Catalytic Enantioselective [6π] Photocyclization Reactions by Chromophore Activation with a Chiral Lewis Acid.

The [6π] photocyclization of 3-[(1,1'-biphenyl)-2-yl]-2-methylcyclopent-2-enones was found to proceed enantioselectively, when a chiral AlBr3-activated oxazaborolidine was employed as photocatalyst. A low Lewis acid catalyst loading (2.5-5.0 mol %) was sufficient to induce a high enantioselectivity in the photochemical reaction. A total number of 21 tetracyclic products were obtained as single diastereoisomers in 78-99% ee upon variation of the terminal phenyl ring in the substrate (39-83% yield). Evidence was collected that the chiral Lewis acid coordinates to the enone and induces a bathochromic shift, which allows for selective excitation of the substrate-catalyst complex at λ = 368 nm or λ = 405 nm. The substrate binds to the Lewis acid by coordination of its carbonyl oxygen atom to the Lewis acidic boron atom of the oxazaborolidine and by a noncovalent hydrogen bond of one of its methylene C-H atoms to the oxygen atom of the heterocycle. The latter interaction restricts rotation around the coordinative B-O bond and favors a distinct conformation. Quantum-chemical calculations suggest that the preferred binding mode of the substrate induces a helical conformation in which the Re face relative to the C2 carbon atom of the substrate is accessible for an attack in the photocyclization. The photocyclization step likely occurs on the triplet hypersurface and leads to an intermediate cyclohexadiene which undergoes a 1,5-hydrogen shift to restore the aromaticity in the two benzene rings of the product. The photocyclization at -80 °C was significantly slowed down by deuterium substitution at the terminal phenyl group of the substrate.