Electrophilic activation of the double bond

The oxidative addition of palladium(O) to aryl bromide generates the arylpalladium(n) intermediate 126 (Scheme 37). The electrophilic activation of the double bond by palladium facilitates the nucleophilic attack, resulting in cyclization. 

Additions to nonactivated olefins and dienes are important reactions in organic synthesis [1]. Although cycloadditions may be used for additions to double bonds, the most common way to achieve such reactions is to activate the olefins with an electrophilic reagent. Electrophilic activation of the olefin or diene followed by a nucleophilic attack at one of the sp carbon atoms leads to a 1,2- or 1,4-addition. More recently, transition metals have been employed for the electrophilic activation of the double bond [2]. In particular, palladium(II) salts are known to activate carbon-carbon double bonds toward nucleophilic attack [3] and this is the basis for the Wacker process for industrial oxidation of ethylene to acetaldehyde [41. In this process, the key step is the nucleophilic attack by water on a (jt-ethylene)palladium complex. 

Allyl alcohols readily react with trichloroacetonitrile to give the corresponding trichloroacetimidates 145. Activation of the double bond with electrophilic reagents results in ring closure to yield oxazolines 146. The most commonly employed electrophiles include iodine, iodine monochloride, phenylselenyl chloride, and mercuric trifluoroacetate. Other nitriles including cyanogen bromide and N,N-dimethylcyanamide can also be used. Since oxazolines readily hydrolyze to amides, the net effect of this reaction sequence is to produce p-amino alcohols 147 from an allyl alcohol. This strategy has been employed in numerous total syntheses of natural products. Examples are listed in Table 8.18 (Fig. 8.7 Scheme 8.43). ° ... 

The reactivity sequence shown above corresponds well to Mayr s [18] model reactions of the electrophilic addition of benzhydryl carbenium ions to substituted alkenes. Table 2 lists the second-order rate constants for the addition of a diarylcarbenium ion to various alkenes and dienes [36]. One alkyl group offers little activation of the double bond a-olefins therefore form only oligomers with isomerized repeat units in low conversions under cationic polymerization conditions. One vinyl group activates the double bond slightly more than alkyl groups do. Table 2 also demon-... 

In order to stereoselectively introduce a nitrogen function on a double bond, a number of methods have been utilized, which conform to the general scheme of activation of the double bond by an electrophile followed by attack of a suitable nucleophile. The geometry of the product depends on the double bond configuration, since all these reactions proceed via anti addition1 -7,215. 

In most palladium-catalyzed oxidations of unsaturated hydrocarbons the reaction begins with a coordination of the double bond to palladium(II). In such palladium(II) olefin complexes (1), which are square planar d8 complexes, the double bond is activated towards further reactions, in particular towards nucleophilic attack. A fairly strong interaction between a vacant orbital on palladium and the filled --orbital on the alkene, together with only a weak interaction between a filled metal d-orbital and the olefin ji -orbital (back donation), leads to an electrophilic activation of the alkene9. 

When the cyclization occurs by activation of the carbon-carbon double bound, the anomeric configuration of the product depends on the stereochemistry of attack of the electrophile to the double bound. The attack preferably occurs from the less hindered face of the most stable conformation, that in which the allylic hydroxyl group lies on the same plane of the double bond. 

If the double bonds of a polyene are not conjugated with other 7r-systems in the molecule, addition to one of the tt-bonds will proceed in a similar fashion to addition to a simple alkene. Usually addition to one of the bonds is preferred, because it is either more highly substituted and, as a result, has enhanced electron density, or because it has fewer substituents and is less hindered and more accessible to the electrophile. Alternatively, one of the double bonds of a polyene may be activated by the presence of a heteroatom at the allylic position. 

Many aspects of the characteristics of the double-bonded functional groups have been reviewed in an impressive series of treatises, published over a period of more than 30 years. These reviews cover mostly the physicochemical aspects of double bonds electrophilic additions to carbon-carbon double bonds1, directing and activating effects of doubly bonded groups2 etc. 

Activation of the triple bond of enynes with electrophilic metal derivatives, especially cationic gold complexes, platinum salts such as PtCl2, and ruthenium derivatives, has been reviewed.117 These catalysts make possible nucleophilic addition of the double... 

From the structure of the double bond we might expect that here again it is an electron source, a base, and hence that the halogen acts as an electrophilic reagent, an acid. This idea is supported by the fact that alkenes usually show the same order of reactivity toward halogens as toward the acids already studied electron-releasing substituents activate an alkene, and electron-withdrawing substituents deactivate an alkene. 

Lewis Acid-Mediated Reactions. The highly nucleophilic double bond of allylsilanes reacts with a vaiiety of electrophiles provided that the electrophiles are activated by a Lewis acid, such as TiCl4, BFj, or AICI3. The y-position of the allylsilane attacks the electrophile to generate a stabilized carbocation 3 to silicon. Subsequent loss of the silyl group results in the transposition of the double bond. ... 

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... 

Usually y.B-unsaturated acids (260) are employed in these lactonizations. The initial step involves an electrophilic attack at the double bond, either by a proton or a reagent X—Y (264). An activated species (261) is thus generated, suitable for the nucleophilic addition of the carboxy group, which in principle may close to a six- or five-membered lactone ring (263 or 262 equation 92). Normally, (262) is preferred on the basis of vector approach analysis. 

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