Inter- and intramolecular hetero diels-alder reactions, 40. Effect of high pressure on the stereoselectivity of intermolecular hetero diels-alder reactions

The hetero Diels-Alder reaction of enamino ketone 1 with the vinyl ethers 7–11 leading to the dihydropyrans 12a–e and 13a–e is studied in dichloromethane under high pressures up to 7 kbar. The kinetics is measured by on-line FT-IR spectroscopy up to 3 kbar. For the first time individual rate coefficients kcis and ktrans have been determined. Pressure-averaged activation volumes, , for the overall reaction leading to the formation of the two diastereomers in dichloromethane solution between -(19.1 ± 1.7) and -(25.4 ± 1.6) cm3 mol−1 are measured. The corresponding activation enthalpies, ΔH‡, are between (62.2 ± 1.6) and (76.3 ± 3.6) kJ mol−1. The cycloaddition shows a remarkable increase in diastereoselectivity in favour of the cis adducts 12a–e toward higher pressure. The pressure-averaged differences in activation volume, , for the two reaction pathways leading to cis and trans diastereomers are found to be between -(4.5 ± 0.3) and -(6.9 ± 0.7) cm3 mol−1. The corresponding differences in activation enthalpy, δδH≠, are between -(4.7 ± 1.4) and -(9.9 ± 1.6) kJ mol−1. Combination of the overall rate coefficient k = kcis + ktrans for the reaction leading to the two diastereomers with the measured product ratio, ccis/ctrans, which is identified with the ratio of the rate coefficients kcis/ktrans, yields the individual coefficients kcis and ktrans. The rate coefficient kcis is strongly influenced by the steric demand of the substituents on both diene and dienophile whereas ktrans varies to a smaller extent, and the observed changes appear to be mainly due to the electronic properties of the substituents.