Rhodium-Catalyzed Enantioselective Synthesis of Phthalides

Significance

The enantioselective synthesis of phthalides 2 via a rhodium-catalyzed intramolecular hydroacylation approach is reported. The appropriate choice of counterion was crucial to avoid decarbonylation and obtain high enantio­selectivity. Substrates bearing EDGs and EWGs on the aromatic ring performed equally well in the reaction. However, introduction of a steric bulk ortho to the ketone (R^¹ = 3-Me) prohibited the ­reaction. Variation in the ketone moiety including primary and secondary alkyl groups and electron-rich or electron-deficient aromatics was also tolerated. Excellent enantioselectivities were observed in almost all cases.