Transition-metal-free electrochemical cross-electrophile coupling of activated benzyl alcohols and primary alkyl bromides.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41481718.
- Also identified by DOI 10.1126/sciadv.aeb3720 and PMC identifier 13162218.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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(sp<sup>3</sup>)─C(sp<sup>3</sup>) 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-<i>tert</i>-butylbenzoyl (TBBz) as an effective activating group for benzyl alcohols. This modular protocol features broad substrate scope, compatibility with CO<sub>2</sub> 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.