Allylic hydroxylation with rearrangement

To explore the mechanism of allylic hydroxylation, three probe substrates, 3,3,6,6-tetradeuterocyclohexene, methylene cyclohexane, and /l-pinenc, were studied (113). Each substrate yielded a mixture of two allylic alcohols formed as a consequence of either retention or rearrangement of the double bond. The observation of a significant deuterium isotope effect (4-5) in the oxidation of 3,3,6,6-tetradeuterocyclohexene together with the formation of a mixture of un-rearranged and rearranged allylic alcohols from all three substrates is most consistent with a hydrogen abstraction-oxygen rebound mechanism (Fig. 4.48). 

An efficient and inexpensive method for the substitution of an allylic hydroxyl group with fluorine, without allylic rearrangement and elimination consists of treating an allylic alcohol with methyllithium followed by p-toluenesulfonyl fluoride, lithium fluoride and 12-crown-4.6 By this method, geranyl fluoride, neryl fluoride, cinnamyl fluoride, ( , )-farnesyl fluoride, retinyl fluoride and 4-fluoro-2-methyl-6-(4-tolyl)hept-2-ene are prepared. 

The product obtained is an allylic alcohol with the hydroxyl group at the other end of the allyl system from where the sulfur started—-a rearrangement has taken place. We have observed the rearrangement in this case because the P(OMe)3 has trapped the rearrangement product but, even without this reagent, allylic sulfoxides are continually and reversibly rearranging into sulfenate esters by the mechanism shown below. 

If, in an attempt to obtain free 6-amino-6-deoxy-L-xt/Io-hexulose, the isopropylidene compound 80 is hydrolyzed at 65° with 2 M hydrochloric acid, an almost quantitative yield of 3-hydroxy-2-pyrldinemeth-anol (86) hydrochloride is obtained instead. The formation of 86 can result only through the intermediate 6-amino-6-deoxy-L-xyfo-hexulo-pyranose (83). The furanose (81) first formed is in equilibrium with the pyranose (83). The latter is dehydrated in acid solution to 82 which, under acid catalysis, rearranges to the intermediate 84. In the following steps, the allylic hydroxyl groups on C-4 and C-5 are readily removed, and aromatization to the pyridine derivative (86) ensues. 

Although Lewis acid-promoted rearrangements of epoxides are well known, it seems that the presence of an a-hydroxyl substituent can substantially alter the standard behaviour. Rearrangements of 2,3-epoxynerol and 2,3-epoxygeraniol for example with very weak Lewis acids, such as Ti(OPr )4, afford allylic diols with high selectivity (Scheme 9). It is hoped that this selectivity can be exploited in more complex examples. 

Replacement of chlorine hy hydroxyl with allyl rearrangement... 

Allylic rearrangements with 3,3,6,6-dj-cyclohexene occurred in 20% of the MMO hydroxylation products compared to 33% for cytochrome P-450. These two experiments suggest that, with M. trichospor-ium OB3b, a rebound reaction must occur with a greater rate constant than with cytochrome P-450, in accord with the radical clock substrate work. 

Selenium dioxide is also an oxygen donor to alkenes. In this case, however, the initial reaction of the double bond is with the selenium center followed by two pericyclic steps. After hydrolysis of the organo-selenium intermediate, the result is a hydroxylation at the allylic carbon position65. Thus, limonene (2) yields racemic p-mentha-l,8(9)-dien-4-ol66. The high toxicity of selenium intermediates and prevalence of many rearrangements has limited the widespread use of the reagent in synthesis. 

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