Organocatalyzed Enantioselective Aza-Morita-Baylis-Hillman Reaction of Cyclic Ketimine with α,β-Unsaturated γ-Butyrolactam

The enantioselective aza-MBH reaction is an efficient strategy for constructing novel carbon-carbon bonds, providing access to multitudinous chiral densely functionalized MBH products. However, the enantioselective aza-MBH reaction of cyclic-ketimines that would generate a versatile synthon is still missing and challenging. Herein, we developed a challenging direct organocatalytic asymmetric aza-MBH reaction involving cyclic ketimines attached to a neutral functional group. Moreover, the alpha,beta- unsaturated gamma-butyrolactam was utilized as a rare nucleophile alkene in this work. The reactions provide enantiomerically enriched 2alkenyl-2-phenyl-1,2-dihydro-3H-indol-3-ones, bearing with a tetra-substituted stereogenic center. Moreover, this reaction features high alpha-selectivities, high enantioselectivities (up to 99% ee), and good yields (up to 80%).

Automated summary

The study developed a challenging direct organocatalytic asymmetric aza-MBH reaction involving cyclic ketimines attached to a neutral functional group. α,β-unsaturated γ-butyrolactam was used as a rare nucleophile alkene in this reaction. The reactions provided enantiomerically enriched 2-alkenyl-2-phenyl-1,2-dihydro-3H-indol-3-ones with high alpha-selectivities, high enantioselectivities (up to 99% ee), and good yields (up to 80%).