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)]X 2 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 equilibrium binding constants of various catalyst inhibitors were also derived from the kinetic analysis. A comparative study was undertaken to elucidate the differences between the bis(oxazoline)−Cu(II) catalyst and the bis(oxazoline) catalysts derived from Fe(III), Mg(II), and Zn(II). Catalyst performance was found to be a function of a subtle relationship between bis(oxazoline) structure and transition metal.