Cyclohexenols epoxidation

The more hindered alkoxide Ti(OiPr)4 was used as the precursor complex with surface silanols of an amorphous silica support this reaction is reported to lead to the same environment of Ti as in TS-1, but only when the reaction is carried in cyclohexanol as the solvent. Epoxidation of octene, cyclohexenol, and norbornene with FI202 in phenylethanol leads to 95-98% epoxide selectivity.147... 

Mixed cyanocuprates (RCuCN)LL The earlier synthesis of 2-cyclohexenols (9, 329 320) has been extended to provide a general route to highly substituted 2-cyclo-hcxenols as shown in equation (I). The crucial step involves a regiospecific 1,4-uddition of a cyonocupralc to an a-cxo-mcthylcne epoxide.2"... 

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. 

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]. 

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. 

Applying the same conditions to cyclohexene la gave preferably enone 3a (39%) and cyclohexenol 2a (48%), while epoxide 4a was detected in only 12% yield. 

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). 

An unusual syn addition to epoxides occurs when 1,3-diene monoepoxides are treated with organozinc reagents. Thus, the cyclic vinyl epoxide 72 was converted to the cis-ethyl-cyclohexenol 75 with diethyl zinc in methylene chloride and trifluoroacetic acid. The syn addition is believed to derive from an initial coordination of the oxiranyl oxygen to the organozinc compound, which then delivers the alkyl group to the same face. This transfer is facilitated by a relaxation of the sp3 hybridization brought about by the Lewis acidic zinc center and the allylic character of the incipient carbocation <020L905>. 

With one exception—when the substituent is a hydroxyl group. When an allylic alcohol is epoxidized, the peroxy-acid attacks the face of the alkene syn to the hydroxyl group, even when that face is more crowded. For cyclohexenol the ratio of syn epoxide to anti epoxide is 24 1 with m-CPBA and it rises to 50 1 with CF3CO3H. 

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). 

Catalyst Substrate Cyclohexenol Cyclohexenone Cyclohexene Epoxide TNb c... 

Cleavage of epoxides (11,147). Cleavage of the epoxide (1), or the acetate or the trimethylsilyl ether of (R)-cyclohexenol with cyanotrimethylsilane (excess) catalyzed by zinc iodide proceeds regio- and stereoselectively to give 2 in 71% yield. This product can be converted into the aminodiol 3 with three contiguous chiral centers. ... 

Mixed cyanocuprates, [RCuCN]Li. These cuprates (1) are prepared by addition of 1 equiv. of copper(I) cyanide to an alkyllithium in ether at -40°. [CH,CuCN]Li and [CeHsCuCNjLi add stereo- and regiospecifically to 1,3-cyclohexadiene monoepoxide (2) to give 3, which can be epoxidized by m-chloroperbenzoic acid to give 4 in high yield. The products (4) are valuable for stereocontrolled synthesis of trisubstituted cyclohexenols (scheme I). ... 

Peracid epoxidations are often favorable due to higher chemoselectivity the diastereoselectivity under standard conditions (e.g., 3-chloroperoxybenzoic acid in dichloromethane, see Section 4.5.1.1.1.) is mostly satisfactory for compounds with equatorial hydroxy groups (95 5 cis-epoxide with 2-cyclohexcnol50), when purification does not give problems. Diastereoselectivity in pcracid epoxidation of compounds with axial hydroxy groups is somewhat lower (90 10 cw-epox-ide with fra s-5-te/Y-butyl-2-cyclohexenol. Trifluoroperoxyacetic acid is reported to be much more diastereoselective (100 1 in both cases, see Houben-Weyl, Vol. E13/2, pp 1263, 1264). 

Vinyl sulfones are useful building blocks for synthetic organic chemistry. Nucleophilic epoxida-tion of chiral (,S )-2-tosyl-2-cyclohexenol (1) and its 0-protected derivatives proceeds with excellent diastcrcosclcctivitics and good yields.. mt-Epoxides 2 of 98% optical purity are obtained, except for the silylated derivative which is much less selective when epoxidized with lithium tt-77-butylperoxide, and, similarly to the acetyl derivative, is incompatible with standard Weitz-Scheffer conditions68. 

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). 

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