Direct stereospecific synthesis of unprotected aziridines from olefins

A process for making an aziridine of the formula AP-1

• where R1A is selected from H, unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, C3-C8 cycloalkyl, and aralkyl;
• each of Ra, Rb, Rc, and Rd is independently selected from:
• H, substituted and unsubstituted aryl, unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, C3-C8 cycloalkyl, C2-C18 alkenyl, C3-C8 cycloalkenyl, and C2-C18 alkenyl, or wherein Rc and Rd form a ring;
• the method comprising:
• reacting an olefin of formula O-1
• with a hydroxylamine amination agent in the presence of a transition metal catalyst selected from copper and rhodium catalysts in a polar, hydroxylic and non-nucleophilic solvent, a carboxylic solvent or mixtures of the same at a temperature less than 30° C.;
• wherein the hydroxylamine amination agent is selected from compounds of formulas AA-1, AA-2, AA-5, AA-6, AA-7, AA-8:
• wherein each R1 and R2 are independently selected from hydrogen, unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, C3-C8 cycloalkyl, —Si(R3)3, allyl, aralkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl;
• wherein R1 and R2 can be connected to form a cyclic amine having from 4 to 7 carbocyclic ring members;
• each R3 is independently selected from unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro and substituted or unsubstituted aryl;
• each R4, R5, R6, R7, and R8 are independently selected from hydrogen, nitro, fluoro, chloro, bromo, unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, C3-C8 cycloalkyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, R16R17NC(O)—, R18O2C—, (R19)4N+—, and (R20)2P(O)—;
• R9 is selected from unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, and C3-C8 cycloalkyl;
• R10 and R11 are independently selected from substituted and unsubstituted aryl;
• wherein the number of substituents for substituted aryl may be from 1 to 5 and independently selected from nitro, fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, R16R17NC(O)—, R18O2C—, (R19)4N+, (R20)2P(O)—, PEGm-, and o-furanyl;
• R12 is selected from unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, C3-C8 cycloalkyl, C1-C18 alkenyl, C3-C8 cycloalkenyl, substituted and unsubstituted aryl;
• wherein the number of substituents for substituted aryl may be from 1 to 5 and independently selected from nitro, fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, R16R17NC(O)—, R18O2C—, (R19)4N+—, (R20)2P(O)—, PEGm-, and o-furanyl;
• R13 is selected from substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro, C3-C8 cycloalkyl, and CCl3, or when R13 forms an aromatic or other ring system with R15, then R13 is selected from O, N, and C—R20;
• wherein the number of substituents for substituted aryl may be from 1 to 5 and wherein the number of substituents for substituted heteroaryl may be from 1 to 4 and each substituent is independently selected from nitro, fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, R16R17NC(O)—, R18O2C—, (R19)4N+—, and (R20)2P(O)—, PEGm-, and o-furanyl;
• R14 is absent or selected from H, substituted and unsubstituted aryl, C3-C8 cycloalkyl, and unsubstituted C1-C18 alkyl or C1-C18 alkyl substituted with fluoro,
• wherein the number of substituents for substituted aryl may be from 1 to 5 and wherein the number of substituents for substituted heteroaryl may be from 1 to 4 and each substituent is independently selected from nitro, fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, R16R17NC(O)—, R18O2C—, (R19)4N+—, and (R20)2P(O)—, PEGm-,
• R15 is selected from selected from substituted and unsubstituted aryl, unsubstituted C1-C8 alkyl or C1-C18 alkyl substituted with fluoro, and C3-C8 cycloalkyl, or when R15 forms an aromatic or other ring system with R13, then R15 is CH or CH2;
• wherein the number of substituents for substituted aryl may be from 1 to 5 and each substituent is independently selected from nitro, fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, R16R17NC(O)—, R18O2C—, (R19)4N+—, and (R20)2P(O)—, PEGm-,
• where each m is independently from 1 to 6;
• each R16, R17, R18, R19, R20 is independently selected from H, C3-C8 cycloalkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and unsubstituted C1-C18 alkyl and C1-C18 alkyl substituted with fluoro;
• wherein the number of substituents for each substituted aryl may be from 1 to 5 and the number of substituents for each substituted heteroaryl may be from 1 to 4 and each substituent is independently selected from nitro, fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, arylsulfonyl, alkylsulfonyl, mono-/di-/tri-fluoroalkylsulfonyl, trifluoromethyl, PEGm.