Highly selective single and multiple deuteration of unactivated C(sp³)-H bonds.

Abstract

Selective deuteration of unactivated C(sp³)-H bonds is a highly attractive but challenging subject of research in pharmaceutical chemistry, material science and synthetic chemistry. Reported herein is a practical, highly selective and economical efficient hydrogen/deuterium (H/D) exchange of unactivated C(sp³)-H bonds by synergistic photocatalysis and hydrogen atom transfer (HAT) catalysis. With the easily prepared PMP-substituted amides as nitrogen-centered radical precursors, a wide range of structurally diverse amides can undergo predictable radical H/D exchange smoothly with inexpensive D₂O as the sole deuterium source, giving rise to the distal tertiary, secondary and primary C(sp³)-H bonds selectively deuterated products in yields of up to 99% and excellent D-incorporations. In addition to precise monodeuteration, this strategy can also achieve multideuteration of the substrates contain more than one remote C(sp³)-H bond, which opens a method to address multi-functionalization of distal unactivated C(sp³)-H bonds.