Alcohols as Alkylating Agents: Photoredox‐Catalyzed Conjugate Alkylation via In Situ Deoxygenation
Year: 2022
Type: article
Abstract: The rapid exploration ofsp3‐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 tosp3‐rich complexity.
Institution: Princeton University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4283204331