Vinyl epoxide route

The key to the success of the vinyl epoxide route would reside in a nucleophilic ring-opening of vinyl epoxide 75. If this ring-opening proceeds regioselectively at C5 via a SN2 pathway, it would have been the most welcome at this stage of our efforts (Scheme 8.21). However, an array of conditions, including Pd(0)-mediated and Lewis acidic conditions, were screened over a period of almost 2 years, but we never observed the desired 1,4-diol 80. Instead, we could at various times see small... 

The relative stability of l, 2 -epoxyvinylbital, and the great instability of its diol, can be gainfully compared with the fate of the corresponding metabolites of phenyl vinyl ether (10.69, R = H) and 4-nitrophenyl vinyl ether (10.69, R = N02), two mutagenic and tumorigenic compounds [144] [145]. Their primary metabolic route is by vinyl epoxidation to the corresponding... 

Vinyl azides have been prepared by treating epoxides (78) with azide ion to give azido alcohols (79) which are then dehydrated to the vinyl azide.30 This method also complements the iodine azide method since the epoxide route usually gives the isomeric vinyl azide. -Hydroxy azides (81) can also be prepared by the sodium borohydride reduction of a-azidoketones (80). 

As the key precursor towards the realization of 1,7-epoxy cyclononanes and 1,8-epoxycyclodecanes, an 1 l-oxatricyclo[6.2.1.02,6]decane skeleton was constructed by using the Hoffmann [4+3] cycloaddition methodology <07EJO4383>. In Majetich s total synthesis of (-)-salviasperanol, the key step was the trifluoroacetic acid-promoted isomerization of a vinyl epoxide to 2,5-dihydrofuran, whose O-thiocarbamate was removed by radical reaction to produce salviasperanol dimethyl ether <07OL85>. The synthetic route is depicted below. 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

Another standard method for the synthesis of 2-oxazolidinones is by reaction of epoxides with isocyanates. Although 4,5-disubstituted derivatives are not readily accessible by this route, it has been shown that iminodioxolanes (192) add to epoxides in the presence of AICI3 to afford these oxazolidinones in high yield <9lJOC2684>. The reaction proceeds through a spirocyclic intermediate (193) (Scheme 96). The reaction of vinyl epoxides with aryl isocyanates is facilitated by palladium catalysis (Equation (28)) <89TL3893>. The products are obtained by a double inversion process, but... 

Cyclic vinyl epoxides are versatile building blocks (Table 11) which have been used in palladium-assisted routes to carbocyclic nucleosides. A formal synthesis of ( )-aris-teromycin101, the carbocyclic analog of adenosine, has been accomplished employing ni-tromethane as the nucleophile which serves as an acyl anion equivalent (Table 11. entry 2). The aldehyde is released by subsequent basic potassium permanganate oxidation. If nitromethane is used diluted in tetrahydrofuran, then a mixture of mono- and bis-alkylated product is formed. Whereas the alkylation of cyclohexenoxide with dimethyl malonate proceeds in a 1,4-crs fashion under palladium(O) catalysis, the 1.2-/ra/i.v-product is formed under basic conditions in the absence of the palladium(O) catalyst. 

The sulfide-catalyzed enantioselective epoxidation reaction is the most extensively studied transformation in ylide catalysis, and two ylide generation methods (aUcylation/deprotonation and carbene transfer) have been developed. Compared with conventional methods for epoxidation via oxygen transfer to the carbon-carbon double bond, such as the Sharpless epoxidation, Jacobsen-Katsuki epoxidation, and Shi epoxidation, the yhde approach can be regarded as an alkyUdene transfer reaction to carbonyl groups (C=0), providing a different retrosynthetic analysis for the construction of epoxides. In particular, in the synthesis of vinyl epoxides, the ylide route has priority over conventional oxidation methods, since the issue of regjoselectivity in the epoxidation of dienes will not be present [32]. 

This strategy can be applied to the synthesis of vinylepoxides, since high enantioselectivity and good regioselectivity can often be obtained in asymmetric dihydroxylation of dienes, resulting in vinylic diols [24, 25], Transformation of the diols into epoxides thus represents an alternative route to vinylepoxides. This strategy was recently employed in the synthesis of (+)-posticlure (Scheme 9.6) [26]. 

Reaction in organic solvent can sometimes provide superior selectivity to that observed in aqueous solution. For example, Keeling et al recently produced enantioenriched a-trifluoromethyl-a-tosyloxymethyl epoxide, a key intermediate in the synthetic route to a series of nonsteroidal glucocorticoid receptor agonist drug candidates, through the enan-tioselective acylation of a prochiral triol using the hpase from Burkholderia cepacia in vinyl butyrate and TBME (Scheme 1.59). In contrast, attempts to access the opposite enantiomer by desymmetrization of the 1,3-diester by lipase-catalysed hydrolysis resulted in rapid hydrolysis to triol under a variety of conditions. 

Babler and Schlidt [86] described a route to a versatile C15 phosphonate, used for a stereoselective synthesis of all E retinoic acid and p-carotene. Base-catalyzed isomerization of the vinyl-phosphonate afforded the corresponding allyl-phosphonate as the sole product. Homer-Emmons olefination with ethyl 3-methyl-4-oxo-2-butenoate concluded the facile synthesis of all E ethyl retinoate. The C15 phosphonate was synthesized starting from the epoxide of P-ionone. Subsequent isomerization with MgBr2, afforded the C14 aldehyde in 93%... 

Spiro epoxidation of a -enones.1 The conversion of ketones to spiro epoxides is usually carried out with dimethylsulfonium methylide, but this reaction can proceed in low and variable yields when extended to a,p-enones. A generally useful route to these vinyl spiro epoxides involves addition of 1, methylation, and ring closure with base, as illustrated for cyclohexenone. 

Animals. The major metabolic routes are epoxidation of the vinyl group, followed by hydration of the intermediate epoxide, and by hydrolytic cleavage of the heterocyclic ring. Eliminated in approximately equal proportions in the urine and feces, with the principal metabolite being Af-(3,5-dichlorophenyl)-2-methyl-2,3, 4-trihydroxybutanamide... 

Takahashi et al. also reported a route to muconin. Their synthesis adopted Keinan et al. s strategy to construct the stereochemistries by Sharpless AD and AE upon multiple olefin containing fatty acid (Scheme 10-35). The di-olefin 214 was subject to Sharpless AD conditions and then treated with acid, yielding a THP-containing diol. This diol was further protected as acetonide 215. The reversion of stereochemistry of alcohol 215 was achieved by Dess-Marlin oxidation and Zn(BH4)2 reduction. Williamson etherification of tosylate 216 and epoxide formation afforded tri-ring intermediate 217. Opening with acetylene, 217 was converted into the terminal alkyne 218, which was coupled with vinyl iodide to finally give muconin. 

This route can be used to generate vinyl oxiranes, useful intermediates for organic synthesis <2000TL7309, 2002JOC9083, 2003JOC2060>. Aryl epoxides have been made and have been used as intermediates in the context of total synthesis venture <2004T9725>. 

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. ... 

The cyclization in Step B is an improvement of Butler s procedure for the synthesis of which employs less convenient reagents, KNH and l-bromo-3-chloroacetone acetal. Beside the acetals derived from neopentyl glycol, those derived from ethanol, 1,3-propanediol and 2,4-pentanediol have been synthesized by the present method. The second part of Step B involves the formation and the electrophilic trapping of cyclopropenyl anion 2, which is the key element of the present preparations. Step B provides a simple route to substituted cyclopropenones, but the reaction is limited to alkylation with alkyl halides. The use of lithiated and zincated cyclopropenone acetal, on the other hand, is more general and permits the reaction with a variety of electrophiles alkyl, aryl and vinyl halides, Me3SiCl, Bu3SnCl, aldehydes, ketones, and epoxides. Repetition of the lithiation/alkylation sequence provides disubstituted cyclopropenone acetals. 

These epoxides can be converted to vinyl siloxycyclopropanes m high yield by treatment with base and trimethylsilyl chloride. Transformations of these interesting intermediates (see Section VII) into various products are demonstrated in equation 103. Isolation of oxaspiropentanes is not required in a route to cyclobutanones which are formed by straightforward acid workup (equation 104) . These can either be expanded to y-butyrolactones by oxidation or to an enol ester by a-formylation and acid-induced fragmentation. The latter sequence has been utilized in a synthesis of acorenone... 

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