Photosynthesis of C-1-Deuterated Aldehydes via Chlorine Radical-Mediated Selective Deuteration of the Formyl C–H Bond
Qingzhu Xu, Wei Ou, Hao Hou, Qiyuan Wang, Lei Yu, Chenliang Su
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 D 2 O. This process is facilitated by chlorine radicals that are generated in situ from low-cost FeCl 3 . 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.