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

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

Synthesis of γ,δ-aziridino α-amino acid derivatives and their stereoselective ring transformation to 2-(aminomethyl)-1-aminocyclopropanecarboxylic acid derivatives

1-Benzyl-2-(bromomethyl)aziridine was successfully substituted with protected glycine esters to afford alkyl 3-(N-benzylaziridin-2-yl)-2-aminopropanoates, as constrained heterocyclic diamino acid derivatives, in good isolated yields. These new aziridines proved to be excellent building blocks for ring transformation to the corresponding stereochemically defined 2-(aminomethyl)-1-aminocyclopropanecarboxylic acid derivatives, including methyl esters, piperidyl amides, and free carboxylic acids