Cu-Catalyzed Oxidative [3+2] Annulation of 2-(Pyridine-2-yl)acetates with Maleimides: Synthesis of 1H-Pyrrolo[3,4-b]indolizine-1,3-diones

A novel protocol for the construction of highly functionalized indolizine derivatives, that is, 1H-pyrrolo[3,4-b]-indolizine-1,3-diones (PIZDOs, 3) from 2-(pyridine-2-yl)acetates and maleimides via a regioselective oxidative [3 + 2] annulation was developed. The cascade oxidative reaction was enabled by heating a mixture of the two substrates in the presence of Ag2CO3 as an oxidant and Cu(OAc)center dot H2O as a catalyst in chlorobenzene. Consequently, a series of PIZDOs 3 were synthesized with high regioselectivity in moderate yields. This protocol can be used in the synthesis of functionalized PIZDOs via the one-pot oxidative annulation reaction rather than through multistep reactions, which is suitable for both combinatorial and parallel syntheses of PIZDOs.

Automated summary

A novel protocol for the synthesis of highly functionalized indolizine derivatives, known as 1H-pyrrolo[3,4-b]-indolizine-1,3-diones (PIZDOs), has been developed through regioselective oxidative [3 + 2] annulation. The cascade oxidative reaction was achieved by heating a mixture of 2-(pyridine-2-yl)acetates and maleimides in the presence of Ag2CO3 and Cu(OAc)center dot H2O catalyst in chlorobenzene. The method allows for the one-pot oxidative annulation reaction to synthesize functionalized PIZDOs instead of multiple steps reactions, making it suitable for both combinatorial and parallel syntheses of PIZDOs.