title: Palladium-catalyzed stereospecific synthesis of 2,6-disubstituted tetrahydropyrans: 1,3-chirality transfer by an intramolecular oxypalladation reaction.
abstract: PdCl2(CH3CN)2 (10 mol %) catalyzed reactions of non-3-ene-2,8-diols 1 and 2 gave 2,6-disubstituted tetrahydropyrans 3 and 4 in excellent yields with high diastereoselectivities (>20:1). Intramolecular cyclizations of the hydroxy nucleophile to the chiral allylic alcohol take place efficiently under mild conditions. A new stereogenic center is generated on the tetrahydropyran ring by 1,3-chirality transfer from the chiral allylic alcohol via a syn-SN2' type process. Cis tetrahydropyran 3E was formed from syn-2,8-diols 1a and 2a, and trans tetrahydropyran 4E was formed from anti-2,8-diol 1b, stereospecifically. Cis tetrahydropyran bearing a cis alkene 3Z was obtained from 2b at -40 degrees C, while 4E was formed from 2b in the presence of catalytic amount of water at -40 degrees C. The face selectivity of these cyclizations can be rationalized by taking a favorable conformation of the intermediary Pd pi-complex with allylic alcohols, escaping the allylic strain and 1,3-diaxial interactions. A stereocontrolled synthesis of optically pure 2-alkenyl-6-methyltetrahydropyran 17 was achieved efficiently in four steps from 6-silyloxy-1-heptyne 13 with an aldehyde and included asymmetric alkynylation, partial reduction of alkyne, deprotection of the silyl group, and the stereospecific cyclization.
authors.affiliation: Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawai
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Lagrange
authors.forename: Masashi
authors.initials: M
authors.lastname: Ohmi
authors.forename: Jun'ichi
authors.initials: J
authors.lastname: Uenishi
mesh_terms: D002384:Catalysis; D003500:Cyclization; D010165:Palladium; D011714:Pyrans / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D011714:Pyrans; D010165:Palladium