Synthesis of α-tertiary amines by polysulfide anions photocatalysis via single-electron transfer and hydrogen atom transfer in relays

Abstract

α,α,α-Trisubstituted amines (α-tertiary amines) are an important class of compounds in drug discovery programs. Herein, we report a photocatalytic method to synthesize α-tertiary amines using polysulfide anions as photocatalysts that facilitate single-electron transfer (SET) and hydrogen atom transfer (HAT) in relays to enable α-C–H functionalization of α-secondary benzylamines with cyanoarenes or aryl ketones under irradiation with visible light. The keys enabling advance in the present protocol take advantage of highly negative photoexcited oxidation potential of polysulfide dianions (S n 2− , n = 4 or 6) to cover a range of cyanoarenes and aryl ketones for their SET reduction as well as the catenated structure of polysulfide anion radicals (S n ⋅– , n = 4 or 6) capable of polarity-driven HAT at the hindered α-amino benzylic C–H bond. Thus, ensuing coupling of cyanoarene radical anions or ketyl anion radicals with α-amino benzylic radicals allows for facile construction of sterically congested α-tertiary amine scaffolds. • Readily available polysulfide anions serve as photocatalysts • Single-electron transfer and hydrogen atom transfer in relays • Protecting group-free approaches toward the synthesis of α-tertiary amines Visible light photocatalysis has made tremendous advancement in contemporary chemical synthesis of complex molecules. In most cases, precious transition metal complexes or organic dyes of heavier molecular weight have been employed as the photocatalyst to drive the desired molecular transformations. In this work, we adopted readily available polysulfide anions as the photocatalysts that perform single-electron transfer and hydrogen atom transfer in relays, enabling the synthesis of α-tertiary amines. The photocatalytic protocol streamlines the coupling of cyanoarenes or aryl ketones with α-secondary benzylamines to afford various α-tertiary amines, which are otherwise difficult to be constructed. A photocatalytic method to synthesize α-tertiary amines has been developed using polysulfide anions as photocatalysts that facilitate single-electron transfer and hydrogen atom transfer in relays to enable α-C–H functionalization of α-secondary benzylamines with cyanoarenes or aryl ketones under irradiation with visible light.