Highly Diastereoselective Synthesis of 2-(1-N-Boc-aminoalkyl)thiazole-5-carboxylates by Reduction of tert-Butylsulfinyl Ketimines

Abstract

Positional isomers of naturally occurring peptide subunits were synthesized via highly diastereoselective reduction of tert-butylsulfinyl ketimines as a key reaction. While NaBH₄ reduction of ketimines derived from 2-thiazolyl ketones afforded the (R_S,R)-isomer with moderate diastereoselectivity, L-Selectride^® reduction afforded the (R_S,S)-isomer as the sole product. In contrast, ketimines derived from tert-butyl 2-thiazolyl ketone afforded the (R_S,R)-isomer with low diastereoselectivity by both NaBH₄ and L-Selectride^® reduction. Stereochemistry of the reaction was discussed based on calculation of the conformational energies for ketimines.

Graphical Abstract