Cyclohexenol, oxidation

Scheme 2.4 indicates the action of a chiral controller (stoichiometric or catalytic) on a racemic substrate. One of the products can be achiral if the reaction involves a competition between destmction of the stereogenic unit of the substrate and a stereoselective functionalization at some site of the substrate, exemplified by rac-2-cyclohexenol oxidized comjretitively between epoxyalcohol and cyclohexenone. 

Hydroxymethylmethyldiazirine (209 unprotonated) formed propionaldehyde as the sole product by thermal nitrogen extrusion 4-hydroxy-l,2-diazaspiro[2.5]oct-l-ene (218) formed a mixture of cyclohexanone (73%), cyclohexenol (21%) and cyclohexene oxide (5%). Thermal decomposition of difluorodiazirine (219) was investigated intensively. In this case there is no intramolecular stabilization possible. On heating for three hours to 165-180 °C hexafluorocyclopropane and tetrafluoroethylene were formed together with perfluorofor-maldazine 64JHC59). 

R = Me, R = H) with cyclohexenol in the presence of F ion followed by NaOCl oxidation gave the tricyclic ether 61 in 65% yield (Scheme 9) [29]. The use of propargyl alcohol and propargyl thiol led, via the acetylenic oximes, to fused tetrahydrofuranoisoxazoles 62 a and 62 b, and tetrahydrothiopheno[3,4-c]isoxa-zole 62 c, respectively. Reaction of l-butyn-4-ol with 0-trimethylsilyl a-bro-moaldoxime 52e (R = R = Me) led to the tetrahydropyranoisoxazole 62 d. 

In 1999, Sanjuan and co-workers [27] reported a very elegant type IIavRH oxidation of cyclohexene to give a mixture of cyclohexane-1, 2-diol, 2-cyclohexenol, and 2-cyclohexenone. The reaction is initiated by excitation of the zeolite-embedded 2,4,6-triphenylpyrylium cation to produce a hydroxy radical (steps 1 and 2... 

The catalytic system has been successfully extended to polymer-bound lithium amide co-bases of type 65 (see Table 4) which, like C—Li bases of type 63 and 64, are efficient regenerating agents of HCLA and poorly reactive toward oxiranes. For instance, the isomerization of cyclohexene oxide by 0.05 equiv of HCLA 55 in the presence of 1.45 equiv of 65 affords ( l-cyclohexenol in 92% ee (entry 15). It is of interest to note that, similarly to co-bases 63 and 64, the use of 65 leads to an increase of selectivity compared to the stoichiometric reaction at room temperature (Table 2, entry. ... 

Oxidation of (15,47 )-4-/ert-butyldimethylsilyloxy-2-cyclohexenol (see p400) and subsequent silyl group removal gave 4-hydroxy-2-cyclopentenone (1) of known R configuration55. 

Autoxidation without Discharge. To compare our results with normal autoxidation, the reaction was carried out using a reaction mixture similar to Run 4 without silent discharge. Low conversion of cyclohexene (0.051% ) was observed at 60°C., indicating that the discharge oxidation was hardly affected by the normal autoxidation process under the present reaction conditions. The major product was 3-cyclohexenylhydroperoxide, and minor products were 3-cyclohexenol, 3-cyclohexenone, cyclohexene oxide, and trace amounts of residue saturated materials such as cyclo-hexanol and cyclohexanone were not detected. The conversion of cyclohexene was raised to 0.15% when the reaction temperature was elevated to 140°C. however, the kinds of product were not changed. 

Considering only the three mild oxidation products in the liquid phase, it can be inferred that the photocatalytic oxidation of cyclohexene occurs at two sites of the molecule mainly the allylic position (86 %), giving the cyclohexenone and the cyclohexenol, and, to much lesser extent, the double bond (14 %) yielding the epoxide. 

Groves et al. found that a simple heme-iodosobenzene system mimics the enzymic reactions.127 Cyclohexane and cyclohexene are oxidized to cyclohexanol and a mixture of cyclohexene oxide and cyclohexenol respectively by this system. Using meso-tetrakis-a,/J,a,/J-(o-acylamidophenyl)por-phinatoiron(III) chloride where the acyl group is (i )-2-phenylpropionyl or (S)-2 -methoxy-carbonyl-l,T-binaphthyl-2-carbonyl, optically active styrene oxides are obtained in 51% e.e. The Fe(TPP)Cl-PhIO system can also oxygenate arenes to arene oxides.128 Based on the following observations, mechanisms involving O—Felv(Por) t as the active species have been proposed (Scheme 30).127... 

The oxidation of cyclohexene was systematically investigated by means of metal porphyrins which have distinct redox potentials due to different metals [134]. The best results were obtained with Mn(III)TPP/L-Cys/NaBH4 which furnished a product mixture consisting of cyclohexenone (46.4%) > cyc-lohexanol (23.8%) > cyclohexenol (19.5%) > cyclohexanone (9.0%) > epoxide (1.4%), relative yields given in parenthesis. In the presence of KOH and riboflavin as an electron transfer reagent the product distribution was similar but the total yield was considerably improved [135]. 

Normally, pseudo-equatorial alcohols in cyclohexenols are oxidized quicker than pseudo-axial ones.94c For example, 3(3-hydroxycholest-4-ene (90) is oxidized 7.3 times quicker than the 3a isomer (91). This can be explained by the lowering of the transition state energy during the hydride transfer due to the better overlap between the tr C-H bond and the alkene n-system. This energy lowering being greater in the pseudo-equatorial isomer due to a better orbital overlap. 

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... 

Gold-catalyzed oxidation of styrene was firstly reported by Choudhary and coworkers for Au NPs supported on metal oxides in the presence of an excess amount of radical initiator, t-butyl hydroperoxide (TBHP), to afford styrene oxide, while benzaldehyde and benzoic acid were formed in the presence of supports without Au NPs [199]. Subsequently, Hutchings and coworkers demonstrated the selective oxidation of cyclohexene over Au/C with a catalytic amount of TBHP to yield cyclohexene oxide with a selectivity of 50% and cyclohexenone (26%) as a by-product [2]. Product selectivity was significantly changed by solvents. Cyclohexene oxide was obtained as a major product with a selectivity of 50% in 1,2,3,5-tetramethylbenzene while cyclohexenone and cyclohexenol were formed with selectivities of 35 and 25%, respectively, in toluene. A promoting effect of Bi addition to Au was also reported for the epoxidation of cyclooctene under solvent-free conditions. 

It is well known that in many brominations and protonations of cyclohexenols (91) axial entry is favored (Eliel et al., 1965). This is attributed to the parallel alignment of the v orbitals on the three centers. The overlap preference is well illustrated in the oxidation of allyl vs. saturated alcohols. Normally, axial alcohols are oxidized more rapidly by chromic acid than equatorial alcohols. In the absence of large strain factors, equatorial allyl alcohols are oxidized faster than axial alcohols by chromic acid hydrogen is abstracted in the rate-determining step. The contribution of a-j8 ketonic resonance lowers the activation energy,... 

Suresh, Lee and coworkers demonstrated oxidation of cyclohexene catalyzed by Mn or Cu complexes using H202 in aqueous phase in a microreador (width = 200 pm and depth = 50 pm) [36], Water-soluble ionic liquid [bmim]BF4 was added (0.5%, v/v) to improve the solubility of cydohexene in the readionbuffer. With the use of a reduced Schiff base-Cu complex, 2-hydroxycyclohexanone was obtained as the maj or produd with 2 5 min residence time, whereas the bulk scale reaction gave 2-cyclohexenol as the major reaction produd. 

The oxidation of cyclohexene by a fully reconstituted cytochrome P-450lm system (5) gave only cyclohexene oxide (1) and cyclohexenol (2) in a ratio of 0.92 1. Results for the peroxide-dependent oxidation of cyclohexene in the presence of cytochrome P 450 are presented in Table I. Inspection of the data suggests that subtle differences exist between the oxidants generated from these four oxidants and lead to the observed sixfold change in the ratio of 1 and 2 in the product mixture. Also apparent is the fact that no obvious correlation exists between the ratio of the products and the nature or effectiveness of the oxidant. 

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. 

We have demonstrated recently that epoxidation and hydroxyl-ation can be achieved with simple iron-porphine catalysts with iodosylbenzene as the oxidant (24). Cyclohexene can be oxidized with iodosylbenzene in the presence of catalytic amounts of Fe(III)TPP-Cl to give cyclohexene oxide and cyclohexenol in 55% and 15% yields, respectively. Likewise, cyclohexane is converted to cyclohexanol under these conditions. Significantly, the alcohols were not oxidized rapidly to ketones under these conditions, a selectivity shared with the enzymic hydroxylations. The distribution of products observed here, particularly the preponderance of epoxide and the lack of ketones, is distinctly different from that observed in an autoxidation reaction or in typical reactions of reagents such as chromates or permanganates (15). 

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) ... 

Even during the induction period of the TPP Mn-02 autoxidation, this TPP Mn-NaBH4-02 oxidation gave a considerable amount of cyclohexenol (see Figure 8). 

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. 

Recently two heterogeneous TPAP catalysts were developed which could be recycled successfully and displayed no leaching In the first example the tetraalkylammonium perruthenate was tethered to the internal surface of mesoporous silica (MCM-41) and was shown [ 101] to catalyse the selective aerobic oxidation of primary and secondary allylic and benzylic alcohols (Fig. 17). Surprisingly, both cyclohexanol and cyclohexenol were unreactive although these substrates can easily be accommodated in the pores of MCM-41. No mechanistic interpretation for this surprising observation was offered by the authors. 

Lithium amide deprotonation of epoxides is a convenient method for the preparation of allylic alcohols. Since the first deprotonation of an epoxide by a lithium amide performed by Cope and coworkers in 19585, this area has received much attention. The first asymmetric deprotonation was demonstrated by Whitesell and Felman in 19806. They enantioselectively rearranged me.vo-cpoxidcs to allylic alcohols for example, cyclohexene oxide 1 was reacted with chiral bases, e.g. (S,S) 3, in refluxing TFIF to yield optically active (/ )-2-cyclohexenol ((/ )-2) in 36% ee (Scheme 1). 

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