Synthesis of chiral α-trifluoromethyl alcohols and ethers via enantioselective Hiyama cross-couplings of bisfunctionalized electrophiles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30177813.
- Also identified by DOI 10.1038/s41467-018-05946-3 and PMC identifier 6120892.
- 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
Methods for synthesis of chiral organic compounds bearing trifluoromethyl-substituted stereocenters are of great interest for agrochemical and pharmaceutical labs and industries in their search for new bioactive materials. We report on employment of bisfunctionalized electrophiles, bearing both a trifluoromethyl and a functional group as direct substituents of the reactive center, in cross-coupling reactions. We exemplify this concept in the asymmetric synthesis of enantioenriched α-trifluoromethyl- and perfluoroalkyl-containing benzylic and allylic ethers and alcohols by nickel-catalyzed stereoconvergent Hiyama cross-coupling reaction. Substrate electrophiles are conveniently prepared in few steps from trifluoroacetic acid. The method represents a conceptually different approach to chiral CF<sub>3</sub>-substituted alcohols and ethers and allows for a rapid catalytic preparation of a wide range of these valuable compounds in high yields and enantioselectivity.