Asymmetric phosphoric acid–catalyzed four-component Ugi reaction

• DOI: 10.1126/science.aas8707
• Publication Date: 2018-09-13T18:23:51Z
• Authors: Jian Zhang; Peiyuan Yu; Shao-Yu Li; He Sun; Shao-Hua Xiang; Jun (Joelle) Wang; Kendall N. Houk; Bin Tan
• Keywords: Phosphoric acid; Ugi reaction; Component (thermodynamics)

Steering together all four Ugi pieces The nearly 60-year-old reaction is a remarkably efficient means of linking molecular building blocks: an aldehyde, amine, carboxylic acid, and isocyanide. Because each component independently tunable, the especially well suited to assembly diverse compound libraries. However, stereoselectivity has been challenge. Zhang et al. now show that chiral phosphoric acids can catalyze four-component coupling with high enantioselectivity (see Perspective by Riva). Theory suggests hydrogen-bonded complex involving acid sets stereochemistry for isocyanide attack on imine intermediate. Science , this issue p. eaas8707 ; see also 1072