Synthesis of Pyrroles by [3+2] Cycloaddition of α-Diazo Oxime Ethers with Alkenes

Significance

The synthesis of polysubstituted pyrroles by [3+2] cycloaddition of α-diazo oximino carbenoids, generated under copper catalysis from the corresponding ethers, with alkenes is reported. The choice of the geometry of the oxime such that the lone pair is disposed trans to the diazo group overcomes the formation of the triazole to lead selectively to the desired α-diazo oxime ethers. A variety of α-diazo oxime ethers were subjected to [3+2] cycloaddition with 3-amino­alkenoates in the presence of catalytic amounts of copper(II) {[Cu(hfacac)₂] or Cu(OTf)₂} to give N-oxygenated pyrroles. Although the thermal release of dimethylamine occurs initially, treatment of the intermediate dihydropyrrole with acid completes the elimination. Numerous pyrrole-3,4-dicarboxylates with various 2-heteroaryl and -alkyl substituents were synthesized in high yields. Two potential mechanisms were suggested from a zwitterionic intermediate formed by nucleophilic addition of the enamine to the carbenoid: a) C-N metalotropy followed by nucleophilic addition into the iminium ion; b) cyclopropanation followed by ring expansion.