title: Enantioselective Diels-Alder reactions of unsaturated beta-ketoesters catalyzed by chiral ruthenium PNNP complexes.
abstract: We report here dicationic ruthenium PNNP complexes that promote the enantioselective Diels-Alder reaction of alpha-methylene beta-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 beta-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 beta-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 beta-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.
authors.affiliation: Laboratory of Inorganic Chemistry, ETH Zürich, CH-8093 Zürich. schotes@inorg.chem.ethz.ch
authors.forename: Christoph
authors.initials: C
authors.lastname: Schotes
authors.forename: Antonio
authors.initials: A
authors.lastname: Mezzetti
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D004970:Estrone / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D004970:Estrone; D012428:Ruthenium