A Practical Synthesis of Densely Functionalized Pyrroles via a Three-Component Cascade Reaction between
Mengxin Xia1, Mallikharjuna Rao Lambu1, Madhu Babu Tatina1
1School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, N1.2-B1-14, Singapore 637459.
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.
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