Biomimetic enantioselective synthesis of β,β-difluoro-α-amino acid derivatives

Although utilization of fluorine compounds has a long history, synthesis of chiral fluorinated amino acid derivatives with structural diversity and high stereoselectivity is still very appealing and challenging. Here, we report a biomimetic study of enantioselective [1,3]-proton shift of beta,beta-difluoro-alpha-imine amides catalyzed by chiral quinine derivatives. A wide range of corresponding beta,beta-difluoro-alpha-amino amides were achieved in good yields with high enantioselectivities. The optically pure beta,beta-difluoro-alpha-amino acid derivatives were further obtained, which have high application values in the synthesis of fluoro peptides, fluoro amino alcohols and other valuable fluorine-containing molecules. Organocatalysed 1,3-proton shifts can offer efficient access to chiral nonracemic fluorinated products. Here chiral amino amides are obtained in high enantiomeric ratio via enantioselective 1,3- proton shift of beta,beta-difluoro-alpha imino amides.

Automated summary

An efficient method for obtaining a wide range of fluorinated products with high enantioselectivity was reported through enantioselective [1,3]-proton shift of beta,beta-difluoro-alpha-imine amides catalyzed by chiral quinine derivatives. Optically pure beta,beta-difluoro-alpha-amino acid derivatives were further obtained, which are highly valuable in the synthesis of fluoro peptides, fluoro amino alcohols, and other fluorine-containing molecules. Organocatalysed 1,3-proton shifts provide a pathway to chiral nonracemic fluorinated products with high enantiomeric ratio.