Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed.The oxidation and functionalization of hydrocarbons is a central facet of the chemical industry for the production of hightonnage commodities and the preparation of high-value pharmaceuticals, agrochemicals and fine chemicals. Therefore, methods for selective oxidation of C-H bonds are of great importance.1 Phenols represent a key class of oxidized hydrocarbon.2 While there are a small number of reports in which arenes are oxidized to the respective phenols using peroxides and strong acids as additives, 3 the oxidation of aromatic C-H bonds still presents a synthetic challenge specifically with respect to avoiding over oxidation. Scheme 1. C-H oxidation using phthaloyl peroxide. 2A recent report from the laboratories of Houk and Siegel described a metal-free oxidation of aromatic carbon-hydrogen bonds which was proposed to proceed through an intriguing reverse-rebound mechanism (Scheme 1). 4Reaction of mesitylene 2 with 1.3 equiv. of phthaloyl peroxide 1 in hexafluoroisopropanol (HFIP) followed by basic solvolysis gave the phenol 3 (97%). The method outlined in Scheme 1 represents a significant advance in arene oxidation. The proposed mechanistic pathway for the transformation suggested homolytic fission of the weak oxygen-oxygen bond leading to diradical 4. Addition of this radical to the arene gives 5 which though H-atom abstraction provides the observed product 6. Ester hydrolysis leads to the phenol 3 (97%, 2 steps). The procedure has wide functional group tolerance and arene over oxidation did not prove problematic. We believed two fundamental opportunities existed for development of this procedure: Firstly, phthaloyl peroxide 1 is known to be very shock sensitive and explodes violently when heated, representing a significant hazard. 5,6 Secondly, the proposed reverse-rebound mechanism leading to 6 was based upon theoretical studies. Provision of experimental evidence to support this pathway would be of great importance to the understanding and development of this procedure. In recent years we have been interested in the chemistry of cyclic diacylperoxides and have shown that malonoyl peroxide 7, 7 and related derivatives, 8 are effective for the syndihydroxylation of alkenes.9 This reagent provides significant advantages over phthaloyl peroxide 1 within the syndihydroxylation reaction in terms of yield, selectivity, reaction rate, substrate scope and operating temperature.10,11 Given our experience in understanding the mechanism of reactions involving the peroxide 7, 12 together with the specific advantages provided in alkene dihydroxylation we el...
A novel method for the Baeyer–Villiger oxidation of ketones has been developed and optimized. The transformation involves a transition metal-free activation of hydrogen peroxide under Payne epoxidation conditions. Reaction of a ketone with hydrogen peroxide in the presence of a nitrile under mildly basic reaction conditions leads to the corresponding ester. The transformation has been successfully applied to a range of ketones in moderate to excellent yields (30–91 and good to excellent regioselectivities (7:1 to 20:1)
The N,O-diacylhydroxylamine derivative 4 has been prepared and its reactivity with nucleophiles investigated. On reaction with lithium enolates of cyclic or acyclic ketones, 4 is converted stereoselectively to the corresponding alkylidene phthalide. The stereochemical outcome of the transformation can be modified by changing the polarity of the reaction medium and the products isomerized under acidic conditions.
The products are formed as mixtures of E/Z isomers only the major isomer of which is isolated in moderate to high yields.
SummaryThe default explanation for good to high diastereomeric excess when reducing N-chiral imines possessing only mediocre cis/trans-imine ratios (>15% cis-imine) has invariably been in situ cis-to-trans isomerization before reduction; but until now no study unequivocally supported this conclusion. The present study co-examines an alternative hypothesis, namely that some classes of cis-imines may hold conformations that erode the inherent facial bias of the chiral auxiliary, providing more of the trans-imine reduction product than would otherwise be expected. The ensuing experimental and computational (DFT) results favor the former, pre-existing, explanation.
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