title: A density functional study of chiral phosphoric acid-catalyzed direct arylation of trifluoromethyl ketone and diarylation of methyl ketone: reaction mechanism and the important role of the CF3 group.
abstract: The detailed mechanism of the chiral phosphoric acid-catalyzed diarylation reaction between acetophenone and indole has been investigated by DFT methods and compared with that of the reaction between 2,2,2-trifluoroacetophenone and indole. The calculated results confirm our previous hypothesis that the CF3 group in the ketone plays a perfect double role in activating the substrate and stabilizing the single arylation product of tertiary alcohol. It is also demonstrated that the different ratio of the F-substitution in the CH3 group of methyl ketone (CH3-nFn, n = 0, 1, 2, 3) affects the activation energy of the key dehydration step for the proposed diarylation process differently, and determines whether the subsequent re-arylation proceeds or is being suppressed. The computational prediction that the prohibitive barriers for CF3 and CHF2 ketones in the rate-determining dehydration step for the diarylation process could be overcome at higher reaction temperature has been validated by our additional experiments at 80 °C. Furthermore, the origin of the high enantioselectivity of the chiral phosphoric acid-catalyzed single arylation of trifluoromethyl ketone has been studied with the two-layer ONIOM method. The experimentally observed enantiomeric excess can be successfully rationalized.
authors: Institute for Computational Science and Engineering, Laboratory of New Fiber Materials and Modern Textile, the Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071, China. faplhl@eyou.com apfu@qdu.edu.cn.
authors: Aiping
authors: A
authors: Fu
authors: Wei
authors: W
authors: Meng
authors: Hongliang
authors: H
authors: Li
authors: Jing
authors: J
authors: Nie
authors: Jun-An
authors: JA
authors: Ma
mesh_terms: D002384:Catalysis; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D010756:Phosphoric Acids / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D007659:Ketones; D010756:Phosphoric Acids; C030242:phosphoric acid