A Practical Synthesis of Densely Functionalized Pyrroles via a Three-Component Cascade Reaction between Carbohydrates, Oxoacetonitriles, and Ammonium Acetate
Mengxin Xia, Mallikharjuna Rao Lambu, Madhu Babu Tatina, Zaher M. A. Judeh
Abstract
A practical three-component reaction between unactivated carbohydrates, oxoacetonitriles, and ammonium acetate gave densely functionalized pyrroles in 75–96% yields. Disaccharides afforded novel pyrrolo-glycosides. This metal-free, Et3N-catalyzed cascade reaction proceeded with exclusive chemo-, regio-, and stereoselectivities and showed a wide substrate scope with high atom economy. It also proceeded successfully at a 2 g scale, demonstrating potential for large-scale synthesis. The functional groups on the pyrroles permit easy transformation to other handles for the construction of more complex structures. The reaction proceeded through a cascade mechanism involving several intermediates identified by mass spectrometric analysis. This work has great potential for the sustainable production of densely functionalized pyrroles from cheap and widely available carbohydrates and represents a key advancement in the sustainable synthesis of these ubiquitous heterocycles.