Allylic hydroxylation mechanism

FIGURE 4.48 Substrates (3,3,6,6-tetradeuterocyclohexene, methylenecyclohexane, and/ -pinene) used to determine the mechanism of cytochrome P450-catalyzed allylic hydroxylation. 

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). 

Figure 7.10 (top) shows the FT-IR spectrum of freshly prepared C60D36. The exposure to air after 1 day causes alterations in the spectrum (Fig. 7.10, middle). In particular it can be noticed the reduction of the intensity of the C-D stretching band at 2,092 cm-1 and the complete disappearance of the C-D bending at 966 cm-1. Evidences of oxidation can be inferred by the C=0 stretching band at 1,710 cm-1 and by the C-OH and C-OOH bending at about 1,040 cm-1 supporting the allylic oxidation mechanism. After 3 days exposure to air an increase in the relative intensity of the ketone, hydroxyl and hydroperoxide bands can be observed (Fig. 7.10, bottom). 

Singleton, D. A., Hang, C. Isotope effects and the mechanism of allylic hydroxylation of alkenes with selenium dioxide. J. Org. Chem. 2000, 65, 7554-7560. 

This problem was taken on by the Jerusalem group who used DFT (B3LYP) computations to model the mechanism of methane hydroxylation -101-103 allylic hydroxylation of propene " - and... 

The allylic hydroxylation of cyclohexene catalyzed by sMMO is accompanied by the allylic rearrangement (20%), as described above [69]. In addition, in the case of oxygenation of terminal olefins, the detected alcohols are only the primary alcohols as shown in eqs. (22) and (23) [75]. This means that all of the carbon radical intermediates must undergo the allylic rearrangement. It seems inadequate to explain the results of eqs. (22) and (23) (the allylic rearrangement of 100%) only by the thermodynamic stability of the inner olefin, and necessary to consider an alternative mechanism which can explain the formation of both allylic alcohol and epoxide in the oxygenation of olefin vide post). 

The mechanism by which the enantioselective oxidation occurs is generally similar to that for the vanadium-catalyzed oxidations. The allylic hydroxyl group serves to coordinate the reactant to titanium. The tartrate esters are also coordinated... 

It has been shown" that isomerization of the exocyclic allylic system of the five-membered ring D of kaurenols depends on the orientation of the C(15) hydroxyl group. The total synthesis of methyl atis-16-en-19-oate, a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane skeleton, has been accomplished" using a homoallyl-homoallyl radical rearrangement process of methyl 12-hydroxykaur-16-en-19-oate monothioimid-azolide (280) as the pivotal step. Two plausible mechanisms have been presented" ... 

The exact nature of the catalytic species remains incompletely understood and very controversial. Recently, Corey proposed a hypothesis on the origin of the enantioselectivity of this reaction (Scheme 29) (69). His mechanism involves an ion pair in which the allylic alcohol, rather than alkoxide, is coordinated to Ti(IV) atom and the hydroxyl proton is... 

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