Coupling of aryl halides

Carbon-oxygen bonds are formed by the Ullmann reaction (- coupling of aryl halides with copper) which has been varied in alkaloid chemistry to produce diaryl ethers instead of biaryls. This is achieved by the use of CuO in basic media (T. Kametani, 1969 R.W. Dos-kotch, 1971). 

This imine is stable to the Fe(acac)3-catalyzed Grignard coupling of aryl halides. 

The coupling of alkyl halides 1 upon treatment with a metal, e.g. elemental sodium, to yield symmetrical alkanes 2, is called the Wurtz reaction. Aryl alkanes can be prepared by the Wurtz-Fittig reaction, i.e. the coupling of aryl halides with alkyl halides. 

A co-solvent that is poorly miscible with ionic liquids but highly miscible with the products can be added in the separation step (after the reaction) to facilitate the product separation. The Pd-mediated FFeck coupling of aryl halides or benzoic anhydride with alkenes, for example, can be performed in [BMIM][PFg], the products being extracted with cyclohexane. In this case, water can also be used as an extraction solvent, to remove the salt by-products formed in the reaction [18]. From a practical point of view, the addition of a co-solvent can result in cross-contamination, and it has to be separated from the products in a supplementary step (distillation). More interestingly, unreacted organic reactants themselves (if they have nonpolar character) can be recycled to the separation step and can be used as the extractant co-solvent. 

Today microemulsions are used in catalysis, preparation of submicron particles, solar energy conversion, extraction of minerals and protein, detergency and lubrication [58]. Most studies in the field of basic research have dealt with the physical chemistry of the systems themselves and only recently have microemulsions been used as a reaction medium in organic synthesis. The reactions investigated to date include nucleophilic substitution and additions [59], oxidations [59-61], alkylation [62], synthesis of trialkylamines [63], coupling of aryl halides [64], nitration of phenols [65], photoamidation of fluoroolefins [66] and some Diels-Alder reactions. 

The coupling of aryl halides with copper is called the Ullmann reaction. The reaction is of broad scope and has been used to prepare many symmetrical and... 

Coupling of aryl halides with organometallic reagents... 

Table 4.7 Sonogashira coupling of aryl halides with terminal acetylenes in the presence of PdCbiPPhj) catalyst [120].

Nanometer size Pd colloids in block copolymer micelles of polystyrene polyvinylpyridine as catalysts have been used is a novel way by Klingelhofer for Heck reaction of C-C coupling of aryl halides with olefins. 

In contrast to the borylation of alkane C-H bonds, the coupling of aryl halides with amines was based on a literature precedent from another group published about a decade before our initial studies. Kosugi, Kameyama and Migita published the coupling of aryl halides with tin amides." Mechanistic studies we conducted on this process led us to the perhaps obvious realization that the reaction" could be conducted with amines and a silylamide base instead of tin amides (equation 4)." Surveys of bases with similar p a values led Janis Louie to conduct reactions with alkoxide bases. Similar studies were conducted at nearly the same time by Steve Buchwald and coworkers."... 

Heck coupling of aryl halides with n-butylacrylate under m/w irradiation. 

Whereas Ullmann chemistry is limited to the coupling of aryl halides, a variety of species including aryl-, alkynyl-, alkenyl-, and alkylcopper species can be produced which are highly reactive toward other substrates. 

COUPLING OF ARYL HALIDES WITH SILANES, STANNANES, GERMANES, AND BORANES 388... 

Nickel complexes also catalyze the coupling of aryl halides with thiolates. In one case, the phosphine ligand on the catalyst was generated in situ from 1,2-dibromobenzene and diphenylphosphine... 

The palladium-catalyzed formation of sulfides can generate polyphenylene sulfide from a dithiol and a dibromoarene, or from 4-bromobenzenethiol (Equation (38)).17 In 1984 Asahi Glass obtained patents for the formation of this polymer in the presence of palladium and nickel catalysts.125,126 In addition, Gingras reported palladium-catalyzed couplings of aryl halides and thiols to form discrete phenylene sulfide oligomers.127,128 A number of polyphenylene sulfide wires, ranging from dimeric to pentameric structures, were prepared by the palladium coupling, albeit in modest yields ... 

The Suzuki reaction (the palladium-catalyzed cross-coupling of aryl halides with boronic acids) is arguably one of the most versatile and at the same time also one of the most often used cross-coupling reactions in modern organic synthesis [32], Carrying out high-speed Suzuki reactions under controlled microwave conditions can today be considered almost a routine synthetic procedure, given the enormous literature precedent for this transformation [7]. 

Today, the Suzuki cross coupling of aryl halides and arylboronic acids is also carried out in aqueous-biphasic operation starting from chlorinated derivatives instead of their more costly bromo or iodo equivalents (Equation 5.6, [39]). 

Muller and co-workers reported the three-component one-pot synthesis of various pyrimidines through the in situ generation of unsaturated carbonyl compounds. The palladium catalyzed coupling of aryl halides bearing electron withdrawing substituents 7 with propargyl alcohols 8 produced unsaturated carbonyl compounds 9 after isomerization, which condensed with amidines 10 to form triaryl pyrimidines 11 . 

Tunney, S.E. and Stille, J.K., Palladium-catalyzed coupling of aryl halides with (trimethylstannyl)diphenylphosphine and (trimethylsilyl)diphenylphos-phine, /. Org. Chem., 52, 748, 1987. 

The Sonogashira coupling is the Pd-catalyzed coupling of aryl halides and terminal alkynes [207], which, in the appropriate cases, can be followed by the spontaneous, or easily induced,... 

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl halides with ethynylmetals, formation of diarylethynes is one of the potential side reactions. Indeed, the Kumada coupling of 2-iodo-5-methylthiophene (29) with ethynylmagnesium chloride gave the desired 2-ethynyl-5-methylthiophene (30) in only 35% yield, along with 24% of bis(5-methyl-2-thienyl)ethyne (31) [29], The high propensity for H-Mg exchange reaction to occur was blamed for the diarylethyne formation. 

Isomerization of 1,3-dienes (12, 36).3 The 1,5-hydrogen shift in isomerization of 1,3-dienes catalyzed by (naphthalene)Cr(CO)3 (1) can be used for synthesis of aryl-substituted exocyclic alkenes, which are not readily available by coupling of aryl halides with exocyclic vinyl halides. 

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]. 

Scheme 63 Electroreductive coupling of aryl halides to biaryls.

Scheme 72 Nickel-catalyzed coupling of aryl halides and alkenes.

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