Oxidations at Allylic Positions

Allylic positions may be oxidized to give unsaturated hydroperoxides, alcohols, esters, and carbonyl compounds. 

Singlet oxygen, generated usually by the irradiation of solutions of oxygen in the presence of sensitizers, is incorporated into alkenes and forms hydroperoxides via an ene mechanism (equations 121 and 122) [75, 19, 26, 1112]. 

An alternative mechanism via dioxetanes or perepoxides has been suggested (equation 123) [27], 

The hydroperoxides can be transformed further into alcohols or carbonyl compounds (equation 124) [22, 23], 

Ally lie alcohols are obtained from allylic hydroperoxides by treatment with alkalies [22] or by reduction with sulfites [27], They are also formed 

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Cis-stilbene is not epoxidized and alkenes containing allylic C-H bonds like cyclohexene are mainly oxidized at allylic positions (Fig.6). Therefore, it is... 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Effective catalysts for heterogeneous oxidations using 02 are mainly Pt and Pd with some activity by Ir70 and Ru.71 Much work has gone into alcohol oxidations that are dehydrogenations to ketones or aldehydes. Also, oxygen may be inserted at allylic positions of alkenes and these may be dehydrogenated to ketones or aldehydes.72 In the case of aldehydes, additional oxidation may be accomplished to produce acids.72,73... 

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. 

Palladium deuteride 1 may act as an activator of C-H bonds at allylic positions and may form Jt-allyl palladium. Via the equilibrium between Jt-allyl palladium and alkene, H-D exchange will occur by C=C double bond migration. As shown in Scheme 5, cyclododecene was converted into the fully deuterated compound by treatment with hydrothermal deuterium oxide in the presence of Pd/C catalyst. Without Pd/C, no deuteration was observed under these reaction conditions [16]. 

Next, some sort of allylic oxidation at the position between the alkene and the benzene ring. This would be with some oxygenation reagent such as FAD peroxide. The position is very reactive and would easily form radicals (Chapter 39). 

Carbon-carbon double bonds, besides being susceptible to addition of oxygen or cleavage, can also react at allylic positions. Synthetic utility requires that there be good regioselectivity. Among the transition-metal oxidants, the CrOs-pyridine reagent in methylene chloride and a related complex in which 3,5-dimethylpyrazole is used in, place of pyridine are the most satisfactory for allylic oxidation. 

In conclusion, a number of sesquiterpenoids were biotransformed by various fungi and mam mals to afford many metabolites, several of which showed antimicrobial and antifungal, antiobe sity, cytotoxic, neurotrophic, and enzyme inhibitory activity. Microorganisms introduce oxygen atom at allylic position to give secondary hydroxyl and keto groups. Double bond is also oxidized... 

The pattern of substitution of both P-eudesmol and a-santonin can be accounted for by assuming that the cyclization of farnesyl diphosphate, followed by (or preceded by) suitable oxidation changes at allylic positions, is as shown in Scheme 11.50. 

Allylic Alcohols. The direct allylic oxidation of alkenes by selenium dioxide has been discussed in a review of modern organoselenium chemistry. The use of selenium dioxide in pyridine" allows oxidation of allylic positions to be performed in the presence of acid-labile groups (acetals, THP ethers) that are normally at least partially cleaved by SeOa. 

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

In practice, however, all attempts to introduce a hydroxyl group at the allylic position C-18 of 73 in order to acquire 56 have failed. These include the attempted oxidation of 73 by Se02 in various solvent systems within a temperature range of 0-100°C. Attempted allylic oxidation of 73 with Se02/H202 in aqueous solution at room temperature results only in the corresponding N-oxide, in which the <5H value of the N-methyl has shifted from 2.20 to 3.03 ppm. 

Allylic CH bonds Aliphatic alkenes frequently undergo allylic substitution by oxidation of the double bond to a radical cation that undergoes deprotonation at the allylic position and subsequent oxidation of the resulting allyl radical to a cation, which finally combines with the nucleophiles from the electrolyte [21, 22]. The selectivity is mostly low. Regioselec-tive allylic substitution or dehydrogenation is, however, found in some cases with activated alkenes, for example, -ionone that reacts to (1) (Fig. 5) as a major product [23], menthone enolacetate that yields 90% (2) [24], and 3,7-dimethyl-6-octen-l-ol... 

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