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Room‐Temperature Palladium‐Catalyzed Deuterogenolysis of Carbon Oxygen Bonds towards Deuterated Pharmaceuticals
Author(s) -
Ou Wei,
Xiang Xudong,
Zou Ru,
Xu Qing,
Loh Kian Ping,
Su Chenliang
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202014196
Subject(s) - chemoselectivity , catalysis , chemistry , palladium , deuterium , molecule , combinatorial chemistry , carbon fibers , small molecule , organic chemistry , materials science , biochemistry , physics , quantum mechanics , composite number , composite material
Site‐specific incorporation of deuterium into drug molecules to study and improve their biological properties is crucial for drug discovery and development. Herein, we describe a palladium‐catalyzed room‐temperature deuterogenolysis of carbon–oxygen bonds in alcohols and ketones with D 2 balloon for practical synthesis of deuterated pharmaceuticals and chemicals with benzyl‐site (sp 3 C−H) D‐incorporation. The highlights of this deoxygenative deuteration strategy are mild conditions, broad scope, practicability and high chemoselectivity. To enable the direct use of D 2 O, electrocatalytic D 2 O‐splitting is adapted to in situ supply D 2 on demand. With this system, the precise incorporation of deuterium in the metabolic position (benzyl‐site) of ibuprofen is demonstrated in a sustainable and practical way with D 2 O.