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

Abstract

AbstractThe 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, magnified image, 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, magnified image, 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.