914402-87-2Relevant academic research and scientific papers
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
Weston, Mitchell H.,Nakajima, Katsumasa,Back, Thomas G.
, p. 4630 - 4637 (2008)
(Chemical Equation Presented) 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 the product of one ring-expansion is converted into a new cyclic α-vinyl amine, followed by a repetition of the conjugate addition and [3,3] rearrangement. This protocol was illustrated by its application to the synthesis of motuporamine A and B.
