Asymmetric Catalytic Ring-Expansion of 3-Methyleneazetidines with a-Diazo Pyrazoamides towards Proline-Derivatives

We realized a highly efficient formal [1,2]-sigmatropic rearrangement of ammonium ylides generated from 3-methylene-azetidines and a-diazo pyrazoamides. The employ of readily available chiral cobalt(II) complex of chiral N,N & PRIME;-dioxide enabled the ring-expansion of azetidines, affording a variety of quaternary prolineamide derivatives with excellent yield (up to 99 %) and enantioselectivity (up to 99 % ee) under mild reaction condition. For the rearrangement of ammonium ylides, the installation of a pyrazoamide group as a masked brick to build chiral scaffolds proved successful. The enantioselective ring expansion process was elucidated by DFT calculations.

Automated summary

We have developed a highly efficient formal [1,2]-sigmatropic rearrangement for the generation of ammonium ylides from 3-methylene-azetidines and a-diazo pyrazoamides. By employing a readily available chiral cobalt(II) complex of chiral N,N'-dioxide, we achieved ring expansion of azetidines to afford various quaternary prolineamide derivatives with excellent yield (up to 99%) and enantioselectivity (up to 99% ee) under mild reaction conditions. The installation of a pyrazoamide group as a masked brick to build chiral scaffolds proved successful for the rearrangement of ammonium ylides, and the enantioselective ring expansion process was elucidated by DFT calculations.