Stereodivergent Synthesis of Enantioenriched α-Deuterated α-Amino Acids via Cascade Cu(I)-Catalyzed H-D Exchange and Dual Cu- and Ir-Catalyzed Allylation

A one-pot Cu-mediated H-D exchange with inexpensive heavy water as the deuterium source, followed by Cu- and Ir-catalyzed stereodivergent allylic alkylation, has been developed, providing efficient access to enantioenriched alpha-deuterium-labeled alpha-amino acids from readily available glycine imine esters in a high yield with excellent stereoselectivity. High deuterium enrichment, exquisite regioselectivity, precise stereoselectivity control, and operationally convenient procedures make this protocol appealing for the preparation of highly synthetically useful alpha-deuterated alpha-amino acids.

Automated summary

In this study, a one-pot Cu-mediated H-D exchange using inexpensive heavy water as the deuterium source, followed by Cu- and Ir-catalyzed stereodivergent allylic alkylation, has been developed to efficiently access enantioenriched alpha-deuterium-labeled alpha-amino acids.