Selective oxidation of unactivated C-H bonds by supramolecular control

Abstract

The objective of this project is to develop efficient methods for selective C-H bond oxidation by supramolecular control. This work focuses to (1) develop an efficient protocol for C-H bond oxidation by dioxiranes generated in situ, (2) study the effect of cyclodextrins on site-selective C-H bond oxidation of aliphatic esters containing multiple tertiary C-H bonds, and (3) investigate the effect of cyclodextrins on selective C-H bond oxidation of hydrocarbon mixtures. Using adamantane as substrate, the reaction conditions for C-H bond oxidation by dioxiranes generated in situ was optimized. The optimized C-H bond oxidation reaction was carried out by stirring 0.1 mmol of adamantane and 0.1 mmol of 1,1,1-trifluoroacetone in a mixture of water (1 mL) and acetonitrile (1.5 mL) at 25 °C, followed by three additions of 0.5 mmol of Oxone and 1.55 mmol of NaHCO₃ at 0 h, 2 h and 4 h. On the basis of ¹H NMR analysis of the crude reaction mixture, the ratio of adamantane to 1-adamantanol to 1,3-adamantandiol was found to be 7 : 50 : 43. Site-selective oxidation of unactivated tertiary C-H bonds on aliphatic esters was achieved by supramolecular approach using cyclodextrins. Using 3,7-dimethyl octyl benzenoate as the substrate, the reaction was performed by stirring 0.2 mmol of substrate, 0.2 mmol of 1,1,1-trifluoroacetone, and 0.22 mmol of β-cyclodextrin in water at 25 °C, followed by eight additions of 0.5 mmol of Oxone and 1.55 mmol of NaHCO₃ at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h and 7 h. 3,7-Dimethyl octyl benzenoate was oxidized to 7-hydroxy-3,7-dimethyl octyl benzenoate and 3-hydroxy-3,7-dimethyl octyl benzenoate with 71% total yield based on 40% conversion (no reaction occurred without β-cyclodextrin). The product ratio of 7-hydroxy-3,7-dimethyl octyl benzenoate to 3-hydroxy-3,7-dimethyl octyl benzenoate was found to be 20 : 1, as determined by ¹H NMR analysis of the crude reaction mixture. This product ratio (20 : 1) was almost three-fold higher than the product ratio (7 : 1) given by the reaction carried out in a mixture of water and acetonitrile without β-cyclodextrin. By ¹H NMR titration experiments, 3,7-dimethyl octyl benzenoate was found to form inclusion complex with β-cyclodextrin in water with an 1 : 1 stoichiometry. The product ratio varied from 14 : 1 to 5 : 1 when the benzenoate moiety of the ester was changed to 4-tert-butylbenzenoate, pivalate and acetate. By 2D ROESY ¹H NMR analysis, the difference in the product ratios could be attributed to the different binding geometries of the substrates to β-cyclodextrin. β-Cyclodextrin was found to achieve selective C-H oxidation of hydrocarbon mixtures in water. In the presence of β-cyclodextrin, the dioxirane-based oxidation of cumene was more favored to ethylbenzene with a product ratio of cumyl alcohol : acetophenone = 8 : 1 while the reaction conducted in the absence of β-cyclodextrin gave cumyl alcohol and acetophenone in a ratio of 2 : 1.