Practical and highly stereoselective method for the preparation of several chiral arylsulfinamides and arylsulfinates based on the spontaneous crystallization of diastereomerically pure N-benzyl-N-(1-phenylethyl)-arylsulfinamides

A novel and simple process for the preparation of enantiomerically pure (SS)-benzenesulfinamide (SS)-3a, (SS)-p-toluenesulfinamide (SS)-3b, (SS)-p-chloro-benzenesulfinamide (SS)-3c and (SS)-p-fluorobenzenesulfinamide (SS)-3d has been developed. The treatment of arylsulfinyl chlorides with (R)-N-benzyl-1-phenylethanamine in the presence of excess triethylamine gave diastereomeric mixtures of N-benzyl-N-(1-phenylethyl)-arylsulfinamides 1, which underwent spontaneous crystallization to furnish diastereomerically pure (R,SS)-N-benzyl-N-(1-phenylethyl)-arylsulfinamides (R,SS)-1a–1d in 28%, 29%, 27% and 31% yields, respectively. The diastereomerically pure compounds (R,SS)-1 were then converted into four enantiopure (RS)-methyl arylsulfinates (RS)-2, and finally into four enantiopure (SS)-arylsulfinamides (SS)-3 in good yields.

Figure optionsDownload as PowerPoint slide

(R,SS)-N-Benzyl-N-(1-phenylethyl)benzenesulfinamideC21H21NOS[α]D20=+42.2 (c 1.1, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,SS)

(R,RS)-N-Benzyl-N-(1-phenylethyl)benzenesulfinamideC21H21NOS[α]D25=+111.1 (c 4.1, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,RS)

(R,SS)-N-Benzyl-N-(1-phenylethyl)-p-toluenesulfinamideC22H23NOS[α]D25=+32.1 (c 1.2, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,SS)

(R,RS)-N-Benzyl-N-(1-phenylethyl)-p-toluenesulfinamideC22H23NOS[α]D25=+128.7 (c 4.4, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,RS)

(R,SS)-N-Benzyl-N-(1-phenylethyl)-p-chlorobenzenesulfinamideC21H20ClNOS[α]D25=+22.7 (c 1.2, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,SS)

(R,RS)-N-Benzyl-N-(1-phenylethyl)-p-chlorobenzenesulfinamideC21H20ClNOS[α]D25=+137.4 (c 2.3, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,RS)

(R,SS)-N-Benzyl-N-(1-phenylethyl)-p-fluorobenzenesulfinamideC21H20FNOS[α]D25=+39.7 (c 1.0, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,SS)

(R,RS)-N-Benzyl-N-(1-phenylethyl)-p-fluorobenzenesulfinamideC21H20FNOS[α]D25=+105.8 (c 1.2, EtOAc)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (R,RS)

(RS)-Methyl benzenesulfinateC7H8O2S[α]D20=-195.0 (c 1.2, EtOH)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (RS)

(RS)-Methyl p-toluenesulfinateC8H10O2S[α]D20=-210.2 (c 1.4, EtOH)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (RS)

(RS)-Methyl p-chlorobenzenesulfinateC7H7ClO2S[α]D20=-173.0 (c 1.3, EtOH)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (RS)

(RS)-Methyl p-fluorobenzenesulfinateC7H7FO2S[α]D20=-171.9 (c 1.3, EtOH)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (RS)

(SS)-BenzenesulfinamideC6H7NOS[α]D20=+83.1 (c 1.0, acetone)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (SS)

(SS)-p-ToluenesulfinamideC7H9NOS[α]D20=+85.5 (c 1.0, CHCl3)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (SS)

(SS)-p-ChlorobenzenesulfinamideC6H6ClNOS[α]D20=+72.3 (c 0.7, CHCl3)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (SS)

(SS)-p-FluorobenzenesulfinamideC6H6FNOS[α]D20=+80.0 (c 0.7, CHCl3)Source of chirality: (R)-1-phenylethanamineAbsolute configuration: (SS)