Asymmetric direct aldol reaction of functionalized ketones catalyzed by amine organocatalysts based on bispidine

J Am Chem Soc. 2008 Apr 30;130(17):5654-5. doi: 10.1021/ja800839w. Epub 2008 Apr 2.

Abstract

Organocatalysts containing primary-secondary amine based on bispidine and amino acid have been designed to catalyze the asymmetric direct aldol reaction of functionalized ketones including alpha-keto phosphonates, alpha-keto esters, as well as alpha,alpha-dialkoxy ketones as aldol reaction acceptors. The corresponding products with chiral tertiary alcohols were obtained in moderate to high yields (up to 97%) and high enantioselectivities (up to 98% ee). A theoretical study of transition structures demonstrated that protonated piperidine was important for the reactivity and enantioselectivity of this reaction.