Diastereodivergent Asymmetric [4+2] Cycloaddition of In Situ Generated ortho-Quinone Methides and Allenyl Ketones Enabled by Chiral Phosphoric Acid Catalysis

Asymmetric diastereodivergent catalysis is a powerful strategy for accessing different stereoisomers of a molecule, which are important in the discovery of biologically and pharmacologically active candidates. While the asymmetric diastereodivergent synthesis of acyclic molecules has seen recent rapid development, the corresponding asymmetric diastereodivergent cycloaddition reactions have received comparatively less attention. Herein, we report the asymmetric diastereodivergent synthesis of chromanes with C2,C3-contiguous tetrasubstituted stereocenters via chiral phosphoric acid (CPA)-catalyzed [4 + 2] cycloadditions of ortho-quinone methides with ?-silyl-substituted allenones. A wide range of C3-epimeric chromanes were generated with high to excellent diastereoselectivities and enantioselectivities, starting from the same substrates but with modifications of the CPA catalysts. The diverse derivatizations of these chiral chromane stereoisomers into complex scaffolds illustrate the utility and value of this method.

Automated summary

Asymmetric diastereodivergent catalysis is an important strategy for accessing different stereoisomers of a molecule. In this study, a new method for the asymmetric diastereodivergent synthesis of chromanes with C2,C3-contiguous tetrasubstituted stereocenters was reported using chiral phosphoric acid catalysts.