Dihydroxylation of cyclohexene

In the dihydroxylation of cyclohexene by Me3N+—O-, catalysed by OsC>4, aromatic amines and aliphatic chelating (TMEDA) or bridging (DABCO, hexamine) amines were found to retard the oxidation, owing to the formation of amine adducts of the dioxomonoglycolatoosmium(VI) ester intermediates, which are more resistant to the further oxidation required for product formation.98 Alkenes derived from Gamer s aldehyde, A-Boc-/V,0-acctonide of the aldehyde of L-serine, may be dihydroxylated by OsC>4 with excellent selectivities that may be explained by A1,3 strain.99... 

The use of resin-supported sulfonic acid, an easily recyclable catalyst, makes it possible to conduct the dihydroxylation of cyclohexene with 30% HP without any solvent, at 70 °C, with 98% yield to trows-l,2-cyclohexandiol [36uj. The mechanism indudes the in situ generation of the resin-supported peroxysulfonic acid, which oxidizes the olefin to cyclohexene epoxide the latter is then quickly hydrolyzed by water to yield the final product. 

This reoxidation of the relatively substitution inert osmium(VI) ester to a substitution labile osmium (Vni) ester is the rate-limiting step [22], This step would be expected to be slower with the more sterically demanding PHP than with TBHP. This is indeed what we observed 0s04-catalyzed dihydroxylation of cyclohexene (1, Table 4) gave a faster reaction with TBHP than with PHP, the final conversion being reached in 6h and 24h respectively. 

Scheme 1.15 Dihydroxylation of cyclohexene using microencapsulated osmium tetroxide...

Cyclic osmic esters have long been known to be involved in the osmium tetroxide-catalyzed cis-dihydroxylation of alkenes, but not arenes. The isolation of compound (18) by Wallis and Kochi following irradiation of the charge-transfer complex between osmium tetroxide and benzene is therefore of particular interest. This suggests that the corresponding use of catalytic quantities of osmixim tetroxide in conjunction with hydrogen peroxide could lead to the formation of polyhydroxylated cyclohexenes and -anes. 

Osmium-catalyzed dihydroxylation of olefins involves an Os(VIII)/Os(VI) substrate-selective redox system [36c-gj. In this system, N-methylmorpholine N-oxide (NMMO) can be used for the reoxidation of Os(VI) to Os(VIII), with NMMO being reduced to NMM. In cyclohexene oxidation catalyzed by Os with HP, the yield to cis-1,2-cyclohexandiol can be improved remarkably by the use of specific mediators for NMM oxidation to NMMO, for instance by means of catalytic fiavin/HP. In this case, a yield to the cis-diol of 91% was obtained, as compared to 50% with the OSO4/HP system alone [36hj. Mixtures of aqueous HP and acetic acid or formic acid are also effective reagents for the dihydroxylation of olefins, but neutralization of the acid solvent is necessary for the recovery of the product. 

One of the most useful modifications of the Woodward dihydroxylation was published by Cambie and Rutledge.12 This modification employs TIOAc in place of AgOAc and describes complementary procedures for the synthesis of cw-diols (Woodward reaction) and frans-diols (Provost reaction).13 Thus, treatment of cyclohexene 13 with TIOAc and I2 in HOAc at 80 °C, followed by the addition of water, affords acetate 14. Hydrolysis of 14 then gives cw-diol 15 in 70-75% yield. On the other hand, exposure of cyclohexene 13 to TIOAc, I2, and HOAc at reflux in the absence of water affords bis-acetate 16, which upon hydrolysis gives /raw-diol 17. 

Oxidative rearrangements, via oxythallation, have been improved in yield and selectivity by the use of thallium(iii) nitrate supported on clay rather than in methanolic solution. Thus, cyclohexene gave an 85% yield of dimethoxymethyl-cyclopentane while 1-tetralone, which normally gives a complex mixture of products, gave a 1 1 mixture of methyl indane-l-carboxylate and 2-methoxytetralone. An efficient, large-scale procedure for the direct cis-dihydroxylation of olefins has been reported. The oxidant is t-butyl hydroperoxide and the catalyst osmium tetroxide, with the reaction conducted under alkaline conditions (E%N OH ), so facilitating a rapid turnover of catalyst via enhanced hydrolysis of the osmate esters. The method appears to be more advantageous for the more substituted olefins than the Hofmann and Miles procedure. 

Dioxygenated compounds can be produced by ozonolytic cleavage of cyclohexenes different work-up procedures allow the differentiation of the termini of the product. Alternatively, cyclohexenes can be dihydroxylated and then cleaved with periodic acid or lead tetraacetate. 

The preparation described here is a slight modification of a route published by King and Sharpless via the osmium-catalyzed asymmetric dihydroxylation (AD) reaction of 1 -phenyl-1-cyclohexene. The major strengths of this process are that either enantiomer can be prepared in high optical purity (> 99.5% ee) v/ithout the need for chromatography. 

Anti dihydroxylation is achieved in two steps—epoxidation followed by opening of the ring with OH or H2O. Cyclohexene, for example, is converted to a racemic mixture of two tram-1,2-cyclohexanediols by anti addition of two OH groups. 

Polycarbonates based on 2-cyclohexen-l,4-diol and a dihydroxy compound liberate benzene through aromatization, a dihydroxyl compound, and carbon dioxide, upon acidolysis [343]. The low volatility of the dihydroxyl compound hampers complete development by heating alone and necessitates wet development. 

Under these conditions the ester 81 was obtained in 90% yield with recovery of the starting material 80 in 10% yield. Obviously the less polar solvent toluene favors the formation of a chelated enolate, and the higher selectivity obtained with the bulkier potassium counter ion is explained by an additional chelation with the oxygen of the sUyl ether, which can reinforce the stability of the chelated transition state 80 (Figure 5.2.2). Metathesis with the Grubbs catalyst [34] afforded in nearly quantitative yield the anticipated cyclohexene derivate 83, which was reduced and dihydroxylated to provide the key structures of fumagiUin. 

In several of the reactions in previous sections, one heteroatom (halogen, oxygen) was added to one side of a 7i-bond and a hydrogen or another heteroatom to the other side. There is another type of reaction in which heteroatoms are incorporated on both carbons of a 71-bond. A specific example incorporates two hydroxyl (OH) units. In one experiment, cyclohexene is treated with OSO4 (osmium tetroxide) in anhydrous er -butyl alcohol (2-methyl-2-propa-nol) at 0°C. After standing overnight, a 45% yield of cis-l,2-cyclohexanediol (124) was obtained.Analysis of this reaction shows that two OH units added and that both oxygen atoms were derived from osmium tetroxide. This reaction is termed a dihydroxylation. Furthermore, the two OH units have a cis relationship. 

For the reaction of either potassium permanganate or osmium tetroxide with an alkene, the manganate ester or the osmate ester is formed in what is effectively a cis addition. Cyclohexene gives the cis diol, 124, and there is none of the trans diol, which means that dihydroxylation is a diastereospe-cific reaction of the two diastereomers cis and trans), only the cis product is formed. Note that dihydroxylation occurs from both sides of the C=C unit, so the reaction gives both enantiomers. Only one diastereomer is formed (diaste-reospecific), but that diastereomer is racemic. 

The two-phase permanganate oxidation of olefins generally affords products of oxidative cleavage. Weber and Shepherd found that when benzyltriethylammonium chloride was used as catalyst and the temperature was maintained near 0°C, internal olefins were oxidized by basic permanganate in dichloromethane to the corresponding czs-glycols in moderate yields (Eq. 11.3) [6]. Cyclohexene, c/s-cyclooctene and trans-cyclododecene were dihydroxylated by this method in 15%, 50%, and 50% yields... 

Cinnamyl bromide 24 and the iodocarbohydrate 23 are combined in a zinc-mediated fragmentation/allylation reaction to afford a highly functionalized 1,7-diene, which is then treated with Hoveyda-Grubbs second-generation catalyst to produce a mixture of diastereomeric cyclohexenes 25 (35% yield) and 26 (32% yield). From the major isomer 25, subsequent Overman rearrangement, dihydroxylation, and deprotection afford the natural product pancrastistatin (28) (Scheme 3.10). 

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