Catalyst-free decarboxylative deuteration using tailored photoredox-active carboxylic acids

Abstract

Achieving precise deuterium labeling in pharmaceutical compounds presents a formidable challenge in medicinal chemistry. Herein, we introduce an innovative approach for circumventing the use of costly and environmentally unfriendly photocatalysts, enabling precise decarboxylative deuteration under mild conditions. Mechanistic investigation unveils the dual functionality of the tailored photoredox-active acid (PAC) with a photosensitive amino protecting group, serving both as a reactant and as a catalyst. This methodology not only represents a sustainable solution, eliminating the need for additional transition-metal catalysts, but also showcases exceptional regio- and chemoselectivity, successfully producing a versatile range of deuterated amines and alkanes, including complex peptides, terpenoids, and steroidal natural products. This breakthrough marks a significant advancement in the realm of photoinduced autocatalytic reaction methodologies.