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