Deuterated methylselenylating reagents designed for diverse Se-methyl-d3 scaffold construction†

Abstract

The deuteromethyl group is an ideal bioisostere to replace “magic methyl” due to its profound pharmacological effects and physical properties in medicinal chemistry and chemical biology. Despite the remarkable advances in the construction of CD₃ units, a compelling challenge that remains to be solved is the deuterium labeling of bioactive and functional molecules to introduce methyl-d₃ groups with high efficiency. Among them, the introduction of Se-methyl-d₃, a promising and vital block and a dual bioisostere for the replacement of the methoxyl or S-methyl entity, is limited to the concise and general process. Herein, we have designed and developed a novel and highly efficient access to the formation of two types of deuterated methylselenylating reagent libraries bearing electrophilicity, nucleophilicity, and radical properties. These reagents can be facilely utilized to achieve late-stage modification of functional molecules and even to construct SeCD₃ substituted pharmaceutical analogues.