Mechanism and Selectivity of Cyclopropanation of 3-Alkenyl-oxindoles with Sulfoxonium Ylides Catalyzed by a Chiral ,'-Dioxide-Mg(II) Complex.

The mechanism and stereoselectivity of an asymmetric cyclopropanation reaction between 3-alkenyl-oxindole and sulfoxonium ylide catalyzed by a chiral ,'-dioxide-Mg(II) complex were explored using the B3LYP-D3(BJ) functional and the def2-TZVP basis set. The noncatalytic reaction occurred a stepwise mechanism, with activation barriers of 21.6-23.5 kcal mol. The C-C bond formed followed by the carbanion S2 substitution, constructing a three-membered ring in spiro-cyclopropyl oxindoles, accompanied by the release of dimethylsulfoxide. The electron-withdrawing -protecting -butyloxy carbonyl (Boc) and acetyl (Ac) groups in isatin enhanced the local electrophilicity of the C2 atom and the repulsion between the two COPh groups in the reactants, contributing to high reactivity as well as good diastereoselectivity results. The -Boc-3-phenacylideneoxindole coordinated to the chiral ligand (L-PiPr) in a bidentate fashion, forming a hexacoordinate-Mg(II) complex as the reactive species. The origin of enantioselectivity was from the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the -face of oxindole. The repulsion between the SO(CH) and COPh groups in 3-alkenyl-oxindole and the neighboring ortho-Pr group in the ligand directed the -face of ylide to attack the -face of oxindole preferably, contributing to the high diastereoselectivity of the product. A metal-ion-ligand matching relationship was important for a good asymmetric induction effect of the chiral ,'-dioxide-metal catalyst. A large chiral cavity in the Zn(II) catalyst weakened the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the prochiral face of oxindole, leading to inferior enantioselectivity observed in the experiment.