Chromium trioxide allylic oxidation

The formation of an epoxyketone (1) is generally favoured when the expected product of oxidation of an allylic alcohol is a cisoid enone. This type of reaction is promoted by acid conditions and may be prevented by using the chromium trioxide-pyridine reagent which gives only the unsaturated ketone (2) corresponding to the starting alcohol. ... 

Snatzke has found that a solution prepared from chromium trioxide and dimethylformamide with a small amount of sulfuric acid has similar chemical properties as the Sarett reagent. It is useful with acid sensitive compounds and oxidation occurs at such a moderate rate that selective oxidations are often possible. Although the position allylic to a A -double bond is not attacked, the 3-hydroxy-A -system cannot be oxidized satisfactorily to the cor-... 

Trifluoro-l-hydroxy-l-methylcthyl)cyclohexene is monooxidized at both allylic positions m the nng with different agents. The major product is the rearranged product C when oxidation is accomplished with chromium trioxide in methylene chlonde [42] (equation 34). 

Examples of the use of chromium(VI) reagents to effect the allylic oxidation of alkenes to give a,3-unsaturated carbonyl compounds are very common in the literature. The reaction was first reported by Treibs and Schmidt for the allylic oxidations of a-pinene to verbenone and verbenol, of dipentene to carvone and caiveol, and of cyclohexene to cyclohexenol and cyclohexenone, using a solution of chromium trioxide in a mixture of acetic anhydride and carbon tetrachloride. However, yields were low and no synthetic use of this observation was made. 

Allylic oxidation of steroids, particularly at the 7-position, has evoked interest over many years. For example, chromium trioxide-acetic acid," sodium dichromate,and r-butyl chromate have all been used in the oxidation of the 5-a-pregnane series e.g. equation 26). 

The discovery of the chromium trioxide-pyridine complex led to die accessibility of allylic oxidation under much less harsh conditions, typically room temperature reaction in (Uchloromethane solution " ... 

With the advent of the chromium trioxide-3,5-dimethylpyrazole complex as an oxidant - allylic oxidation has become far more valuable as a synthetic transfonnation. The reagent was applied by Sala-mond to the allylic oxidation of cholesteryl benzoate to give the correspondbg A -7-ketone (equation 35). However, a 20 molar excess of reagent was still requii to effect the reaction in less than 30 min at room temperature. 

A number of other chromium-based reagents have been developed for allylic oxidation for example that of stnoids by t-butyl hydroperoxide in the presence of a catalytic amount (0.0S-0.S mol equiv.) of chromium trioxide in dichloromethane solution at room temperature (equation 39). Yields vary from 32 to 69%. This modification is useful in terms of cost, operational simplicity and yields. 

Two independent syntheses of quadrone eiiq>loyed an allylic oxidation with rearrangement, as shown in equation (3), where the chromium trioxide-(3,5-dimethylpyrazole) reagent (CrOs DMP) was used. In some cases, the success of the reaction strongly depends on the nature of the oxidant, as shown in an iq>proach to (-)-upial (equation 4). Here the chi ium trioxide-heterocycle reagents, which are weaker oxidants, are quite inferior compared to the Fieser reagent ... 

An alternative mechanism has also been proposied in which oxidation at the double bond leads to a ketol derivative, elimination of water from which then gives the unsaturated ketone (Scheme 18a)." Limited kinetic data are available and suggest that Scheme 17 is obtained for chromic acid oxidations. The discovery of the chromium trioxide-pyridine complex led to the accessibility of allylic oxidatitm under much less harsh conditions, typically room temperature reaction in dichloromethane solution ... 

An attempted allylic oxidation of (68 equation 29) was found by Paquette to be difficult to achieve using a range of reagents due to problems with polymerization and rearrangement. The chromium trioxide-pyridine complex was the only reagent combination found to be successful, albeit in low yield. 

Dimethylaminopyridinium chlorochromate, 4-(CH3)2NCsH4NH CrOsCI, is a yellow-orange solid prepared by the addition of 1 mol of 4-liimethylaminopyridine to a solution of 1 mol of chromium trioxide in dilute hydrochloric acid. The reagent is light sensitive [530]. For the oxidation of allylic and benzylic alcohols to aldehydes in dichloromethane at room temperatures, 4-6 mol of 4-dimethylaminopyridinium chlorochromate is used. Saturated alcohols are not oxidized [5Jd]. 

Pyridinium dichromate, prepared from chromium trioxide in a minimum amount of water and pyridine, forms a bright-orange solid and is soluble in water, dimethylformamide, dimethyl sulfoxide, and dimethyl-acetamide sparingly soluble in dichloromethane, chloroform, and acetone and almost insoluble in hexane, toluene, ether, and ethyl acetate. Allylic secondary alcohols are oxidized more rapidly than their saturated analogues. Oxidations are carried out in dichloromethane solutions at 25 °C, and ketones are obtained in high yields (equation 251) [603. ... 

The oxidation of diols having alcoholic groups of the same nature, for example, both alcoholic groups are primary, secondary, allylic, or benzylic, is usually carried out at both groups to yield dialdehydes [832] or diketones [552], Such reactions are achieved by chromium trioxide [582], barium manganate [832], dimethyl sulfoxide activated with acetic anhydride [1013], and others (equations 284 and 285). 

Allylic oxidations of the menthadiene system are still of interest because it would be economically useful to have a really cheap method for obtaining carvone from limonene. One of the more effective methods recently described makes use of the chromium trioxide-pyridine complex in methylene chloride which Dauben et al. found to give 36% of carvone (130) and 33 % of isopiperiten-one (129). Perhaps if the same technique were applied in the oxidation of... 

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