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This account describes the development of novel dearomatization reactions of phenols using transition-metal-catalyzed ipso-Friedel-Crafts-type processes. In general, phenols function as O-nucleophiles in transition-metal-catalyzed allylic substitution reactions, providing the corresponding aryl ethers. We found that, however, an intramolecular ipso-Friedel-Crafts allylic alkylation of phenols proceeded smoothly in the presence of a palladium catalyst, producing various spiro[4.5]cyclohexadienone derivatives. This finding led us to launch detailed investigations into this type of reaction. Pd-catalyzed intramolecular Friedel-Crafts allylic alkylation of phenols was next examined to synthesize 10-vinyl 9,10-dihydrophenanthrene derivatives. This reaction was successfully extended to a catalytic asymmetric process. We also developed a novel synthetic method for spiro[5.5]cyclohexadienones based on a Pd-catalyzed intramolecular ipso-Friedel-Crafts-type addition of phenols to ç3-propargylpalladium(II) intermediates. Mechanistic studies revealed that the present reaction proceeds through a rearomatization-assisted oxidative addition. Moreover, a Au-catalyzed intramolecular ipso-Friedel-Crafts alkenylation of phenols with a terminal alkyne is discussed. [ABSTRACT FROM AUTHOR]

We have developed a novel method for synthesizing trisubstituted cyclopropane derivatives by a palladium-catalyzed intramolecular allylic alkylation of ƒ¿-aryl esters. By using ƒ¿-aryl ƒ¿-(methoxycarbonyl) ƒÁ-vinyl ƒÁ-lactones as substrates, decarboxylative formation of ƒÎ- allylpalladium(II) intermediates followed by an intramolecular allylic alkylation of the ester enolates proceeded in the presence of 5 mol% of a palladium catalyst, producing 1-aryl-1-(methoxycarbonyl)-2-vinylcyclopropanes in good to excellent yields and high diastereoselectivities. The relative configuration of the major isomer was determined by transforming the product into a known intermediate of milnacipran synthesis. When we extended our method to asymmetric catalysis, we obtained methyl (1S,2S)-1-phenyl-2-vinylcyclopropanecarboxylate in up to 55% ee by using (S)-[2Œ-(diphenylmethoxy)-1,1Œ-binaphthalen-2- yl](diphenyl)phosphine as a chiral monodentate phosphorus ligand. [ABSTRACT FROM AUTHOR]

A novel method of the enantioselective synthesis of 2-substituted hexahydroquinolin-4-ones is described. The method relies on a Pd-catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand and diastereoselective intramolecular Mannich reaction. The developed synthetic method could be applied to the catalytic asymmetric synthesis of (+)-2-epi-cis-195A. [ABSTRACT FROM AUTHOR]