Science of Synthesis

Wang, S.-H.; Tu, Y.-Q.; Tang, M., Science of Synthesis: Applications of Domino Transformations in Organic Synthesis, (2015) 1, 273.

C-Aza quaternary center units are widespread in alkaloids, with the nitrogen atom often located at a highly sterically congested tertiary carbon. Tu and co-workers have designed and successfully developed a tandem semipinacol/Schmidt reaction of α-siloxy epoxy azides ‌15‌ for the efficient construction of many such aza quaternary carbon units.[‌12‌] In most cases, a new pyrrolidine ring is formed and the starting ring is usually expanded by two atoms (including a nitrogen atom). The reaction likely proceeds through the intermediate ‌16‌, where chelation of titanium(IV) with two oxygen atoms induces epoxide ring opening and a synchronous antiperiplanar migration that leads to the diastereoselective formation of intermediate ‌17‌. Next, the subsequent antiperiplanar migration of the quaternary carbon in intermediate ‌18‌ to the electron-deficient nitrogen proceeds with retention of configuration to provide the final polycyclic product ‌19‌ (‌Scheme 6‌).

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References