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Control of Regioselectivity and Stereoselectivity in (4 + 3) Cycloadditions of Chiral Oxyallyls with Unsymmetrically Disubstituted Furans

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posted on 19.02.2016 by Yunfei Du, Elizabeth H. Krenske, Jennifer E. Antoline, Andrew G. Lohse, K. N. Houk, Richard P. Hsung
The regioselectivities and stereoselectivities of ZnCl2-catalyzed (4 + 3) cycloadditions between chiral oxazolidinone-substituted oxyallyls and unsymmetrical disubstituted furans have been determined. The substitution pattern on the furan is found to provide a valuable tool for controlling the stereochemistry (endo-I or endo-II) of the 7-membered cycloadduct. While cycloadditions with monosubstituted furans usually favor endo-I products, from addition of the furan to the more crowded face of the oxyallyl, cycloadditions with 2,3- and 2,5-disubstituted furans instead favor the endo-II stereochemistry. Density functional theory calculations are performed to account for the selectivities. For monosubstituted furans, the crowded transition state leading to the endo-I cycloadduct is stabilized by an edge-to-face interaction between the furan and the oxazolidinone 4-Ph group, but this stabilization is overcome by steric clashing if the furan bears a 2-CO2R group or is 2,3-disubstituted.