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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 η3-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. 1 Introduction 2 Pd-Catalyzed Intramolecular Friedel–Crafts Allylic Alkylation of Phenols 2.1 Synthesis of Spirocyclohexadienone Derivatives by Pd-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic Alkylation of Phenols 2.2 Mechanistic Considerations 2.3 Application to Cascade Reaction Processes 2.4 Asymmetric Synthesis of Dihydrophenanthrene Derivatives by Pd-Catalyzed Asymmetric Intramolecular Friedel–Crafts Allylic Alkylation of Phenols 3 Dearomatization of Phenols by Activation of Propargyl Carbonates with a Pd Catalyst 4 Au-Catalyzed Intramolecular ipso-Friedel–Crafts Alkenylation of Phenols 5 Summary and Outlook

We have developed a novel method for synthesizing trisubstituted cyclopropane derivatives by a palladium-catalyzed intramolecular allylic alkylation of α-aryl esters. By using α-aryl α-(methoxycarbonyl) γ-vinyl γ-lactones as substrates, decarboxylative formation of π-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)-[2′-(diphenylmethoxy)-1,1′-binaphthalen-2-yl](diphenyl)phosphine as a chiral monodentate phosphorus ligand.

A novel method of the enantioselective synthesis of 2-substitutedhexahydroquinolin-4-ones is described. The method relies on a Pd-catalyzedasymmetric allylic amination using a chiral diaminophosphine oxide(DIAPHOX) preligand and diastereoselective intramolecular Mannichreaction. The developed synthetic method could be applied to thecatalytic asymmetric synthesis of (+)-2- EPI- CIS-195A.

Stereoselective synthesis of the acyl side chain segment 2 of GE3 (1), a potent inhibitor of cell progression of the cell cycle from the Gl to S phase, has been achieved by using Sharpless' asymmetric dihydroxylation and Evans' and Paterson's stereoselective aldol methodologies.

The pyrroloquinoline moiety of Martinelline, a naturally occurring bradykinin receptor antagonist, has been synthesized from 1,2-dihydroquinoline which was prepared by using a tandem Michael-aldol reaction as a key step.