Preparation of conformationally restricted ß(2,2)- and ß(2,2,3)-amino esters and derivatives containing an all-carbon quaternary center.

ß-Amino acids are routinely incorporated into peptidic drugs to increase their stability and to incur conformational biases. However, the synthesis of highly substituted ß-amino acids still represents a great challenge. A new approach to their preparation is reported involving a Vilsmeier-Haack reaction with nonaromatic carbon nucleophiles. The highly challenging preparation of contiguous tertiary and all-carbon quaternary centers was successfully used to generate several ß(2,2,3)-amino esters, such as derivatives of homoproline, homoalanine, and homopipecolinic esters.