Lipase-catalysed N-acylation of β2-amino esters

The Candida antarctica lipase A-catalysed N-acylation of ethyl 3-amino-2-ethylpropanoate rac-3 and methyl 3-amino-2-isopropylpropanoate rac-6 was performed with ethyl butanoate in tert-amyl alcohol at 4 °C. The resulting enantiomerically enriched derivatives were isolated as N-Boc-protected amino esters (R)-9 and (R)-10 and butyramides (S)-7 and (S)-8 (ee: 76–95%).

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Ethyl (S)-2-(butyramidomethyl)butanoateC11H21NO3Ee = 95%[α]D25=+26.0 (c 1.0, MeOH)Source of chirality: CAL-A-catalysed N-acylationAbsolute configuration: (S)

Ethyl (R)-2-[(tert-butoxycarbonylamino)methyl]butanoateC12H23NO4Ee = 85%[α]D25=-18.9 (c 0.5, MeOH)Source of chirality: CAL-A-catalysed N-acylationAbsolute configuration: (R)

Methyl (S)-2-butyramidomethyl-3-methylbutanoateC11H21NO3Ee = 78%[α]D25=+26.4 (c 1.0, MeOH)Source of chirality: CAL-A-catalysed N-acylationAbsolute configuration: (S)

Methyl (R)-2-(tert-butoxycarbonylamino)methyl-3-methylbutanoateC12H23NO4Ee = 76%[α]D25=-13.4 (c 1.0, MeOH)Source of chirality: CAL-A-catalysed N-acylationAbsolute configuration: (R)