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.
(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.
Posner
Gary H.
GH
Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, and Grace Davison Division, W.R. Grace & Co., Columbia, Maryland 21044.
Dai
Haiyan
H
Bull
D. Scott
DS
Lee
Jae-Kyoo
JK
Eydoux
Franck
F
Ishihara
Yuji
Y
Welsh
William
W
Pryor
Neil
N
Petr
Stan
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