Alkyl halides, reactions with arene

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

Alkyl radical addition reactions to styrene chromium tricarbonyl can be accomplished using alkyl halides (10 equiv) and (TMSlsSiH (5 equiv) in the presence of AIBN in refluxing benzene, for 18 h (Reaction 66). " These reactions are believed to proceed through intermediates in which the unpaired electron is interacting with the adjacent arene chromium tricarbonyl moiety since the analogous reaction with styrene affords only traces of addition products. 

Alternatively, the Sn2 nucleophilic substitution reaction between alcohols (phenols) and organic halides under basic conditions is the classical Williamson ether synthesis. Recently, it was found that water-soluble calix[n]arenes (n = 4, 6, 8) containing trimethylammonium groups on the upper rim (e.g., calix[4]arene 5.2) were inverse phase-transfer catalysts for alkylation of alcohols and phenols with alkyl halides in aqueous NaOH solution to give the corresponding alkylated products in good-to-high yields.56... 

Electron-rich carbyne complexes can react at the carbyne carbon atom with electrophiles to yield carbene complexes. Numerous examples of such reactions, mostly protonations, have been reported [519]. Depending on the nucleophilicity of the carbyne complex, such reactions will occur more or less readily. The protonation of weakly nucleophilic carbyne complexes requires the use of strong acids, such as triflic [533], tetrafluoroboric [534] or hydrochloric acid [535,536]. More electron-rich carbyne complexes can, however, even react with phenols [537,538], water [393,539], amines [418,540,541], alkyl halides, or intramolecularly with arenes (cyclometallation, [542]) to yield the corresponding carbene complexes. A selection of illustrative examples is shown in Figure 3.25. 

This Lewis acid-catalyzed electrophilic aromatic substitution allows the synthesis of alkylated products via the reaction of arenes with alkyl halides or alkenes. Since alkyl substituents activate the arene substrate, polyalkylation may occur. A valuable, two-step alternative is Friedel-Crafts Acylation followed by a carbonyl reduction. 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Ni(0)-Ni(I)-Ni(II) Catalysis Coupling Reactions of Alkyl Halides with Unsubstituted Arenes... 

Suzuki reaction the palladium-catalyzed reaction of an aryl or vinyl halide with an aryl boronic acid to give an arylated or vinylated arene. In some cases, primary alkyl halides can react in place of the aryl or vinyl halides Wacker process the palladium-catalyzed oxidation of ethene to acetaldehyde by oxygen... 

In contrast to the IIT mechanism, the clement effect on the Arens path is expected to be A (I) > A (Br) > A (C1) as is also the case with S 2 reactions of alkyl halides (Table 25) . This reactivity order has been observed in the reactions of l-halo-2-(2-thienyDacetylenes with sulphides and thiolates in methanol-water in which the C—X bond is presumably broken in the rate-determining step by attack on halogen (see Section Il.C.l.d). In both 5 n2 and halogen abstraction reactions, the magnitude of the element effect is quite large (Table 25). 

Alkylation of arenes and perfluoro or perchlorofluoro compounds proceeds readily under SbFg catalysis [4,21]. In addition to alkyl halides, alkyl esters and haloesters have also been used to alkylate arenes under these reaction conditions. For example, perfluorotoluene reacts with pentafluorobenzene to form perfluorodiphenylmethane in 68 % yield when the reaction mixture is quenched with HR If H2O is used for quenching, perfluorobenzophenone is obtained in 93 % yield (Eq. 8) [21a]. 

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