Synthesis of Spirocyclic and Fused Cyclic Compounds by Transition-Metal-Catalyzed Intramolecular Friedel-Crafts-Type Reactions of Phenol Derivatives

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 (3)-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