Enantioselective Robinson-Type Annulation Reaction Catalyzed by Chiral Phosphoric Acids

摘要

The Robinson annulation reaction is one of the most useful methods for the construction of the cyclohexenone structure and is widely employed in the synthesis of complex natural products. It consists of three consecutive processes: 1) Michael addition of a carbonyl compound to an α,β-unsaturated ketone, 2) an intramolecular aldol reaction, and 3) dehydration. Both acid and base catalysts have been extensively utilized in the Robinson annulation reaction. To synthesize the cyclohexenone substructures in an optically pure form with the Robinson annulation reaction, a chiral ketone is used as the starting material and an enantioenriched Robinson annulation product is furnished by the diastereo-selective Michael addition reaction.Alternatively, the enantioselective Michael addition reaction is a key reaction for the enantioselective Robinson annulation reaction. In the 1970s Hermann and Wynberg conducted seminal work on the enantioselective conjugate addition of β-keto esters to methyl vinyl ketone in the presence of cinchona alkaloid as catalyst. Sasai and Shibasaki disclosed the highly enantioselective conjugate addition reaction of β-keto esters with methyl vinyl ketone. Chiral scandium(III) catalysts, palla-dium catalysts, and ruthenium catalysts have been also employed. Maruoka and co-workers have reported phase-transfer catalysis.