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Three-Component Coupling Reactions of Silyl Glyoxylates, Vinyl Grignard Reagent, and Nitroalkenes: An Efficient, Highly Diastereoselective Approach to Nitrocyclopentanols


  • This project was supported by Award Number R01 GM084927 from the National Institute of General Medical Sciences. Additional support from Novartis and Amgen is gratefully acknowledged. Glyoximide 10 was generously provided by Prof. Richard Hsung and Dr. Ziyad Al-Rashid. X-ray crystallography was performed by Dr. Peter White.


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Quick and easy: A regio- and stereoselective three-component coupling reaction generates functionalized (Z)-silyl enol ethers through a vinylation/[1,2]-Brook rearrangement/vinylogous Michael reaction cascade. These adducts can then undergo a diastereoselective deprotection/intramolecular Henry sequence to rapidly assemble densely functionalized nitrocyclopentanols with three contiguous stereocenters (see scheme; TES=triethylsilyl).