 139.8, 137.8, 135.6, 133.1, 130.3, 128.5, 127.4, 123.4, 114.1, 84.1, 74.4, 55.3, 53.0. Methyl 3-bromo-5-((4- (28). A vial was charged with 27 (95 mg, 0.22 mmol) and Selectfluor™ (235.19 mg, 0.66 mmol, 3 equiv). The vial was then evacuated and backfilled with argon (X3), and degassed MeCN:H2O (4.4 mL, 4:1) was then added into the vial via syringe. The reaction was irradiated at 40-50 °C (radiant heating) at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 16 h. Then Et3N (0.15 mL, 1.1 mmol, 5 equiv) and 1-methylpiperazine (73.21 µL, 0.66 mmol, 3 equiv) were added to the reaction mixture and stirred at 40 °C for 16 h. Upon completion, the reaction mixture was diluted with water, and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain the corresponding sulfonamide 28 as a white solid (35 mg, 42% yield);1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1H), 8.30 (s, 1H), 8.06 (s, 1H), 3.97 (s, 3H), 3.10 (s, 4H), 2.51 (s, 4H);13C NMR (101 MHz, CDCl3) δ 164.4, 138.3, 136.8, 134.5, 133.1, 127.3, 123.5, 54.0, 53.1, 46.1, 45.8; HRMS (ESI-TOF) m / z: [M+H]+calc’d for C13H18BrN2O4S 377.0171; found: 377.0179.

[0004] Synthesis of BCl-6 Inhibitor Analog to general procedure A4, 31 (754 mg, 2.798 mmol), oNB-R-Na (2 g, 8.39 mmol), L (75.69 mg), CuI (53.29 mg), and K3PO4(1.20 g, 2.798 mmol) in 7 mL DMSO yielded 32 as a yellow solid (537 mg, 57 % yield).1H NMR (400 MHz, CDCl3δ 8.07 (d, J = 8.2 Hz, 1H), 7.91 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.65 (dd, J = 11.9, 6.0 Hz, 3H), 7.58 – 7.44 (m, 2H), 5.24 (s, 2H), 4.71 (s, 2H), 3.98 (s, 2H);13C NMR (101 MHz, CDCl3) δ 147.2, 137.4, 133.7, 133.0, 132.7, 129.4, 129.0, 128.8, 127.2, 127.1, 124.8, 86.0, 71.7; HRMS (ESI-TOF) m / z: [M+H]+calc’d for C15H17N2O5S 337.0858; found: 337.0861.

[0005] 4,5-Dichloro-N-(3-((((2-nitrobenzyl yl)benzyl)pyrimidin-2-amine (34). To the solution of 32 (370 mg, 1.10 mmol, 1.2 equiv) and 33 (151.22 mg, 0.92 mmol) in 12 mL 1,4- dioxane, was added 0.2 mL DIPEA. The resulting mixture was stirred at 100 °C for 16 hours. After completion of reaction, the reaction mixture was allowed to warm at room temperature and then POCl3(0.26 mL, 2.76 mmol, 3 equiv) was added. The resulting mixture was stirred for 2 hours at 100 °C. The product was extracted with CH2Cl2and washed with brine. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with ethyl acetate / hexanes) to obtain 34 as a yellow solid (334 mg, 75% yield);1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 7.7 Hz, 1H), 7.70 – 7.44 (m, 5H), 5.80 (s, 1H), 5.22 (s, 2H), 4.69 (m, 4H);13C NMR (101 MHz, CDCl3) δ 160.0, 158.4, 157.8, 147.3, 140.5, 137.7, 133.9, 133.5, 132.6, 129.7, 129.1, 127.9, 125.0, 117.2, 86.2, 71.9, 45.1; HRMS (ESI-TOF) m / z: [M+H]+calc’d for C19H17Cl2N4O5S 483.0297; found: 483.0286. 5-Chloro-N2-(3-((((2-nitrobenzyl) -N4-phenylpyrimidine-2,4- diamine (S17). A sealed microwave vial was charged with 34 (300 mg, 0.62 mmol, 2 equiv), aniline (28.34 µL, 0.31 mmol), Pd(OAc)2(6.26 mg, 9 mol%), XantPhos (17.94 mg, 10 mol%), and Cs2CO3(141.40 mg, 0.43 mmol,1.4 equiv). The vial was then evacuated and backfilled with argon (X3), and degassed dioxane (0.8 mL) was then added into the vial via syringe. The reaction mixture was stirred at 110 °C in an oil bath for 24 h. After cooling to room temperature, the mixture was filtered while hot to remove excess salts. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash chromatography (eluting with ethyl acetate / hexanes) to afford S17 as a light yellow solid (160 mg, 96% yield).1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.2 Hz, 1H), 7.92 (s, 1H), 7.91 (s, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.69 – 7.39 (m, 7H), 7.28 (m, 1H), 7.07 (t, J = 7.4 Hz, 1H), 6.98 (s, 1H), 5.59 (s, 1H), 5.18 (s, 2H), 4.64 (m, 4H);13C NMR (101 MHz, CDCl3) δ 160.1, 155.5, 154.1, 146.9, 141.6, 138.0, 137.3, 133.8, 133.1, 132.6, 128.8, 128.7, 127.4, 127.3, 124.8, 123.8, 120.8, 85.9, 71.7, 45.0; HRMS (ESI-TOF) m / z: [M+H]+calc’d for C25H23ClN5O5S 540.1108; found: 540.1114. 3-(((5-Chloro-5-fluoro-4-hydroxy- dihydropyrimidin-2- yl)amino)methyl)benzenesulfonyl fluoride (35). A vial was charged with S17 (80 mg, 0.15 mmol) and Selectfluor™ (265.69 mg, 0.75 mmol, 5 equiv). The vial was then evacuated and backfilled with argon (X3), and degassed MeCN:H2O (3 mL, 4:1) were then added into the vial via syringe. The reaction was irradiated at 40-50 °C at approximately 5.0 cm from a Kessil blue LED (λmax= 440 nm, 100% intensity) for 36 h. Upon completion, the reaction mixture was diluted with water, and the product was extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by high-performance liquid chromatography with a C18 column (Agilent 50 mm x 150 mm) and a gradient of acetonitrile / water to obtain 35 as a yellow solid ( 34 mg, 53% yield).1H NMR (400 MHz, CD3CN) δ 11.63 (s, 1H), 10.98 (s, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.90 (s, 1H), 7.68 (dt, J = 15.4, 7.9 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.41 (dd, J = 8.5, 6.9 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 5.42 (s, 1H), 4.71 (s, 2H);13C NMR (101 MHz, CD3CN) δ 160.7 (d, J = 19.8 Hz), 157.9, 141.6, 135.9, 135.8, 133.7 (d, J = 24.3 Hz), 131.5, 130.1, 128.8, 128.4, 127.6, 124.4, 97.9 (d, J = 266.0 Hz), 77.5 (d, J = 26.3 Hz), 45.50;19F NMR (376 MHz, CDCl3) δ 64.7, -138.7 HRMS (ESI-TOF) m / z: [M+H]+calc’d for C17H16ClF2N4O3S 429.0600; found: 429.0602. Results and Discussion Synthesis of aryl SFs In addition to SMOPS, TBS-R, and Rongacyl, three additional SPGs were envisioned. Para-methoxybenzyl-Rongalite (PMB-R) and ortho-nitrobenzyl Rongalite (oNB-R) were intended to be deprotected under oxidizing conditions and light, respectively, while 2- trimethylsilylethylsulfone (SES) would be deprotected with fluoride. SES is a common protecting group for sulfonamides; however, its use as a sulfinate protecting group is much rarer with only a single report showing its use in forming sulfinates. Combined with the already known protecting groups of TBS-R, Rongacyl, and SMOPS, PMB-R, oNB-R, and SES should provide orthogonal deprotection conditions and stability profiles. The use of a copper catalyst and the proline-derived ligand, (2S,4R)-4-hydroxy-N-(2- methylnaphthalen-1-yl)pyrrolidine-2-carboxamide (HMNPC) facilitates the S-arylation of sulfinates with aryl iodides under mild conditions. The sulfinate salts of SMOPS, TBS-R, and Rongacyl are all known. PMB-R and oNB-R sulfinate salts were made from the corresponding chloromethyl ether in a facile manner on gram scale. The resulting solids were shelf stable (2+ months), non-hygroscopic powders. SES sulfinate was made from vinyltrimethylsilane according to a modified literature procedure. All reactions proceeded in high yield. The PMB-R, oNB-R, and SES sulfinates coupled with aryl iodides in high yields at 50 °C in the presence of CuI / HMNPC (FIG.3B). In contrast, SMOPS, TBS-R, and Rongacyl sulfinate resulted in either low yields or no product. Wide ranging conditions have been reported for the coupling of aryl bromides and various nucleophiles, including sulfinates, using nickel and the photocatalyst 4CzIPN. The SMOPS, PMB- R, and SES sulfinates were effectively coupled with aryl bromides using NiBr2(DME), 4CzIPN, and DABCO in 66%, 80%, and 75% yield, respectively (FIG.3C). The oNB-R sulfinate failed to engage and Rongacyl degraded. This photocatalytic method provides a straightforward method to access protected sulfinates from the much more readily accessible aryl bromide. Efforts are ongoing to further the utility of this reaction. It is also possible to access the aryl SPG from the thiol via alkylation and subsequent oxidation with sodium tungstate (FIG.3D). PMB-R and oNB-R can all be made via this route in high yield. SES and SMOPS are made via the addition of the thiol to the vinyl trimethylsilane and methyl acrylate with AIBN, respectively. TBS-R and Rongacyl cannot be accessed via this method due to the inability to obtain the corresponding alkyl halide. To access alkyl SPGs, benzyl bromide was reacted with the corresponding sulfinate in high yield (FIG.3E). Stability of SPGs As with any protecting group, broad stability is required. To provide insight for their use in any synthetic endeavor, the stability of SPGs was investigated under a variety of synthetic conditions. Ten of the most used synthetic transformations in medicinal chemistry were chosen for SPG stability testing. The results are shown in Table 1. Table 1. SPG Stability Study Reaction Conditions[a]Percent protected sulfinate compound recovered[b]3 8 0 0 Model aryl and benzyl SPGs 1-6 and 2a, 5a, and 6a, were added to the reaction mixture for a certain transformation, and upon reaction completion, the percentage of recovered SPG was calculated. Sulfonyl fluoride 7 was also subjected to these same conditions. The conditions chosen were the most common conditions found for each transformation. It is possible that in optimizing a reaction, one may find specific conditions that are less harsh and therefore result in greater retention of the SPG. In each transformation, the reaction itself proceeded in greater than 70% yield unless otherwise noted. Overall, all SPGs were stable under mild reaction conditions such as amide coupling, amine SN2, and acidic Boc deprotection. Similarly, under reductive amination and hydrogenation conditions, most SPGs demonstrated high stability. The oNB-R protecting group (5 and 5a) was reduced to the aniline under hydrogenation conditions and did not deprotect. It is worth noting that under hydrogenation conditions the PMB-R (4) protecting group was stable. In reactions with harsher conditions, such as SNAr, Suzuki coupling, and ester hydrolysis, PMB-R, oNB-R, and SES (4, 5, and 6) were superior to known SPGs, which degraded under these conditions. Only the SES protecting group was stable under Buchwald-Hartwig coupling conditions with potassium tert-butoxide as base. Switching the base, however, to cesium carbonate and Xantphos as ligand, resulted in a higher retention of oNB-R, 5. As a point of comparison, the parent sulfonyl fluoride (7) only survived SN2, acidic deprotection, and amide coupling, highlighting the need, in some cases, for SPGs. Deprotection Deprotection of TBS-R (3) and Rongacyl (2b) were accomplished according to their literature methods. TBS-R (3) has the benefit of being a one-pot deprotection (CsF, Selectfluor™). SMOPS (1) and Rongacyl (7) requires a two-step procedure with deprotection via sodium hydride (SMOPS) and sodium hydroxide (Rongacyl) followed by workup and Selectfluor™ addition (Table 2). Table 2. Overview of stability and deprotection / fluorination of SPGs. Using either iridium or acridinium photocatalysis in the presence of blue light and Selectfluor™ led directly to sulfonyl fluoride (Table 3, entry 2 and 3). Table 3. Optimization of PMB-R Deprotection / Fluorination[a] Interestingly, however, deprotection and fluorination was able to occur (89% yield) in the absence of photocatalysis provided that three equivalents of Selectfluor™ were present (entry 1). These conditions provide a direct, metal free method to mildly deprotect and fluorinate PMB-R- protected aryl sulfones. Lower yields were obtained when 1 or 2 equivalents of Selectfluor™ was used (entry 4 and 5). The presence of water facilitated the successful removal of the protecting group (entry 6). Switching to NSFI or addition of TEMPO resulted in little to no product confirming a radical-based mechanism involving the 1,4-diazoniabicyclo[2.2.2]octane (TEDA) radical cation. No reaction occurred in the absence of Selectfluor™ and light (entries 8 and 12 respectively). A small scope was investigated for this deprotection (FIG.4). yields refer to isolated yields; yields in brackets refer to NMR yields with 4-fluoroacetophenone as an internal standard. Conditions for deprotection of 13a-21a: 13 (0.2 mmol), Selectfluor™ (5.0 equiv), (MeCN:H2O (0.2 M), 40 °C, 16 h, N2; for deprotection of 13b-21b: 13b (0.2 mmol), Selectfluor™ (3.0 equiv), (MeCN:H2O (0.2 M), 40 °C, 16 h, N2(FIG.4). The deprotection of the PMB was tolerable to both electron deficient ring systems (e.g., 13b, 15b, and 17b) as well as electron rich ring systems (e.g., 14b). Amides were tolerable, as well as pyridine and thiophene heterocycles (19b and 20b). Alcohols were also well tolerated (16b). Alkyl benzyl sulfinates were also deprotected cleanly (21b). Turning to the oNB-R protecting group, deprotection and fluorination can occur cleanly under irradiation with blue light in the presence of Selectfluor™ via a Norrish-type II deprotection mechanism. The scope of this reaction was similarly wide with high yields for electron rich, electron poor, and heterocyclic ring systems (Table 3, 13a-21a). Both protecting groups were transformed directly into the corresponding sulfonamide by the addition of an amine after fluorination (FIG. 5). Conditions for amination of 15a in FIG.5 are Et3N (5 equiv), piperidine (3 equiv), 85 °C, 16 h; for amination of 15b: Et3N (5 equiv), piperidine (3 equiv), 40 °C, 16 h. In drug discovery, introduction of sulfonamides or sulfonyl fluorides often occurs from the sulfonyl chloride or thiol. This narrows the scope of SAR studies to commercially available sulfonyl halides or thiols. Overall, SPGs can be used in drug discovery programs to streamline the synthesis of sulfonyl fluorides and sulfonamides through SPG building blocks (FIG.6A–C and FIG.7A–B). SPG building blocks have an aryl SPG with an additional coupling handle. These coupling handles can be applied to numerous synthetic reactions anywhere in a synthetic route. Specifically, SPG building blocks can be used for late-stage diversification of common intermediates to expand structural diversity leading to both complex sulfonyl fluorides and sulfonamides. For example, a Suzuki Building Block can be used to form a variety of advanced biaryl substrates (FIG.6A). To demonstrate this, bromoiodobenzene was coupled to the PMB- R-Na to yield building block 21, which was then borylated. At this point the boronic ester was coupled via a Suzuki reaction to 23a and 23b. Deprotection yielded the corresponding sulfonyl fluoride, which could be further functionalized if necessary. Applications In the literature AZD2858, a GSK3 inhibitor, is synthesized from the parent sulfonyl chloride by first forming sulfonamide and a subsequent Suzuki reaction with N-methyl pyrazine (FIG.6B). In an SAR study of this molecule, each sulfonamide must be synthesized first from the sulfonyl chloride, borylated, and then finally coupled. The lack of availability of certain thiol or sulfonyl halide ring systems would therefore lead to a restricted coverage of chemical space in the SAR study. Therefore, accessing sulfonamides that are not readily available commercially, such as building block 27, was pursued (FIG.6B). As a proof of concept, 3-bromo-5-iodobenzoate was coupled to the PMB-R-Na to yield 27, which can be readily converted into sulfonamide 28. At this point the boronic ester can be coupled via a Suzuki reaction to N-methyl pyrazine following known procedures. Similarly, SPG-Amine Building Blocks, which contain an aryl SPG and an amine coupling handle, can also be employed as demonstrated in the synthesis of analogs of BCl-6 inhibitor TMX- 2164 (30, FIG.7A). The literature synthesis of TMX-2164 proceeds via SNAr, Buchwald coupling with the m-bromobenzylamine, and finally sulfonylation via Willis’ palladium-DABSO conditions (FIG. 7A). In the development of SAR for molecule TMX-2164, one would want to be able to diversify the aryl amine component last; having a SF would not allow for this late stage SNAr. Instead, a benzylamine SPG building block can advantageously be employed. Benzyl amine 31 was first coupled to the oNB-R-Na to yield the SPG building block 32. Subsequent SNAr with chloropyrimidine followed by chlorination of the hydroxyl group yielded 34. No degradation of the SPG was noted during these harsh steps. Finally, Buchwald coupling of aniline yielded the corresponding analog 34a, which was subsequently deprotected and fluorinated to obtain BCl-6 analog 35 (FIG.7B). Conclusions In conclusion, a comprehensive assessment of sulfinate protecting group stability was generated by subjecting six different sulfinate protecting groups to a variety of common synthetic transformations. Additionally, methods to synthesize aryl containing SPGs were also assessed. Ultimately, the SPG chosen in a synthetic endeavor should be tailored to the synthetic conditions used and the functionality present. The studies above outline the benefits and drawbacks of each SPG while providing additional groups with novel, orthogonal deprotection conditions. Overall, these groups should allow for a more structural diversity in the synthesis of SF containing small molecule inhibitors or probes.

Claims

CLAIMS What is claimed:

1. A salt of formula (I): , wherein: a is 1 or 2;X+ais a cation having a +a charge; R1is hydrogen, –NO2, –OC1-4alkyl, C1-4alkyl, F, or Cl; and R2is hydrogen, –OC1-4alkyl, C1-4alkyl, or –NO2; with the proviso that at least one of R1and R2is not hydrogen.

2. The salt of claim 1, wherein a is 1.

3. The salt of claim 1, wherein a is 2.

4. The salt of claim 2 or 3, wherein X+ais Na+1, K+1, Li+1, Mg+2, Zn+2, or Bu4N+1.

5. The salt of any one of claims 1-4, wherein R1is hydrogen.

6. The salt of any one of claims 1-4, wherein R1is –NO2.

7. The salt of any one of claims 1-4, wherein R1is –OC1-4alkyl.

8. The salt of any one of claims 1-4, wherein R1is C1-4alkyl.

9. The salt of any one of claims 1-4 or 6-8, wherein R2is hydrogen.

10. The salt of any one of claims 1-8, wherein R2is –OC1-4alkyl.

11. The salt of any one of claims 1-8, wherein R2is C1-4alkyl.

12. The salt of any one of claims 1-8, wherein R2is –NO2.

13. The salt of any one of claims 1-12, wherein the salt of formula (I) is a salt of any one of formulae (I-a)-(I-j): b) d) f) h) j)14. A method of synthesizing a sulfinate compound, the method comprising reacting the salt of any one of claims 1-13 with a compound of formula (II): X1–Y1(II), to provide a compound of formula (III):I), wherein: X1is a leaving group; Y1is G1, –C1-6alkylene–G1, C1-10alkyl, C2-10alkenyl, or C2-10alkynyl; G1, at each occurrence, is independently a 6- to 12-membered aryl, a 4- to 12-membered heterocyclyl, a 3- to 12-membered carbocyclyl, or a 5- to 12-membered heteroaryl, wherein the heteroaryl and heterocyclyl each contain 1-4 heteroatoms independently selected from the group consisting of O, N, and S, and G1is optionally substituted with a first substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, oxo, –OR1x, –N(R1x)2, –SR1x, –SO2R1x, –C(O)R1x, –C(O)OR1x, –C(O)N(R1x)2, G1a, –C1-6alkylene–OR1x, –C1-6alkylene–SR1x, –C1-6alkylene–N(R1x)2, –C1-6alkylene–SO2R1x, –C1-6alkylene– C(O)R1x, –C1-6alkylene–C(O)OR1x, –C1-6alkylene–C(O)N(R1x)2, and –C1-6alkylene– G1a, and optionally further substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, and –OR1x; R1x, at each occurrence, is independently hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, –C1-3alkylene–C3-6cycloalkyl, phenyl, or –C1-3alkylene–phenyl, wherein each cycloalkyl or phenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C1-4alkyl, and C1-4haloalkyl; and G1ais a phenyl, a 5- to 6-membered heteroaryl containing 1-3 heteroatoms, a 4- to 8- membered heterocyclyl containing 1-2 heteroatoms, or a 3- to 8-membered carbocyclyl, wherein the heteroatoms are independently selected from the group consisting of O, N, and S, and G1a, at each occurrence, is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, –C1-6alkylene–OH, oxo, OH, –OC1-4alkyl, –OC1-4haloalkyl, C3-4cycloalkyl, and –C1-3alkylene–C3-4cycloalkyl.

15. The method of claim 14, wherein X1is I, Br, Cl, or –SH.

16. The method of claim 14 or 15, wherein Y1is G1or –C1-3alkylene–G1.

17. The method of any one of claims 14-16, the method further comprising reacting the compound of formula (III) with a compound containing –Y2to provide a compound of formula (IV): , wherein: Y2is G2or –C1-C2-10alkynyl; G2, at each occurrence, is independently a 6- to 12-membered aryl, a 4- to 12-membered heterocyclyl, a 3- to 12-membered carbocyclyl, or a 5- to 12-membered heteroaryl, wherein the heteroaryl and heterocyclyl each contain 1-4 heteroatoms independently selected from the group consisting of O, N, and S, and G2is optionally substituted with a first substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, oxo, –OR2x, –N(R2x)2, –SR2x, –SO2R2x, –C(O)R2x, –C(O)OR2x, –C(O)N(R2x)2, G2a, –C1-6alkylene–OR2x, –C1-6alkylene–SR2x, –C1-6alkylene–N(R2x)2, –C1-6alkylene–SO2R2x, –C1-6alkylene– C(O)R2x, –C1-6alkylene–C(O)OR2x, –C1-6alkylene–C(O)N(R2x)2, and –C1-6alkylene– G2a, and optionally further substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, and –OR2x; R2x, at each occurrence, is independently hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, –C1-3alkylene–C3-6cycloalkyl, phenyl, or –C1-3alkylene–phenyl, wherein each cycloalkyl or phenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C1-4alkyl, and C1-4haloalkyl; and G2ais a phenyl, a 5- to 6-membered heteroaryl containing 1-3 heteroatoms, a 4- to 8- membered heterocyclyl containing 1-2 heteroatoms, or a 3- to 8-membered carbocyclyl, wherein the heteroatoms are independently selected from the group consisting of O, N, and S, and G2a, at each occurrence, is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, –C1-6alkylene–OH, oxo, OH, –OC1-4alkyl, –OC1-4haloalkyl, C3-4cycloalkyl, and –C1-3alkylene–C3-4cycloalkyl.

18. The method of any one of claims 14-17, the method further comprising reacting the compound of formula (III) or formula (IV) with a fluorinating agent in the presence of light.

19. The method of claim 18, wherein the fluorinating agent is or.

20. any one of claims 1-13 to synthesize a sulfinate compound.

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