Preparation of non-racemic single-stereocentre α-aminonitriles and a study of their fate in Bruylants reactions

[摘要] A number of chiral carboxamide dehydration methods were investigated for the preparation of four representative enantiomerically enriched alpha-aminonitriles possessing only one stereogenic centre; best results were observed using Burgess' salt (yield up to 87%, er up to 92/8) or the trifluoroacetic anhydride-triethylamine combination (yield up to 98%, er up to 86/14). Two of the aminonitriles thus obtained were subjected to Bruylants reactions with a methyl Grignard reagent to furnish the corresponding tertiary amines; these products, along with any unreacted starting materials, were obtained essentially in racemic form. In accord with the accepted mechanism for this reaction, a magnesium species is implicated in the formation of an iminium, the common intermediate for both chemical transformation and racemization processes. (c) 2006 Elsevier Ltd. All rights reserved.

[发布日期] 2006-12-18