Annulation of Enals with Carbamoylpropiolates via NHC-Catalyzed Enolate Pathway: Access to Functionalized Maleimides/Iso-maleimides and Synthesis of Aspergillus FH-X-213

Herein we report the N-heterocyclic carbene (NHC)-catalyzed
[3 + 2] annulation of α,β-unsaturated aldehydes with carbamoylpropiolates
via an unusual enolate pathway leading to the construction of highly
functionalized maleimides or isomaleimides. The electronic effect
imposed by the alkyl/aryl group present on the amide nitrogen of carbamoylpropiolates
plays a crucial role in the selective formation of these important
five-membered heterocyclic building blocks. The developed protocol
is mild and tolerates a wide range of substituents on both substrates.
The application of this protocol in the synthesis of the antibacterial
natural product Aspergillus FH-X-213 has also been demonstrated.