Tandem Conjugate Additions and 3-Aza-Cope Rearrangements of Tertiary Allyl Amines and Cyclic α-Vinylamines with Acetylenic Sulfones. Applications to Simple and Iterative Ring Expansions Leading to Medium and Large-Ring Nitrogen Heterocycles

Tertiary acyclic allyl amines and tertiary cyclic α-vinyl amines undergo conjugate additions to acetylenic sulfones to produce zwitterion intermediates, followed by 3-aza-Cope rearrangements. In the case of cyclic α-vinyl amines, the process results in ring-expansion, providing a novel route to 9- to 17-membered cyclic amines. The Hammett plot for the reaction of 8b with 2a−2f shows ρ = +1.19, which is consistent with formation of the proposed zwitterion in the rate-determining step, where electron-withdrawing substituents on the arylsulfonyl moiety stabilize the negative charge and enhance the rate of the reaction. Alternative pathways were observed in methanol in the case of 11, where a methoxy substituent promotes a dissociative mechanism of the corresponding zwitterion via a stabilized allyl cation, whereas the zwitterion derived from amine 12 undergoes ring-opening by direct attack of methanol upon the strained aziridinium moiety instead of by rearrangement. An iterative process was developed, where ...