Palladium-catalyzed difluorocarbene transfer enables access to enantioenriched chiral spirooxindoles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39353887.
- Also identified by DOI 10.1038/s41467-024-52392-5 and PMC identifier 11445564.
- 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
We disclose herein an unprecedented Pd-catalyzed difluorocarbene transfer reaction, which assembles a series of structurally interesting chiral spiro ketones with generally over 90% ee. Commercially available BrCF<sub>2</sub>CO<sub>2</sub>K serves as the difluorocarbene precursor, which is harnessed as a user-friendly and safe carbonyl source in this transformation. Preliminary mechanistic studies exclude the formation of free CO in the reaction process, and importantly, we also find that BrCF<sub>2</sub>CO<sub>2</sub>K outcompete gaseous CO and several common CO surrogates in this asymmetric process. The reaction mechanism, including the in-situ progressive release of the difluorocarbene, the rapid migratory insertion of ArPd(II) = CF<sub>2</sub> species, and subsequent defluorination hydrolysis by water to introduce the carbonyl group, accounts for the overall high efficiency and uniqueness. This work clearly showcases the advantage and potential of the difluorocarbene in synthesis and supplies a mechanistically distinct route for asymmetric carbonylative cyclization reactions.