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.
Huang, L.;Ackerman, L. K. G.; Olivares, A. M.; Weix, D. J. LiCl Accelerated Multimetallic Cross-Coupling of Aryl Chlorides with Aryl Triflates. J. Am. Chem. Soc. 2019, 141, 10978-10983
https://pubs.acs.org/doi/10.1021/jacs.9b05461#