Synthesis of novel β-amino alcohols and their application in the catalytic asymmetric sulfoxidation of sulfides

Novel chiral norephedrine-based β-amino alcohol ligands containing a thiophene ring were prepared from norephedrine and substituted furan carbaldehydes (methyl- or ethyl-substituted) and used in combination with VO(acac)2 for the asymmetric oxidation of aryl methyl sulfides using H2O2 as an oxidant. Amino alcohol derived Schiff bases 4,5a–b gave higher enantiomeric excesses than amino alcohol-derived reduced Schiff based ligands 6,7a–b. Of these chiral ligands, (1S,2R)-5b and (1S,2R)-7b gave high yields (90%) with moderate to high enantioselectivities (78%, 96% ee, respectively). The oxidation of other aryl methyl sulfides with (1S,2R)-5b and (1S,2R)-7b as ligands afforded the corresponding sulfoxides in 60–89% yields and with 92–99% ee.

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(1R,2S)-2-((5-Methylthiophen-2-yl)methyleneamino)-1-phenylpropan-1-olC15H17NOS[α]D25=-1.25 (c 0.48, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1R,2S)

(1R,2S)-2-((5-Ethylthiophen-2-yl)methyleneamino)-1-phenylpropan-1-olC16H19NOS[α]D25=-1.1 (c 0.42, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1R,2S)

(1S,2R)-2-((5-Methylthiophen-2-yl)methylamino)-1-phenylpropan-1-olC15H19NOS[α]D25=+0.7 (c 0.57, CHCl3)Source of chirality: (1S,2R)-norephedrineAbsolute configuration: (1S,2R)

(1S,2R)-2-((5-Ethylthiophen-2-yl)methylamino)-1-phenylpropan-1-olC16H21NOS[α]D25=+1.3 (c 0.46, CHCl3)Source of chirality: (1S,2R)-norephedrineAbsolute configuration: (1S,2R)