title: Lewis Acid-Promoted, Stereocontrolled, Gram Scale, Diels-Alder Cycloadditions of Electronically Matched 2-Pyrones and Vinyl Ethers: The Critical Importance of Molecular Sieves and the Temperature of Titanium Coordination with the Pyrone.
abstract: (R)-(+)-Binol-titanium coordinates with commercial methyl 2-pyrone-3-carboxylate and promotes mild, highly enantiocontrolled Diels-Alder cycloadditions with electron-rich vinyl ether CH(2)=CHOCH(2)-1-naphthyl and vinyl silyl ether CH(2)=CHOSiMe(2)Bu-t leading to valuable 1alpha,25-dihydroxyvitamin D(3) (calcitriol) intermediate (-)-2. Unexpectedly, two subtle variables were found to be critical for obtaining reproducibly over 90% enantioselectivities in gram scale cycloadditions: (1) the moisture content (15-17% is best) of the molecular sieves used to prepare the binol-titanium complex according to the Mikami protocol and (2) the temperature (50 degrees C is best) at which the pyrone ester is mixed with the binol-titanium complex. Unsubstituted 2-pyrone undergoes ytterbium-promoted, high-pressure, regioselective, and stereoselective Diels-Alder cycloaddition with benzyl vinyl ether to form versatile bicyclic lactone (+/-)-4 on gram scale.
authors.affiliation: Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, and Grace Davison Division, W.R. Grace & Co., Columbia, Maryland 21044.
authors.forename: Gary H.
authors.initials: GH
authors.lastname: Posner
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dai
authors.forename: D. Scott
authors.initials: DS
authors.lastname: Bull
authors.forename: Jae-Kyoo
authors.initials: JK
authors.lastname: Lee
authors.forename: Franck
authors.initials: F
authors.lastname: Eydoux
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishihara
authors.forename: William
authors.initials: W
authors.lastname: Welsh
authors.forename: Neil
authors.initials: N
authors.lastname: Pryor
authors.forename: Stan
authors.initials: S
authors.lastname: Petr