Enantioselective Diels-Alder Reactions of Unsaturated β-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes

Abstract

We report here dicationic ruthenium PNNP complexes that promote the enantioselective Diels-Alder reaction of α-methylene β-ketoesters with various dienes. Complex [Ru(OEt₂)₂(PNNP)](PF₆)₂, formed in situ from [RuCl₂(PNNP)] and (Et₃O)PF₆ (2 equiv.), catalyzes the Diels-Alder reaction of such unsaturated β-ketoesters to give novel alkoxycarbonyltetrahydro-1-indanone derivatives (nine examples) with up to 93% ee. The crystal structure of the substrate–catalyst adduct shows that the lower face of the substrate is shielded by a phenyl ring of the PNNP ligand, which accounts for the high enantioselectivity. The attack of the diene from the open re enantioface of the unsaturated β-ketoester is consistent with the absolute configuration of the product. A useful application of this method is the reaction with Dane’s diene to give estrone derivatives with up to 99% ee and an ester-exo:endo ratio of up to 145:1 (after recrystallization). Besides the enantioselective formation of all-carbon quaternary centers, this methodology is notable because unsaturated β-ketoesters have been rarely used in Diels-Alder reactions. Furthermore, enantiomerically pure estrone derivatives are interesting in view of their potential applications, including the treatment of breast cancer.