Transition-metal-free electrochemical cross-electrophile coupling of activated benzyl alcohols and primary alkyl
Guang Chen1, Changhao Huang1, Like Luo1
1State Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
Abstract:
Cross-electrophile coupling (XEC) has emerged as a powerful strategy for constructing carbon─carbon bonds. Here, we report the first transition-metal-free electrochemical XEC between readily available benzyl alcohol derivatives and primary alkyl bromides, enabling the efficient construction of C(sp3)─C(sp3) bonds to access valuable benzylic quaternary and tertiary carbon centers. This method expands the reaction profiles of both benzyl alcohols and electrochemistry. A key to unlocking this transformation is the identification of 4-tert-butylbenzoyl (TBBz) as an effective activating group for benzyl alcohols. This modular protocol features broad substrate scope, compatibility with CO2 and chlorosilanes as coupling partners, and is amenable to gram-scale synthesis. The synthetic utility of this method is exemplified by the simplified synthesis of high-value commercial building blocks and advanced intermediates for bioactive compounds, as well as the facile access to bioisosteric analogs of drug molecules.
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