LiCl-Accelerated Multimetallic Cross-Coupling of Aryl Chlorides with Aryl Triflates
Year: 2019
Type: article
Abstract: While the synthesis of biaryls has advanced rapidly in the past decades, cross-Ullman couplings of aryl chlorides, the most abundant aryl electrophiles, have remained elusive. Reported here is the first general cross-Ullman coupling of aryl chlorides with aryl triflates. The selectivity challenge associated with coupling an inert electrophile with a reactive one is overcome using a multimetallic strategy with the appropriate choice of additive. Studies demonstrate that LiCl is essential for effective cross-coupling by accelerating the reduction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts. The modified conditions tolerate a variety of functional groups on either coupling partner (42 examples), and examples include a three-step synthesis of flurbiprofen.
DOI: 10.1021/jacs.9b05461
Institutions: University of Wisconsin–Madison, University of Rochester
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Funders: National Science Foundation, Boehringer Ingelheim, Camille and Henry Dreyfus Foundation, Novartis, University of Rochester, National Institutes of Health, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, National Institute of General Medical Sciences, Division of Graduate Education
OpenAlex ID: W2954845784