Mechanism of the Enantioselective Intramolecular [2 + 2] Photocycloaddition Reaction of Coumarin Catalyzed by a Chiral Lewis Acid: Comparison with Enone Substrates

Abstract

The asymmetric catalysis of the intramolecular enone [2 + 2] photocycloaddition reaction relies on a complicated regulation mechanism to control its reactivity and selectivity as well as quantum yield. The multiconfiguration perturbation theory associated with energy-consistent relativistic pseudopotentials offers a mechanistic comparison between representative coumarin and enone substrates. A pair of bright ππ* states govern the unselective background reaction of the free coumarin through the direct cycloaddition in the singlet hypersurface and the elimination of the reaction channel in the triplet manifold due to the existence of anti El Sayed type singlet-triplet crossing. The opening of a reaction channel in the triplet state is repeatedly verified to depend on the presence of relativistic effects, i.e., spin-orbit coupling due to heavy atoms in the chiral Lewis acid catalyst.

Chiral 1,3,2-Oxazaborolidine Catalysts for Enantioselective Photochemical Reactions

“…In the case of the coumarins ( Figure 10 b), direct excitation to the 1 ππ* was calculated to take place in both the uncatalyzed and catalyzed reaction. 47 Because the 1 ππ* → 3 ππ* transition is slow, ISC is a minor pathway without catalyst, and the photocycloaddition reaction can, if at all, only follow a pathway on the singlet hypersurface. With the AlBr 3 -activated oxazaborolidine catalyst, spin–orbit coupling is again increased and leads to an accelerated ISC.…”

“…Aluminum bromide also plays a significant role in the photochemical reactions through direct excitation with oxazaborolidine catalysts, as studied by Wang et al (Figure ). , Based on calculations, they concluded that the heavy atoms of the AlBr 3 -activated oxazaborolidine catalyst facilitate spin–orbit coupling. This relativistic effect allows for efficient ISC, which is crucial for the successful enantioselective [2 + 2] photocycloaddition of coumarins and 5,6-dihydro-4-pyridones.…”

“…Qualitative, simplified energy diagrams highlighting calculated photophysical processes , of (a) 5,6-dihydro-4-pyridones and (b) coumarins in the absence and presence of Lewis acid (energy levels not to scale).…”

Enantioselective Intermolecular [2+2] Photocycloaddition Reaction of Cyclic Enones and Its Application in a Synthesis of (−)-Grandisol

“…So far, only intramolecular Lewis acid-catalyzed [2+2] photocycloaddition reactions had been studied with substrates (dihydropyridones, β-alkoxyenones) that bear a tethered olefin in β- or γ-position. Assuming a reaction on the triplet hypersurface, the first bond formation step in these cases occurs rapidly in the β-position. Intermolecular trapping of photoexcited enones, such as 2-cyclohexenone ( 1a ), in a Lewis acid complex is likely slower and it occurs with high preference in α-position (vide infra).…”

Editorial for the Special Issue on Photocatalysis

“…Thus, useful photochemical synthesis was often limited to highly conjugated organic substrates that could absorb longer wavelength, lower energy light. In select circumstances, catalysts could lower the activation barriers needed for the photochemical process (Figure 1C), 4 but this approach is not general.…”