Asymmetric decarboxylative [3 + 2] cycloaddition for the diastereo- and enantioselective synthesis of spiro[2.4]heptanes via cyclopropanation

Abstract

Asymmetric cycloaddition reactions have emerged as one of the powerful and reliable strategies for the construction of enantioenriched molecules, especially those with polycyclic frameworks. Herein, we report the asymmetric decarboxylative [3 + 2] cycloaddition of γ-methylidene-δ-valerolactones with nitroolefins under the cooperative catalysis of a palladium complex and a chiral urea-tertiary amine, delivering a variety of chiral spiro[2.4]heptanes in good yields with high enantioselectivities and moderate diastereoselectivities. The mild reaction conditions, in conjunction with good functional group tolerance, provided an easy access to multisubstituted chiral spiro[2.4]heptanes bearing three contiguous stereogenic centers including an all-carbon quaternary stereocenter. Moreover, this study reports the first asymmetric decarboxylative and dearomative [3 + 2] reaction of 2-nitrobenzofurans with 1,4-dipoles to afford complex polycyclic scaffolds. Large-scale synthesis and synthetic transformations of the product further demonstrate its synthetic utility.