N,N′-Dioxide/Nickel(II)-Catalyzed Asymmetric Inverse-Electron-Demand Hetero-Diels-Alder Reaction of β,γ-Unsaturated α-Ketoesters with Enecarbamates

N,N'-Dioxide/nickel(II) complexes have been developed to catalyze the inverse-electron-demand hetero-Diels-Alder reaction of beta,gamma-unsaturated alpha-ketoesters with acyclic enecarbamates. After detailed screening of the reaction parameters, mild optimized reaction conditions were established, affording 3,4-dihydro-2H-pyranamines in up to 99% yield, 99% ee and more than 95:5 d.r. The catalytic system was also efficient for beta-substituted acyclic enecarbamates, affording more challenging 2,3,4-trisubstituted 3,4-dihydro-2-Hpyranamine with three contiguous stereogenic centers in excellent yields, diastereoselectivities, and enantioselectivities. The reaction could be scaled up to a gram scale with no deterioration of either enantioselectivity or yield. Based on these experiments and on previous reports, a possible transition state was proposed.