Asymmetric Synthesis of Tetrahydropyridines via Diels-Alder Reaction

Significance

The catalytic asymmetric hetero-Diels-Alder reaction of N-sulfonyl-1-azadienes 1/5 with electron-rich alkenes 2/6 to provide tetrahydropyridines 3/7 is reported. After extensive optimization, two sets of conditions were identified, relying on the presence of the coordinating 2-pyridylsulfonyl or 8-quinolinylsulfonyl groups at the imine nitrogen. Using substrates 1 under copper(II) catalysis, the desired products 3 were obtained in high yield and with high endo-selectivity but only moderate enantioselectivity. Switching to a more reactive system based on 1-azadienes 5 under nickel catalysis gave, in general, improved yields and enantioselectivities (typically 77-92% ee), again with excellent endo-selectivity.