Transition metal-free photocatalytic reductive deuteration of ketone derivatives

Abstract

Deuterium labelling techniques have shown widespread applications in organic synthesis, analytic chemistry, life science and material science. The design of practical deuteration reactions which is environmentally friendly is highly desired for pharmaceutical development and industrial processes while remaining underexplored. We herein report a convenient, transition metal-free strategy for reductive deuteration of ketone derivatives to α-deuterated alcohols by employing a conjugated aryl amine-based organophotocatalyst, a dipropyl disulfide co-catalyst and an inorganic reductant. Upon irradiation with visible light and under an air atmosphere, a variety of diaryl ketones, heteroaryl ketones, cyclic ketones, α-ketoesters, benzil derivatives, aliphatic ketones and drug-like molecules were converted into corresponding α-deuterated aryl alcohols in good to excellent yields and with high deuterium incorporation (up to 99% D-incorporation). Only low toxic side-products, such as sodium salts and carbon dioxide, were generated. Consequently, the synthetic utility of this method is highlighted by the preparation of several D-labeled drug-like molecules, including orphenadrine, carbinoxamine and modafinil.

Keywords

• Deuteration
• Photoredox
• Organocatalysis
• Visible light
• α-Deuterated alcohols