Alcohols as Alkylating Agents: Photoredox‐Catalyzed Conjugate Alkylation via In Situ Deoxygenation

Abstract

The rapid exploration of sp3‐enriched chemical space is facilitated by fragment‐coupling technologies that utilize simple and abundant alkyl precursors, among which alcohols are a highly desirable, commercially accessible, and synthetically versatile class of substrate. Herein, we describe an operationally convenient, N‐heterocyclic carbene (NHC)‐mediated deoxygenative Giese‐type addition of alcohol‐derived alkyl radicals to electron‐deficient alkenes under mild photocatalytic conditions. The fragment coupling accommodates a broad range of primary, secondary, and tertiary alcohol partners, as well as structurally varied Michael acceptors containing traditionally reactive sites, such as electrophilic or oxidizable moieties. We demonstrate the late‐stage diversification of densely functionalized molecular architectures, including drugs and biomolecules, and we further telescope our protocol with metallaphotoredox cross‐coupling for step‐economic access to sp3‐rich complexity.

Cross-Double Deoxygenative Carbon–Carbon Bond Formation between Benzyl Benzoates and Allylic Alcohols

“…Recently, the Macmillan group developed a general strategy for deoxygenative cross-coupling reactions of alcohols with several coupling partners to construct C­(sp 3 )-C bonds. − Particularly, during the preparation of the manuscript, they reported a double deoxygenative cross-coupling of two alcohols to construct C­(sp 3 )-C­(sp 3 ) bonds . The key to these reactions is the use of innovative N -heterocyclic carbene (NHC) salts to activate the C–O bond in alcohols.…”

“…On the bias of the reported precedents on alcohol C–O bond activation using NHC salts ,− and the aforementioned experiments and DFT calculations, a preliminary mechanism is proposed in Scheme . The reaction of N1 and allylic alcohols first takes place to afford the NHC-allyl alcohol adduct ( Int 1 ) under basic conditions.…”