Chemoselective Hydroxylation of Aliphatic sp³ C–H Bonds Using a Ketone Catalyst and Aqueous H₂O₂

Abstract

The first ketone-catalyzed method for the oxidation of aliphatic C-H bonds is reported. The reaction conditions employ aryl trifluoromethyl ketones in catalytic amounts and hydrogen peroxide as the terminal oxidant. Hydroxylation is stereospecific and chemoselective for tertiary over secondary C-H bonds. A catalytic cycle invoking a dioxirane as the active oxidant is proposed.

Synthesis and evaluation of phenylalanine-derived trifluoromethyl ketones for peptide-based oxidation catalysis

“…We recently explored the possibility that peptide-based ketones 5,6 might also be effective catalysts for oxidation, perhaps for both epoxidation and C–H hydroxylation reactions. 7,8 In an earlier study, for example, we found that a peptide-based trifluoromethyl ketone exhibited good catalytic properties, such that certain olefins could undergo epoxidation with enantiomeric ratios of up to 91:9 and good yields with use of 10 mol% of the catalyst (Figure 1b). 6 However, certain limitations were encountered, including the compatibility of an N -terminal amino acid residue as the moiety carrying the trifluormethyl ketone as the catalytic side chain.…”

“…p -Fluoroarene substitution, for example, demonstrated by Hilinski to be advantageous in ketone-catalyzed C–H hydroxylation reactions. 7 The successful synthesis of these unusual compounds, and the demonstration of their suitability as competent catalysts for olefin epoxidation is the subject of this report.…”

Continued Progress towards Efficient Functionalization of Natural and Non‐natural Targets under Mild Conditions: Oxygenation by C−H Bond Activation with Dioxirane

“…[78] Although the authors demonstrated the feasibility of catalysis, this methodw as limited only to specific substrates, which were oxidized with moderate conversions. [78] In 2017, after extensive investigation, they reported a second-generation approachtoketone-catalyzed hydroxylation that addresses these limitations. [79] Indeed, the hydroxylation of the CÀHb ond wasa ccomplished by treatment with ac ommerciallya vailable alkyl trifluoromethyl ketone 48 combined with oxone as oxidant(Scheme20).…”

cis-Decalin oxidation as a stereochemical probe of in-MOF versus on-MOF catalysis

“…Trans-decahydronapthalen-9-ol were prepared according to literature methods. 10 Under an N2 atmosphere, a round-bottom flask was charged with a chromium trioxide (0.610 g, 6.10 mmol, 2.96 equiv), CH2Cl2 (3 mL) and CH 3 CN (9 mL). The mixture was stirred vigorously for 20 min and then cooled to -40 °C.…”