Tandem Inter [4 + 2]/Intra [3 + 2] Nitroalkene Cycloadditions. 5. Origin of the Lewis Acid Dependent Reversal of Stereoselectivity

The stereochemical course of the tandem [4 + 2]/[3 + 2] nitroalkene cycloaddition with chiral enol ethers has been shown to exhibit remarkable sensitivity to the nature of the Lewis acid promoter. Cycloadditions using (+)-camphor-derived vinyl ether 3 or (−)-trans-2-phenylcyclohexanol-derived vinyl ether 6 gave a predominance of the 1S hydroxy lactam 4 when promoted by Ti(O-i-Pr)₂Cl₂. The same vinyl ethers selectively produced the 1R hydroxy lactam 4 when promoted by MAPh. The (E)- and (Z)-1-propenyl ethers of (−)-trans-2-phenylcyclohexanol have been used to investigate the reversal of selectivity. Cycloadditions promoted by Ti(O-i-Pr)₂Cl₃ were found to be endo selective (12:1), while MAD and MAPh favored exo approach of the dienophile. High levels of asymmetric induction were observed in the endo mode of the cycloaddition for propenyl ethers (E)-13 and (Z)-13, 97.9% ee and 82.2% ee, respectively, but an erosion of selectivity occurred in the exo mode (72.2% ee) presumably through an s-cis enol ether conformation.