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

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 (<i>endo-I</i> or <i>endo-II</i>) of the 7-membered cycloadduct. While cycloadditions with monosubstituted furans usually favor <i>endo-I</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 <i>endo-II</i> stereochemistry. Density functional theory calculations are performed to account for the selectivities. For monosubstituted furans, the crowded transition state leading to the <i>endo-I</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