| A development of aza-[3 + 3] annulation methodology utilizing tetronamides as latent acyclic vinylogous amides toward synthesis of polyfunctionalized piperidines is described here.; A detailed investigation of aza-[3 + 3] annulation of tetronamides with alpha,beta-unsaturated iminium salts was performed. This investigation uncovers regioisomeric cycloadducts that were not found in previous studies involving aza-[3 + 3] annulation and an unexpected rearrangement that led to pyridines and dihydropyridines. Both stereochemical and regiochemical issues raised in this study provided further mechanistic insights to this annulation. With careful control of reaction temperatures, the desired cycloadducts were obtained.; It was demonstrated that aza-[3 + 3] annulations could be rendered in highly stereoselective manner using chiral enals. In addition to being an attractive strategy for construction of various nitrogen heterocycles, this stereoselective manifold represents a unique and valuable opportunity to explore fundamental knowledge in a torquoselective ring-closures of 1-azatrienes containing chirality at the C-terminus, thereby it was studied in details. The stereochemical model based on a potential rotational preference was proposed to rationalize the observed torquoselectivity.; The concept of utilizing tetronamides as latent acyclic vinylogous amides for the aza-[3 + 3] annulation was illustrated by developing stereoselective protocols for transformation of the aza-[3 + 3] cycloadducts into functionalized piperidinyl derivatives. Quest for suitable conditions for this transformation as well as current progress toward synthesis of selected alkaloids are described. |
