Study on The Generation of Reactive Intermediates through Thermal Hydrogen Shift and Their Application to Selective Heterocycle Synthesis

为了将肟类和肼类化合物的热氢变换生成的1，3-偶极中间体应用于杂环化合物的合成，对其氢变换过程进行了研究。得到的N-未取代的1，3-偶极通过在偶极的NH和同一分子中的羰基氧之间形成氢键来稳定。因此，应允许增加偶极子的浓度以使其应用于与亲偶极分子的分子间环加成反应，这在很少的文献中被发现。虽然杂环醛的反应为NH-硝酮的分子间环加成反应提供了第二个例子，但马来酰亚胺仅作为一种亲偶极分子，在体系中实现了简单的肼-甲亚胺异构化反应，生成的偶极与亲烯基偶极分子间的环加成反应得到了高效、立体选择性的环加成产物。…的酸处理更多的环加合物导致杂环部分裂解，得到2-吡咯啉衍生物，也被认为是C-未取代的氰亚胺和烯类偶极化合物的环加成物。由于关于C-未取代氰亚胺的文献很少，从合成的角度来看，将这些结果等同于C-未取代氰亚胺的反应是非常有趣的。含有氨基酸酯的杂环醛的N-苯基亚胺在相邻位置的热反应得到杂环体系融合的2-吡咯啉衍生物，其中α，β-不饱和甲亚胺的1，5-电环闭环是通过亚胺的热1，6-氢转移产生的。苯胺基和酯基之间的相对构型取决于氨基酸酯的结构；无环氨基酸酯的顺式构型和环状氨基酸酯的反式构型。这种构型的差异可以用环化过程过渡态几何构型中的空间相互作用来解释，如上所述，这些合成反应是通过一个简单的步骤进行的，只需要“加热”，并且提供了许多高效和立体选择性的杂环。我想我已经提出了一种符合生态和环境观点的新颖的综合方法论。较少

In order to apply the 1,3-dipolar intermediates generated by thermal hydrogen shift of oximes and hydrazones to heterocycles synthesis, investigations on the hydrogen shift process were done. The resultant N-unsubstituted 1,3-dipoles were stabilizing by forming an hydrogen bond between the NH of the dipoles and the carbonyl oxygen located in the same molecule. Consequently, an increase of the concentration of the dipoles should be allowed to apply the dipoles to intermolecular cycloaddition reactions with dipolarophiles, which were found in few literatures. Although the reaction of the heterocyclic aldehyde oximes provided the second example for the intermolecular cycloaddition of NH-nitrone, maleimides were limited as a dipolarophile.The facile hydrazone-azomethine imine isomerization in the system was accomplished and the intermolecular cycloaddtion of the resultant dipole with olefinic dipolarophiles to afford cycloadducts efficiently and stereoselectively. The acid treatment of the … More cycloadducts caused the fission of the heterocyclic moiety to afford 2-pyrroline derivatives, which were also considered as cycloadducts of a C-unsubstituted nitrile imine and the olefinic dipolarophiles. Since only few papers on C-unsubstituted nitrile imines were found, it is very interesting from a synthetic point of view to consider these results as an equivalent reaction to C-unsubstituted nitrile imines' one.The thermal reaction of N-phenyl imines of the heterocyclic aldehyde bearing amino acid ester moieties at the adjacent position gave 2-pyrroline derivatives fused by the heterocyclic system, in which the 1,5-electrocyclic ring-closure of the α,β-unsaturated azomethine ylides generated by thermal 1,6-hydrogen shift of the imines. The relative configuration between the anilino group and the ester moiety depended on the structure of the amino acid esters; a cis configuration for acyclic amino acid esters and a trans one for cyclic amino acid esters. The discrepancy of the configuration is explained by the steric interaction in the transition state geometries of the cyclization process.As mentioned above, these synthetic reactions were performed by a simple procedure, only "heating", and afforded many heterocycles efficientiy and stereoselectively. I think that I have proposed a novel synthetic methodology matching to ecological and environmental points. Less