Umpolung Chemistry under Brønsted Acid Catalysis and Photocatalysis

Abstract

Part I. Umpolung Chemistry under Brønsted Acid Catalysis

Oxidative coupling of 1,3-enynamides using DMSO as a terminal oxidant has been developed. Carbon- as well as unmodified heteroatom nucleophiles, including aliphatic alcohols, thiols and hydrazides, could be efficient alkylated in a highly regioselective fashion. The kinetic analysis suggested a dienolonium cation as the reaction intermediate, which stands in sharp contrast to a concerted SN2’ mechanism in the ynamides oxidation. Thus, the remote site-selectivity was ascribed to the development of positive charge at the terminal carbocationic center.

Part II. Umpolung Chemistry under Photocatalysis Nitrogen-centered radicals are a versatile class of reactive species that can undergo various radical transformations. In recent decades, photolytic catalysis has emerged as a powerful method to render a diverse range of radical intermediates. Toward this end, we introduced a range of photocatalysis reactions employing N-enoxybenzotriazoles. Upon visible-light irradiation, homolytic fragmentation of the N-enoxybenzotriazoles would afford an α-carbonyl radical and a benzoytriazolyl radical. Despite the comprehensive development of nitrogen-centered radicals, generation and synthetic utility of benzotriazolyl radicals has been underexplored. In the first study, we disclosed a triplet-triplet energy transfer that can trigger the homolytic cleavage of the N-O bond of N-enoxybenzotriazoles. The resulting benzotriazolyl radicals underwent a formal 1,3-O to C-shift affording a variety of α-benzotriazolyl ketones. Benzotriazoles and their derivatives possess a broad range of pharmacological reactivity. Thus, the benzotriazole-incorporated products could be of potential benefits for the relevant drug discovery. Next, we introduced a α-C-H functionalization of cyclic and acyclic ethers. Interestingly, the reaction proceeded via an energy transfer pathway and the addition of terminal oxidants was unnecessary. Mechanistic studies revealed that the benzotriazolyl radical abstracted the α-hydrogen atom from ethers, forming α-substituted ethers. Finally, we explored the photocatalytic Mannich-type reaction of tertiary amines coupled with N-enoxybenzotriazoles. In contrast with the two above-mentioned energy transfer process, this transformation proceeded through oxidative deprotonation of amines, rendering the α-amino radicals. A variety of β-amino ketones was yielded by this method. Intriguingly, in this event, the benzotriazolyl radical was found to be capable of abstracting the α-hydrogen atom of amines, regenerating the α-amino radical for a chain process. The unveiling of the ability to abstract a hydrogen atom of the benzotriazolyl radicals and the mechanistic understanding of the photocatalysis process could enrich the photochemistry of the nitrogen-centered radicals.