Epoxides unsaturated, allylic alkylation

Most attention has been devoted to the conversion of epoxides derived from 2-alkoxy-5,6-dihydro-2ff-pvrans into unsaturated allylic alcohols, that is, alkyl 3,4-dideoxy-DL-ald-3-enopvranosides (256). Ad-... 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

These mesoporous mixed titania-silica oxides are hydrophilic materials and are excellent catalysts for epoxidations of olefins, allylic alcohols and a,jff-unsaturated ketones with alkyl hydroperoxides in non-aqueous media [37]. Their performance can be improved even further by adding organic or inorganic bases to neutralize acid sites present on the surface [38,39], The latter cause side-reactions, especially with acid sensitive epoxides. Amine addition was particularly effective and led to the development of a mesoporous Ti-Si mixed oxide containing surface-tethered tertiary amino groups as an active, selective, and recyclable catalyst for the epoxidation of allylic alcohols [38]. 

Heteropoly acids can be synergistically combined with phase-transfer catalysis in the so-called Ishii-Venturello chemistry for oxidation reactions such as oxidation of alcohols, allyl alcohols, alkenes, alkynes, P-unsaturated acids, vic-diols, phenol, and amines with hydrogen peroxide (Mizuno et al., 1994). Recent examples include the epoxidations of alkyl undecylenates (Yadav and Satoskar, 1997) and. styrene (Yadav and Pujari, 2000). 

During the past year, chloroperoxidase (CPO) was found to catalyze the smooth asymmetric epoxidation of functionalized cii-alkenes, such as the unsaturated ester 32. The reaction appears to be limited to 2-alkenes (i.e., methyl group on one side of the alkene), although some branching on the longer alkyl chain is tolerated. Allylic alcohols are oxidized to the corresponding unsaturated aldehydes but without epoxide formation <99TL1641>. 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, 5 which are very useful synthetic Intermediates. They react with a variety of electrophiles such as carbon dioxide,5,6 epoxides,5,6 aldehydes,6 allylic halides,7 alkyl halides,7 and acetylenic halides 7 they undergo conjugate addition to a,6-unsaturated esters,5 6 ketones,6 aldehydes,6 and sulfones.8 Finally they add smoothly to activated triple bonds6 such as HCSC-OEt, HC3C-SEt, HC=C-CH(0Et)2. In most cases these cuprates transfer both alkenyl groups. The uses and applications of the carbocupration reaction have been reviewed recently.9 The configurational purity in the final product 1s at least 99.951 Z in the above transformations. 

In the first approach shown in Scheme 9, ketoester 77 was alkylated successively with 4-bromobutene and 1,3-dibromopropene. After decarboxylation, 78 was converted into iV-aziridinylimine 79 in good yield. The pivotal radical cyclization reaction proceeded smoothly to produce a mixture of isomeric propellane compounds 80, which was purified after the epoxidation step. For the synthesis of modhephene, the mixture of epoxides was rearranged into the corresponding allylic alcohols 81 and then the allylic alcohols were oxidized, giving a separable mixture of unsaturated ketones 82a and 82b. The major product 82a possessed the correct stereochemistry of the methyl group of modhephene. Since 82a had already been converted into modhephene, a formal total synthesis of dZ-modhephene has thus been completed. The isomeric ratio of 80 reflects the stereoselectivity during the radical cyclization reaction. The selectivity was very close to the ratio reported by Sha in his radical cyclization reaction. ... 

Hodgson et al. have further expanded upon this methodology to epoxides derived from unsaturated hetero- (oxa and aza)cycles, such that the /3-leaving group is retained in the product after elimination. Their initial studies examined epoxides derived from cyclic allylic ethers (i.e., 3,4-epoxytetrahydrofuran, Scheme 48), from which alkylated ene diols were obtained in good yields <20010L3401, 2002S1145>. 

Vinylcopper reagents react with a wide variety of electrophilic reagents such as halogens, alkyl halides, allylic halides, acid chlorides, epoxides, a,(3-unsaturated ketones, and a,p-acetylenic esters with complete retention of the double bond stereochemistry. To enhance the reactivity of vinylcopper intermediates toward carbon electrophiles, the coupling is often carried out in the presence of activators such as HMPT, DMPU, and/or P(OEt)3 (triethylphosphite). Some representative examples of stereospecific... 

Sturtz et al. have described the deprotonation of the allyl bis(dimethylamido)phosphonate (9). Treatment of (9) with two equivalents of base, followed by reaction with an epoxide and hydrolysis, yields the y-lactone (Scheme 10). Alkylation with alkyl and alkenyl halides occurs at the y-carbon and hydrolysis yields the saturated and unsaturated carboxylic acids respectively. 

Lithium aminoborohydrides are obtained by the reaction of -BuLi with amine-boranes [FF2, FH5, NT2]. They can be generated in situ as THF solutions or as solids when formed in diethylether or hexane (n-BuLi must then be used in sub-stoichiometric amounts). They are stable under dry air and are slowly decomposed by water [NT2] or methanol so that workup of the reactions mixtures can be carried out with 3M HCl. They reduce alkyl halides (Section 2.1), epoxides (Section 2.3), aldehydes, and ketones (Section 3.2.1) (in the latter case with an interesting stereoselectivity [HFl]), and esters to primary alcohols (Section 3.2.5). a,(3-Unsaturated aldehydes, ketones, and esters are reduced to allyl alcohols (Section 3.2.9) [FF2, FS2]. Depending on the bulkiness of the amines associated with the reagent and to the substrate, tertiary amides give amines or alcohols (Section 3.2.8) [FFl, FF2]. Amines are also formed from imines (Section 3.3.1) [FB1 ] and from azides (Section 5.2) [AFl]. However, carboxylic acids remain untouched. 

Benzyl, allyl, vinyl, and aryl, but also some aliphatic, halides have been transformed into carboxylic acids (Eq. 10). Under other conditions, couplings with CO to give symmetrical or unsymmetrical ketones were possible. Epoxides yielded unsaturated hydroxy acids, and a-oxo-butyrolactones (Eq. 11), couplings of alkynes and alkyl halides gave hydroxybutenolides (Eq. 12) and other more complex conversions could also be realized. 

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