Electrophilic Iodination Reagent-Catalyzed Oxidative Annulation of Alkynoates and Nitriles to Oxazoles via Putative α,α′-Dicarbonyl Iodocarbenoids

Abstract

Electrophilic halogenation reagent-promoted alkyne functionalizations are among the most essential reactions in organic synthesis but have predominantly remained restricted to 1,2-difunctionalizations. Thus, developing new reaction modes is crucial not only for accessing new structural types but also for discovering new mechanisms and reactive intermediates. Herein, we report a diiodohydantoin (DIH)-catalyzed oxidative [3+2] annulation of alkynoates with nitriles that proceeded via a putative Fischer-type iodocarbenoid intermediate. The density functional theory calculations (DFT) supported the idea that the DIH-catalyzed pyridine N-oxide oxidation of alkynoates first generated an α-iodo-α,α′-dicarbonyl carbocation, which resonates as an iodocarbenoid stabilized by iodine lone-pair delocalization. This transient species was then trapped by nitriles to afford pharmaceutically relevant oxazoles with a broad substrate scope and good scalability, and the products were amenable to diverse derivatizations. This work provides experimental and computational evidence for the putative Fischer-type iodocarbenoid, enabling new oxidative transformations of alkynes.