Allylic compounds Other methods

Several Pd(0) complexes are effective catalysts of a variety of reactions, and these catalytic reactions are particularly useful because they are catalytic without adding other oxidants and proceed with catalytic amounts of expensive Pd compounds. These reactions are treated in this chapter. Among many substrates used for the catalytic reactions, organic halides and allylic esters are two of the most widely used, and they undergo facile oxidative additions to Pd(0) to form complexes which have o-Pd—C bonds. These intermediate complexes undergo several different transformations. Regeneration of Pd(0) species in the final step makes the reaction catalytic. These reactions of organic halides except allylic halides are treated in Section 1 and the reactions of various allylic compounds are surveyed in Section 2. Catalytic reactions of dienes, alkynes. and alkenes are treated in other sections. These reactions offer unique methods for carbon-carbon bond formation, which are impossible by other means. 

Example 22 removal of allyl group attached to a phosphorus centre with Pd, Pt and Rh complexes is a well established procedure [51] but is inconvenient for synthesis of therapeutic compounds on a large scale. During the deprotection step the palladium catalyst is susceptible to poisoning especially with P-S compounds resulting in loss of catalytic efficiency. Furthermore traces of organometallic compounds remain in the product after deprotection. In the paper of Manoharan et al. other methods of deprotection of allyl... 

While treatment in HBr + AcOH by the Tarbell method424 leads directly from allylphenols 168 to compounds 169, other methods involve the formation of the brominated derivative obtained by adding HBr (in the presence of diphenylamine) to the allylphenol.432 Ring closure is effected by sodium ethoxide. Thus, the ll//-furo[3,2-a]xanthone derivative (177) can be obtained either directly from the allyl derivative (175) or via the bromo derivative (176).432 433 Similarly, 179 has been obtained from the chromone 178.434... 

Methylmagnesium N-cyclohexyliso-propylamide, 189 By oxidation at an allylic carbon Selenium dioxide, 272 By reduction of a,0-unsaturated carbonyl compounds Sodium borohydride, 278 Sodium dithionite, 281 Other methods r-Butyllithium, 58 Butyllithium-Potassium f-butoxide,... 

In spite of these complications, the allylic alcohol substitution reaction provides a simple method for preparing a variety of carbonyl compounds and alcohols often not readily accessible by other methods. Some examples of the reaction are shown in Table IX. 

Substitution of the CO ligand for others in (143) has proved to be fairly facile. The mixing of equimolar amounts of (143) and a number of phosphines or phosphites results in the formation of complexes (145), through the intermediacy of ( -allyl)Fe(CO)2(NO)(PR3) complexes. Selected compounds of type (145) have also been prepared by the allyl halide attack method. Even in compound (145 L = P(OMe)3) the remaining CO ligand has been shown to be capable of replacement by an NO hgand from NO+PFe" to give cationic complexes (146). ... 

To date, several jt-allylmthenium complexes have been prepared and reported. The representative methods for introducing an allyl group to a ruthenium complex are quite similar to those for other transition metals for example, (1) the reaction of ruthenium halides with allyl Grignard reagents (2) the insertion of conjugated dienes into a hydrido-ruthenium bond and (3) the oxidative addition of several allylic compounds to low-valence ruthenium complexes. 

Epoxidation of allylic alcohols with peracids or hydroperoxide such as f-BuOaH in the presence of a transition metal catalyst is a useful procedure for the synthesis of epoxides, particularly stereoselective synthesis [587-590]. As the transition metal catalyst, molybdenum and vanadium complexes are well studied and, accordingly, are the most popular [587-590], (Achiral) titanium compounds are also known to effect this transformation, and result in stereoselectivity different from that of the aforementioned Mo- and V-derived catalysts. The stereochemistry of epoxidation by these methods has been compared for representative examples, including simple [591] and more complex trcMs-disubstituted, rrans-trisubstituted, and cis-trisubstituted allyl alcohols (Eqs (253) [592], (254) [592-594], and (255) [593]). In particular the epoxidation of trisubstituted allyl alcohols shown in Eqs (254) and (255) highlights the complementary use of the titanium-based method and other methods. More results from titanium-catalyzed diastereoselective epoxidation are summarized in Table 25. 

Slightly more unusual is the elimination and hydrolysis or reduction of iodolactonisation products 20 (chapter 17). Elimination replaces the alkene but in a different position 20 and cleavage of the lactone bridge4 by methanolysis gives 21 or by reduction gives 22. As we get on to the reactions of allyl alcohols you will see how these and other methods are used to make particular compounds. 

One of the best methods developed by Whitesides et al. was an indium mediated direct nucleophilic addition of ethyl 2-(bromomethyl)acrylate to unprotected aldoses in aqueous media [111] (Scheme 36). An other advantage of this reaction is that it can be compatible with a variety of functional groups [111,112], The resulting allyl-compounds were produced in good yield. Ozonolysis, then cyclization of the resulting ketones afforded the corresponding ulosonic acids. 

From this value and known C-H bond dissociation energies, we can calculate the pK values. Early application of these methods gave estimates of the pA of toluene of about 45 and of propene of about 48. Methane was estimated to have a pK in the range of 52-62. Electrochemical measurements in DMF have given the results in Table 6.3. These measurements put the pK of methane at about 48, with benzylic and allylic stabilization leading to values of 39 and 38 for propene and toluene, respectively. These values are several units smaller than those determined by other methods. The electrochemical values overlap with the pA d sq scale for compounds such as diphenylmethane and triphenylmethane, and these values are also somewhat lower than those found by equilibrium studies. 

Allylic compounds containing other leaving groups are also reactive toward substitution. Thus alkoxycarbonylation of allylic phosphates is a method of homologation, on which an interesting /3-lactam synthesis is based. Using PhjSiOH as nucleophile in the displacement, 2,4-hexadiene-l,6-diols are synthesizedfrom buta-dienyloxiranes. Desilylation of the products is achieved with KF. 

Extensive studies have been devoted to allylation of earbon pronucleophiles as important methods of C—C bond formation. As described before briefly, reactions with allylic carbonates and alkenyloxiranes proceed under neutral conditions due to in situ generation of alkoxides which abstract protons from nucleophiles. Also allylation with allyl aryl ethers can be carried out without addition of bases. Reactions of allylic acetates and other allylic compounds are carried out in the presence of bases [5]. 

Pd-catalyzed hydrogenolysis of allylic compounds with formates is an efficient and mild method. The hydride generated from the palladium formate attacks the more substimted side of the allylic system to give less substituted olefins in contrast to the case with other hydride sources. Pd-catalyzed hydrogenolysis of propargylic compounds affords either aUenes or alkynes depending on the structure of the propargylic compounds. 

This one-step transformation of an alkene to an allylic acetate compares well with other methods of preparation such as hydride reduction of a, 8-unsaturated carbonyl compounds followed by esterification. The scope and limitations of the reaction have been investigated. The allylic acetoxylation proceeds via a TT-allylpalladium intermediate, and as a result, substituted and linear alkenes generally give several isomeric allylic acetates. With oxygen nucleophiles the reaction is quite general, and reactants and products are stable towards the reaction conditions. This is normally not yet the case with nitrogen nucleophiles, although one intramolecular palladium-catalyzed allylic amination mechanistically related to allylic acetoxylation has been reported. ... 

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