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 (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.