Allylic epoxide

The application of the AE reaction to kinetic resolution of racemic allylic alcohols has been extensively used for the preparation of enantiomerically enriched alcohols and allyl epoxides. Allylic alcohol 48 was obtained via kinetic resolution of the racemic secondary alcohol and utilized in the synthesis of rhozoxin D. Epoxy alcohol 49 was obtained via kinetic resolution of the enantioenriched secondary allylic alcohol (93% ee). The product epoxy alcohol was a key intermediate in the synthesis of (-)-mitralactonine. Allylic alcohol 50 was prepared via kinetic resolution of the secondary alcohol and the product utilized in the synthesis of (+)-manoalide. The mono-tosylated 3-butene-1,2-diol is a useful C4 building block and was obtained in 45% yield and in 95% ee via kinetic resolution of the racemic starting material. 

Pineschi and Feringa reported that chiral copper phosphoramidite catalysts mediate a regiodivergent kinetic resolution (RKR) of cyclic unsaturated epoxides with dialkylzinc reagents, in which epoxide enantiomers are selectively transformed into different regioisomers (allylic and homoallylic alcohols) [90]. The method was also applied to both s-cis and s-trans cyclic allylic epoxides (Schemes 7.45 and 7.46,... 

While little biosynthetic information is available, it has been suggested [38] that 25 and 26 may be formed from AA (24) and EPA (14) via a cyclization mechanism (Scheme 3) similar to that which forms trans-cyclopropyl-containing diol 28 upon treatment of linoleic acid with performic acid [40]. An alternative biogenetic mechanism (Scheme 4), based upon that proposed for the structurally related red algal metabolites constanolactone A and B [41], would involve the formation and opening of an allylic epoxide intermediate created as a result of a 15-/ -LPO acting on either AA or EPA. Related compounds have been isolated from the coral Plexaura homomalla and the mollusc Aplysia kurodai (see below). 

The analogous process involving allylic epoxides is more complex, as issues such as the stereochemistry of substituents on the ring and on the alkene play major roles in determining the course of the reaction [38]. Addition of the Schwartz reagent to the alkene only occurs when an unsubstituted vinyl moiety is present and, in the absence of a Lewis acid, intramolecular attack in an anti fashion leads to cyclopropane formation as the major pathway (Scheme 4.10). cis-Epoxides 13 afford cis-cyclopropyl carbinols, while trans-oxiranes 14 give mixtures of anti-trans and anti-cis isomers. The product of (S-elimi-... 

Scheme 4.10. Intramolecular cyclization or p-elimination of hydrozirconated allylic epoxides.

Scheme 3.43. Reactions of a-aminoalkylcuprates with allylic epoxides [171] and propargylic substrates (Boc = t-butoxy-carbonyl) [172].

A variety of rhodium complexes, including [Rh(CO)2Cl]2 and [Rh(COD)Cl]2 when used in combination with a variety of bisphosphine ligands, will catalyze the ring opening of vinyl epoxides in the presence of aniline nucleophiles [19, 20]. These reactions occur under very mild and neutral conditions (at room temperature or with mild heating) and are highly regio- and stereoselective. In all cases, nucleophilic attack occurs at the allylic epoxide carbon atom and proceeds with inversion of stereochemistry (Scheme 9.11). 

Allyl amides (enamides), for example, 225, 228, and 230 cyclize to oxazolines, for example, 226, 229, and 231 when the double bond is activated by an electrophile. The double bond can also be conjugated to a ketone, or present as an allylic epoxide. Reagents commonly used to promote the cyclization include acids,iodine,selenium reagents,and trimethylsilyl triflate (Scheme 8.63). ... 

Allylic epoxide cyclization led from irans-epoxide 2 exclusively to product 3 containing three contiguous stereogenic centers (see p 483 for the determination of relative configuration)105. 

The first mechanism, with one small refinement, explains satisfactorily the neighboring-group effect discussed above. The transith> > state for allylic epoxidation is represented by Henbeet and Wilson. 41 by Albrecht and Tamm.16 and also by Saeaiver and English,15-- ii shown in Eq. (41)... 

Selective opening of allylic epoxides (9, 329-330). The reaction of the trimethyl-silyl enol ether (I) of a, /Tepoxycyclohexanone with lithium dimethylcuprate (or di-n-butylcuprate) in THF proceeds as expected to give 2.25,26 However when the reaction is conducted in ether, 2 and 3 are formed in about equal amounts.26... 

On treatment with sodium bis (2-methoxyethoxy)aluminium hydride (Scheme 16), 122 gave the aldehyde 123, which was converted by standard synthetic operations, into the methyl-O-benzylester 124. Acid hydrolysis of 124 followed by allylic epoxidation of the diol furnished the p-oxirane 125. On heating 125 in water containing sodium benzoate a remarkable chain of chemical events took place that resulted in the generation of (+)-pancratistatin (94) in 2% overall yield starting from bromobenzene. 

Stradi, B. A. Kohn, J. P. Stadtherr, M. A. Brennecke, J. F. Phase Behavior of the Reactants, Products and Catalysts Involved in the Allylic Epoxidation of trans-2-Hexen-l-ol to (2R,3R)-( + )-3-Propyloxiramethanol in High Pressure Carbon Dioxide. J. Supercrit. Fluids 1998, 12, 109-122. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Similarly, Jung and D Amico have shown that chiral tertiary allylic epoxides undergo a stereospecific rearrangement in the presence of BF3-OEt2 to give optically active quaternary aldehydes 74. The stereospecificity of the process is rationalized on the basis of hindered rotation of the intermediate carbocation. Furthermore, eclipsing interactions hinder the... 

The tolerance of the RCM reaction to diverse functional groups is illustrated by the synthesis of 14-membered macrocycles monocillin I and radicicol, reported by Danishefsky and coworkers [63]. In the presence of catalyst G2, cyclization of dienic substrates 90 and 91, which comprise an allylic epoxide and a ketone function protected as a dithiane, occurs in 55-60% yields, generating intermediate macrocy-clic dienes 92 and 93 of 6E,ttZ stereochemistry (Scheme 2.36). It is interesting to... 

The addition of lithium (.Sj-iV-allyl-A -o -methylbenzylamide to unsaturated esters was shown to be an effective method for producing RCM precursors <02SL1146> for piperidine synthesis, as was the addition of allylamine to the enantiomerically-enriched allylic epoxide 37 <02TL779> (Scheme 20). 

A sequence of allylation, epoxidation and an acid-mediated 6-exo cyclisation converts salicylaldehydes into 2-hydroxymethyl-2-methyl-27/-[l]benzopyrans. A bicyclic chroman arising from attack of the hydroxymethyl group on the intermediate benzylic cation has been isolated <02SL322>. A twelve-step enantioselective synthesis of a 2-hydroxymethyl-2-methylchroman with an overall yield of 48% uses related methodology and introduces the chirality through an asymmetric Sharpless epoxidation <02JCS(P1)496>. 

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