Phase transfer aryl halides

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Aryl sulfides are prepared by the reaction of aryl halides with thiols and thiophenol in DMSO[675,676] or by the use of phase-transfer catalysis[677]. The alkenyl sulfide 803 is obtained by the reaction of lithium phenyl sulfide (802) with an alkenyl bromide[678]. 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

This reaction is similar to 13-1 and, like that one, generally requires activated substrates. With unactivated substrates, side reactions predominate, though aryl methyl ethers have been prepared from unactivated chlorides by treatment with MeO in HMPA. This reaction gives better yields than 13-1 and is used more often. A good solvent is liquid ammonia. The compound NaOMe reacted with o- and p-fluoronitrobenzenes 10 times faster in NH3 at — 70°C than in MeOH. Phase-transfer catalysis has also been used. The reaction of 4-iodotoluene and 3,4-dimethylphenol, in the presence of a copper catalyst and cesium carbonate, gave the diaryl ether (Ar—O—Ar ). Alcohols were coupled with aryl halides in the presence of palladium catalysts to give the Ar—O—R ether. Nickel catalysts have also been used. ... 

The reaction can be carried out efficiently using aryl diazonium tetrafluoroborates with crown ethers, polyethers, or phase transfer catalysts.103 In solvents that can act as halogen atom donors, the radicals react to give aryl halides. Bromotrichloromethane gives aryl bromides, whereas methyl iodide and diiodomethane give iodides.104 The diazonium ions can also be generated by in situ methods. Under these conditions bromoform and bromotrichloromethane have been used as bromine donors and carbon tetrachloride is the best chlorine donor.105 This method was used successfully for a challenging chlorodeamination in the vancomycin system. 

Recently, a Pd/Cu-catalyzed three-component coupling reaction of aryl halides, norbomadiene, and alkynols was reported to generate 2,3-disubstituted norbomenes in high yields in the presence of aqueous NaOH and a phase-transfer catalyst in toluene at 100°C (Eq. 3.39).151... 

The complexes [PdCl2(133)2] catalyze the hydrogenolysis of 1-chloromethylnaphthalene with K[HCOO] or Na[HCOO]. Both the solid methanoates and their aqueous solutions could be used. Addition of [R4N]+X phase transfer agents significantly accelerated the hydrogenolysis of aryl halides with methanoates.347... 

The reaction of benzotriazoles with aryl halides catalyzed by a mixture of Pd(dppe)Cl2 (DPPE = bis-(diphenylphosphino)ethane) or Pd(dppf)Cl2, copper(I)iodide or copper(II)carboxylates, and a phase-transfer catalyst has been shown to proceed in good yield in DMF solvent.104 Both copper and palladium were required for these reactions to occur at the N-l position in high yields. Similar results for the coupling of amines with aryliodonium salts in aqueous solvent were observed.105... 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

Partitioning of carbocations between addition of nucleophiles and deprotonation, 35, 67 Perchloro-organic chemistry structure, spectroscopy and reaction pathways, 25, 267 Permutations isomerization of pentavalent phosphorus compounds, 9, 25 Phase-transfer catalysis by quaternary ammonium salts, 15, 267 Phenylnitrenes, Kinetics and spectroscopy of substituted, 36, 255 Phosphate esters, mechanism and catalysis of nucleophilic substitution in, 25, 99 Phosphorus compounds, pentavalent, turnstile rearrangement and pseudoration in permutational isomerization, 9, 25 Photochemistry, of aryl halides and related compounds, 20, 191 Photochemistry, of carbonium ions, 9, 129... 

In the unconventional synthesis of thioethers (Scheme 4.11), cyanide ion is displaced from thiocyanates by carbanions [52, 53], which have been generated under phase-transfer catalytic conditions (cf. 4.1.12). Thiocyanates are readily obtained by a standard catalysed nucleophilic substitution reaction [4, 54-58] (see Table 4.19). Aryl thiocyanates are obtained from activated aryl halides [4, 57] (see Chapter 2). 

A number of modified reaction conditions have been developed. One involves addition of silver salts, which activate the halide toward displacement.94 Use of sodium bicarbonate or sodium carbonate in the presence of a phase-transfer catalyst permits especially mild conditions to be used for many systems.95 Tetraalkylammonium salts often accelerate reaction.96 Solid-phase catalysts in which the palladium is complexed by polymer-bound phosphine groups have also been developed.97 Aryl chlorides are not very reactive under normal Heck reaction conditions, but reaction can be achieved by inclusion of triphenylphosphonium salts with Pd(OAc)2 or PdCl2 as the catalyst.98... 

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). 

The Sonogashira reaction of 2-iodothiophene with 2-methyl-3-butyne-2-ol or trimethylsilylacetylene under phase transfer conditions using sodium hydroxide as base led to the formation of the expected products, which released their end group spontaneously under the applied conditions giving rise to the intermediate formation of 2-ethynylthiophene. This terminal acetylene, in turn, reacted with another molecule of aryl halide, yielding either non symmetrical or symmetrical diarylethynes. When 2-methyl-3-butyn-2-ol was used as acetylene equivalent68 it was possible to introduce a benzothiophene moiety in the second step, while the reaction of 2-iodothiophene and trimethylsilylacetylene led to the formation of l,2-bis(2 -thienyl)acetylene (6.47.),69... 

Thioethers (sulfides) can be prepared by treatment of alkyl halides with salts of thiols (thiolate ions).7S2 R may be alkyl or aryl. As in 0-35, RX cannot be a tertiary halide, and sulfuric and sulfonic esters can be used instead of halides. As in the Williamson reaction (0-12), yields are improved by phase-transfer catalysis.753 Instead of RS ions, thiols themselves can be used, if the reaction is run in benzene in the presence of DBU (p. 1023).754 Neopentyl bromide was converted to Me3CCH2SPh in good yield by treatment with PhS in liquid NH3 at -33°C under the influence of light.755 This probably takes place by an SrnI mechanism (see p. 648). Vinylic sulfides can be prepared by treating vinylic bromides with PhS in the presence of a nickel complex,756 and with R3SnPh in the presence of Pd(PPh3)4.757 R can be tertiary if an alcohol is the substrate, e.g,758... 

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