Diastereoselective Piperidine Synthesis through DDQ-Mediated Oxidative Cyclization of Enamides, N-Vinyl Carbamates, and N-Vinyl Sulfonamides

The DDQ-mediated oxidative cyclization chemistry that was previously developed in our group for the synthesis of tetrahydropyrones from allylic and benzylic ethers has been expanded for use with enamides, N-vinyl carbamates, and N-vinyl sulfonamides to synthesize piperidine rings. This chemistry provides a new oxidative method to generate N-acyliminium and N-sulfonyliminium ions. Cyclization onto the oxidatively generated α,β-unsaturated N-acyliminium and N-sulfonyliminium ions has been performed with a variety of tethered nucleophiles. The cyclization reaction suffers no difficulties in regards to chemoselectivity or over oxidation. Moreover, the resulting unit of unsaturation in the products provides an additional synthetic handle not generated through more classical iminium ion chemistry. Significantly, stereocontrol in the reaction was achieved through the use of (E)- and (Z)-allylsilanes and silyl enol ethers. Transition state models were formulated through information obtained from studies of monocyclic and bicyclic compounds synthesized through the oxidative cyclization reaction. Finally, the reaction was made catalytic through regeneration of DDQ via oxidation of the DDQ byproduct by Mn(OAc)3. This chemistry provides a powerful new method for generating nitrogen heterocycles and will provide new ways of accessing alkaloids