Halides, aryl, with active

Hydroxamic acids undergo facile nucleophilic Ai-arylation with activated aryl halides such as 31 (equation 22). While hydroxamates are known to be ambident nucleophiles in alkylation reactions, arylation of hydroxylamines results exclusively in Ai-substituted hydroxamates of type 32 (equation 22)". ... 

The terminal amino group of 2-hydrazino-4-phenylthiazole is also the reactive center in reactions with activated aryl halides such as 288. A solution of the product (289) obtained from this reaction when shaken with PbOj gives a deeply colored radical, whose structure has been studied by ESR (Scheme 173) (532. 533). 

Aryl bromides were also perfluoroethylated under these conditions [205] The key to improved yields was the azeotropic removal of water from the sodium perfluoroalkylcarboxylate [205] Partial success was achieved with sodium hepta-fluorobutyrate [204] Related work with halonaphthalene and anthracenes has been reported [206 207] The main limitation of this sodium perfluoroalkylcarboxylate methodology is the need for 2 to 4 equivalents of the salt to achieve reasonable yields A trifluoromethylcopper solution can be prepared by the reaction of bis(tri-fluoromethyl)mercury with copper powder in /V-methylpyrrolidone (NMP) at 140 °C [208] (equation 138) or by the reaction of N-trifluoromethyl-A-nitro-sotnfluoromethane sulfonamide with activated copper in dipolar aprotic solvents [209] This trifluoromethylcopper solution can be used to trifluoromethylate aro matic [209], benzylic [209], and heterocyclic halides [209]... 

Other sulfur nucleophiles also react with activated aryl halides ... 

Activated aryl halides react with thiols [e.g. 4] to produce aryl thioethers and thioethers, derived from non-activated aryl halides, can be synthesized via the Cr(CO), complexes of the haloarenes [29] (Scheme 4.2, see also Chapter 2). 

Catalytic processes based on the use of electrogenerated nickel(O) bipyridine complexes have been a prominent theme in the laboratories of Nedelec, Perichon, and Troupel some of the more recent work has involved the following (1) cross-coupling of aryl halides with ethyl chloroacetate [143], with activated olefins [144], and with activated alkyl halides [145], (2) coupling of organic halides with carbon monoxide to form ketones [146], (3) coupling of a-chloroketones with aryl halides to give O -arylated ketones [147], and (4) formation of ketones via reduction of a mixture of a benzyl or alkyl halide with a metal carbonyl [148]. 

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

Nucleophilic substitution of halogen atom in aromatic and heteroaromatic halides with a hydroxyamino group proceeds only in substrates that are activated by a strong electron-withdrawing substituent in the benzene ring (e.g. 27, equation 17). Despite this limitation this reaction is useful for synthesis of arylhydroxylamines and usually provides good yields of products. Along with activated aryl halides and sulfonates, activated methyl aryl ethers such as 28 can be used (equation 18). 

Tertiary and aromatic nitroso compounds react with aryl Grignard or aryl-lithium reagents giving the corresponding hydroxylamines . This reaction is useful for preparation of alkyl- and aiylhydroxylamines (e.g. 109, equation 80 and 110, equation 81) and can be considered as complementary to arylation of hydroxy lamines with activated aryl halides. It has been used for functionalization of cyclophanes with the hydroxy amino group. The main limitation of the reaction is the relatively restricted choice of available aliphatic nitroso components, so most of reactions were done with 2-nitroso-2-methylpropane. There is no literature data about the possibility of removal of the tert-butyl group from these compounds. 

Arylzinc reagents can be made from aryl halides with activated zinc118 or from Grignard reagents by metal-metal exchange with zinc salts.119... 

Alkylation (with dialkyl sulfates, alkyl tosylates, and alkyl halides) and arylation (with nitro-activated aryl halides) of the llf-naphtho[l,8-deltriazine (89) and of the structurally related 6,7-dihydro-lif-... 

Arylation. Arylation of 2,4-diaryl-5(4//)-oxazolones 170 with activated aryl halides has been reported to proceed under phase-transfer conditions (Scheme 7.51). The yields of 2,4-diaryl-4-(2,4-dinitroaryl)-5(47/)-oxazolones 171 are often modest. Heteroarylation of 170 was accomplished using 2-chloro-3,5-dinitropyridine. Representative examples are shown in Table 7.19 (Fig. 7.21). 

In 2002, Furstner and coworkers reported that aryl halides react with Grignard reagents under the conditions previously used for the coupling of alkenyl halides. They proposed that the active iron species is Fe(MgX)2, a complex described by Bogdanovic and coworkers ° a few years earlier (Scheme 30). This iron(-II) species is formed by addition of four equivalents of the Grignard compounds to FeCl2. 

An important alternative to the Ullmann method is the use of certain nickel complexes,193 This method has also been used intramolecularly.194 Aryl halides ArX can also be converted to Ar—Ar195 by treatment with activated Ni metal,196 with Zn and nickel complexes,197 with aqueous alkaline sodium formate, Pd-C, and a phase transfer catalyst,l9li and in an electrochemical process catalyzed by a nickel complex,199... 

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