External Flash Generation of Carbenoids Enables Monodeuteration of Dihalomethanes
Kazuhiro Okamoto, Ryosuke Higuma, Kensuke Muta, Keita Fukumoto, Yuta Tsuchihashi, Yosuke Ashikari, Aiichiro Nagaki
Abstract
In this study, incorporation of one deuterium atom was achieved by H-D exchange of one of the two identical methylene protons in various dihalomethanes (halogen=Cl, Br, and I) through a rapid-mixing microflow reaction of lithium diisopropylamide as a strong base and deuterated methanol as a deuteration reagent. Generation of highly unstable carbenoid intermediate and suppression of its decomposition were successfully controlled under high flow-rate conditions. Monofunctionalization of diiodomethane afforded various building blocks composed of boryl, stannyl, and silyl groups. The monodeuterated diiodomethane, which served as a deuterated C1 source, was subsequently subjected to diverted functionalization methods to afford various products including biologically important molecules bearing isotope labelling at specific positions and homologation products with monodeuteration.