（来源：康龙化成）

转自：康龙化成

Quaternary Carbon Centers via Electrochemical Direct Dehydroxylative Alkylation

Yue-Ming Cai+, Kang-Ning Yuan+, Pei-Yi Huang, Tian Xie, and Ming Shang*

State Key Laboratory of Synergistic Chem-Bio Synthesis, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China;

—Angew. Chem. Int. Ed., 2025, 10.1002/anie.202520816

Recommended by Xuemei Yao_MC3

KEY WORDS: Electro chemistry, Dehydroxylation, Alkylation (反应类型), tertiary alcohols, Michael acceptors, benzyl chlorides (原料), Quaternary Carbon Centers alkyl compounds (产物), Csp3-Csp3(成键类型), Polar to Radical (其他)

ABSTRACT: The construction of all-carbon quaternary centers remains a formidable challenge in organic synthesis due to the steric congestion and limited accessibility of suitable precursors. Herein, we report a modular electrochemical strategy for the direct dehydroxylativealkylation of tertiary alcohols via a polar-to-radical transduction mechanism. This unified activation platform enables C(sp3)-C(sp3) bond formation with electron-deficient alkenes and benzyl chlorides, employing readily available reagents under mild, operationally simple conditions. Key to this transformation is the use of halide-based reagents that mediate Lewis acid-promoted C─OH bond cleavage while enabling subsequent radical generation via cathodic reduction. The method exhibits broad substrate scope, including complex and functionalized tertiary alcohols, diverse Michael acceptors, and sterically hindered coupling partners. It is further applicable to the late-stage modification of bioactive molecules and scalable synthesis. Mechanistic studies support the involvement of both carbocation and carbon radical intermediates, validating the effectiveness of this dual-mode strategy. This work provides a general and practical approach to quaternary carbon construction from unactivated tertiary alcohols, expanding the synthetic toolbox for C(sp3)-C(sp3) bond formation.

Background: Strategies for Constructing Quaternary Carbon Centers from Tertiary Alcohols

Substrate Scope

Proposed Mechanism

Prof. Ming Shang and co-workers developed a direct electrochemical dehydroxylative alkylation of tertiary alcohols, enabling the construction of all-carbon quaternary centers through coupling with electron-deficient alkenes and benzyl chlorides. By leveraging a “polar-to-radical” transduction strategy, this method synergistically combines the advantages of two electron (polar) and one-electron (radical) pathways, achieving C─OH bond activation under mild conditions using simple reagents and operationally straightforward procedures. This protocol exhibits a broad substrate scope, excellent functional group tolerance, and is applicable to the late stage functionalization of complex molecules. Mechanistic investigations provided compelling evidence for the involvement of both carbocation and carbon radical intermediates, underscoring the mechanistic novelty of this transformation. Overall, this work establishes the feasibility and versatility of the polar-to-radical strategy indehydroxylative functionalization of unactivated tertiary alcohols, paving the way for future development and application in modular C(sp3)-C(sp3) bond construction.