Stereoselective synthesis of highly functionalized (Z)-chloroalkene dipeptide isosteres containing an α,α-disubstituted amino acid

Described here is the first stereoselective synthesis of highly functionalized chloroalkene dipeptide isosteres containing an alpha,alpha-disubstituted amino acid (alpha alpha AA). This synthesis requires the construction of a quaternary carbon center, and this challenge was overcome by the Aza-Darzens condensation of ketimine with alpha,alpha-dichloroenolate, producing 2-chloroaziridines with quaternary carbon centers including spirocyclic motifs, which are valuable for the previously elusive synthesis of various alpha alpha AA-containing chloroalkene isosteres.

Automated summary

This study describes the first stereoselective synthesis of highly functionalized chloroalkene dipeptide isosteres containing an alpha,alpha-disubstituted amino acid (alpha alpha AA). The key step involves the construction of a quaternary carbon center through Aza-Darzens condensation, providing valuable compounds for the synthesis of various alpha alpha AA-containing chloroalkene isosteres.