Haloarene derivatives

Haloarene derivatives used for coordination polycondensation are primarily represented by halostyrenes and haloarylacetylenes which undergo selfcoupling to poly(arylene vinylene)s [scheme (2)] and poly(aryleneacetylene)s [scheme (3)] respectively, and by dihaloarenes which, mainly in a combination with alkenes or divinylarenes and acetylenes or diacetylenes, undergo crosscoupling to poly(arylene vinylene)s [schemes (4) and (5)] and poly(arylene acetylene)s [schemes (6) and (7)] respectively [2] ... 

Catalysts for coordination polycondensation involving haloarene derivatives are usually based on Pd complexes, although Ni complexes can be employed in some instances. 

Polycondensation via Carbon-Carbon Coupling Reactions Involving Haloarene Derivatives... 

Acrylates and styrenes were suitable olefin partners however, 1-octene and vinyl acetate generated mixtures of regioisomers. Arylation at C5 was also possible using benzene and haloarene derivatives (eq 8), although toluene and iodobenzene produced inseparable mixtures of isomers. 

The complete elimination of functional groups is often an undesirable side reaction in organic synthesis, but on the other hand it is a possibility for the recycling of environmentally harmful compounds, for example phenols and haloarenes such as polychlorinated dibenzodioxins (PCDDs or dioxins ). For example, aryl chlorides can be effectively dechlorinated with Pd(0) NPs in tetra-butylammonium salts with almost quantitative conversions also after 19 runs (entry H, Table 1.4) [96]. On the other hand, a C-0 bond cleavage reaction also seems suitable for the fragmentation of sugar-based biomass such as cellulose or cello-biose in that way, sugar monomers and bioalcohol can be derived from renewable resources (entry F, Table 1.4) [164]. 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

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). 

Vinylic halides are virtually unreactive and a high selectivity is to be found in the preferential cleavage of aliphatic carbon-halogen bonds of haloalkanoic amides and esters, and of nitro- and cyanoaryl derivatives. Activated haloarenes, e.g. 1-chloro-2,4-dinitrobenzene, however, give a complex mixture of products [7]. 

Coupling of 1 with iodobenzene under Heck reaction conditions gave the phenyl-substituted diene 242-Ph which was isolated in up to 78% yield [146-148]. When heated at 80 °C in DMF or MeCN with various dienophiles 244-R (acrylate, maleate, or fumarate), 242-Ph and its analogs 242-Ar obtained from 1 and other haloarenes cleanly gave the spiro[2.5]octene derivatives 245-Ar (Scheme 57). 

The extension of the above radical intramolecular cyclization of /V-haloaryl-p-lactams to 2-azetidinones bearing the proradical center at C3 was also explored. The treatment of haloarenes 109a-c under similar conditions for the preparation of benzocarbapenems and benzocarbacephems 104—108 gave the fused tricyclic (1-lactams llOa-c (Scheme 37, Table 2). Compounds 110a and 110b were obtained as mixtures of diastereomers, which are epimers at the newly formed C5 stereocenter, while the amino derivative 110c could be prepared as a single isomer. 

The thermolysis of iodonium salts in which their counteranion is a halide may be performed in the molten state or in solution the products are an iodoarene and a haloarene. The reaction which is a nucleophilic aromatic substitution is, however, not preparatively useful an exception was 3-indolyl phenyliodonium trifluoroace-tate which on heating with various chlorides and bromides in DMSO afforded variable mixtures of 2- and 3-haloindoles. By contrast, the jV-methyl and N-benzyl analogues gave only 2-chloro derivatives [58], Sometimes useful products may be obtained from the thermolysis of dibenziodolium or other heterocyclic salts, as exemplified in the preparation of l-iodo-2-(2-iodophenyl)naphthalene [59] ... 

Examples in which heterocyclic haloarenes have been used include the photostimulated reactions of 2-chlorothiazole, 2-chloro-4-methylthiazole and 2-chloro-5-methylthiazole with pinacolone potassium enolate which lead to the formation of mono- and bis-2-thia-zolyl ketones672 and a study of the reactions of 3-halo-2-amino derivatives of benzo[ ]thio-phene with the potassium salts of acetophenone, pinacolone and cyclohexanone which indicated that, under S l conditions, mainly reduction products were formed673. 

The reactivity of complexed haloarenes toward thiolates has been studied, and it has been reported that o-, m-, and p-dichlorobenzenetricarbonylchromium complexes 18a-c react with thiolates (RS R = Me, nBu, tBu Scheme 17, path i) under phase-transfer conditions or in DMSO to give 39 and 40a-c. The ortho- and para-complexes 18a and 18c undergo stepwise substitution of the two Cl atoms in a reaction sequence that can be easily controlled by the amount of added thiolate. The meta complex 18b shows a lower selectivity and gives a mixture of mono- and disubstituted products even in the presence of substoichiometric amounts of thiolate (Scheme 17) [22]. Similarly, LiCH(C02Et)CN and BuSH react with the o-dichlorobenzene complex 18a to give complex 39d and then disubstituted arene 40d, showing that this substitution can be performed with two different nucleophiles (Scheme 17) [23]. Phase-transfer catalysis has also been applied to fluoroarene-Cr(CO)3 complexes, which are more reactive toward thiolates than are the corresponding chloro derivatives [22]. 

An important feature of the Suzuki reaction is that it allows cr/Z Z-alkenyl or alkyl-aryl coupling of fi-a//cy/-9-borabicyclo[3.3.3]nonane derivatives with haloalkenes and haloarenes without concomitant p-hydride elimination. The required organoboranes are obtained by hydroboration of the appropriate alkenes or functionally substituted alkenes with 9-BBN. The coupling reaction tolerates the presence of functional groups in both reaction partners, thus circumventing a requirement of their prior pro-tection. ... 

Aromatic amines are found in biologically active natural products, common pharmaceuticals, dyestuffs, materials with conductive and emissive properties, and ligands for transition-metal-catalyzed reactions. For these reasons much effort has been spent for more than a century on methods to prepare aromatic amines. The synthetic methods to obtain these materials range from classical methods, such as nitration and reduction of arenes, direct displacement of the halogens in haloarenes at high temperatures, or copper-mediated chemistry, as well as modem transition-metal-catalyzed processes and improved copper-catalyzed processes. The following sections describe each of these synthetic routes to aromatic amines, including information on the scope and mechanism of most of these routes to anilines and aniline derivatives. 

S n7 reactions of haloarenes. The displacement of aromatic halides with eno-lates of acetic acid derivatives in liquid NHj to give arylacetic acid derivatives (esters, amides, etc.) has a broad scope. The reaction is initiated by electron transfer. 

Alkyl halides, alkyl tosylates or dialkyl sulfates bring about A-quatemization of pyridine to give A-alkylpyridinium salts 3, while activated haloarenes, e.g. l-chloro-2,4-dinitrobenzene, form A-arylpyri-dinium salts 4. A-Alkylation also involves the acid-induced Michael addition of pyridine to acrylic acid derivatives (e.g. to give 5, A = CN, CO2R) in the presence of HX, as well as the synthetically useful King-Ortoleva reaction (see p 309) between reactive methyl or methylene compounds and pyridine in the presence of I2, e.g. ... 

Following an initial report [2] including carbon nucleophiles for the cycliza-tion, a series of papers have defined useful possibilities with heteroatom nucleophiles, especially N and O derivatives [2]. The ortho-lithio haloarene complexes (e.g., 16) are highly basic, and the electrophilic trapping species is restricted to those with low kinetic acidity and high electrophilicity. Good results are obtained with isocyanates, ketenes, and acyl derivatives with a-protons of low acidity. 

Triplet sensitization of sulfonium salts proceeds exclusively by the homolytic pathway, and that the only arene escape product is benzene, not biphenyl or acetanilide. However, it is difficult to differentiate between the homolytic or heterolytic pathways for the cage reaction, formation of the isomeric halobiaryls. Our recent studies on photoinduced electron transfer reactions between naphthalene and sulfonium salts, have shown that no meta- rearrangement product product is obtained from the reaction of phenyl radical with diphenylsulfinyl radical cation. Similarly, it is expected that the 2- and 4-halobiaryl should be the preferred products from the homolytic fragments, the arene radical-haloarene radical cation pair. The heterolytic pathway generates the arene cation-haloarene pair, which should react less selectively and form the 3-halobiaryl, in addition to the other two isomers. The increased selectivity of 2-halobiaryl over 3-halobiaryl formation from photolysis of the diaryliodonium salts versus the bromonium or chloronium salts, suggests that homolytic cleavage is more favored for iodonium salts than bromonium or chloronium salts. This is also consistent with the observation that more of the escape aryl fragment is radical derived for diaryliodonium salts than for the other diarylhalonium salts. 

Some catalytic pathways have been exploited to assist the cyclization step or even the initial O-acylation of the amidoxime. In this context, Zn(II) catalysts have been explored and efficiendy used for 1,2,4-oxadiazole production, although the proposed catalytic role still remains to be supported by further mechanistic studies (2014IC10312). An interesting approach to 5-aryl derivatives 14, still involving an O-acylamidoxime intermediate (13), produces such an intermediate by a three-component coupling using a haloarene 12, the amidoxime 5, and carbon monoxide in the presence of a Pd(0) catalyst (Scheme 4 2014ASC3074). 

These reports on copper-mediated coupling reactions set the stage for pioneering reports by UUmarm and Irma Goldberg (his later wife) on the use of catalytic amounts of copper for coupling reactions of haloarenes. Thus, the arylation of phenol (16) and its derivatives with low catalyst loadings of copper enabled the selective syntheses of diarylethers (Scheme 1.5) [29]. 

---