Chromium reagents allylic oxidation

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. 

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 ... 

The procedure is commendable for its sinq>licity, reduced toxicity (chromium in all its oxidation states is carcinogenic) and achieves good yields of ketones from alcohol, for example, octan-2-ol is oxidized into octan-2-one (92%), cyclohexanol into cyclohexanone (90%) and menthol into menthone (98%). Pyridinium chromate is also a well-known oxidant for allylic oxidations. As a silica gel supported reagent, this is turned into an efficient alcohol oxidant that will leave acid-labile functions unscathed. Another advantage of the reagent is the long shelf-life of more than a year. These solid-supported oxidants also greatly facilitate pr uct work-up, when compared with their solution counterparts. 

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. 

Chromium, trioxobisfpyridine)- Collins reagent, CrO)Py2, CrOy 2Py) allylic oxidation of alkenes, 116,120 oxn. of prim, alcohols, 125 oxn. of sec. alcohols (selective), 135 Chugaev pyrolysis of thioesters, 138,140-141 Cinchona alkaloids pr., 290... 

Pioneering work in the synthesis of 8,12-eudesmanolides from santonin was carried out by Yamakawa and coworkers [47], These authors reported an allylic oxidation, with Cr(VI)-based oxidants, of methyl 3-oxoeudesm-1,4,6-trienoate (291) to give the corresponding 8-oxo-compound 294. Compound 291 was prepared from santonin (1) in a multi-step synthesis in 20% overall yield. Subsequent allylic oxidation of 291 with chromium reagents proceeded in low yield and the 8-oxo-compound (294) obtained in this way presented further difficulties when reduction of the carbonyl group at C(8) into a hydroxyl group was attempted. 

Allylic oxidation reactions employing chromium(VI) reagents theidme appear to be very much dependent upon the intrinsic nature of the substrate as to their regiochemkal outcome. This is exemplified by the r-butyl chromate allylic oxidation of (+)-3-carene (67 equation 28) where no great preference for either pr uct exists. 

A 3,5-dimethylpyrazole-chromium trioxide complex, prepared at -20 °C by quickly adding 3,5-dimethylpyrazole to chromium trioxide in CH2CI2 has been shown to be an efficient reagent for allylic oxidation. A -Steroids (e.g. choles-teryl benzoate) are oxidized very rapidly in about 75% yield to the corresponding A -ketone, there being a rate increase of 100-fold compared with using a pyridine-chromium trioxide complex. This increased activity is thought to be partly due to the increased solubility of the complex and more importantly to the possibility of intramolecular acceleration due to the pyrazole nucleus. 

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-... 

---