Enantioselective Conversion of Achiral Cyclohexadienones to Chiral Cyclohexenones by Desymmetrization

The enantioselective reduction of prochiral 4,4-disubstituted 2,5-cyclohexa­dienones to chiral 2-cyclohexenones has been accomplished by the use of a carefully selected chiral bisphosphine–CuI complex and diisobutyl­aluminum hydride–hexa­methyl­phosphoric triamide complex. This reagent has provided access to a key bicyclic intermediate for the total synthesis of the natural enantiomer of the pentacyclic sesterterpene retigeranic acid that involves spatial discrimination between CH3 and CH2CH2R substituents, an operation that has been elusive previously. In addition, a second method for desymmetrization is described using catalytic enantioselective [4 + 2]-cycloaddition of cyclopentadiene to prochiral 4,4-disubstituted 2,5-cyclohexa­dienones.