Theoretical prediction and experimental tests of conformational switches in transition states of Diels-Alder and 1,3-dipolar cycloadditions to enol ethers

Transition structures for the cycloadditions of butadiene, acrolein, nitrosoethylene, and methylenenitrone to 1-butene, silyl vinyl ether, and methyl vinyl ether have been located using ab initio RHF theory with the 3-21G basis set and with density functional theory using the Becke3LYP functional and the 6-31G* basis set. The computational results show that there is a snitch in the conformation of the enol ether from syn (COCC = 0 degrees), which is favored by 2.3 kcal/mol in the reactant, to anti (COCC = 180 degrees), which is favored by 1.2-6.6 kcal/mol in the various transition structures studied here. The results are consistent with the experimental stereoselectivities in reactions of chiral enol ethers observed by Denmark and Reissig. The preference of the anti conformation in the transition structures is due primarily to electrostatic effects and, to a lesser extent, steric effects. The preference is predicted to be influenced significantly by polar solvents. The magnitude of this preference was calculated theoretically and measured experimentally: the rates of cycloadditions of conformationally fixed enol ethers, 2,3-dihydrofuran and 2-methylenetetrahydrofuran, with 1-nitroso-1-phenylethylene and with C-benzoyl-N-phenylnitrone were studied. Observed relative rates are in good agreement with prediction and confirm that enol ethers adopt the s-trans conformation in transition states of cycloadditions.