Cooperative Catalysis with Coupled Chiral Induction in 1,3‐Dipolar Cycloadditions of Azomethine Ylides

Abstract

1,3‐Dipolar cycloadditions (1,3‐DC) between imino esters (as precursors of N‐metallated azomethine ylides) and π‐deficient alkenes are promoted by cooperative asymmetric Lewis acid/Brønsted base catalysis. The components of these catalytic pairs are silver salts derived from enantiopure commercially available BINOL‐based phosphoric acids and Cinchona alkaloids. Chiral phosphoric silver(I) salts promote HOMO raising of in situ formed 1,3‐dipoles, whereas protonated cinchona alkaloids generate a LUMO lowering for the dipolarophiles resulting in a global acceleration of the 1,3‐DC. The best results were obtained with BINOL‐derived silver phosphate and hydrocinchonine. Matching between both cooperative metallo‐ and organocatalyst results in an enhanced enantiomeric excess, superior to that reached by both separate components. NOESY experiments and DFT calculations are compatible with a non‐covalent interaction (hydrogen bond) between both catalysts, which results in close contacts and mutually coupled chiral environments.