Pyrazolium-Ylide [3+2] Cycloaddition/Oxidative Aromatization for the Construction of 1H-pyrrolo[1,2-b]pyrazoles

Abstract

Despite their simple 10π aromatic nature and considerable functional potential, the chemistry of 5/5-fused N-heteroaromatic systems remains underdeveloped. Herein, we report a general strategy for accessing 1H-pyrrolo[1,2-b]pyrazoles, a largely unexplored “orphan” class of heterocycles. The methodology features the generation of pyrazolium ylides followed by [3+2] cycloaddition with alkynes under mild conditions, and a subsequent oxidative aromatization step that effectively suppresses undesired ring-opening and excessive addition pathways. The substrate scope demonstrates broad functional-group tolerance and accommodates diverse substitution patterns. Combined experimental and computational studies indicate a stepwise cycloaddition mechanism, the involvement of intrinsically unstable cycloadducts, and the presence of competing pathways that render the chemoselectivity highly sensitive to subtle changes in reaction conditions. Finally, downstream derivatization highlights the utility of the 5/5-fused framework as a versatile platform for constructing more structurally complex and/or functionally enriched molecules.