Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

Abstract

The asymmetric synthesis of new chiral gamma-chloro-alpha,beta-diaminocarboxylamide derivatives by highly diastereoselective Mannich-type reactions of N-(diphenylmethylene) glycinamides across chiral alpha-chloro-N-p-toluenesulfinylaldimines was developed. The resulting (S-S,2S,3S)-gamma-chloro-alpha,beta-diaminocarboxylamides were formed with the opposite enantiotopic face selectivity as compared to the (S-S,2R,3R)-gamma-chloro-alpha,beta-diaminocarboxyl esters obtained via Mannich-type addition of analogous N-(diphenylmethylene) glycine esters across a chiral alpha-chloro-N-p-toluenesulfinylaldimine. Selective deprotection under different acidic reaction conditions and ring closure of the gamma-chloro-alpha,beta-diaminocarboxylamides was optimized, which resulted in N-alpha-deprotected syn-gamma-chloro-alpha,beta-diaminocarboxylamides, N-sulfinyl-beta,gamma-aziridino-alpha-aminocarboxylamide derivatives, a trans-imidazolidine, and an N-alpha,N-beta-deprotected syn-gamma-chloro-alpha,beta-diaminocarboxylamide