Ketones allylic oxidation

Now that the allylic oxidation problem has been solved adequately, the next task includes the introduction of the epoxide at C-l and C-2. When a solution of 31 and pyridinium para-tolu-enesulfonate in chlorobenzene is heated to 135°C, the anomeric methoxy group at C-l 1 is eliminated to give intermediate 9 in 80% yield. After some careful experimentation, it was found that epoxy ketone 7 forms smoothly when enone 9 is treated with triphenyl-methyl hydroperoxide and benzyltrimethylammonium isopropoxide (see Scheme 4). In this reaction, the bulky oxidant adds across the more accessible convex face of the carbon framework defined by rings A, E, and F, and leads to the formation of 7 as the only stereoisomer in a yield of 72%. 

Dipyridiue-chromium(VI) oxide2 was introduced as an oxidant for the conversion of acid-sensitive alcohols to carbonyl compounds by Poos, Arth, Beyler, and Sarett.3 The complex, dispersed in pyridine, smoothly converts secondary alcohols to ketones, but oxidations of primary alcohols to aldehydes are capricious.4 In 1968, Collins, Hess, and Frank found that anhydrous dipyridine-chromium(VI) oxide is moderately soluble in chlorinated hydrocarbons and chose dichloro-methane as the solvent.5 By this modification, primary and secondary alcohols were oxidized to aldehydes and ketones in yields of 87-98%. Subsequently Dauben, Lorber, and Fullerton showed that dichloro-methane solutions of the complex are also useful for accomplishing allylic oxidations.6... 

The Pacman catalyst selectively oxidized a broad range of organic substrates including sulfides to the corresponding sulfoxides and olefins to epoxides and ketones. However, cyclohexene gave a typical autoxidation product distribution yielding the allylic oxidation products 2-cyclohexene-l-ol (12%) and 2-cyclohexene-1-one (73%) and the epoxide with 15% yield [115]. 

The activity of the FePeCli6-S/tert-butyl hydroperoxide (TBHP) catalytic system was studied under mild reaction conditions for the synthesis of three a,p-unsaturated ketones 2-cyclohexen-l-one, carvone and veibenone by allylic oxidation of cyclohexene, hmonene, and a-pinene, respectively. Substrate conversions were higher than 80% and ketone yields decreased in the following order cyclohexen-1-one (47%), verbenone (22%), and carvone (12%). The large amount of oxidized sites of monoterpenes, especially limonene, may be the reason for the lower ketone yield obtained with this substrate. Additional tests snggested that molecular oxygen can act as co-oxidant and alcohol oxidation is an intermediate step in ketone formation. 

The heterogeneous catalytic system iron phthalocyanine (7) immobilized on silica and tert-butyl hydroperoxide, TBHP, has been proposed for allylic oxidation reactions (10). This catalytic system has shown good activity in the oxidation of 2,3,6-trimethylphenol for the production of 1,4-trimethylbenzoquinone (yield > 80%), a vitamin E precursor (11), and in the oxidation of alkynes and propargylic alcohols to a,p-acetylenic ketones (yields > 60%) (12). A 43% yield of 2-cyclohexen-l-one was obtained (10) over the p-oxo dimeric form of iron tetrasulfophthalocyanine (7a) immobilized on silica using TBHP as oxidant and CH3CN as solvent however, the catalyst deactivated under reaction conditions. 

Catalytic activity. Figure 49.1 shows the catalytic activity of FePcCli6-S for the allylic oxidation of 1, 2, and 3. High olefin conversion was observed the highest ketone yield was obtained with cyclohexene. The lower ketone yields... 

The ring-opening of the cyclopropane nitrosourea 233 with silver trifiate followed by stereospecific [4 + 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-eyclohexen-l-ones [131], allylic oxidation of oc,/ -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

A catalytic method for the allylic oxidation of alkenes was first reported by Umbreit and Sharpless in 1977, who utilized TBFIP as oxidant and Se02 as catalyst for selective aUylic oxidation. Yields were moderate providing aUylic alcohols or ketones with 54-86% yield. The reaction did not proceed under strictly anhydrous conditions but with one equivalent of water present the oxidation proceeds smoothly at room temperature. In... 

The same catalytic system (SeOi/TBHP) has also been used by Chabaud and Sharpless in the allylic oxidation of alkynes. The oxidation products resulting from the Se02-catalyzed allylic oxidation with TBHP are the allylic alcohol, the allylic diol, the allylic ketone, the ketol and the enynone (Scheme 127). The main product of the reaction is either the alcohol or the diol, depending on the substrate employed (together 76-100% of the whole yield). The yields of allylic oxidation products together range from 15 to 88%. From the observed results with unsymmetrical alkynes it could be concluded that the reactivity sequence for the carbon attached to the triple bond of alkynes is CH2 CH > CH3. 

Sheldon and coworkers have developed chromium-substituted molecular sieves (CrAPO-5) as recyclable solid catalysts for several selective oxidations, among them also the allylic" and benzylic ° " ° " ° oxidations using TBHP or O2 as the terminal oxidants (equation 63), which yielded the corresponding benzylic ketones in moderate yield (conv. 13-70%) and moderate to good selectivity (41%, 65-97%). The benzylic alcohols were formed as side products. Allylic oxidation also proceeded with good conversions, while selectivities were lower and both possible products, the allylic ketone (31-77% selectivity) and the allylic alcohol (0-47% selectivity), were formed. Chromium sUicalite showed activity for selective benzylic oxidation in the presence of TBHP as well as giving mainly the allylic ketone (2-cyclohexen-l-one with 74% selectivity) and the allylic alcohol as minor product (2-cyclohexen-l-ol with 26% selectivity) -. ... 

Muzart and coworkers investigated the CrOs/TBHP catalyzed oxidation of various benzylic methylenes and the allylic oxidation of A - and A -cholesten-3-one to the corresponding ketones in CH2Cl2 as well as benzotrifluoride (BTF) as solvent (Scheme 130) °. It could be shown that BTF in most cases improved the results even though the reactions were carried out with less TBHP than in CH2CI2 (4 eq. compared to 7 eq.). Yields in CH2CI2 varied from 21 to 94% and those in BTF from 40 to 99%. 

Tropones are obtained in good over-all yields when the dihalocarbene adducts of A2- and A3-norcarenes are first allylically oxidized and the resulting ketones subsequently subjected to a dehydrohalogenation sequence [136]. 

Allylic oxidation offers another route to ketones. Michael P. Doyle of the University of Maryland has found (/ Am. Chem. Soc. 2004,126, 13622) that Rh caprolactam is a very active (0.1 mol %) catalyst for this conversion. 

Synthetic methods for 2(5jF/)-furanones have been developed in the preparation of cardenolides (65MI31200). The ketone (171) when reacted with lithium ethoxyacetylide gives the carbinol (172) which undergoes acid catalyzed rearrangement to the a,/3-unsaturated ester (173). Allylic oxidation of (173) with selenium dioxide under mild conditions gives digitoxigenin acetate (174) (Scheme 38). 

Solid heteropoly compounds are suitable oxidation catalysts for various reactions such as dehydrogenation of O- and N-containing compounds (aldehydes, carboxylic acids, ketones, nitriles, and alcohols) as well as oxidation of aldehydes. Heteropoly catalysts are inferior to Mo-Bi oxide-based catalysts for the allylic oxidation of olefins, but they are much better than these for oxidation of methacrolein (5). Mo-V mixed-oxide catalysts used commercially for the oxidation of acrolein are not good catalysts for methacrolein oxidation. The presence of an a-methyl group in methacrolein makes the oxidation difficult (12). The oxidation of lower paraffins such as propane, butanes, and pentanes has been attempted (324). Typical oxidation reactions are listed in Table XXXI and described in more detail in the following sections. 

Freshly prepared Mn02 is a useful reagent in organic chemistry and has been used in a large variety of oxidative transformations.311 These reactions involve the allylic oxidation of alkene to a,/3-unsaturated carbonyl compounds, the transformation of methylarenes to benzaldehyde and benzoic acid derivatives, the oxidation of secondary methylene groups to ketones, and the oxidation of alcohols to carbonyl compounds.311 The yields are generally fair to good. 

Selenium dioxide, Se02, is a widely used reagent for the allylic oxidation of alkenes and ketones. The subject has been extensively covered by recent review articles56,291 293 and only a short summary will be given in this chapter. 

Figure 7.10 (top) shows the FT-IR spectrum of freshly prepared C60D36. The exposure to air after 1 day causes alterations in the spectrum (Fig. 7.10, middle). In particular it can be noticed the reduction of the intensity of the C-D stretching band at 2,092 cm-1 and the complete disappearance of the C-D bending at 966 cm-1. Evidences of oxidation can be inferred by the C=0 stretching band at 1,710 cm-1 and by the C-OH and C-OOH bending at about 1,040 cm-1 supporting the allylic oxidation mechanism. After 3 days exposure to air an increase in the relative intensity of the ketone, hydroxyl and hydroperoxide bands can be observed (Fig. 7.10, bottom). 

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