2-Cyclohexenol, formation

We have examined the hydrogen-isotope effect for cyclohexenol formation as a probe of the nature of C-H bond cleavage in the NADPH-dependent and cumene-hydroperoxide-dependent oxidation of cyclohexene. 

The latter observation is interesting, since coupled with the results of the radical inhibition, this suggests that there are two direct oxidation mechanisms as well as the autoxidation that lead to the products of the TPP Mn-NaBH4-02 reaction a direct oxidation via a free-radical intermediate, but not through the autoxidation in which cyclohexenol formation is inhibited by 2,6-di-t-butyl-p-cresol and another direct uninhibited oxidation that leads to cyclohexene oxide. 

This procedure for stereoselective 1,4-functionalization of 1,3-dienes is based on 1,4-acetoxychlorination,2 and allows the preparation of 1,4-disubstituted 2 cyclohexenes with full stereocontrol of the carbon-carbon bond formation in the 4-position. It is also highly regioselective. Other procedures3 4 for obtaining 4-alkyl-substituted 3-cyclohexenol derivatives use 1,3-cyclohexadiene monoepoxide as starting material. None of the previous methods allow the selective preparation of both stereoisomers as shown here. 

A material prepared by anchoring titanium(IV) on to the walls of a high-area, crystalline mesoporous silica (MCM41) has been used as an alkene epoxidation catalyst with alkyl hydroperoxides.204 The effect of replacing one of the three O—Si= groups to which the Ti(IV) is bound by an O—Ge= group is reported to lead to an increase in catalytic activity of up to 18% in die epoxidation of cyclohexene, although no explanation is provided and it is notable diat the selectivity towards the formation of cyclohexene oxide (versus cyclohexenol and cyclohexane-1,2-diol) was inferior to that with the non-modified system.205... 

Cyclohexenone, the major product of cyclohexene autoxidation was reduced to cyclohexanol and cyclohexenol in a ratio of 1 1.4 under the oxidation condition without oxygen, while cyclohexenol was not reduced appreciably. Thus, the reduction of cyclohexenone during the oxidation can account for only a part of the cyclohexanol formation in the TPPMn-NaBH4-02 reaction, and a much more important source of cyclohexanol seems to be cyclohexene oxide this is leased on the following observations (see Figure 11) ... 

Unfortunately, attempts to perform this substitution reaction on cyclohexenol and geraniol led to the exclusive formation of the corresponding silyl ethers. It thus would seem that one requirement for effective carbon-carbon bond formation is that allylic alcohols be secondary and have possess y,y-disubstitution. Pearson, however, discovered a method with less restriction on the natiue of the substrate he used allylic acetates with y-mono-substitution or primary alcohols [96]. Not only ketene silyl acetals but also a diverse set of nucleophiles including aUyl silane, indoles, MOM vinyl ether, trimethylsilyl azide, trimethylsilyl cyanide, and propargyl silane participate in the substitution of y-aryl allylic alcohol 90 to give allylated 91 (Sch. 45). Further experimental evidence suggests that these reactions proceed via ionization to allylic carboca-tions—alcohols 90 and 92 both afforded the identical product 93. 

A concerted bond-forming and bond-breaking process is an alternative to Eq. (m). Methyllithium-TMED in CsHi4, or PhLi in THE does not add to PhCHOHCH=CH2 t-BuLi adds exclusively at the terminal carbon to form PhCH=CHCH2Bu-t and PhCHLiCH(Bu-t)CH2Bu-t. Alkene formation is the dominant reaction with 2-cyclopentenol and 2-cyclohexenol ... 

For acyclic allylic alcohols, very little a,p-unsaturated enone formation was observed besides epoxidation. Chemoselectivity was much less for cyclic allylic alcohols, for which oxidation of fhe allylic alcohol group competed significantly with epoxidation. In the case of 2-cyclohexenol as the substrate, the enone was even found to be the main product. A comparative sandwich POM-catalyzed epoxidation study of various (subsfifufed) cycloalkenols revealed that the enone versus epoxide chemoselectivity is controlled by the C=C-C-OH dihedral angle Ma in the allylic alcohol substrate. The more this dihedral angle deviates from fhe optimum C=C-C-OW dihedral angle otw for allylic acohol epoxidation, the more enone is formed (Fig. 16.5). 

Treatment of cyclohexenol with HBr gives the corresponding allylic bromide. Only one compound is formed because attack at either end of the allylic cation gives the same product, formation of the cyclohexenyl cation... 

Evidence for the formation of singlet oxygen from Posner was based on chemical trapping. Photolysis of dibenzothiophene sulfoxide in a 90 10 mixture of cyclohexene and acetic acid provided a sample that tested positive for peroxides. After reduction with Nal, 2-cyclohexenol was obtained in 22-34% yield. The authors noted a lack of cyclohexanone and cyclohexene epoxide. This was rationalized as outlined below [97]. 

The reaction below shows the formation of a cation close in structure to the allyl cation. A very strong acid (called super-acid —see Chapter 15) protonates the OH group of 3-cyclohexenol, which can then leave as water. The resulting cation is, not surprisingly, unstable and would normally react rapidly with a nucleophile. However, at low temperatures and if there are no nucleophiles present, the cation is relatively stable and it is even possible to record a NMR spectrum (at -80 °C). 

In the presence of RhC PPhajs, monohydrosilanes reduce cyclohex-2-enone to cyclohexanone, whereas trihydrosilanes give cyclohexenol. Reductions using dihydrosilanes resulted in the formation of both products. ... 

Early model studies concerning the P-450 type oxygen activation, i.e., the reductive oxygen activation catalyzed by metalloporphyrins, were carried out by Tabushi et al. In 1979, Tabushi and Koga examined oxidation of cyclohexene by Mn(TPP)/02/NaBH4 and found the exclusive formation of cyclohexanol and cyclohexenol in a 4 1 ratio [175]. The production of cyclohexanol was explained by the reduction of cyclohexene oxide and cyclohexenone, respectively (Scheme 5) [175]. To avoid possible reduction of primary products, Tabushi and Yazaki replaced the reduction system with H2/colloidal Pt [176]. Under the optimal conditions, the Mn(TPP)/l-methylimidazole/02/H2-colloidal Pt system oxidized cyclohexene to cyclohexene oxide and cyclohexenone with a turnover number of 7,000. These systems were further improved to show stereospecific and regioselective mono epoxidation [177]. 

Cis- and diol eliminates to give the cyclohexenol as the major product, but the trans isomer yields mainly 1,4-epoxycyclohexane. The rate of dehydration of the trans isomer is about fifty times faster than than of the traiw-isomers. The intramolecular concerted ring closure through a boat conformation has been suggested for the formation of 1,4-expoxycyclohexane. ... 

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