Enantioselective Photochemical Generation of a Short-Lived, Twisted Cycloheptenone Isomer: Catalytic Formation, Detection, and Consecutive Chemistry

Cyclohept-2-enone-3-carboxylic acid undergoes a photochemical isomerization from its cis- to its trans-form either upon direct irradiation (λ = 366 nm) or in the presence of a triplet sensitizer (λ = 459 nm). The intermediate chiral trans-isomer was detected by step-scan FTIR, displaying a lifetime of 130 µs (r.t., CH₂Cl₂). Ensuing Diels–Alder reactions of the trans-isomer occurred smoothly and produced chiral trans-fused cycloaddition products (14 examples, 24%–98% yield). Benzylation led to esters, which were separated by chiral HPLC and which were employed to evaluate a possible enantioselective reaction course. It was discovered that a chiral phosphoric acid with a pendant sensitizing group induces a notable enantioselectivity in the photoisomerization step. The planar chirality of the trans-cycloheptene translates into point chirality in the Diels–Alder reaction (seven examples, up to 38% ee). Computational studies suggest that the chiral conformation of the cis-isomer adopted within the assembly to the chiral phosphoric acid induces the enantioselectivity in a one-bond flip (OBF) toward the trans-isomer. Trajectory surface hopping (TSH) simulations showed exemplarily how a chiral trans-cyclohept-2-enone is formed from a chiral cis-conformer. For the Diels–Alder reaction, a weak ground state selectivity was found to attenuate the enantioselectivity achieved in the photochemical step.