Copper-Catalyzed Synthesis of Multideuterium-Labeled Alcohols from Styrenes with CO and D₂ as the Source of the Hydroxymethyl Group

Abstract

Deuterated compounds have important applications, especially in the pharmaceutical field. Hence, the development of new and straightforward synthetic methods for the construction of deuterated compounds is becoming more and more attractive. We describe here a copper-catalyzed hydroxymethylation of aryl olefins with CO and D2 as the source of hydroxymethyl group. Various multideuterium 1,1,2,3-d 4-labeled alcohols were produced directly. Mechanistic investigations established that the hydroxymethylation reaction proceeds via an in situ-generated carbon carbene intermediate.

Cobalt-Catalyzed Hydroxymethylation of Alkyl Halides with CO as the C1 Source

“…Since the pioneering work of Roelen, Nozaki’s group and Beller’s group have reported dual rhodium/ruthenium-based or ruthenium-based catalytic systems, where one-carbon-extended alcohols were achieved by hydroxymethylation of alkenes with syngas (CO/H 2 ) (Scheme a) . Recently, our group developed a copper-catalyzed hydroxymethylation of styrenes that enabled the synthesis of branched alcohols (Scheme b) . A similar procedure was also reported by using CO 2 and a silane reductant in place of CO/H 2 .…”