A,p-Epoxy alcohols

P-Hydroxy ketones can be prepared by treating the silyl ethers (53) of a,p-epoxy alcohols with TiCU- ... 

Contra-trans-diaxial cleavage of epoxides.2 The reaction of the a, p-epoxy alcohol 2 with NaSeC6H5 provides the 1,3-diol 3 in 90% yield. Use of 1 results in the opposite regioselectivity to provide 4 as the major product. 

Reduction of CL, -epoxy ketones. a,p-Epoxy ketones are reduced by NaTeH re-gioselectively to p-hydroxy ketones. Unactivated epoxides, such as stilbene oxide and a,p-epoxy alcohols, are not reduced. 

OLy Epoxy alcohols In the presence of Ti(0-/-Pr)4, allylic hydroperoxides are converted into a,p-epoxy alcohols. The precursors are readily available by the ene reaction of alkenes with singlet oxygen. The oxygen transfer involves the corresponding allylic alcohol. 

Epoxidation of oleic and linoleic acid was readily achieved by treatment with the acetonitrile complex of hypofluorous acid (55). Phase-transfer-catalyzed biphasic epoxidation of unsaturated triglycerides was accomplished with ethylmethyldioxirane in 2-butanone (56). The enantioselective formation of an a,P-epoxy alcohol by reaction of methyl 13()S)-hydroperoxy-18 2(9Z,llfi) with titanium isopropoxide has been reported (57). An immobilized form of Candida antartica on acrylic resin (Novozyme 435) was used to catalyze the perhydrolysis and the interesterification of esters. Unsaturated alcohols were converted with an ester in the presence of hydrogen peroxide to esters of epoxidized alcohols (e.g., epoxystearylbutyrate) directly (58). Homoallyl ethers were obtained from olefinic fatty esters by the ethylaluminium-in-duced reactions with dimethyl acetals of formaldehyde, acetaldehyde, isobutyralde-hyde, and pivaldehyde (59). Reaction of 18 2(9Z, 12Z) with 50% BF3-methanol gave monomethoxy and dimethoxy derivatives (60). A bulky phosphite-modified rhodium catalyst was developed for the hydroformylation of methyl 18 1 (9Z)and 18 1(9 ), which furnished mixtures of formylstearate and diformylstearate (61). 

Piazza, G.J., T.A. FogUa, andA. Nunez, Enantioselective Conversion of Linoleate Hydroperoxide to an a,P-Epoxy Alcohol by Niobium Ethoxide, J. Am. Oil Chem. Soc. 75 939-943 (1998). 

Epoxidations of the allylic alcohols (144), (145), (146 equation 50) and (148 equation 51) are highly stereoselective. The transformation of (148) to (149) is an example of the use of silyloxytdkenes in the stereoselective synthesis of trans a,p-epoxy alcohols. The epoxidation of tiie ester (150), which has a hydroxy allylic to a tra/ir-disubstituted double bond, does not exhibit high stereoselectivity (equation S2) the epoxidation is regioselective, involving only the C(13)—C(14) double bond. 

In 2004, Bode and Rovis independently and concurrently reported the catalytic coupling of reducible aldehydes and alcohols. This mode of reactivity is most closely related to the work published by Wallach, who generated dichloroacetic acid from chloral under cyanide catalysis in aqueous media [108]. Bode and coworkers reported the catalytic, diastereoselective synthesis of P-hydroxy esters from a,P-epoxy aldehydes using thiazolium pre-catalyst 173 Eq. 16a [109]. MeOH, EtOH, and BnOH are effective nucleophiles providing upwards of >10 1 diastere-oselectivity. Aziridinylaldehyde 174 has also been shown to provide the desired iV-tosyl-P-aminoester 175 in 53% yield Eq. 16b. 

The method is a modification of one used by Barton and McCombie.8 Reduction of ketones.9 Ketones can be reduced to alcohols by Bu3SnH in the presence of either AIBN or a Lewis acid, but this reaction is limited to unhindered ketones. However, even sterically hindered ketones, such as f-butyl methyl ketone, can be reduced under high pressure (10 kbar) in the absence of a catalyst. This method is particularly useful in the case of cyclopropyl and a,p-epoxy ketones, which are reduced to the corresponding alcohols. Reduction of these ketones with Bu3SnH under radical conditions results in ring-opened products. 

A variety of a,p-epoxy sulfones have been converted into a range of mono-, di-, and tri-substituted allylic alcohols using the epoxy-Ramberg-Backlund reaction (ERBR) (Scheme 7).41 Modification of this method has enabled the preparation of enantio- enriched allylic alcohols following the diastereoselective epoxidation of enantio-enriched vinyl sulfones that were accessed efficiently from the chiral pool. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

The oxidative rearrangement of allylic alcohols to a -unsaturated kelmies or alddiydes is one of the most widely used synthetic reactions in this group, and forms part of a 1,3-carbonyl tran sition sequence. Scheme 7 shows this reaction and the related conversion of the allylic alcdiol to an a,p-epoxy carbonyl compound. Chromate reagents induce some allylic alcohol substrates to undergo a directed qmxidation of the alkene without rearrangement, but this reaction is beyond the scope of the present discussion. 

Zinc borohydride was effective for the reduction of a,P-epoxy ketones (49) to the corresponding anti-a,3-epoxy alcohols (50) in ether at 0 °C irrespective of the substituents on the epoxide (equation 14). The selectivity was rationalized by intramolecular hydride delivery from a five-membered zinc chelate avoiding the epoxide ring. In a limited study of the stereoselective reduction of y,8-epoxy ketones (51), LAH and di-2-(o-toluidinomethyl)pyrrolidine in ether at -78 C gave the desired c/j-epoxy alcohols (52) required for ionophore synthesis with good selectivity (>10 1) (equation 15). ... 

This transformation has found extensive use in converting cyclopentenone and cyclohexenone ring systems to the rearranged allylic alcohols during the course of the total syntheses of natural products. In the preparation of ( )-quadrone (Scheme 12), the tricyclic enone was epoxidized and the resulting a,P-epoxy ketone treated with hydrazine to afford the allylic alcohol. The cyclopropane-directed epoxidation shown in Scheme 13 gives an allylic alcohol that is taken on to (-)- and (+)-carenones. In the total syn-... 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a,p-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a P.y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopentene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place... 

Reductions. Aldehydes, ketones, acid chlorides, carboxylic acids, and N-Boc amino acids are reduced to the corresponding alcohols, generally in excellent yields. The reduction of a,P-epoxy ketones gives alcohols without affecting the heterocycle. ... 

Reduction of a,P-epoxy ketones by hydrazine to allylic alcohols. 

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