Enantioselective synthesis of quaternary stereogenic centers through catalytic asymmetric addition of dimethylzinc to α-ketoesters with chiral cis-cyclopropane-based amide alcohol as ligand

A new amino alcohol with a chiral cyclopropane backbone has been developed and used in the catalytic asymmetric diethylzinc addition to various types of α-ketoesters. This cyclopropane-based chiral amino alcohol shows moderate enantioselectivity in the addition of organozinc to α-ketoesters. For dimethylzinc addition to α-ketoesters, up to 81% ee are obtained, respectively.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(1R,3S)-N-Benzyl-3-(hydroxymethyl)-2,2-dimethylcyclopropanecarboxamideC14H19NO2Ee = 99%[α]D18=+41.0 (c 1.14, CHCl3)Source of chirality: methyl (+)-cis-chrysanthemateAbsolute configuration: (1R,3S)