Transition-Metal Free Chemoselective Hydroxylation and Hydroxylation–Deuteration of Heterobenzylic Methylenes
Yonghai Liu, Yang Yu, Chengyu Sun, Yiwei Fu, Zhiguo Mang, Lei Shi, Hao Li
Abstract
We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41–76% yields. Using DMSO-d6, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.
Topics & Concepts
ChemistryHydroxylationOrganic chemistryDeuteriumCombinatorial chemistryEnzymeQuantum mechanicsPhysicsChemical Reactions and IsotopesAsymmetric Hydrogenation and CatalysisSynthesis and Catalytic Reactions