Collins allylic oxidation

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... 

Allylic oxidations were also explored using PCC, Collins reagent, and selenium dioxide. While the desired enone 108 formed, the less strained, less substituted olefin 107 was invariably the dominant product. Use of the Collins reagent afforded the best yields (40%), but produced the same inseparable mixture of regioisomers (3 1,107 108). 

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... 

Allylic oxidation of some cyclopentenes and cyclohexenes to the corresponding enones, using Collins reagent prepared in situ, has been found to proceed satisfactorily if all the reagents are kept very dry. ... 

Collins reagent is used for the introduction of carbonyl groups at allylic positions." This transformation of alkenes into enones is much slower than the oxidation of alcohols, requiring a great excess of Cr03 2Py and prolonged reaction times. Consequently, alcohols can be oxidized to aldehydes and ketones by Collins reagent without interference from alkenes. 

Collins reagent can transform tertiary allylic alcohols into rearranged enones,101 similar to PCC, which is routinely used for this purpose (see page 55). As this reaction is normally slower than the oxidation of primary and secondary alcohols, these can be oxidized with Collins reagent with no interference from tertiary allylic alcohols present in the same molecule.102... 

Similar to Jones reagent, Collins reagent can produce a hydroxy directed epoxidation of allylic alcohols. This side-reaction only occurs in a limited number of allylic alcohols, most of them being oxidized uneventfully to the corresponding enones.117... 

Wittig rearrangement of allyl silyl ethers, followed by Simmons-Smith cyclopropana-tion and Collins oxidation, produces a-cyclopropyl acyl silanes, e.g. 22, in 10-85% yields (Scheme 55)85. 

Alternatively it is possible to oxidize a primary alcohol no further than to give the aldehyde. This is the domain of the Collins reagent, PCC, PDC, or activated dimethyl sulfoxide. The oxidation of primary alcohols with K2Cr207 in aqueous solution to nothing but the aldehyde, (i.e., without further oxidation to the carboxylic acid) is possible only if a volatile aldehyde results and is distilled off as it is formed. This is the only way to prevent the further oxidation of the aldehyde in the (aqueous) reaction mixture. Selective oxidations of primary alcohols to aldehydes with the Jones reagent succeed only for allylic and benzylic alcohols. Otherwise, the Jones reagent directly converts alcohols into carboxylic acids (see above). 

The Collins oxidation is efficient for the preparation of carbonyl compounds in the presence of a wide range of functionalities (Table 2) however, Dauben and cowoikers observed that extended exposure to the complex (24 h at room temperature) can give moderate to excellent yields of allylic C—oxidation products (equations 3 to 5). ... 

In a similar fiashion to the Collins reagent, PCC will also induce oxidative rearrangement of tertiary allylic alcohols (Table S). PCC, and several other chromium oxidants, will also cause tertiary cyclopropyl alcohols to rearrange to give 3,y-unsaturated carbonyl compounds (equation 8). ... 

Pyridinium chlorochromate (PCC) Corey and Suggs prepared PCC by mixing CrOs with pyridine in HCl. PCC is used for the oxidation of primary and secondary alcohols in CH2CI2. This reagent is less efficient than Collins reagent for the oxidation of allyl alcohols. 

The mode of interaction of the oxidant with the acetoxypalladation adduct is not certain. The oxidant could be removing electrons from Pd as the Pd(II)—C bond is broken and Pd(0) is never formed, or the Pd(II) could be oxidized to Pd(IV) which would leave much more easily than Pd(II). Another possibility is that the organic radical is transferred to the oxidant followed by decomposition. It would be difficult to distinguish between the various possibilities. Related reactions are the cleavage of a-bonded palladium complexes with Collins reagent (280), decomposition of rr-allyls with oxidants (164), and the decomposition of oxypalladation adducts of diolefins with oxidants (Section IV, B). 

Oxidative decomplexation of the above described palladium alkyl or allyl complexes with Collin s reagent gave norbornenones 20 and nortricyclenones 21 in varying ratios depending on the starting material. ... 

However, a source of the non-natural 9S isomer (2) was first required. The ready availability of natural crinitol made a racemization/resolution route, as illustrated in Scheme 1, attractive. Racemization was accomplished by Collins oxidation (16,25) to the dicarbonyl compound (14), followed by lithium aluminum hydride (LAH) reduction to give the racemic mixture (1 + 2). Resolution via diastereomeric derivatives seemed plausible. Esterification with enantiomerically pure a-methoxy-a-(trifluoromethyl) phenylacetic acid (MTPA) (17), followed by separation of diastereomers by recycle-HPLC (R-HPLC), had earlier been used to purify enantiomers of ipsenol and ipsdienol (26). A model system, the resolution of -3-nonen-2-ol, a secondary allylic alcohol naturally occurring in Rooibos tea (16,27), also worked satisfactorily. Therefore, the route using the bis-(MTPA) esters was selected for crinitol. 

This chromyl chloride based reagent is inferior to Collins reagent for oxidation of allylic alcohols since cis-trans isomerization occurs. It has also been found to be unsatisfactory for oxidation of m-hydroxybenzyl alcohol (38%... 

---