Studies on the Formal [3 + 2] Cycloaddition of Aziridines with Alkenes for the Synthesis of 1‑Azaspiroalkanes

The Lewis acid-mediated
[3 + 2] cycloaddition of N-sulfonyl- and N-sulfamoylaziridines with alkenes
provides a rapid and efficient access to 1-azaspiro­[4.n]­alkanes. Experimental studies have been combined with DFT calculations
to explore the mechanism of the reaction. They demonstrate that the
nature of the electron-withdrawing nitrogen protecting group has a
very limited influence on the course of the reaction and, particularly,
on the initial formation of the 1,3-zwitterionic species through C–N
bond cleavage, which has been found to be the rate-determining step.
Compared to N-sulfonylaziridines, N-sulfamoylaziridines have proved to be more synthetically useful
synthons that afford crystalline polycyclic structures in good yields.
A short sequence of catalytic C­(sp3)-H amination–cyclization–[3
+ 2] cycloaddition has then been successfully designed to afford the
homologue 1-azaspiro­[5.n]­alkanes, thereby illustrating
the higher versatility of sulfamates in these cycloadditions.

路易斯酸（Lewis acid）介导的N-磺酰基与N-氨磺酰基氮丙啶与烯烃的[3+2]环加成反应，可快速高效地构建1-氮杂螺[4.n]烷烃类化合物。本研究将实验研究与密度泛函理论（DFT）计算相结合，对该反应的机理进行了探究。结果表明，吸电子氮保护基的类型对反应进程影响极小，尤其是对通过C-N键断裂生成1,3-两性离子物种的初始步骤——该步骤被证实为反应的决速步——的影响。与N-磺酰基氮丙啶相比，N-氨磺酰基氮丙啶被证明是更具合成应用价值的合成子，可高产率得到结晶性多环结构。随后，我们成功设计了一条包含催化C(sp3)-H胺化、环化与[3+2]环加成的短序列反应，得到了同系物1-氮杂螺[5.n]烷烃，由此体现出氨磺酸酯在这类环加成反应中更高的多功能性。