Synthesis of Polysubstituted Piperidines by Diels-Alder Reaction of N-Alkenyl Iminiums

Significance

The synthesis of piperidine derivatives by the [4+2] cycloaddition of N-alkenyl iminium ion 2 with alkene dienophiles is reported. Treatment of methoxymethyl enamine 1 with TiCl₄ gave diene 2, which was trapped in situ with a range of alkenes to give iminium cycloadducts 3, 5, 8, and 10. Addition of a nucleophile (allyl silane, indole) afforded piperidines 4, 6, 7, and 9 in excellent yield with complete endo selectivity. Quenching iminium salt 10 with triethylamine generated the tetrahydropyridine 11 as a single isomer.