Atom economy. Palladium-catalyzed formation of coumarins by addition of phenols and alkynoates via a net C-H insertion.
A strategy to achieve ortho substitution of phenols initiated by an ortho-palladation to create coumarins was examined. Indeed, treatment of alkynoates with electron-rich phenols in the presence of a palladium catalyst and an acid does generate coumarins. The scope of the reaction with respect to the phenol and the alkynoates is defined. With unsymmetrical aromatic substrates, generally good regioselectivity that reflects the HOMO coefficients can be observed. In the course of these studies, numerous important naturally occurring coumarins have been synthesized, including fraxinol methyl ether, ayapin, herniarin, xanthoxyletin, and alloxanthoxyletin. The fact that a Pd(0) is the precatalyst rather than a Pd(+2) species and that an acid that reduces Pd(+2) salts, formic acid, functions better than other carboxylic acids raises doubts about the initial working hypothesis. A novel mechanism involving a palladium phenoxide formed from a hydridopalladium carboxylate and phenol is invoked to rationalize the results.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA. bmtrost@stanford.edu
Toste
F Dean
FD
Greenman
Kevin
K
D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D003374:Coumarins / Q000138:chemical synthesis*; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*
D000480:Alkynes; D003374:Coumarins; D009942:Organometallic Compounds; D010636:Phenols; D010165:Palladium