Enantioselective [4+2]‐Cycloaddition Reaction of a Photochemically Generated o‐Quinodimethane: Mechanistic Details, Association Studies, and Pressure Effects

Abstract

1,2,3,4‐Tetrahydro‐2‐oxoquinoline‐5‐aldehyde (2) was prepared from m‐aminobenzoic acid and 3‐ethoxyacryloyl chloride (4) in 19 % overall yield. Compound 2 underwent a photochemically induced [4+2]‐cycloaddition reaction with various dienophiles upon irradiation in toluene solution. The exo product 10 a was obtained with acrylonitrile (9 a) as the dienophile, whereas methyl acrylate (9 b) and dimethyl fumarate (9 c) furnished the endo products 11 b and 11 c (69–77 % yield). The reactions proceeded at −60 °C in the presence of the chiral complexing agent 1 (1.2 equiv) with excellent enantioselectivity (91–94 % ee). The enantiomeric excess increases in the course of the photocycloaddition as a result of the lower product association to 1. The intermediate (E)‐dienol 8 was spectroscopically detected at −196 °C in an EPA (diethyl ether/isopentane/ethanol) glass matrix. The association of the substrate 2 to the complexing agent 1 was studied by circular dichroism (CD) titration. The measured association constant (K_A) was 589 M⁻¹ at room temperature (25 °C) and normal pressure (0.1 MPa). An increase in pressure led to an increased association. At 400 MPa the measured value of K_A was 703 M⁻¹. Despite the stronger association the enantioselectivity of the reaction decreased with increasing pressure. At 25 °C the enantiomeric excess for the enantioselective reaction 2 + 9 a→10 a decreased from 68 % ee at 0.1 MPa to 58 % ee at 350 MPa. This surprising behavior is explained by different activation volumes for the diastereomeric transition states leading to 10 a and ent‐10 a.