External Flash Generation of Carbenoids Enables Monodeuteration of Dihalomethanes.

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.