Copper-Mediated Oxidative [3+2]-Annulation of Nitroalkenes and Ylides of 1,2-Diazines: Assembly of Functionalized Pyrrolo[1,2-b]pyridazines

Oxidative [3+2]-annulation reactions between nitroalkenes and pyridazinium ylides mediated by Cu(OAc)(2).H2O were investigated. Functionalized pyrrolo[1,2-b]pyridazines and pyrrolo[1,2-a]phthalazines were accessed via this route. Starting from alpha-fluoronitroalkenes the reaction provides the first preparative synthesis of a broad scope of 5-fluoro-pyrrolo[1,2-b]pyridazines. The substrate scope in the case of alpha-unsubstituted nitroalkenes was investigated. Mechanistic features of the oxidative annulation reaction were studied to support the stepwise [3+2]-cycloaddition/oxidation/HNO2 elimination mechanism. Partially saturated primary [3+2]-adducts were isolated and characterized as key intermediates.

Automated summary

The oxidative [3+2]-annulation reactions between nitroalkenes and pyridazinium ylides mediated by Cu(OAc)(2).H2O were explored, leading to functionalized pyrrolo[1,2-b]pyridazines and pyrrolo[1,2-a]phthalazines. Mechanistic features of the reaction were studied to support the stepwise [3+2]-cycloaddition/oxidation/HNO2 elimination mechanism, with partially saturated primary [3+2]-adducts identified as key intermediates.