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
- 1 January 1996
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (2) , 671-676
- https://doi.org/10.1021/jo9515900
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 CH2CHOCH2-1-naphthyl and vinyl silyl ether CH2CHOSiMe2Bu-t leading to valuable 1α,25-dihydroxyvitamin D3 (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 °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.Keywords
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