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Total Synthesis of Pyrolaside B: Phenol Trimerization through Sequenced Oxidative C−C and C−O Coupling
Author(s) -
Neuhaus William C.,
Kozlowski Marisa C.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915654
Subject(s) - trimer , chemistry , natural product , phenol , yield (engineering) , xanthene , phenols , oxidative coupling of methane , catalysis , combinatorial chemistry , total synthesis , stereochemistry , organic chemistry , dimer , materials science , metallurgy
A facile method to oxidatively trimerize phenols using a catalytic aerobic copper system is described. The mechanism of this transformation was probed, yielding insight that enabled cross‐coupling trimerizations. With this method, the natural product pyrolaside B was synthesized for the first time. The key strategy used for this novel synthesis is the facile one‐step construction of a spiroketal trimer intermediate, which can be selectively reduced to give the natural product framework without recourse to stepwise Ullmann‐ and Suzuki‐type couplings. As a result, pyrolaside B can be obtained expeditiously in five steps and 16 % overall yield. Three other analogues were synthesized, thus highlighting the utility of the method, which provides new accessibility to this area of chemical space. A novel xanthene was also synthesized through controlled Lewis acid promoted rearrangement of a spiroketal trimer.