Allyl electrophilic addition

Allyl electrophiles, addition to zirconacycles, 10, 281 Allyl ethers, isomerization, 10, 85... 

Sn2 substitutions of allylic electrophiles, additions to oxo-carbenium ions, and many others. Suitable leaving groups in these substitution reactions include alkyl chlorides, bromides, iodides, mesylates, tosylates, and acetates. Often these processes are conducted under phase-transfer conditions, or require the use of 18-crown-6 to solubilize the salt and enhance the nucleophilicity of the acetate anion. The use of ionic solvents, such as butyl methylimidazolium tetrafluoroborate (Btnim BF4), has also proven useful. The following examples are representative (eqs 2-9). 

Both resonance forms of the allylic carbocation from 1 3 cyclopentadiene are equivalent and so attack at either of the carbons that share the positive charge gives the same product 3 chlorocyclopentene This is not the case with 1 3 butadiene and so hydrogen halides add to 1 3 butadiene to give a mixture of two regioisomeric allylic halides For the case of electrophilic addition of hydrogen bromide at -80°C... 

Later in this chapter we ll see how allylic carbocations are involved in electrophilic addition to dienes and how the principles developed in this section apply there as well. 

Electrophilic Additions to Conjugated Dienes Allylic Carbocations 48i... 

When the allylic cation reacts with Br to complete the electrophilic addition, reaction can occur either at Cl or at C3 because both carbons share the positive charge (Figure 14.4). Thus, a mixture of 1,2- and 1,4-addition products results. (Recall that a similar product mixture was seen for NBS bromination of alkenes in Section 10.4, a reaction that proceeds through an allylic radical.)... 

Electrophilic addition of HCJ to a conjugated diene involves the formation of allylic carbocation intermediates. Thus, the first step is to protonate the two ends of the diene and draw the resonance forms of the two allylic carbocations that result. Then... 

Although at first glance addition to the central carbon and formation of what seems like an allylic carbonium ion would clearly be preferred over terminal addition and a vinyl cation, a closer examination shows this not to be the case. Since the two double bonds in allenes are perpendicular to each other, addition of an electrophile to the central carbon results in an empty p orbital, which is perpendicular to the remaining rr system and hence not resonance stabilized (and probably inductively destabilized) until a 90° rotation occurs around the newly formed single bond. Hence, allylic stabilization may not be significant in the transition state. In fact, electrophilic additions to allene itself occur without exception at the terminal carbon (54). 

Cu-catalysed additions of ZnEt2 to Baylis-Hillman-derived allylic electrophiles with BINOL-based thioether ligand. 

Both allenes141 and alkynes142 require special consideration with regard to mechanisms of electrophilic addition. The attack by a proton on allene might conceivably lead to the allyl cation or the 2-propenyl cation. 

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

The tandem zirconocene-induced co-cyclization of dienes or enynes/insertion of allyl carbenoid/addition of electrophile is a powerful method for assembling organic structures. Two illustrations of its application are the synthesis of the dollabelane natural product acetoxyodontoschismenol 99 [57,62,63] and the one-pot construction of linear terpenoids 100 (Scheme 3.25) [59,64],... 

Addition reactions, 20 243. See also Electrophilic addition reactions aldehydes, 2 63-64 allyl alcohol, 2 234-239 butadiene, 4 368—370 carboxylic acids, 5 44-45 ethylene, 10 597—598 quinoline, 21 184 quinone, 21 246-261 toluene, 25 165... 

Compared to the intensive and successful development of copper catalysts for asymmetric 1,4-addition reactions, discussed in Chapt. 7, catalytic asymmetric al-lylic substitution reactions have been the subjects of only a few studies. Difficulties arise because, in the asymmetric y substitution of unsymmetrical allylic electrophiles, the catalyst has to be capable of controlling both regioselectivity and enan-tioselectivity. 

Woodward et al. have used the binaphthol-derived ligand 40 in asymmetric conjugate addition reactions of dialkylzinc to enones [46]. Compound 40 has also been studied as a ligand in allylic substitutions with diorganozinc reagents [47]. To allow better control over selectivity in y substitution of the allylic electrophiles studied, Woodward et al. investigated the influence of an additional ester substituent in the jS-position (Scheme 8.25). 

Addition to linear 1,1-disubstituted allylic acetates is slower than addition to monosubstituted allylic esters. Additions to allylic trifluoroacetates or phosphates are faster than additions to allylic carbonates or acetates, and reactions of branched allylic esters are faster than additions to linear allylic esters. Aryl-, vinyl, alkynyl, and alkyl-substituted allylic esters readily undergo allylic substitution. Amines and stabilized enolates both react with these electrophiles in the presence of the catalyst generated from an iridium precursor and triphenylphosphite. 

Reactions of allylic electrophiles with stabilized carbon nucleophiles were shown by Helmchen and coworkers to occur in the presence of iridium-phosphoramidite catalysts containing LI (Scheme 10) [66,69], but alkylations of linear allylic acetates with salts of dimethylmalonate occurred with variable yield, branched-to-linear selectivity, and enantioselectivity. Although selectivities were improved by the addition of lithium chloride, enantioselectivities still ranged from 82-94%, and branched selectivities from 55-91%. Reactions catalyzed by complexes of phosphoramidite ligands derived from primary amines resulted in the formation of alkylation products with higher branched-to-linear ratios but lower enantioselectivities. These selectivities were improved by the development of metalacyclic iridium catalysts discussed in the next section and salt-free reaction conditions described later in this chapter. 

Additional mechanistic insights were gained when Hartwig and coworkers isolated and characterized the first 7t-allyl complexes that are chemically and kinetically competent to be intermediates in iridium-catalyzed allylic substitution [46]. These complexes were prepared independently from allylic electrophiles that are more reactive than allylic carbonates. The isolation and structural characterization of these species provided a detailed view into the origins of enantioselectivity. 

The kinetics of chlorination of ethylene, allyl chloride, 3,4-dichlorobutene, 2,3-dichlo-ropropene, and 1,2-dichloroethylene in 1,2-dichloroethane have been investigated in the presence of BU4NCI. The mathematical treatment of the results was performed with due regard to the equilibrium constants of the formation of complexes between CI2 and CP. For all the substrates at 256K, the introduction of CP into the system has been found to result in an increase in the rate of the addition. The reaction turned out to be of first order with respect to both the substrate and the salt and second order with respect to chlorine. As expected, the dependence of the reaction rate on the substiments at the double bond is compatible with the electrophilic addition, initiated by electrophilic chlorine."... 

This could complicate an allylic bromination reaction, and it is necessary to choose conditions that minimize any addition to the double bond. This is achieved by carrying out the reaction in a solvent of low polarity, e.g. CCU, which suppresses the possibility of the polar electrophilic addition, whilst keeping the concentration of bromine very low to suppress radical addition. 

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

Ring expansion of cycloproparenes to cycloheptatrienes or tropones has been discussed in the context of electrophilic addition to cycloproparenes. When 1,1 -di-chloro-2,5-diphenylbenzocyclopropene (22) is thermolyzed in refluxing benzene, the dimer 373 is formed as a mixture of /Z-isomers. It is believed to arise via dimerization of the carbene 372, which, in turn results from an allylic rearrangement of22to371. ... 

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