Chiral Bis(oxazoline)copper(II) Complexes as Lewis Acid Catalysts for the Enantioselective Diels−Alder Reaction

Abstract

Bis(oxazoline)copper(II) complexes are highly enantioselective catalysts in Diels−Alder reactions involving bidentate dienophiles. Cationic [Cu((S,S)-t-Bu-box)]X2 complexes with different counterions have been used as catalysts, revealing a profound influence of the counterion on the rate and stereoselectivity of the catalyst. A square-planar catalyst−substrate complex is proposed to account for the high diastereo- and enantioselectivities observed. Three bis(oxazoline)−Cu(II) X-ray structures have been obtained that support this model. Double-stereodifferentiating experiments, performed employing chiral dienophiles, afforded results that are fully consistent with the proposed square-planar transition-state assemblage. In addition to imide-based substrates, α,β-unsaturated thiazolidine-2-thiones have been introduced as a new class of dienophiles with enhanced reactivity. Kinetics experiments were performed to quantify the role that product inhibition plays in the course of the reaction. Rate and equilibri...