NMR and X-ray study of the diastereoselective [3+2] cycloaddition reaction of chiral acridine with stable 2,4,6-trimethylbenzonitrile N -oxide

The [3+2] cycloaddition of a chiral acridine-derived alkene with 2,4,6-trimethylbenzonitrile N-oxide yields two regioisomeric isoxazoline cycloadducts, each formed as a pair of diastereomers. Single-crystal X-ray diffraction analysis of (1S,2R,5S)-5-methyl-2-(propan-2-yl)cyclohexyl (4S,5S)-5-(acridin-4-yl)-3-(2,4,6-trimethylphenyl)-4,5-dihydro-1,2-oxazole-4-carboxylate (6b) and (1S,2R,5S)-5-methyl-2-(propan-2-yl)cyclohexyl (4R,5R)-4-(acridin-4-yl)-3-(2,4,6-trimethylphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate (7a) cycloadducts, both C₃₆H₄₀N₂O₃, unambiguously establishes the regiochemistry of the cycloaddition and the relative configuration at the newly formed stereogenic centres. The molecular structures reveal a rigid acridine framework linked to a slightly puckered isoxazoline ring, with the ester substituent adopting distinct orientations depending on the regiochemical outcome. In the solid state, the molecules are stabilized by weak C-H...O contacts involving the isoxazoline and ester functionalities, and by weak C-H...π interactions. These crystallographic results provide reliable structural benchmarks for acridine-based isoxazoline derivatives obtained via 1,3-dipolar cycloaddition reactions.