Photosynthesis of C-1-Deuterated Aldehydes via Chlorine Radical-Mediated Selective Deuteration of the Formyl C-H Bond.

Abstract

C-1-deuterated aldehydes are essential building blocks in the synthesis of deuterated chemicals and pharmaceuticals. This has led chemists to devise mild methodologies for their efficient production. Ideally, hydrogen-deuterium exchange (HDE) is the most effective approach. However, the traditional HDE for creating C-1-deuterated aldehydes often requires a complex system involving multiple catalysts and/or ligands. In this study, we present a mild photocatalytic HDE of the formyl C-H bond with D2O. This process is facilitated by chlorine radicals that are generated in situ from low-cost FeCl3. This strategy demonstrated a broad reaction scope and high functional group tolerance, affording good yields and ≤99% D incorporation. To bridge the gap between research and industrial applications, we designed a new flow photoreactor equipped with a high-intensity light-emitting diode bucket, enabling the synthesis of C-1-deuterated aldehydes on a scale of 85 g. Finally, we successfully produced several important deuterated aldehydes that are integral to the synthesis of deuterated pharmaceuticals.