Visible-light-induced Markovnikov addition of olefin for construction of deuterated α-tertiary amino acid derivatives

Abstract

Deuterated α-tertiary amino acids serve as crucial constituents in the synthesis of deuterated pharmaceuticals and find utility in various biologically relevant compounds. Herein, we present a redox-neutral strategy for Markovnikov addition of oxazolones to olefins, enabling the facile construction of functionally diverse deuterated α-tertiary amino acids using deuterium oxide (D₂O) as the deuterium source under mild conditions devoid of metals and photocatalysts. Our method exhibits a broad substrate scope, affording high deuterated ratios and excellent regioselectivity ([D] > 20 : 1, rr > 20 : 1), and can be readily extended to the deuteration of oxindole substrates. Gram-scale synthesis via flow chemistry underscores its potential for industrial-scale production and commercial viability. Mechanistic investigations reveal that the reaction proceeds via an alkene radical anion-mediated pathway, where the C-2-addition products efficiently undergo conversion to C-4-addition products through an energy transfer (EnT) process, resulting in outstanding regioselectivity.