Total Synthesis of Pyrolaside B: Phenol Trimerization through Sequenced Oxidative C−C and C−O Coupling

Abstract

Af acile method to oxidatively trimerizep henols using ac atalytic aerobic copper system is described. The mechanism of this transformation was probed, yielding insight that enabled cross-coupling trimerizations.W ith this method, the natural product pyrolaside Bw as synthesized for the first time.The key strategy used for this novel synthesis is the facile one-step construction of as piroketal trimer intermediate, which can be selectively reduced to give the natural product framework without recourse to stepwise Ullmann-and Suzukitype couplings.A saresult, pyrolaside Bc an be obtained expeditiously in five steps and 16 %overall yield. Three other analogues were synthesized, thus highlighting the utility of the method, whichp rovides new accessibility to this area of chemical space.Anovel xanthene was also synthesized through controlled Lewis acid promoted rearrangement of aspiroketal trimer.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.