Hydroxy-directed epoxidation

For the formation of substituted THF rings (Route a, Scheme 8.1), Kishi developed a procedure based on the hydroxy-directed epoxidation of a y-alkenol [10]. Epoxidation of bishomoallylic alcohol 3 by TBHP/VO(acac)2 by this approach, followed by treatment of the intermediate epoxide 4 with acetic acid, gave the TH F derivative 5 of isolasalocid A (a 5-exo cydization Scheme 8.2) [11]. Further epoxidation of 5 (a y-alkenol) under the same conditions, followed by acetylation, afforded epoxide 6. For the synthesis of the natural product, the configuration of epoxide 6 had to be inverted before the second cydization reaction. Epoxide 6 was consequently hydrolyzed under acid conditions to the corresponding diol and was then selectively... 

The structure of glabrescol was subsequently revised, and the new structure was synthesized enantioselectively through sequential hydroxy-directed anti-oxidative cyclization of acyclic y-alkenols with VO(acac)2/TBHP to construct the adjacent THF rings via epoxides under acid conditions [35b],... 

Stereospecfic ring expansion can be done by taking advantage of the hydroxy-directed epoxidation and SnCl4-mediated rearrangement of 1-hydroxycycloalkyl epoxides.69... 

Holton s Construction of the Polycyclic Ring. In Holton s synthesis,23 compound 97, which can be prepared from camphor derivatives, is the starting material. Hydroxy-directed epoxidation of compound 97 gives unstable compound 98, which fragments in situ to provide compound 99, thus furnishing the AB skeleton of taxol (Scheme 7-31).24... 

Carbonylation of epoxides provides direct access to a large variety of hydroxy carbonyl compounds, such as /Mac tones, useful synthons in organic synthesis, and poly(3-hydroxyalkanoate), important biodegradable polyesters. Thus, the development of efficient catalysts for such carbonylations has been widely studied. 

Similar to Jones reagent, Collins reagent can produce a hydroxy directed epoxidation of allylic alcohols. This side-reaction only occurs in a limited number of allylic alcohols, most of them being oxidized uneventfully to the corresponding enones.117... 

The expected enone is obtained in 40% yield. A 15% yield of the product, resulting from hydroxy-directed epoxidation followed by oxidation to ketone, is obtained. A third product, obtained in 30% yield, can be explained by the equilibration of the initially formed allylic chromate ester with an isomeric chromate ester that directs the epoxidation of an alkene, giving an epoxy alcohol that is further oxidized to an... 

Isolated carbon-carbon multiple bonds are not normally attacked by Jones reagent, but some doublebond isomerization may occur during the preparation of a, -unsaturated aldehydes. Hydroxy-directed epoxidation (presumably via chromate ester formation, followed by oxygen transfer to the double bond) has also been observed in steroidal substrates for axial alcohols (equation 1). Equatorial alcohols undergo oxidation to give the expected enone. 

In the nonsteroidal conformation of (64), the axial hydroxy is suitably oriented for forming a hydrin bond with the peroxy acid in the transition state. That the epoxidation of (64 R = OH) is indeed hydroxy-directed is supported by the observation that the epoxidation of the acetate (64 R = OAc) furnishes exclusively the a-epoxide (66 R = OAc). 

Hydroxy-directed epoxidation of (138d) with TBHP/Ti(OPr )4 is complete in 2 h at -3S C and gives in 87% yield the corresponding a-epoxide. In contrast, the epoxidation of the diol (138c) is extremely sluggish, probably due to the strong coordination of the Ti cation to the diol. ... 

Vanadium-catalyzed epoxidation of the diene (156) having hydroxy allylic to one double bond and homoallylic to the other double bond does not furnish exclusively (157 equation 54). ° The epoxidation of (156) with dibutyltin oxyperoxide is regioselective, fUmishing exclusively the regioisomer (157) as a 9S S mixture of erythro and threo diastereoisomers."" Epoxidations of the diol (159) and its epimer (160) take place selectively from the a-face. On the basis of this observation and further studies it has been concluded that in (159) and (160) the epoxidation is directed by the homoallylic, but not the allylic,... 

Since epoxidation at the vinyl double bond is unproductive, it is desirable to direct reaction on the al-lene moiety. This can be accomplished by taking advantage of the hydroxy-directed epoxidation of allylic alcohols using the t-butyl hydroperoxide/vanadium(V) system.The directing effects of both allylic and homoallylic type hydroxy groups have been examined at both positions of the vinylallene unit. " At the 1-position (64), primary, secondary and tertiary allylic tdcohols are effective, while only primary homoallylic alcohols have bran examined (equation 35). Presumably the directing effect of the hydroxy groups favors formation of the intermediate allene oxide (65). A sample of the compounds prepared by this route is shown in Scheme 32. ... 

In analogy to the Peterson alkenation, the intermediate hydroxyphosphine oxidn (269) cm be prepared by addition to epoxide derivatives (268 Scheme 36). Overall yields are high for this process, and this sequence can be applied to the synthesis of phosphonate intermediates as well. Warren has studied hydroxy-directed epoxidation. Provided the allylic phosphine oxide is trisubstituted, as is (270) in equation (6S), these oxidations proceed with good selectivity. Ring opening can then be undertaken to generate the hyth-oxyphosphine oxide. 

Holton s plan for the synthesis of the ab ring system of taxanes e.g. 83) involves fragmentation of an easily accessible tricyclic compound derived from patchouli alcohol. Hydroxy-directed epoxidation of the tertiary alcohol (84) (from patchino 90) gives an unstable substance which undergoes gmentation in situ to provide the keto alcohol (85 Scheme 29). 

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