Allyl alcohols 4- pyridinium chlorochromate

The use of pyridinium-based chromium(vi) oxidising agents (cf. Section 5.7.1, p. 587) is illustrated by the use of the supported reagent, pyridinium chlorochromate-alumina, for the conversion of the cyclic allylic alcohol, carveol, into the corresponding oc,/ -unsaturated ketone, carvone125 (Expt 5.88). 

Although in principle naturally occurring (—)-galanthamine could have been prepared by an identical sequence of reactions commencing with D-tyrosine, an alternate route to 319, the enantiomer of 314, was developed. Thus, epimeriza-tion of the methyl ester group at C-6 of the A -trifluoroacetamide derived from 315 followed by oxidation of the allylic alcohol with pyridinium chlorochromate furnished 319 in 78% optical purity, albeit in low chemical yield. Since 319 could be converted to (-)-galanthamine (291) by the same sequence of reactions outlined for the transformation of 314 to (+)-galanthamine, its preparation may be considered to represent a formal total synthesis of 291 from L-tyrosine (163). 

The chroniium(VI) oxide-dipyridine complex also has beoi found to cause oxidative rearrangement of tertiary allylic alcohols to a,3-epoxy aldehydes and small amounts of a,3-unsaturated aldehydes (equation 6 and Table 3). This is potentially useful as a homologation sequence since the starting materials are readily available from vinyl metal addition to ketones. Use of pyridinium chlorochromate (PCC) for this transformation gives mosdy a,3 unsaturated aldehydes. 

Imidazolium dichromate is a selective oxidant for allylic and benzylic hydroxy groups. (Allylic alcohols are oxidized faster than benzylic alcohols.) The selectivity over saturate alcohols is similar to that of 4-(dimethylamino)pyridinium chlorochromate. DMF is recommended as the solvent for oxidations, since it appears that the choice of solvent is critical to obtaining high yields. This reagent has also been observed to cause some ( )/(Z)-isomerization during the oxidation of allylic alcohols. 

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. 

Oxidations by pyridinium chlorochromate resemble those by dipyridine chromium(VI) oxide, both in scope and the mild conditions required. At room temperature, primary alcohols give aldehydes [604, 605], secondary alcohols afford ketones [605], allylic and benzylic methylene groups are oxidized to carbonyl groups [606, 6d7], enol ethers are converted into esters [608] or lactones [609], trimethylsilyl ethers of diphenols are transformed into quinones [610], and alkylboranes are converted into aldehydes (yll]. 

Not only allylic alcohols but also homoallylic alcohols can be epoxi-dized. A peculiar transannular oxidation takes place when 1-methyl-4-cycloocten-l-ol is treated with the Fieser reagent, [CrOj-(CH3C0>20-CH3C00H], or with pyridinium chlorochromate. Two dia-stereomeric keto oxides are formed in different ratios (equation 281) [535],... 

The allyl alcohol in the seven-membered ring is oxidized to the corresponding a,P-unsaturated ketone as expected, whereas the allyl alcohol in the five-membered ring is oxidized to afford the transposed a,P-unsaturated ketone after [3,3]-sigmatropic rearrangement. This behavior is only observed with cyclic, tertiary allyl alcohols upon treatment with one equivalent of pyridinium chlorochromate. The desired oxidation product 34 is obtained in 90 % over two steps. 

Pyridinium Chlorochromate. The need for improved oxidation of primary alcohols and greater ease for isolation of products prompted further research into the nature of Cr(VI) reagents. Corey found that addition of pyridine to a solution of chromium trioxide in aqueous HCl allowed crystallization of a solid reagent characterized as 31, pyridinium chlorochromate (PCC). This reagent was superior for the conversion of primary alcohols to aldehydes in dichloromethane but less efficient than the Collins oxidation when applied to allylic alcohols. Oxidation of 1-heptanol with PCC in dichloromethane gave 78% of heptanal, for example. As stated by Corey, PCC is an effective oxidant in dichloromethane although aqueous chlorochromate species are not very effective oxidants. Oxidation of secondary alcohols to ketones is straightforward, as in Banwell s synthesis of y-lycorane, in which 32 was oxidized by PCC to the ketone (33). ... 

A useful application of chromium-based oxidants, especially pyridinium chlorochromate, is in the conversion of allylic tertiary alcohols to their transposed a,(3-unsaturated ketones. For example, treatment of the allylic alcohol 24 with PCC gave the a,p-unsaturated ketone 25 (6.23). The reaction is thought to proceed by rearrangement of the chromate ester of the allylic alcohol to give a new allyl chromate ester that is oxidized to the ketone. 

In order to remove the primary hydroxy group, the protected triol 24 was acet-ylated and treated with pyridinium tosylate to yield the monoester 25. Selective tosylation of the primary hydroxy group followed by Finkelstein exchange for iodine yielded the iodo derivative 26 which was transformed into the protected cyclohexene diol 27 by reductive removal of the iodine with tributyltin hydride followed by protection of the tertiary hydroxy group with dihydopyran. After removal of the benzoyl group by alkaline saponification the resulting allylic alcohol was oxidised to the desired enone 28 with pyridinium chlorochromate in buffered solution (ref. 16). 

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