Harnessing Indole-Derived Hydrazones for Enantioselective Synthesis of Pyrroloindolones via NHC-Catalyzed Formal [3+2]-Cycloaddition

Abstract

Pyrrolo[1,2-a]indole derivatives are widely present in bioactive alkaloids and pharmaceuticals, with pyrroloindolones, containing a γ-lactam fused to an indole scaffold, forming a significant class of heteroaromatic compounds due to their presence in numerous natural products and biologically active molecules. In this study, we explored the potential of indole-derived hydrazones as 1,2-dinucleophiles in the N-heterocyclic carbene (NHC)-catalyzed formal [3+2]-cycloaddition with α-bromo-α,β-unsaturated aldehydes. A broad substrate scope was investigated, revealing the versatility of the method with various aldehydes and hydrazones. Subsequent transformations of the cycloaddition products demonstrated the synthetic utility of the developed methodology, preserving the optical purity of the final products.