General alkyl fluoride functionalization via short-lived carbocation-organozincate ion pairs.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38424080.
- Also identified by DOI 10.1038/s41467-024-45756-4 and PMC identifier 10904780.
- 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
Fluorinated organic compounds are frequently used across the chemical and life sciences. Although a large, structurally diverse pool of alkyl fluorides is nowadays available, synthetic applications trail behind the widely accepted utility of other halides. We envisioned that C(sp<sup>2</sup>)-C(sp<sup>3</sup>) cross-coupling reactions of alkyl fluorides with fluorophilic organozinc compounds should be possible through a heterolytic mechanism that involves short-lived ion pairs and uses the stability of the Zn-F bond as the thermodynamic driving force. This would be mechanistically different from previously reported radical reactions and overcome long-standing limitations of organometallic cross-coupling methodology, including competing β-hydride elimination, homodimerization and hydrodefluorination. Here, we show a practical C<sub>sp3</sub>-F bond functionalization method that expands the currently restricted synthetic space of unactivated primary, secondary and tertiary C(sp<sup>3</sup>)-F bonds but also uses benzylic, propargylic and acyl fluorides. Many functional groups and sterically demanding substrates are tolerated, which allows practical carbon-carbon bond formation and late-stage functionalization.