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.