Palladium‐Catalyzed Asymmetric [4+2] Cycloaddition of 2‐Methylidenetrimethylene Carbonate with Alkenes: Access to Chiral Tetrahydropyran‐Fused Spirocyclic Scaffolds

Abstract

A palladium-catalyzed asymmetric [4+2] cycloaddition of 2-methylidenetrimethylene carbonate with alkenes derived from pyrazolones, indandione, or barbiturate has been successfully developed, affording pharmacologically interesting chiral tetrahydropyran-fused spirocyclic scaffolds. The target compounds were generated in good to excellent yields and with high enantioselectivity (up to 99 % ee). Furthermore, this cycloaddition reaction could be efficiently scaled up, and several synthetic transformations were accomplished for the construction of other useful chiral spiropyrazolone and spiroindandione derivatives.