Chiral quaternary nitrogen guanidine salt derived from amino acid as well as preparation method and application of chiral quaternary nitrogen guanidine salt

Abstract

The invention belongs to the field of catalysts, and particularly relates to chiral quaternary nitrogen guanidine salt derived from amino acid as well as a preparation method and application of the chiral quaternary nitrogen guanidine salt. The invention provides a compound shown in a formula I and a preparation method thereof. The compound has good catalytic performance in an asymmetric alkylation reaction and / or an arylation reaction. Experiments show that the catalytic performance of the compound disclosed by the invention in catalyzing the asymmetric arylation reaction in which benzyne participates is superior to that of the existing chiral quaternary ammonium salt catalyst or chiral quaternary phosphonium salt catalyst. Therefore, the method has a good application prospect. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of catalysts, and in particular relates to a chiral quaternary nitrogen guanidine salt derived from an amino acid, a preparation method thereof and a use thereof. Background Art

[0002] Phase transfer catalysts are widely used in the construction of chiral centers, catalytic synthesis of natural products and drug molecules due to their diverse structural modifications, simple experimental operations and mild reaction conditions. The most studied phase transfer catalysts are quaternary ammonium salts (R4N + X - ), but most of the NR4 + It is very easy to decompose and become inactivated under strong alkaline conditions, which limits its application in industry to a certain extent [(a) Hughes, D.; Dolling, U.; Ryan, K.; Schoenewaldt, E.; Grabowski, EJ Org. Chem. 1987, 52, 4745-4752; (b) Gratzer, K.; Waser, M. Synthesis 2012, 44, 3661-3670.].

[0003]

[0004] Chiral amino acids, as cheap and readily available chiral sources, have been used to synthesize a variety of chiral catalysts (Liu, XH; Dong, SX; Lin, LL; Feng, XM Chem. J. Chem. 2018, 36, 791-797.), and have achieved efficient chiral induction in various types of reactions. 2 Based on the guanidine salt structure of the hybrid nitrogen center (Patel, N., Sood, R. & Bharatam, P. Chem. Rev. 2018, 118, 8770-8785), a chiral quaternary nitrogen guanidine salt catalyst was designed and synthesized. This type of compound is more effective as a phase transfer catalyst than traditional quaternary ammonium salts (R4N + X — ) phase transfer catalysts have the advantages of enhanced stability, simple synthesis method, easy modification and rich structural variations. At the same time, the catalytic activity and enantioselectivity of current efficient phase transfer catalysts in many asymmetric reactions are not ideal. Therefore, it is still necessary to develop new and efficient phase transfer catalysts in this field to be applicable to more catalytic reaction types. Summary of the invention

[0005] In view of the problems of the prior art, the object of the present invention is to provide a chiral quaternary nitrogen guanidine salt derived from an amino acid, a preparation method thereof and use thereof.

[0006] The compound represented by formula I, or its stereoisomer, or its salt:

[0007]

[0008] Among them, R 1 , R 2 Each independently selected from: hydrogen, hydroxyl, halogen, carboxyl, substituted or unsubstituted C1-C 11 Carbonyl, substituted or unsubstituted C1~C 11 Ester group, substituted or unsubstituted C1~C 11 Alkenyl, substituted or unsubstituted C1~C 11 Alkynyl, substituted or unsubstituted C1~C 11 Alkyl, substituted or unsubstituted C1~C 11 Alkoxy, substituted or unsubstituted benzyl, substituted or unsubstituted benzyloxy, polysubstituted siloxy, wherein the substituent is selected from C1 to C 11 Alkyl, C3~C 10 Cycloalkyl, C6~C 10 Aryl, halogen substituted C6~C 10 Aryl, cyano, hydroxy, carboxyl or halogen;

[0009] or, R 1 With R 2 Connected to form substituted or unsubstituted C6~C 10 Aryl, substituted or unsubstituted C5~C 10 Cycloalkyl, wherein the substituent is selected from C1 to C 11 Alkyl, C6~C 10 Aryl, cyano, hydroxy, carboxyl or halogen;

[0010] R 3 Selected from: hydrogen, substituted or unsubstituted C1~C 13 Alkyl, substituted or unsubstituted C1~C 13 Alkynyl, substituted or unsubstituted benzyl, wherein the substituent is selected from C1 to C 11 Alkyl, C6~C 10 Aryl, cyano, hydroxy, carboxyl or halogen;

[0011] R 4 Selected from: hydrogen, hydroxyl, substituted or unsubstituted C1-C 10 Primary amine, substituted or unsubstituted C1~C 10 Alkoxy, substituted or unsubstituted C1~C 21alkylamine, substituted or unsubstituted phenoxy, substituted or unsubstituted aniline, substituted or unsubstituted benzyloxy, substituted or unsubstituted benzylamino, substituted or unsubstituted 1-naphthyloxy, substituted or unsubstituted 1-naphthylamino, substituted or unsubstituted 2-naphthyloxy, substituted or unsubstituted 2-naphthylamino, wherein the substituent is selected from C1 to C 11 Alkyl, C6~C 10 Aryl, C1~C 11 Alkyl substituted C6~C 10 Aryl, cyano, hydroxy, carboxyl, halogen, amino,

[0012] R a Selected from C1-C6 alkyl, substituted or unsubstituted C6-C 10 Aryl, wherein the substituent is selected from C1 to C 11 Alkyl, cyano, hydroxyl, carboxyl, halogen;

[0013] R 5 , R 6 , R 7 , R 8 Each is independently selected from: C1-C6 alkyl;

[0014] or, R 5 With R 6 Connected to form a 5- to 7-membered heterocyclic ring;

[0015] or, R 7 With R 8 Connected to form a 5- to 7-membered heterocyclic ring;

[0016] or, R 6 With R 7 Connected to form a 5- to 7-membered heterocyclic ring;

[0017] n is selected from 0 and 1;

[0018] X - It is an anion.

[0019] Preferably, the structural formula of the compound is as shown in Formula Ia or Formula Ib:

[0020]

[0021] Preferably, R 1 Selected from: hydrogen, hydroxyl, halogen, substituted or unsubstituted benzyloxy, substituted or unsubstituted C2 ester, substituted or unsubstituted C1-C2 alkoxy, multi-substituted siloxy, wherein the substituent is selected from C1-C 10 Alkyl, C3~C 10 Cycloalkyl, C6~C 10 Aryl, halogen substituted C6~C10 Aryl, halogen;

[0022] R 2 Selected from hydrogen;

[0023] or, R 1 With R 2 Connected to form phenyl, cyclopentane or cyclohexane;

[0024] R 3 Selected from hydrogen.

[0025] Preferably, R 4 Selected from: hydroxyl, substituted or unsubstituted C1-C2 alkylamine, substituted or unsubstituted C1 alkoxy, substituted or unsubstituted anilino, wherein the substituent is selected from halogen, C1-C4 alkyl, C6-C 10 Aryl, methyl-substituted phenyl, amino,

[0026] R a It is selected from C1-C6 alkyl, substituted or unsubstituted phenyl, wherein the substituent is selected from C1-C4 alkyl, halogen.

[0027] Preferably, R 5 , R 6 , R 7 , R 8 are C1-C4 alkyl groups;

[0028] or, R 5 With R 6 Connected to form a 5- to 7-membered heterocyclic ring;

[0029] or, R 7 With R 8 Connected to form a 5- to 7-membered heterocyclic ring;

[0030] or, R 6 With R 7 Connected to form a 5- to 7-membered heterocyclic ring.

[0031] Preferably, X is selected from the group consisting of chloride ion, bromide ion, iodide ion, triflate ion, borate ion or phosphate ion.

[0032] Preferably, the structural formula of the compound is as shown in Formula Ic:

[0033]

[0034] in,

[0035] R b independently selected from halogen, C1-C4 alkyl, substituted or unsubstituted phenyl; wherein the substituent is selected from halogen, fluorine-substituted C1-C4 alkyl, C1-C4 alkyl, C6-C10 Aryl;

[0036] R c1 , R c2 are independently selected from substituted or unsubstituted C6 to C 10 Aryl; wherein the substituent is selected from halogen, C1~C4 alkyl, C6~C 10 Aryl;

[0037] i and j are independently selected from 1, 2 or 3; k is selected from 1 or 2.

[0038] Preferably, the structural formula of the compound is selected from one of the following structures:

[0039]

[0040]

[0041] The present invention also provides a method for preparing the above compound, comprising the following steps:

[0042]

[0043] Step 1, reacting compound I-1 with alcohol or amine to obtain compound I-2;

[0044] When R 1 When R is hydroxyl, proceed to step 2 and step 3. 1 When it is not a hydroxyl group, proceed to step 3;

[0045]

[0046] Step 2, compound I-2 and R 9 -LG reaction to obtain compound I-2′;

[0047] Among them, R 9 Selected from hydrogen, substituted or unsubstituted C1-C 11 alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted 1-methylnaphthalene, substituted or unsubstituted 2-methylnaphthalene, substituted or unsubstituted 9-methylanthracene, polysubstituted silicon, substituted or unsubstituted C1~C 11 Acyl; substituent selected from C1~C 11 Alkyl, C6~C 10 Aryl, cyano, carboxyl, halogen, amino; LG is selected from Cl, Br, I, OTf;

[0048]

[0049] Step 3, reacting compound I-2 or compound I-2′ with trifluoroacetic acid to obtain compound I-3;

[0050]

[0051] Step 4, reacting compound I-3 with imidazoline chloride to obtain compound I-4;

[0052]

[0053] Step 5, reacting compound I-4 with a metal salt to obtain a compound of formula I.

[0054] Preferably, in step 1, the reaction is carried out in a solvent of dichloromethane or tetrahydrofuran, the alcohol or amine in the reactant is selected from one of primary amine, secondary amine, primary alcohol and secondary alcohol, the reaction temperature is 20-50° C., and the reaction time is 4-24 h;

[0055] And / or, in step 2, the reaction is carried out in tetrahydrofuran solvent, the reaction is carried out under the action of a base, the base is selected from at least one of sodium hydride, triethylamine or imidazole, the reaction temperature is 0-25° C., and the reaction time is 5-24 h;

[0056] And / or, in step 3, the reaction is carried out in a solvent of dichloromethane, the reaction temperature is 0-25°C, and the reaction time is 1-2h;

[0057] And / or, in step 4, the reaction is carried out in acetonitrile as a solvent, the reaction is carried out under the action of a base, the base is selected from triethylamine, the reaction temperature is 25-80° C., and the reaction time is 10-24 h;

[0058] And / or, in step 5, the reaction is carried out in a solvent of dichloromethane or tetrahydrofuran, the reaction temperature is 20-35° C., and the reaction time is 4-10 h.

[0059] The present invention also provides the use of the above compound, or its stereoisomer, or its salt as a phase transfer catalyst for catalyzing asymmetric alkylation reaction and / or arylation reaction.

[0060] The compounds and derivatives provided in the present invention can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, Columbus, OH) nomenclature system.

[0061] Definitions of terms used in the present invention: Unless otherwise stated, the initial definitions provided for groups or terms in this document apply to the groups or terms throughout the specification; for terms that are not specifically defined in this document, the meaning that a person skilled in the art can give them should be given based on the disclosure and context.

[0062] "Substitution" refers to the replacement of a hydrogen atom in a molecule by another different atom or molecule.

[0063] The minimum and maximum carbon atom content in a hydrocarbon group is indicated by a prefix, for example, the prefix C a -C b Alkyl refers to any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, "C1-C4 alkyl" refers to an alkyl group containing 1-4 carbon atoms.

[0064] "Alkyl" refers to a saturated hydrocarbon chain with a specified number of member atoms. For example, C1-C6 alkyl refers to an alkyl group with 1 to 6 member atoms, such as 1 to 4 member atoms. The alkyl group can be straight or branched. Representative branched alkyl groups have one, two or three branches. The alkyl group may be optionally substituted with one or more substituents as defined herein. Alkyl includes methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl and tert-butyl), pentyl (n-pentyl, isopentyl and neopentyl) and hexyl. The alkyl group may also be a part of other groups, such as C1-C6 alkoxy.

[0065] "Cycloalkyl" refers to a saturated or partially saturated cyclic group having 3 to 14 carbon atoms and no ring heteroatoms and having a single ring or multiple rings (including fused, bridged and spirocyclic systems). For polycyclic systems with aromatic and non-aromatic rings without ring heteroatoms, when the point of attachment is located at a non-aromatic carbon atom, the term "cycloalkyl" (e.g., 5,6,7,8,-tetrahydronaphthalene-5-yl) is applicable. The term "cycloalkyl" includes cycloalkenyl groups, such as cyclohexenyl. Examples of cycloalkyl groups include, for example, adamantyl, cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, cyclooctyl, cyclopentenyl and cyclohexenyl.

[0066] "Alkenyl" refers to a straight or branched chain hydrocarbon group having 2 to 10 carbon atoms, and in some embodiments 2 to 6 carbon atoms or 2 to 4 carbon atoms, and having at least one site of vinyl unsaturation (>C=C<). a -C b Alkenyl refers to an alkenyl group having from a to b carbon atoms and is intended to include, for example, ethenyl, propenyl, isopropenyl, 1,3-butadienyl, and the like.

[0067] "Alkynyl" refers to a straight chain monovalent hydrocarbon group or a branched monovalent hydrocarbon group containing at least one triple bond. The term "alkynyl" is also intended to include those hydrocarbon groups having one triple bond and one double bond. For example, C2-C6 alkynyl is intended to include ethynyl, propynyl, etc.

[0068] "Halogen" is fluorine, chlorine, bromine or iodine.

[0069] "Heterocycle" and "heterocycloalkyl" refer to a saturated ring or a non-aromatic unsaturated ring containing at least one heteroatom; wherein the heteroatom refers to a nitrogen atom, an oxygen atom, or a sulfur atom;

[0070] "Heteroaryl" refers to an aromatic unsaturated ring group containing at least one heteroatom; wherein the heteroatom refers to a nitrogen atom, an oxygen atom, or a sulfur atom;

[0071] “R a and R b "connected to form a heterocyclic ring" refers to R a and R b There is at least one atom connected by a chemical bond in each of the two, so that R a and R b The atoms or chains of atoms that are connected together as part of the ring structure are related to R a and R b Together they form a heterocycle.

[0072] "Stereoisomers" include enantiomers and diastereomers.

[0073] The present invention is based on cheap and readily available chiral amino acid raw materials and sp 2 Based on the guanidine salt structure of the hybrid nitrogen center, a chiral quaternary nitrogen guanidine salt catalyst was designed and synthesized. This type of compound is more effective as a phase transfer catalyst than traditional quaternary ammonium salts (R4N + X — ) phase transfer catalyst, it has the advantages of enhanced stability, simple synthesis method, easy modification and rich structural changes, and also shows efficient catalytic effect in catalyzing asymmetric arylation reactions involving benzyne.

[0074] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0075] The following is a further detailed description of the above contents of the present invention through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies implemented based on the above contents of the present invention belong to the scope of the present invention. DETAILED DESCRIPTION

[0076] In the following examples and experimental examples, reagents and raw materials not specifically described are all commercially available products.

[0077] Example 1: Synthesis of amide compound I-2-1

[0078]

[0079] Add a magnetic particle to a round-bottom flask, weigh in Boc-protected amino acid (1.0 equiv.), dichloromethane (0.5 M) or tetrahydrofuran (0.5 M) as solvent. Cool to 0°C, slowly add triethylamine (1.2 equiv.) at this temperature, then slowly drop isobutyl chloroformate (1.2 equiv.), warm to room temperature for reaction for 30 minutes, and then cool to 0°C again. Add primary or secondary amine (1.2-1.5 equiv.) at this temperature, and react at 20-50°C for 4-24 hours. After the reaction is completed, dichloromethane (0.5 M) or ethyl acetate (0.5 M) is added to the reaction system to dilute, and wash once with saturated potassium hydrogen sulfate, saturated sodium bicarbonate, and saturated sodium chloride in sequence. Dry the organic phase with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and proceed directly to the next step.

[0080] Example 2: Synthesis of ester compound Ⅰ-2-2

[0081]

[0082] Add a magnetic particle to a round-bottom flask, weigh in the Boc-protected amino acid (1.0 equiv.), and dichloromethane (0.5 M) as a solvent. Cool to 0°C, slowly add thionyl chloride (1.5 equiv.) at this temperature, react for 30 minutes, add the substituted alcohol (1.5-15.0 equiv.), and then return to room temperature to react for 3-5 hours. After the reaction is completed, spin dry the solvent to obtain a crude product, and proceed directly to the next step.

[0083] Example 3: Synthesis of amide compound Ⅰ-2′ (R 1 =OH)

[0084]

[0085] Add a magnetic bar to a round-bottom flask, weigh in Boc-protected amide I-2 (1.0 equiv.), tetrahydrofuran (0.4 M) as solvent, cool to 0°C, add NaH (2.5 equiv., 60% dispersed in mineral oil), triethylamine (2.5 equiv.) or imidazole (2.5 equiv.) in batches, react for 30 minutes, then slowly drop R 9 -LG (1.5-2.5 equiv.), then the reaction system is heated to room temperature to react until the amide substrate I-2 is completely consumed (5-24h). After the reaction is completed, the reaction system is cooled to 0°C, ice water and aq. KHSO4 or HCl (2.0M) are added to quench the reaction, ethyl acetate (3х50mL) is extracted, and the organic phases are combined. The organic phase is washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 4:1-3:1) to obtain the target product I-2'.

[0086] Example 4: Synthesis of amide compound I-3

[0087]

[0088] Transfer Ⅰ-2 obtained in Example 2 or Example 3 into a round-bottom flask, add a magnetic particle, and use dichloromethane (1.0M) as a solvent. Cool to 0°C, slowly add trifluoroacetic acid (1.0mL / mmol) at this temperature, warm to room temperature and react for 1 hour, and monitor the reaction by TLC spot plate. After the substrate Ⅰ-2 is completely reacted, cool the reaction system to 0°C, add dichloromethane (0.5M) to dilute, and slowly add 50% aq.NaOH to adjust the pH to 11-12. Extract with dichloromethane and combine the organic phases. The organic phase is washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 4:1-0:1) to obtain the target product Ⅰ-3.

[0089] Example 5: Synthesis of Quaternary Nitrogen Chloride Guanidine Salt I-4

[0090]

[0091] Add a magnetic bar to a 25 mL round-bottom flask, weigh compound I-3 (1.0 equiv.), acetonitrile (1.0 M) as solvent, slowly add triethylamine (2.5 equiv.) and the newly prepared imidazoline chloride (1.5 equiv.) under stirring, and reflux at 25-80 ° C. After the reaction is completed, add 2M HCl to quench, extract with dichloromethane, and combine the organic phases. The organic phase is washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: ethyl acetate: methanol = 10: 1-6: 1) to obtain the target product I-4.

[0092] Example 6: Synthesis of Quaternary Nitrogen Guanidine Salt I

[0093]

[0094] Add a magnetic particle to a 10 mL catalytic test tube, weigh compound I-4 (1.0 equiv.), MX (1.1-10.0 equiv.), dichloromethane (0.2 M) or tetrahydrofuran (0.2 M) as solvent, and react at 20-35°C for 4-10 hours. Add diatomaceous earth and filter, wash the filter cake with dichloromethane, and spin dry the solvent to obtain product IA-IAL.

[0095] It should be noted that in the reaction formulas of Examples 1-6 above, the specific structure of each substituent is determined according to the structure of the corresponding group of Compounds IA-IAL.

[0096] Example 7: Synthesis of Quaternary Nitrogen Guanidine Salt IA

[0097] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0098]

[0099] Yellow solid, melting point 211–212°C; total yield 78%; [α] 20 D =+139.2(c=0.556g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ8.79(d,J=9.2Hz,1H),7.59–7.57(m,2H),7.41–7.39(m,2H),7.30–7.24(m,4H), 7.20–7.15(m,2H),6.18(d,J=9.2Hz,1H),5.22(dd,J=6.4,4.4Hz,1H),3.71–3.08(m,9H),2.18–1.57(m,14H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ171.0,157.9,141.7,128.7,128.7,128.2,127.4,127.2,59.5,57.7,49.0,30.6,25.2,21.1.HRMS(ESI)calcd for C 28 H 37 N4O + ([MI - ]) + =445.2962,Found 445.2962.

[0100] Example 8: Synthesis of Quaternary Nitrogen Guanidine Salt IB

[0101] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0102]

[0103] White solid, melting point 240–241°C; total yield 57%; [α] 22 D =+141.9(c=0.955g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ8.56(d,J=9.2Hz,1H),7.55–7.53(m,2H),7.46–7. 44(m,2H),7.29–7.26(m,4H),7.21–7.16(m,2H),6.22(d,J=9.2Hz,1H),5.53–5.4 9(m,1H),4.28–4.22(m,1H),3.60–3.54(m,4H),3.40–3.32(m,4H),2.94–2.90(m, 1H),2.86–2.78(m,1H),2.16–2.01(m,2H),1.97–1.86(m,5H),1.80–1.54(m,8H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.8,156.4,142.1,141.3,128.6,128.5,127.9,127 .5,127.2,69.6,65.0,57.9,50.7,44.8,35.8,30.7,28.3,25.1,23.7.HRMS(ESI)calcd for C 30 H 39 N4O + ([MI - ]) + =471.3118,Found 471.3118.

[0104] Example 9: Synthesis of Quaternary Nitrogen Guanidine Salt IC

[0105] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0106]

[0107] Yellow solid, melting point 143–144°C; total yield 55%; [α] 22 D =+69.0(c=1.643g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ9.47(d,J=9.6Hz,1H),7.62–7.60(m,2H),7.54–7.52(m,2H),7.33–7.30–7.28(m,4H),7.22–7.12(m,6H),6 .28(d,J=9.6Hz,1H),5.27(dd,J=9.2,5.2Hz,1H),4.55(d,J=13.6Hz,1H),4.25(d,J=13.6Hz,1H),3.85–2.81(m,10H),2.24–1.39(m,8H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.2,157.1,141.9,141.5,133.9,132.8,128.6,128.3,128.2 ,128.1,127.4,127.3,127.1,127.0,125.5,58.5,57.8,50.5,49.9,33.3,25.2.HRMS(ESI)calcd for C 32 H 37 N4O + ([MI - ]) + =493.2962,Found493.2962.

[0108] Example 10: Synthesis of Quaternary Nitrogen Guanidine Salt ID

[0109] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0110]

[0111] Pale yellow solid, melting point 234–235°C; total yield 37%; [α] 22 D =+116.8(c=0.788g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ9.35(s,1H),7.03–6.96(m,3H),5.54–5.50(m,1H),3.63–3.49(m,6H),3.4 4–3.40(m,4H),3.10–3.05(m,1H),2.20(s,6H),2.09–2.02(m,5H),1.95–1.91(m,2H),1.86–1.77(m,4H). 13 C{1 H}NMR(101MHz,Chloroform-d)δ169.6,154.7,135.2,133.5,128.1,127.3,62.8,51.8,50.4,46.4,32.6,25.8,25.7,19.0.HRMS(ESI)calcd for C 22 H 33 N4O + ([MI - ]) + =369.2649,Found 369.2648.

[0112] Example 11: Synthesis of Quaternary Nitrogen Guanidine Salt IE

[0113] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0114]

[0115] Pale yellow solid, melting point 247–248°C; total yield 43% yield, [α] 22 D =+99.6 (c=0.515g / 100mL, λ=589nm, in CH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ9.25(s,1H),7.23–7.20(m,1H),7.11–7.09(m,2H),5.64–5.59(m,1H),3.69–3.60(m,4H),3.57–3.50(m,2H) ),3.47–3.43(m,4H),3.21–3.18(m,1H),3.03–2.96(m,2H),2.11–2.06(m,5H),2.04–1.96(m,2H),1.93–1.80(m,4H),1.20–1.16(m,12H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.9,154.9,146.1,130.9,128.5,123.5,62.8,52.0,50.6,32.5,28.9,26.0,25.8.HRMS(ESI)calcd forC 26 H 41 N4O + ([MI - ]) + =425.3275,Found 425.3273.

[0116] Example 12: Synthesis of Quaternary Nitrogen Guanidine Salt IF

[0117] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0118]

[0119] White solid, total yield 76%; [α] 23 D =+113.2(c=0.865g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR (400MHz, Chloroform-d) δ7.77(s,1H),7.29-7.23(m,11H),6.16(s,1H),4.86(s,1H),3.55-3.26(m,10H),2.70(s,1H),2.05-1.65m,11H). 13 C NMR (101MHz, Chloroform-d) δ169.8,154.7,141.8,141.1,128.8,127.6,127.5,127.2,63.0,57.5,51.3,50.0,32.0,25.6. 19 F NMR(377MHz,Chloroform–d)δ–71.8,-73.7.HRMS(ESI)calcd for C 27 H 35 N4O + ([M–PF6 – ]) + =431.2805,Found 431.2810.

[0120] Example 13: Synthesis of Quaternary Nitroguanidine Salt IG

[0121] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0122]

[0123] White solid, total yield 76%; [α] 22 D =+110.6(c=1.685g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ7.99(d,J=9.2Hz,1H),7.38–7.36(m,2H),7.31– 7.27(m,6H),7.24–7.19(m,2H),6.14(d,J=9.2Hz,1H),4.88(dd,J=9.6,7.2Hz, 1H),3.57-3.50(m,1H),3.45-3.38(m,5H),3.26-3.21(m,4H),2.79–2.73(m,1H ),2.05–1.96(m,2H),1.94–1.89(m,4H),1.86–1.76(m,1H),1.67-1.54(m,4H). 13 C NMR (101MHz, Chloroform-d) δ169.9,154.8,141.9,141.2,128.8,128.8,127.5,127.4,127.4,127.0,62.9,57.4,51.0,49.7,31.9,25.8,25.4. 19 F NMR(377MHz,Chloroform–d)δ–151.8,-151.8.HRMS(ESI)calcd forC 27 H 35 N4O + ([M–BF4 – ]) + =431.2805,Found 431.2810.

[0124] Example 14: Synthesis of Quaternary Nitrogen Guanidine Salt IH

[0125] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0126]

[0127] White solid, total yield 76%; [α] 22 D =+86.9(c=1.155g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ8.48(d,J=8.4Hz,1H),7.38–7.31(m,8H),7.27–7.22(m,2H),6.13(d,J=8.4Hz,1H),4.85(dd,J=9.6,7.2Hz,1H),3.5 8-3.52(m,1H),3.46-3.39(td,J=9.9,6.2Hz,4H),3.33–3.29(m,1H),3.2 4-3.20(m,4H),2.76-2.70(m,1H),2.08–1.80(m,7H),1.70-1.58(m,4H). 13 C NMR(101MHz,Chloroform-d)δ170.1,154.7,141.6,141.2,128.4,128.2,127.5,127.0,126.9,120.5(d,J C-F =321.6Hz),62.8,57.5,51.0,49.8,31.8,25.7,25.4. 19 F NMR(377MHz,Chloroform–d)δ–77.9.HRMS(ESI)calcd forC 27 H 35 N4O + ([M–OTf – ]) + =431.2805,Found 431.2810.

[0128] Example 15: Synthesis of Quaternary Nitrogen Guanidine Salt II

[0129] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0130]

[0131] Viscous liquid, total yield 85%; 1 H NMR(400MHz,Chloroform-d)δ8.23(s,1H),7.57–7.55(m,2H),7.36–7.17(m,8H),6.26(d,J=8.8Hz,1H),6.05(s,1H), 3.74–2.96(m,10H),2.64–2.51(m,2H),2.05–1.95(m,3H),1.60–1.30(m,13H),1.17–1.02(m,2H),1.00–0.67(m,12H). 13C NMR(101MHz,Chloroform-d)171.3,158.0,141.3,141.0,128.2,128.0,126.2,126.1,6 8.6,52.4,49.4,49.3,48.5,33.6,30.2,24.3,20.9,20.7,13.8,13.6.HRMS(ESI)calcd for C 35 H 55 N4O + ([M–I – ]) + =674.3421,Found 674.3420.

[0132] Example 16: Synthesis of Quaternary Nitrogen Guanidine Salt IJ

[0133] For the specific operation, refer to Examples 2 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0134]

[0135] Viscous liquid, total yield 29%; [α] 22 D =+95.2(c=3.250g / 100mL, λ=589nm, inCH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ4.52(dd,J=9.2,7.6Hz,1H),3.94-3.90(m,1H),3.71(s,3H),3. 56–3.45(m,9H),3.13-3.07(m,1H),2.55-2.49(m,1H),2.08-2.01(m,5H),1.92-1.82(m,5H). 13 C NMR(101MHz,Chloroform-d)δ172.1,154.8,61.2,53.5,53.0,51.1,50.2,46.0,30.8,25.7,25.6,8.8.HRMS(ESI)calcd for C 15 H 26 N3O2 + ([M–Cl – ]) + =280.2020,Found280.2024.

[0136] Example 17: Synthesis of Quaternary Nitrogen Guanidine Salt IK

[0137] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0138]

[0139] Pale yellow solid; melting point: 241–242°C; total yield 49%; [α] 21 D =+86.8(c=0.630g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ8.63–8.54(m,1H),7.08(s,2H),6.64–6.63(m,1H),5.29–5.28 (m,1H),4.13–4.03(m,2H),3.74–3.57(m,10H),3.36–3.31(m,2H),2.91–2.80(m,1H),2.78–2 .68(m,1H),2.14–2.05(m,5H),2.01–1.88(m,7H),1.81–1.74(m,2H),1.69–1.67(m,1H),1.5 6–1.53(m,1H),1.44–1.42(m,1H),1.26–1.20(m,18H),1.10–1.05(m,2H),0.92–0.84(m,1H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ174.6,154.0,152.1,148.9,136.5,123.7,61.5,59.9,54.2,52. 0,50.7,34.1,32.6,31.4,31.3,29.5,25.9,25.7,25.0,24.6,24.6,23.9,23.7.HRMS(ESI)calcd for C 35 H 58 N5O3S + ([MI - ]) + =628.4255,Found 628.4255.

[0140] Example 18: Synthesis of Quaternary Nitrogen Guanidine Salt IL

[0141] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0142]

[0143] White solid, melting point: 254–255°C; total yield 56%; [α] 21 D =+181.2(c=0.713g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ9.17(d,J=3.6Hz,1H),8.82–8.80(m,1H),8.58(d,J=2.4Hz,1H),7.86–7.78(m,1H),7.60–7.55(m,3H),7.22–7.1 2(m,3H),7.07–7.03(m,1H),5.49–5.36(m,1H),3.64–3.50(m,5H),3.33 –3.28(m,5H),2.88–2.81(m,1H),2.14–1.99(m,7H),1.80–1.73(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.24–169.21(m),154.97–154.90(m),153.45–15 3.34(m),138.32,138.26,130.98–130.92(m),128.8,128.08–127.96(m),127.13–1 27.10(m),126.39–126.37(m),124.64–124.53(m),124.27–124.03(m),119.94,63. 91–63.84(m),51.16–51.15(m),50.34,31.94–31.87,25.82,25.66.HRMS(ESI)calcd for C 27 H 34 35 ClN6O2 + ([MI - ]) + =509.2426, Found 509.2428; C 27 H 34 37 ClN6O2 + ([MI - ]) + =511.2397,Found 511.2402.

[0144] Example 19: Synthesis of Quaternary Nitrogen Guanidine Salt IM

[0145] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0146]

[0147] Light brown solid, melting point: 197–198°C; total yield 37%; [α] 22 D =+104.3(c=0.798g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ8.87–8.78(m,1H),7.49–7.39(m,4H),7.35–7.10(m,16H),6.35(d,J=9.0Hz,1H),6.12–6. 06(m,1H),4.74–4.64(m,1H),4.47–4.40(m,3H),3.89–3.86(m,1H),3.53–3.47(m,1H),3.13(s,6H),2.21–2.14(m,1H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ 168.5,161.8,141.4,141.2,135.9,129.6,129.5,128.9,128.8,127.7,127.6, 127.5,127.3,127.1,75.7,62.4,58.9,58.3,51.8,40.9,37.4.HRMS(ESI)calcd for C 35 H 36 35 ClN4O + ([MI - ]) + =563.2572, Found 563.2570; C 35 H 36 37 ClN4O + ([MI - ]) + =565.2543,Found 565.2551.

[0148] Example 20: Synthesis of Quaternary Nitrogen Guanidine Salt IN

[0149] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0150]

[0151] White solid, melting point: 231–232°C; total yield 36%; [α] 22 D =+117.3(c=0.448g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ8.98(d,J=9.2Hz,1H),7.50–7.46(m,2H),7.43–7.39(m, 2H),7.35–7.30(m,2H),7.26–7.17(m,9H),7.17–7.13(m,4H),7.10–7.06(m,1H),6.36 (d,J=9.2Hz,1H),6.03(t,J=8.4Hz,1H),5.04(s,1H),4.67(s,1H),4.42(s,2H),4.13( dd,J=10.0,1.6Hz,1H),3.97(dd,J=10.0,2.8Hz,1H),3.07(s,6H),2.04–1.99(m,2H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.7,162.9,141.5,141.4,136.0,129.6,129.4,128.8,12 8.8,127.8,127.5,127.4,127.3,127.1,75.7,70.3,62.5,58.2,40.4,37.1.HRMS(ESI)calcd for C 35 H 37 N4O2 + ([MI - ]) + =545.2911,Found 545.2912.

[0152] Example 21: Synthesis of Quaternary Nitrogen Guanidine Salt ⅠO

[0153] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0154]

[0155] Pale yellow solid, melting point: 243–244°C; total yield 94%; [α] 22 D =+226.8(c=0.585g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ8.92(d,J=9.2Hz,1H),7.55–7.53(m,2H),7.41–7.39(m,2H),7.34–7.25 (m,4H),7.22–7.16(m,2H),6.20(d,J=9.2Hz,1H),5.34–5.30(m,1H),4.74(s,1H),4.53(s,1H),3.86– 3.83(m,1H),3.57–3.53(m,2H),3.46–3.24(m,4H),3.15–3.10(m,1H),3.03–2.91(m,2H),2.56–2.52( m,1H),2.27–2.15(m,1H),1.93–1.87(m,1H),1.71–1.53(m,8H),1.43–1.35(m,2H),1.03–1.01(m,1H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,160.2,141.9,141.1,128.7,128.7,128.1,127.6,127.3,6 9.8,61.4,59.1,58.0,50.7,50.2,49.7,39.6,25.7,25.2,25.0,24.8,23.8,23.3.HRMS(ESI)calcd for C 29 H 39 N4O2 + ([MI - ]) + =475.3068,Found 475.3066.

[0156] Example 22: Synthesis of Quaternary Nitrogen Guanidine Salt IP

[0157] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0158]

[0159] Pale yellow solid, melting point: 243–244°C; total yield 33%; [α] 21 D =+140.7(c=1.355g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ8.84(d,J=9.2Hz,1H),7.52–7.50(m,2H),7.40–7.38 (m,2H),7.33–7.26(m,4H),7.22–7.17(m,2H),6.19(d,J=9.2Hz,1H),5.45(dd,J=10 .0,6.8Hz,1H),4.83(s,1H),4.52(s,1H),3.83–3.81(m,1H),3.63–3.61(m,1H),3.4 4–3.35(m,8H),2.82(dd,J=13.2,6.8Hz,1H),1.94–1.87(m,5H),1.67–1.60(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,154.6,141.7,141.1,128.6,127.8,127.6,127.3,127.3,70.0,61.2,58.6,57.8,50.1,39.5,25.4.HRMS(ESI)calcd for C 27 H 35 N4O2 + ([MI - ]) + =447.2755,Found 447.2753.

[0160] Example 23: Synthesis of Quaternary Nitrogen Guanidine Salt IQ

[0161] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0162]

[0163] White solid, melting point 176–177°C; total yield 33%; [α] 22 D =+55.8(c=1.915g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ7.74–7.72(m,8H),7.56–7.55(m,4H),7.38–7.28(m,6H),7.20–7.13(m,4H),6.17–6.12(m,2H),4.60(dd,J=10.0,7.2 Hz,1H),4.53(s,1H),3.65–3.61(m,1H),3.39–3.05(m,9H),2.44(dd,J=1 2.8,7.2Hz,1H),2.11–2.04(m,1H),1.99–1.94(m,4H),1.78–1.58(m,5H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ168.2,161.8(q, 2 J C-F =50.0Hz),154.9,140.4,139.8,134.9,129.5–129.4(m),129.2,128.9-1 28.8(m),128.7,128.6–128.5(m),128.4,128.3,127.2,126.9,124.7(d, 1 J C-F =273.6Hz),120.6,117.8–117.6(m),69.8,61.1,58.1,57.9,50.0,39.1,25.4. 19 F{ 1 H}NMR(377MHz,Chloroform-d)δ-62.3.HRMS(ESI)calcd for C 27 H 35 N4O2 + ([M-BAr F 4 - ]) + =447.2755,Found 447.2755.

[0164] Example 24: Synthesis of Quaternary Nitrogen Guanidine Salt IR

[0165] For the specific operation, refer to Examples 1 and 4-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0166]

[0167] Pale yellow solid, total yield 46%; [α] 21 D=+104.43(c=1.015g / 100mL, λ=589nm, inCH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ10.51(d,J=8.8Hz,1H),7.36–7.30(m,4H),7.19–7.05 (m,6H),5.14–5.10(m,1H),5.04–5.00(m,1H),4.36(d,J=7.2Hz,1H),3.70(s,2H),3. 53–3.46(m,1H),3.37–3.31(m,4H),3.20–3.16(m,1H),3.07–3.02(m,4H),2.85–2.79 (m,1H),2.02–1.96(m,1H),1.93–1.84(m,5H),1.70–1.60(m,1H),1.53–1.38(m,4H). 13 C NMR(101MHz,Chloroform-d)δ169.7,154.7,140.5,140.4,128.2,128.1,127.8,12 7.6,127.3,127.2,63.2,60.4,60.2,51.1,49.7,31.7,25.7,25.2.HRMS(ESI)calcd for C 28 H 38 N5O + ([M-Cl - ]) + =460.3071,Found 460.3072.

[0168] Example 25: Synthesis of Quaternary Nitrogen Guanidine Salt IS

[0169] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0170]

[0171] Pale yellow solid, melting point: 167–168°C; total yield 39%; [α] 21 D =+116.9(c=0.898g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ9.24(d,J=9.6Hz,1H),7.58–7.53(m,3H),7.51–7.48(m,4H),7.20–7 .24(m,4H),7.21–7.16(m,2H),6.22(d,J=9.6Hz,1H),5.70(dd,J=9.6,7.2Hz,1H),5.02(d,J=12.0 Hz,1H),4.36(d,J=12.0Hz,1H),4.24–4.22(m,1H),3.71(dd,J=10.4,2.8Hz,1H),3.53–3.46(m,4H ),3.40–3.33(m,2H),3.25–3.20(m,4H),2.02–1.94(m,4H),1.85–1.88(m,1H),1.69–1.56(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.7,154.5,142.0,142.0,141.1,133.2,129.9,128.6,128.6,12 8.6,127.9,127.6,127.3,127.3,122.9,69.3,61.3,58.1,57.1,50.1,35.3,25.4.HRMS(ESI)calcd for C 34 H 39 79 Br2N4O2 + ([MI - ]) + =693.1434,Found693.1431;C 34 H 39 79 Br 81 BrN4O2 + ([MI - ]) + =695.1414, Found 695.1412; C 34 H 39 81 Br2N4O2 + ([MI - ]) + =697.1393,Found 697.1396.

[0172] Example 26: Synthesis of Quaternary Nitrogen Guanidine Salt IT

[0173] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0174]

[0175] Light brown solid, melting point: 141–142°C; total yield 38%; [α] 23 D =+136.7(c=0.683g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ9.29–9.26(m,1H),8.19–8.17(m,1H),7.81–7.75(m,2H),7.68–7.65(m,1H ),7.59–7.57(m,2H),7.55–7.50(m,3H),7.46–7.36(m,2H),7.31–7.24(m,4H),7.21–7.14(m,2H),6.21( d,J=9.6Hz,1H),5.77–5.71(m,1H),5.46–5.42(m,1H),4.88–4.82(m,1H),4.24–4.22(m,1H),3.62–3.58 (m,1H),3.47–4.38(m,5H),3.24–3.21(m,1H),3.15–3.11(m,4H),1.93–1.81(m,5H),1.63–1.53(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,154.4,142.0,141.2,133.8,133.3,132.0,128.8,128.7,128.6,128.5,128.0,1 27.9,127.7,127.3,126.5,125.8,125.5,124.7,76.3,76.3,69.5,61.4,58.2,57.2,50.0,35.4,25.4.HRMS(ESI)calcd for C 38 H 43 N4O2 + ([MI - ]) + =587.3381,Found 587.3380.

[0176] Example 27: Synthesis of Quaternary Nitrogen Guanidine Salt IU

[0177] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0178]

[0179] Gray solid, melting point: 129–130°C; total yield 35%; [α] 23 D =+164.1(c=0.315g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ9.23(d,J=9.2Hz,1H),7.59–7.57(m,2H),7.50–7.48(m,2H),7.30–7.26( m,4H),7.20–7.16(m,2H),6.19(d,J=9.2Hz,1H),5.63(dd,J=9.4,7.2Hz,1H),4.14–4.12(m,1H),3.91–3 .85(m,1H),3.70(dd,J=10.6,3.6Hz,1H),3.55–3.48(m,4H),3.38–3.32(m,1H),3.26–3.14(m,6H),2.01 –1.95(m,4H),1.84(m,1H),1.72–1.58(m,9H),1.55–1.31(m,3H),1.25–1.07(m,3H),0.95–0.84(m,2H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.2,154.6,142.0,141.1,128.7,128.6,128.1,127.7,127.3,6 7.4,61.5,58.3,57.3,50.1,37.1,35.5,34.7,33.6,33.5,26.7,26.4,26.4,25.5.HRMS(ESI)calcd for C 35 H 49 N4O2 + ([MI - ]) + =557.3850,Found 557.3851.

[0180] Example 28: Synthesis of Quaternary Nitrogen Guanidine Salt IV

[0181] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0182]

[0183] White solid, melting point: 291–292°C; total yield 18%; [α] 22 D =+122.9(c=0.685g / 100mL, λ=589nm, in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ9.59(d,J=9.2Hz,1H),7.70–7.61(m,6H),7.53–7 .51(m,2H),7.45–7.35(m,6H),7.30–7.26(m,4H),7.20–7.15(m,2H),6.17(d,J= 9.2Hz,1H),5.86–5.82(m,1H),4.48–4.47(m,1H),3.50–3.41(m,5H),3.16–3.1 2(m,4H),2.89–2.83(m,2H),2.09–1.92(m,5H),1.65–1.52(m,4H),1.08(s,9H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.2,154.5,142.1,141.2,136.0,135.8,133.8,132.6,130.2,130.0,128.7, 128.6,128.1,127.9,127.8,127.2,77.4,71.3,61.7,58.4,58.3,50.0,39.6,27.1,25.4,19.2.HRMS(ESI)calcd for C 43 H 53 N4O2Si + ([MI - ]) + =685.3932,Found 685.3931.

[0184] Example 29: Synthesis of Quaternary Nitrogen Guanidine Salt IW

[0185] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0186]

[0187] Gray solid, melting point: 126–127°C. Total yield 45% yield, [α] 24 D =+142.3(c=0.215g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.22(d,J=9.2Hz,1H),7.60–7.58(m,2H),7.51–7.49(m,2H) ,7.30–7.26(m,4H),7.21–7.16(m,2H),6.20(d,J=9.2Hz,1H),5.60–5.56(m,1H),4.08–4. 07(m,1H),3.69(dd,J=10.4,3.2Hz,1H),3.56–3.49(m,5H),3.25–3.11(m,6H),2.81(d,J= 8.4Hz,1H),2.05–1.92(m,7H),1.89–1.81(m,1H),1.65–1.59(m,13H),1.53–1.50(m,3H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.2,154.7,142.0,141.1,128.7,128.6,128.1,127.8, 127.3,79.7,61.6,58.3,57.0,50.1,39.6,37.3,35.7,34.1,28.4,25.5.HRMS(ESI)calcd for C 38 H 51 N4O2 + ([MI - ]) + =595.4007,Found595.4006.

[0188] Example 30: Synthesis of Quaternary Nitrogen Guanidine Salt IX

[0189] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0190]

[0191] Pale yellow solid, melting point: 129–130°C. Total yield 51%; [α] 21 D =+134.4(c=0.570g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.35–9.33(m,1H),7.60–7.58(m,2H),7.52–7.50(m,2H),7.32–7.24( m,4H),7.22–7.14(m,2H),7.04(s,2H),6.89(s,1H),6.21(d,J=9.2Hz,1H),5.78–5.69(m,1H),4.90 –4.85(m,1H),4.41–4.37(m,1H),4.24–4.20(m,1H),3.69–3.67(m,1H),3.57–3.42(m,4H),3.37–3. 28(m,2H),3.22–3.17(m,4H),2.28(s,6H),2.00–1.96(m,4H),1.89–1.71(m,1H),1.63–1.62(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.1,154.6,142.1,141.2,138.1,137.5,129.6,128.7,128.6,128 .0,127.7,127.3,126.5,76.0,70.9,61.4,58.3,57.3,50.0,35.3,25.4,21.4,21.3.HRMS(ESI)calcd for C 36 H 45 N4O2 + ([MI - ]) + =565.3537,Found 565.3536.

[0192] Example 31: Synthesis of Quaternary Nitrogen Guanidine Salt IY

[0193] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0194]

[0195] Gray solid, melting point: 173–174°C; total yield: 41% yield; [α] 22 D =+132.8(c=0.690g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.28(d,J=9.2Hz,1H),7.59–7.58(m,2H),7.51–7.50(m,2H),7.31–7.25(m ,4H),7.21–7.16(m,2H),6.64(m,2H),6.37–6.36(m,1H),6.21(d,J=9.2Hz,1H),5.78–5.74(m,1H),4.94– 4.89(m,1H),4.38–4.36(m,1H),4.25–4.23(m,1H),3.78(s,6H),3.68(dd,J=10.4,3.6Hz,1H),3.54–3.4 5(m,4H),3.35–3.31(m,2H),3.23–3.28(m,4H),2.00–1.96(m,4H),1.87–1.74(m,1H),1.69–1.56(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,160.9,154.5,142.0,141.2,140.1,128.7,128.6,128.0,127 .6,127.3,106.4,100.3,76.2,70.9,61.4,58.2,57.2,55.9,55.8,50.0,35.3,25.4.HRMS(ESI)calcd for C 36 H 45 N4O4 + ([MI - ]) + =597.3435,Found 597.3434.

[0196] Example 32: Synthesis of Quaternary Nitrogen Guanidine Salt IZ

[0197] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0198]

[0199] Pale yellow solid, melting point: 180–181°C; total yield: 39% yield; [α] 21 D =+128.8(c=0.533g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.38(d,J=9.6Hz,1H),7.59–7.57(m,2H),7.51–7.49(m,2H),7.34–7.33(m ,1H),7.32–7.26(m,4H),7.25–7.12(m,4H),6.21(d,J=9.6Hz,1H),5.80–5.76(m,1H),4.94(d,J=11.2Hz ,1H),4.36(d,J=11.2Hz,1H),4.25–4.23(m,1H),3.70(dd,J=10.0,3.2Hz,1H),3.54–3.48(m,4H),3.39– 3.27(m,3H),3.23–3.18(m,4H),2.00–1.95(m,4H),1.90–1.77(m,1H),1.68–1.54(m,4H),1.31(s,18H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.1,154.5,150.9,142.0,141.2,136.7,128.7,128.6,128.0,127.7,12 7.3,123.2,121.9,76.1,71.6,61.5,58.2,57.4,50.0,48.0,35.2,35.0,31.7,25.6,25.4.HRMS(ESI)calcd for C 42 H 57 N4O2 + ([MI - ]) + =649.4476,Found 649.4476.

[0200] Example 33: Synthesis of Quaternary Nitrogen Guanidine Salt IAA

[0201] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0202]

[0203] Yellow solid, melting point: 266–267°C; total yield 60%; [α] 23 D =+98.0(c=0.545g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ9.26(d,J=9.6Hz,1H),7.59–7.57(m,2H),7.49–7.45(m, 2H),7.41–7.39(m,2H),7.32–7.26(m,6H),7.23–7.17(m,3H),6.18(d,J=9.6Hz,1H),5 .86(dd,J=10.0,7.2Hz,1H),5.36–5.35(m,3H),3.80–3.77(m,3H),3.51–3.44(m,4H), 3.23(dd,J=11.2,2.0Hz,1H),3.15–3.05(m,5H),2.07–1.97(m,5H),1.66–1.54(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ171.4,169.5,154.3,141.9,141.0,133.8,130.0,128.8,128. 7,128.1,127.6,127.4,127.1,72.3,61.7,58.3,55.8,50.3,41.6,36.8,25.5.HRMS(ESI)calcd for C 35 H 41 N4O3 + ([MI - ]) + =565.3173,Found 565.3176.

[0204] Example 34: Synthesis of Quaternary Nitrogen Guanidine Salt IAB

[0205] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0206]

[0207] Yellow solid, melting point: 166–167°C; total yield: 76% yield; [α] 21 D =+164.7(c=0.338g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.31(d,J=9.6Hz,1H),7.60–7.59(m,2H),7.52–7.50(m,2H),7.31–7.25(m, 6H),7.22–7.16(m,3H),7.08–7.06(m,1H),6.21(d,J=9.6Hz,1H),5.76(dd,J=9.2,7.6Hz,1H),4.94(d,J=1 1.6Hz,1H),4.43(d,J=11.6Hz,1H),4.24–4.22(m,1H),3.68(dd,J=10.4,3.2Hz,1H),3.53–3.47(m,4H),3. 38–3.30(m,2H),3.22–3.18(m,4H),2.33(s,3H),2.00–1.96(m,4H),1.89–1.81(m,1H),1.69–1.61(m,5H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.1,154.6,142.0,141.2,138.2,137.6,129.5,128.7,128.7,128.6,1 28.5,128.0,127.7,127.3,125.9,76.1,71.0,61.5,58.3,57.3,50.1,35.3,25.4,21.5.HRMS(ESI)calcd for C 35 H 43 N4O2 + ([MI - ]) + =551.3381,Found 551.3381.

[0208] Example 35: Synthesis of Quaternary Nitrogen Guanidine Salt IAC

[0209] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0210]

[0211] Pale yellow solid, melting point: 137–138°C; total yield: 49% yield; [α] 21 D =+137.3(c=0.758g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.33(d,J=9.6Hz,1H),7.58–7.57(m,2H),7.50–7.48(m,2H),7.39–7.37( m,2H),7.33–7.31(m,2H),7.30–7.24(m,4H),7.19–7.15(m,2H),6.20(d,J=9.6Hz,1H),5.73–5.68(m,1H ),4.94–4.90(m,1H),4.40–4.38(m,1H),4.23–4.20(m,1H),3.69–3.66(m,1H),3.52–3.44(m,4H),3.33 –3.30(m,2H),3.20–3.15(m,4H),1.96–1.95(m,4H),1.86–1.81(m,1H),1.67–1.54(m,4H),1.27(s,9H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,154.5,150.8,142.0,141.2,134.6,128.6,128.6,128.0, 127.6,127.3,125.4,76.1,70.7,61.4,58.2,57.3,50.0,35.3,34.6,31.4,25.4.HRMS(ESI)calcd for C 38 H 49 N4O2 + ([MI - ]) + =593.3850,Found 593.3849.

[0212] Example 36: Synthesis of Quaternary Nitrogen Guanidine Salt IAD

[0213] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0214]

[0215] Light brown solid, melting point: 157–158°C. Total yield: 36% yield; [α] 21 D =+144.8(c=0.930g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.26(d,J=9.6Hz,1H),7.60–7.50(m,10H),7.42–7.39(m,2H) ,7.33–7.24(m,5H),7.20–7.15(m,2H),6.23(d,J=9.6Hz,1H),5.73–5.69(m,1H),5.02–4.9 9(m,1H),4.47–4.44(m,1H),4.25–4.24(m,1H),3.69–3.65(m,1H),3.49–3.45(m,4H),3.37 –3.31(m,2H),3.20–3.16(m,4H),1.96–1.92(m,4H),1.88–1.79(m,1H),1.61–1.58(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.9,154.5,142.0,141.1,140.9,140.6,136.7,129.3,128.8,128.6,128.5,1 27.9,127.6,127.3,127.2,127.2,127.2,127.1,76.3,70.6,61.4,58.1,57.2,50.0,35.3,25.3.HRMS(ESI)calcd for C 40 H 45 N4O2 + ([MI - ]) + =615.3537,Found 615.3538.

[0216] Example 37: Synthesis of Quaternary Nitrogen Guanidine Salt IAE

[0217] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0218]

[0219] Pale yellow solid, melting point: 237–238°C; total yield: 49% yield; [α] 21 D =+151.2(c=0.955g / 100mL, λ=589nm, in CH2Cl2). 1H NMR (400MHz, Chloroform-d) δ9.26 (d, J=9.6Hz, 1H), 7.78–7.76 (m, 1H), 7.60–7.58 (m, 2H), 7.51–7. 48(m,3H),7.31–7.25(m,6H),7.20–7.10(m,3H),6.22(d,J=9.6Hz,1H),5.73(dd,J=9.6,7.2Hz,1H), 5.00(d,J=11.2Hz,1H),4.51(d,J=11.2Hz,1H),4.33–4.32(m,1H),3.75–3.71(m,1H),3.53–3.47(m, 4H),3.39–3.28(m,2H),3.21–3.17(m,3H),1.97–1.88(m,5H),1.85–1.79(m,1H),1.69–1.54(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.9,154.4,142.0,141.1,136.9,132.4,131.6,129.5,128.6,128.5 ,128.0,127.8,127.6,127.3,127.2,124.1,70.6,61.4,58.1,56.9,50.0,35.7,25.4.HRMS(ESI)calcd for C 34 H 40 79 BrN4O2 + ([MI - ]) + =615.2329, Found 615.2326; C 34 H 40 81 BrN4O2 + ([MI - ]) + =617.2309,Found617.2304.

[0220] Example 38: Synthesis of Quaternary Nitrogen Guanidine Salt IAF

[0221] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0222]

[0223] Pale yellow solid, melting point: 248–249°C; total yield 12%; [α] 23 D=+113.1(c=1.443g / 100mL,λ=589nm,in CH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ9.71(d,J=9.6Hz,1H),8.17(s,1H),8.05(s,1H),7.84–7.81(m,2H),7.76–7.63(m,6H),7.51–7.50(m,1H),7.46–7.45(m,2H),7.40–7.38(m,4H),6.53(d,J=9.2Hz,1H),5.71(dd,J=10.0,7.2Hz,1H),4.91(d,J=12.0Hz,1H),4.20(d,J=12.0Hz,1H),4.06–4.04(m,1H),3.61(dd,J=10.8,3.2Hz,1H),3.42–3.24(m,6H),3.15–3.08(m,4H),1.82–1.72(m,5H),1.50–1.46(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,154.4,142.0,139.2,138.4,133.3,133.3,133.2,132.6,129.8,128.5,128.5,128.3,128.1,127.6,127.6,126.5,126.3,126.2,126.2,126.1,126.0,125.9,122.9,77.4,69.1,61.3,58.3,57.1,49.9,35.1,25.3.HRMS(ESI)calcd forC 42 H 43 79 Br2N4O2 + ([M-I - ]) + =793.1747,Found 793.1746;C 42 H 43 79 Br 81 BrN4O2 + ([M-I - ]) + =795.1727,Found 795.1727;C 42 H 43 81 Br2N4O2 + ([M-I - ]) +=797.1706,Found 797.1716.

[0224] Example 39: Synthesis of Quaternary Nitrogen Guanidine Salt IAG

[0225] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0226]

[0227] Pale yellow solid, melting point: 191–192°C; total yield: 25% yield; [α] 23 D =+81.3(c=1.723g / 100mL, λ=589nm, in CH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ9.07(d,J=9.2Hz,1H),7.88–7.86(m,1H),7.52–7.51(m,3H),7.21–7.04(m ,7H),6.50(d,J=9.2Hz,1H),5.62–5.58(m,1H),5.01(d,J=11.6Hz,1H),4.27(d,J=11.6Hz,1H),4.21–4. 20(m,1H),3.92–3.87(m,1H),3.73–3.67(m,2H),3.40–3.20(m,6H),3.12–2.94(m,2H),2.27(s,3H),2.1 5(s,3H),2.01–1.93(m,5H),1.83–1.76(m,2H),1.66–1.30(m,8H),1.23–1.11(m,1H),0.98–0.88(m,1H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ168.8,160.3,141.8,139.3,138.2,136.1,135.3,133.3,130.2,130.1,128.5,128.4,127.4,127.1,126.4,126.2,1 22.9,77.4,76.5,69.3,60.9,57.8,52.6,52.5,52.3,52.1,51.2,35.3,29 .9,29.9,29.6,29.1,27.2,27.0,26.4,25.2,19.5,19.4.HRMS(ESI)calcd for C 40 H 51 79 Br2N4O2 +([MI - ]) + =777.2373,Found777.2373;C 40 H 51 79 Br 81 BrN4O2 + ([MI - ]) + =779.2353, Found 779.2353; C 40 H 51 81 Br2N4O2 + ([MI - ]) + =781.2332,Found 781.2339.

[0228] Example 40: Synthesis of Amide Compound I-7

[0229]

[0230] The amide compound I-5 (1.0 g, 1.7 mmol), K3PO4 (4.2 g, 12 mmol), 3,4,5-trifluorophenylboric acid (1.25 g, 7.0 mmol) and Pd(dppf)Cl2 (256 mg, 0.35 mmol) were weighed into a 100 mL round-bottom flask, a magnetic bar was added and a reflux device was installed, the system was replaced with a nitrogen atmosphere, THF / H2O (17 mL: 4 mL) was added as a solvent, and the reflux reaction was carried out until the entire system turned black (~5-8 h). After the reaction was completed, THF was removed by rotation, and dichloromethane (20 mL) was added to dissolve, the organic phase was washed with water three times, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 1: 1-0: 1) to obtain the target product I-6 (gray solid, 87% yield).

[0231] Example 41: Synthesis of Quaternary Nitrogen Guanidine Salt IAH

[0232] For specific operations, refer to Examples 1, 3-6 and 40, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0233]

[0234] White solid, melting point: 220–221°C; total yield 55%; [α] 23 D =+69.1(c=0.405g / 100mL, λ=589nm, in CH2Cl2); 1H NMR(600MHz,Chloroform-d)δ9.62(d,J=9.0Hz,1H),7.72–7.71(m,1H),7.68–7.68(m,2H),7.48–7.48(m,1H) ,7.32–7.25(m,5H),7.21–7.18(m,1H),7.14–7.07(m,5H),6.49(d,J=9.0Hz,1H),5.81(dd,J=9.0,6.6Hz,1H), 5.16(d,J=10.8Hz,1H),4.52(d,J=10.8Hz,1H),4.35–4.34(m,1H),3.76(dd,J=10.8,3.6Hz,1H),3.53–3.41( m,6H),3.26–3.24(m,4H),2.29(s,3H),2.18(s,3H),2.04–2.01(m,4H),1.91–1.87(m,1H),1.70–1.69(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.2,154.6,151.6(ddd,J C-F =251.0,9.6,3.5Hz),140.8,139.8,139.2,138.3,138.2,136.8-136.6(m),136.0,135 .5,130.4,130.4,128.2,127.9,127.6,127.4,127.3,126.6,126.3,124.8,111.4(dd,J C-F =16.2,6.0Hz),77.4,70.4,61.2,57.3,51.5,50.2,35.6,25.5,19.4,19.4. 19 F{ 1 H}NMR(377MHz,Chloroform-d)δ-133.7,-133.8,-162.0,-162.0,-162.1.HRMS(ESI)calcd forC 48 H 47 F6N4O2 + ([MI - ]) + =825.3598,Found 825.3602.

[0235] Example 42: Synthesis of Quaternary Nitrogen Guanidine Salt IAI

[0236] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0237]

[0238] White solid, melting point: 167–168°C; total yield: 65% yield; [α] 24 D =+113.4(c=1.160g / 100mL, λ=589nm, in CH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ9.39(d,J=9.2Hz,1H),7.53–7.52(m,1H),7.50–7.49(m,2H),7.38–7.36( m,1H),7.32–7.22(m,4H),7.19–7.15(m,1H),6.92–6.88(m,2H),6.19(d,J=9.2Hz,1H),5.68(dd,J=10. 0,7.2Hz,1H),4.97(d,J=12.0Hz,1H),4.35(d,J=12.0Hz,1H),4.26–4.25(m,1H),3.72(dd,J=10.8,3.2 Hz,1H),3.57–3.50(m,4H),3.43–3.23(m,6H),2.05–1.98(m,4H),1.89–1.83(m,1H),1.75–1.59(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.1,162.7(d, 1 J C-F =247.5Hz),154.5,143.8(d, 3 J C-F =7.0Hz),142.9(d, 3 J C-F =6.9Hz),142.0,133.2,130.4,130.3,129.8,123.7(d, 4 J C-F =2.8Hz),123.5(d, 4 J C-F =2.9Hz),122.9,114.9(d, 2 J C-F =22.1Hz),114.8(d, 2 J C-F =22.4Hz),114.5(d, 2 J C-F =20.8Hz),114.4(d, 2 JC-F =21.0Hz),69.3,61.1,57.2,57.1,50.1,35.3,25.4. 19 F{ 1 H}NMR(377MHz,Chloroform-d)δ-112.3,-112.4.HRMS(ESI)calcd forC 34 H 37 79 Br2F2N4O2 + ([MI - ]) + =729.1246, Found 729.1246; C 34 H 37 79 Br 81 BrF2N4O2 + ([MI - ]) + =731.1225, Found 731.1228; C 34 H 37 81 Br2F2N4O2 + ([MI - ]) + =733.1205,Found 733.1213.

[0239] Example 43: Synthesis of Quaternary Nitrogen Guanidine Salt IAJ

[0240] For the specific operation, refer to Examples 1 and 3-6, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0241]

[0242] Light brown solid, melting point: 153–154°C; total yield: 34% yield; [α] 23 D =+76.4(c=2.400g / 100mL, λ=589nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ9.11(d,J=9.6Hz,1H),7.54–7.51(m,5H),7.48–7.46(m,2H),7.3 0–7.24(m,4H),6.17(d,J=9.6Hz,1H),5.68(dd,J=10.0,6.8Hz,1H),5.01(d,J=12.0Hz,1H),4.3 7(d,J=12.0Hz,1H),4.24–4.22(m,1H),3.71(dd,J=10.6,3.2Hz,1H),3.51–3.40(m,5H),3.34–3 .22(m,5H),1.96–1.91(m,4H),1.88–1.79(m,1H),1.69–1.50(m,4H),1.24(s,9H),1.21(s,9H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.4,154.5,149.8,149.7,142.0,139.3,138.2,133.2,129.8,127. 4,127.1,125.5,125.4,122.8,69.3,61.3,57.4,57.0,50.0,35.2,34.4,31.3,25.3.HRMS(ESI)calcd for C 42 H 55 79 Br2N4O2 + ([MI - ) + =805.2686,Found805.2679;C 42 H 55 79 Br 81 BrN4O2 + ([MI - ]) + =807.2666, Found 807.2664; C 42 H 55 81 Br2N4O2 + ([MI - ]) + =809.2645,Found809.2652.

[0243] Example 44: Synthesis of Quaternary Nitrogen Guanidine Salt IAK

[0244] For specific operations, refer to Examples 1, 3-6 and 40, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0245]

[0246] Gray solid, melting point: 196–197°C; total yield: 49% yield; [α] 23 D =+67.0 (c=2.518g / 100mL, λ=589nm, in CH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ8.87(d,J=8.8Hz,1H),7.69–7.66(m,2H),7.56(s,2H),7.49–7.47(m,6H),7 .26–7.25(m,1H),7.21–7.09(m,6H),6.50(d,J=8.8Hz,1H),5.72(t,J=8.4Hz,1H),5.09(d,J=12.4Hz,1H) ,4.68(d,J=12.4Hz,1H),4.34–4.33(m,1H),3.71(dd,J=10.4,3.2Hz,1H),3.59–3.53(m,4H),3.42–3.27( m,6H),2.29(s,3H),2.19(s,3H),2.05–2.00(m,4H),1.93–1.87(m,1H),1.76–1.69(m,4H),1.40(s,36H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.4,154.3,151.2,143.3,140.7,139.1,138.5,138.1,135.9,135.4,130.3,130.2,128.1,127.9,127.4,12 7.2,126.5,126.4,126.2,126.1,122.0,121.6,77.4,75.4,70.6,61.1,57.4,51.4,50.1,35.5,35.0,31.6,25.5,19.3,19.3.HRMS(ESI)calcd for C 64 H 85 N4O2 + ([MI - ]) + =941.6667,Found941.6667.

[0247] Example 45: Synthesis of Quaternary Nitrogen Guanidine Salt IAL

[0248] For specific operations, refer to Examples 1, 3-6 and 40, and the reaction raw materials are replaced according to the corresponding substituent differences in the products.

[0249]

[0250] Gray solid, melting point: 155–156°C; total yield: 32% yield; [α] 24 D =+57.7(c=1.343g / 100mL, λ=589nm, in CH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ9.01(d,J=8.8Hz,1H),8.07–8.07(m,4H),7.88–7.87(m,2H),7.82–7.81(m,2H),7.74–7.70( m,1H),7.65–7.64(m,1H),7.19–7.15(m,1H),6.89–6.76(m,4H),6.39(d,J=8.8Hz,1H),5.79(dd,J=10.0,7.2Hz,1H),5.32 (d,J=11.2Hz,1H),4.56(d,J=11.2Hz,1H),4.38–4.36(m,1H),3.77(dd,J=10.4,3.2Hz,1H),3.58–3.51(m,5H),3.39(dd,J =10.4,2.4Hz,1H),3.27–3.23(m,4H),2.25(s,3H),2.14(s,3H),2.08–2.00(m,4H),1.88–1.81(m,1H),1.70–1.69(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.2,162.0(d, 1 J C-F =246.2Hz),161.9(d, 1 J C-F =245.9Hz),154.6,142.7,140.3,139.7,138.3(d, 3 J C-F =7.7Hz),137.8(d, 3 J C-F =7.8Hz),134.8(d, 4 J C-F =2.7Hz),133.8(d, 4 J C-F =2.7Hz),132.8,132.3(d, 2J C-F =33.4Hz),131.8,130.0(d, 3 J C-F =8.6Hz),129.8(d, 3 J C-F =8.6Hz),128.0,127.7,127.6,127.5,125.6,123.4(d, 1 J C-F =273.7Hz),121.6–121.4(m),119.3,117.1(d, 2 J C-F =21.7Hz),117.1(d, 2 J C-F =21.2Hz),113.0(d, 2 J C-F =21.1Hz),112.7(d, 2 J C-F =20.6Hz),77.4,76.8,70.4,61.1,57.5,50.5,50.1,35.3,25.5,19.4. 19 F{ 1 H}NMR(377MHz,Chloroform-d)δ-62.6,-115.7,-116.1.HRMS(ESI)calcd for C 52 H 47 F 14 N4O2 + ([MI - ]) + =1025.3470,Found1025.3468

[0251] Example 46: Asymmetric alkylation reaction catalyzed by chiral quaternary nitrogen guanidine salt

[0252]

[0253] Catalyst IAH (9.5 mg, 0.01 mmol), Schiff base derived from glycine (29.5 mg, 0.1 mmol), cesium carbonate (65.2 mg, 0.2 mmol), dichloromethane (1.0 mL) and benzyl bromide (34.2 mg, 0.2 mmol) were weighed into a dry reaction tube in sequence, and the reaction was continued at 20°C for two days, followed by column chromatography separation (eluent: petroleum ether: ethyl acetate = 12:1) to obtain the corresponding α-alkylated product. The product was a colorless liquid with a yield of 41% and an enantioselectivity of 21%. 1H NMR(400MHz,Chloroform-d)δ7.59–7.56(m,2H),7.40–7.28(m,6H),7.21–7.14(m,3H),7.06–7.04(m,2H) ,6.60(d,J=7.6Hz,1H),4.11(dd,J=9.2,3.6Hz,1H),3.25–3.13(m,2H),1.44(s,9H).HRMS(ESI-FT)calcd for C 26 H 28 NO2 + ([M+H + ])=385.2042,Found385.2043

[0255] Example 47: Asymmetric α-arylation of benzyne catalyzed by chiral quaternary nitrogen guanidine salt

[0256]

[0257] In a glove box, various phase transfer catalysts (0.01 mmol), β-ketoamide substrate (32.4 mg, 0.1 mmol), cesium fluoride (45.6 mg, 0.3 mmol), tetrahydrofuran: toluene (0.5 mL / 0.1 mL) as solvents were added to the reaction tube in sequence, and Kobayashi's benzyne precursor was added. After reacting at 20°C for three days, column chromatography separation (eluent: petroleum ether: ethyl acetate = 16:1) was performed to obtain the corresponding product. White solid, 1 H NMR(400MHz,Chloroform-d)δ8.18–8.16(m,1H),7.51–7.47(m,1H),7.37–7.26(m,4H),7.24–7.18(m,3H),6.44(s,1H ),3.04–2.96(m,1H),2.87–2.80(m,1H),2.72–2.60(m,2H),2.05–2.02(m,3H),1.95–1.94(m,6H),1.65–1.63(m,6H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ199.1,168.5,144.6,140.2,134.1,132.7,128.9,128.8, 128.4,127.5,127.4,126.9,63.4,52.2,41.3,36.5,33.8,29.5,26.2.HRMS(ESI-FT)calcd for C 27 H 29 NO2Na +([M+Na + ])=422.2091,Found 422.2091

[0258] The technical solution of the present invention is further illustrated by experiments below.

[0259] Experimental Example 1 Comparison of catalytic performance of some quaternary nitrogen guanidine salt catalysts and existing catalysts

[0260] 1. Experimental Methods

[0261] The catalytic reaction was carried out according to the method of Example 47, using compound IP, IAB-IAL and the following four compounds as catalysts respectively:

[0262]

[0263] The optical purity of the target product was analyzed by HPLC, and the yield and Ee were calculated.

[0264] 2. Experimental Results

[0265] Table 1

[0266]

[0267]

[0268] The results are shown in Table 1. The most commonly used chiral phase transfer catalysts, such as chiral quaternary ammonium salt catalysts QA1 / QA2 and chiral quaternary phosphonium salt catalysts QP1 / QP2, have extremely low Ee values ​​in the catalytic asymmetric arylation reaction involving benzyne, indicating that their chiral induction effect is not good. The compounds IP and IAB-IAL provided by the present invention both show chiral induction effects that are superior to these existing catalysts. At the same time, when the compounds IP and IAB-IAL of the present invention are used as chiral phase transfer catalysts, the catalytic yield reaches 36-89%, which meets the needs of industrial applications.

[0269] The above embodiments and experimental examples can prove that the present invention provides a new type of phase transfer catalyst, which has broad application prospects in the field of asymmetric catalysis.

Claims

1. A compound represented by formula I, or a stereoisomer thereof, or a salt thereof: in, R 1 , R 2 Each independently selected from: hydrogen, hydroxyl, halogen, carboxyl, substituted or unsubstituted C1-C 11 Carbonyl, substituted or unsubstituted C1~C 11 Ester group, substituted or unsubstituted C1~C 11 Alkenyl, substituted or unsubstituted C1~C 11 Alkynyl, substituted or unsubstituted C1~C 11 Alkyl, substituted or unsubstituted C1~C 11 Alkoxy, substituted or unsubstituted benzyl, substituted or unsubstituted benzyloxy, polysubstituted siloxy, wherein the substituent is selected from C1 to C 11 Alkyl, C3~C 10 Cycloalkyl, C6~C 10 Aryl, halogen substituted C6~C 10 Aryl, cyano, hydroxy, carboxyl or halogen; or, R 1 With R 2 Connected to form substituted or unsubstituted C6~C 10 Aryl, substituted or unsubstituted C5~C 10 Cycloalkyl, wherein the substituent is selected from C1 to C 11 Alkyl, C6~C 10 Aryl, cyano, hydroxy, carboxyl or halogen; R 3 Selected from: hydrogen, substituted or unsubstituted C1~C 13 Alkyl, substituted or unsubstituted C1~C 13 Alkynyl, substituted or unsubstituted benzyl, wherein the substituent is selected from C1 to C 11 Alkyl, C6~C 10 Aryl, cyano, hydroxy, carboxyl or halogen; R 4 Selected from: hydrogen, hydroxyl, substituted or unsubstituted C1-C 10 Primary amine, substituted or unsubstituted C1~C 10 Alkoxy, substituted or unsubstituted C1~C 21 alkylamine, substituted or unsubstituted phenoxy, substituted or unsubstituted aniline, substituted or unsubstituted benzyloxy, substituted or unsubstituted benzylamino, substituted or unsubstituted 1-naphthyloxy, substituted or unsubstituted 1-naphthylamino, substituted or unsubstituted 2-naphthyloxy, substituted or unsubstituted 2-naphthylamino, wherein the substituent is selected from C1 to C 11 Alkyl, C6~C 10 Aryl, C1~C 11 Alkyl substituted C6~C 10 Aryl, cyano, hydroxy, carboxyl, halogen, amino, R a Selected from C1-C6 alkyl, substituted or unsubstituted C6-C 10 Aryl, wherein the substituent is selected from C1 to C 11 Alkyl, cyano, hydroxyl, carboxyl, halogen; R 5 , R 6 , R 7 , R 8 Each is independently selected from: C1-C6 alkyl; or, R 5 With R 6 Connected to form a 5- to 7-membered heterocyclic ring; or, R 7 With R 8 Connected to form a 5- to 7-membered heterocyclic ring; or, R 6 With R 7 Connected to form a 5- to 7-membered heterocyclic ring; n is selected from 0 and 1; X - It is an anion.

2. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that The structural formula of the compound is shown in Formula Ia or Formula Ib:

3. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that: R 1 Selected from: hydrogen, hydroxyl, halogen, substituted or unsubstituted benzyloxy, substituted or unsubstituted C2 ester, substituted or unsubstituted C1-C2 alkoxy, multi-substituted siloxy, wherein the substituent is selected from C1-C 10 Alkyl, C3~C 10 Cycloalkyl, C6~C 10 Aryl, halogen substituted C6~C 10 Aryl, halogen; R 2 Selected from hydrogen; or, R 1 With R 2 Connected to form phenyl, cyclopentane or cyclohexane; R 3 Selected from hydrogen.

4. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that: R 4 Selected from: hydroxyl, substituted or unsubstituted C1-C2 alkylamine, substituted or unsubstituted C1 alkoxy, substituted or unsubstituted anilino, wherein the substituent is selected from halogen, C1-C4 alkyl, C6-C 10 Aryl, methyl-substituted phenyl, amino, R a It is selected from C1-C6 alkyl, substituted or unsubstituted phenyl, wherein the substituent is selected from C1-C4 alkyl, halogen.

5. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that: R 5 , R 6 , R 7 , R 8 are C1-C4 alkyl groups; or, R 5 With R 6 Connected to form a 5- to 7-membered heterocyclic ring; or, R 7 With R 8 Connected to form a 5- to 7-membered heterocyclic ring; or, R 6 With R 7 Connected to form a 5- to 7-membered heterocyclic ring.

6. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that: X is selected from the group consisting of chloride, bromide, iodide, triflate, borate, and phosphate.

7. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that: The structural formula of the compound is shown in Formula Ic: in, R b independently selected from halogen, C1-C4 alkyl, substituted or unsubstituted phenyl; wherein the substituent is selected from halogen, fluorine-substituted C1-C4 alkyl, C1-C4 alkyl, C6-C 10 Aryl; R c1 , R c2 are independently selected from substituted or unsubstituted C6 to C 10 Aryl; wherein the substituent is selected from halogen, C1~C4 alkyl, C6~C 10 Aryl; i and j are independently selected from 1, 2 or 3; k is selected from 1 or 2.

8. The compound according to claim 1, or its stereoisomer, or its salt, characterized in that: The structural formula of the compound is selected from one of the following structures:

9. A method for preparing the compound according to any one of claims 1 to 8, characterized in that: The steps include: Step 1, reacting compound I-1 with alcohol or amine to obtain compound I-2; When R 1 When R is hydroxyl, proceed to step 2 and step 3. 1 When it is not a hydroxyl group, proceed to step 3; Step 2, compound I-2 and R 9 -LG reaction to obtain compound I-2′; Among them, R 9 Selected from hydrogen, substituted or unsubstituted C1-C 11 alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted 1-methylnaphthalene, substituted or unsubstituted 2-methylnaphthalene, substituted or unsubstituted 9-methylanthracene, polysubstituted silicon, substituted or unsubstituted C1~C 11 Acyl; substituent selected from C1~C 11 Alkyl, C6~C 10 Aryl, cyano, carboxyl, halogen, amino; LG is selected from Cl, Br, I, OTf; Step 3, reacting compound I-2 or compound I-2′ with trifluoroacetic acid to obtain compound I-3; Step 4, reacting compound I-3 with imidazoline chloride to obtain compound I-4; Step 5, reacting compound I-4 with a metal salt to obtain a compound of formula I.

10. The preparation method according to claim 9, characterized in that: In step 1, the reaction is carried out in a solvent of dichloromethane or tetrahydrofuran, the alcohol or amine in the reactant is selected from one of primary amine, secondary amine, primary alcohol and secondary alcohol, the reaction temperature is 20-50° C., and the reaction time is 4-24 hours; And / or, in step 2, the reaction is carried out in tetrahydrofuran solvent, the reaction is carried out under the action of a base, the base is selected from at least one of sodium hydride, triethylamine or imidazole, the reaction temperature is 0-25° C., and the reaction time is 5-24 h; And / or, in step 3, the reaction is carried out in a solvent of dichloromethane, the reaction temperature is 0-25°C, and the reaction time is 1-2h; And / or, in step 4, the reaction is carried out in acetonitrile as a solvent, the reaction is carried out under the action of a base, the base is selected from triethylamine, the reaction temperature is 25-80° C., and the reaction time is 10-24 h; And / or, in step 5, the reaction is carried out in a solvent of dichloromethane or tetrahydrofuran, the reaction temperature is 20-35° C., and the reaction time is 4-10 h.

11. Use of the compound according to any one of claims 1 to 8, or a stereoisomer thereof, or a salt thereof as a phase transfer catalyst for catalyzing an asymmetric alkylation reaction and / or an arylation reaction.

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