Multistep Cascade Catalyzed by a Single-Chiral Lewis Acid: Efficient Asymmetric Synthesis of Macrocyclic Chiral Dilactones and Dilactams.

Abstract

A Cu-(II)-catalyzed asymmetric cascade process was successfully developed by the dimerization of β,γ-unsaturated α-keto tryptophol esters or β,γ-unsaturated α-keto tryptamino amides under mild reaction conditions, furnishing the corresponding macrocyclic dilactones and dilactams in good yields with excellent regio-, diastereo-, and enantioselectivities. The transformation involved a four-step cascade of double Friedel-Crafts alkylation and double N-hemiketalization, providing efficient access to a variety of macrocyclic dilactone and dilactam scaffolds bearing four new stereocenters in a one-pot and highly atom-economic fashion. The resultant chiral macrocyclic compounds were further applied as ligands in the copper-catalyzed asymmetric Friedel-Crafts alkylation reactions and also tested as multifunctional chiral host molecules in binding with quinine and quinidine.