Alcohols, unsaturated epoxidation

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

The reductive demercuration was marred by the loss of about half of the peroxide due to competing deoxymercuration which afforded 4-cycloocten-l-ol. An additional complication was the formation of a small amount of trans-1,2-epoxy-cw-cyclooct-5-ene. The bicyclic peroxide 50 was readily separated from the unsaturated alcohol by silica chromatography, but complete removal of the epoxide was more difficult. Preservation of the peroxide linkage was markedly higher in the bromodemercuration. The diastereoisomeric dibromoperoxides 51 were separated by HPLC, although only one isomer was fully characterised. 

V.C.8.1. Alkenes and Alcohol Functions. Although TS-1 and other titanosi-licates oxidize alcohols to the corresponding aldehydes and ketones, the rates are suppressed in the presence of compounds containing C=C bonds. CH3OH, for example, is not oxidized at all during epoxidations of alkene reactants. Higher alcohols, however, are partially oxidized. The oxidation of unsaturated alcohols in the presence of TS-1 is shown in Table XVII (193). 

Highly regioselective cyclizations of 3,4-, 4,5- and 5,6-unsaturated alcohols to yield tetrahydrofuranols and tetrahydropyranols have been carried out with the TS-I-H2O2 system (this is a titanium silicate molecular sieve-H202 complex.) The reactions involve the intermediate formation of epoxides and their Ni ring opening. 

Because V(V) is a better oxidant, it exhibits low selectivity in the oxidation of simple nonsubstituted alkenes and is used mainly in the epoxidation of unsaturated alcohols, just as Ti(IV).244... 

Results of oxidation of unsaturated alcohols are shown in Table 3. Both 2-penten-1 -ol and 3-methyl-2-buten-1 -ol exhibited higher reactivity than cyclohexene. A decrease around 20-50% in catalytic activity of organically functionalized samples has been observed. This is probably due to the inhibition of access of the rather hydrophilic substrates to the Ti-active sites surrounded by the organic groups of increased hydrophobicity. It is noteworthy that the epoxidation was favorable for the organically functionalized samples whereas the alcohol oxidation was retarded. 

Hydration of Massively substituted epoxides in acid can be expected to yield significant amounts of elimination and/or rearrangement products derivable from an intermediate c rbonium ion This expectation is amply fulfilled with 2,3- poxy-2r4J4-trim thylpentane (Eq. 610), which yields in addition to the desired 1,2-diol, an unsaturated alcohol, a ketone, and several other products.61 ... 

Epoxidation of unsaturated alcohols One advantage of H2Oz epoxidation catalyzed by Na2W04 is that the reaction can be effected in water or water-alcohol mixtures. However, glycols are obtained unless the medium is buffered [NaOAc or (CH3)3NO] at about pH 4.5. Under these conditions, isolated double bonds react very slowly at 25°. 

Optically active diisopinocamphenylborane can be used to resolve racemic olefins. The reagent adds to one enantiomer, and the other is unchanged. Optical purities on the order of 37-65% are possible. Chiral ally lie alcohols can be resolved with chiral epoxidizing agents derived from tartrate complexes of titanium. One enantiomer is epoxidized and the other is not. Thus, die two alcohol enantiomers can be separated, one as the unsaturated alcohol and one as the epoxy alcohol. Use of die other tartrate isomer reverses die stereoselectivity. Selectivities on die order of >100 are possible with this method. As in any kinetic resolution, however, only one enantiomer can be recovered. The other is converted to a different chiral product. 

As observed from reaction (6.19) and experimental data [41,120,121], ROOH satisfactorily replaces molecular oxygen and the reducer. When oxidized with hydroperoxides in the presence of iron porphyrin catalysts (cytochrome P-450 analogs), olefins mostly convert to allyl oxidation products, namely unsaturated alcohols and ketones, whereas the quantity of epoxides does not exceed 1% [122], According to current suggestions [121] such behavior of iron porphyrin catalysts is explained by olefin epoxidation with the cata-lyst-ROOH complex by the heterolytical mechanism according to the following equation ... 

In cyclic unsaturated alcohols, a vast array of orientations of the hydroxy group relative to the double bond to be epoxidized may occur. For a general discussion of a force-field analysis of the peracid epoxidation see Section 4.5.1.1.1. 

The oxidahon of olefins with aqueous hydrogen peroxide in methanol can produce several products, by different reachon paths double bond epoxidation, allylic H-abstraction, epoxide solvolysis, alcohol and glycol oxidation (Scheme 18.6). Normally, oxide catalysts of Group IV-Vl metals are poorly selechve, because of their acidic properhes, the inhibition they are subject to in aqueous media and homo-lytic side reachons with hydrogen peroxide. The only excephon concerns the epoxidahon of a,(3-unsaturated alcohols and acids, which are able to bind on the... 

Epoxidation of olefins with hydrogen peroxide in the presence of Fe(acac)3 has been examined in the cases of stilbene, unsaturated alcohols, and fatty acids. From cis- and trans-olefins the main product is the trans isomer, formed via a biradical intermediate. Cholesterol undergoes /3-epoxidation. ... 

Epoxidations of unsaturated alcohols, aldehydes, ketones, and acids and their derivatives are discussed in the appropriate sections. 

These mixed bridged-dinuclear Rh complexes [Rh2(//-Cl)(//-SR)(CO)2(PR 3)2] also catalyze the transformation of epoxides or unsaturated alcohols into the corresponding ketones [39]. 

Sulfonyl carbanions are even more stable than sulfinyl carbanions and are consequently of greater significance in synthesis. They can be alkylated and acylated at the a-carbon atom using organolithium bases, and cyclic sulfones can be formed by intramolecular alkylation, (see Chapter 10, p. 202). Sulfonyl carbanions (73) also react with terminal epoxides, and this reaction is applicable for the synthesis of unsaturated alcohols (74) (Scheme 33). 

The general trend is that metals which react via an oxometal pathway show a very similar behaviour using these two hydroperoxides as oxidant, e.g. the selenium catalyzed allylic oxidation of olefins to the corresponding a, p-unsaturated alcohols. Reactions which involve a peroxometal pathway, e.g. the molybdenum catalyzed epoxidations of olefins, show a completely different behaviour using these two hydroperoxides, namely virtually no reaction is observed with the bulky PHP. We conclude that PHP is a suitable mechanistic probe for distinguishing between oxometal and peroxometal pathways in catalytic oxidation. 

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