Asymmetric syntheses of (1r,3R,4S)- and (1s,3R,4S)-(3,4-difluorocyclopentyl)-alanine derivatives

By employing a sequence of epoxide opening, asymmetric alkylation, and fluorination, polyfluorinated cyclopentylamino acids with defined stereochemistries were prepared.

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(S)-Methyl 2-(benzyloxycarbonylamino)-3-((1s,3R,4S)-3,4-difluorocyclopentyl)propanoate(S)-methyl 2-(benzyloxycarbonylamino)-3-((1r,3R,4S)-3,4-difluorocyclopentyl)propanoateC17H21F2NO4Ee = > 98%[α]D23=+3.2(c0.51,CH2Cl2)Source of chirality: asymmetric alkylation

(S)-Methyl 2-(benzyloxycarbonylamino)-3-((1s,3R,4S)-3,4-difluorocyclopentyl)propanoate(S)-methyl 2-(benzyloxycarbonylamino)-3-((1s,3R,4S)-3,4-difluorocyclopentyl)propanoateC17H21F2NO4Ee = > 98%[α]D23=+1.95(c0.51,CH2Cl2)Source of chirality: asymmetric alkylation