Arylboronic Suzuki coupling

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

A closely related reaction that is currently receiving much attention is the palladium-catalysed Suzuki coupling of arylboronic acids with aryl halides (Fu and Littke, 1998). For example, this technology has recently been applied by Clariant workers for the production of o-tolyl-benzonitrile (Eqn. (13)), an intermediate to a series of so-called angiotensin-II antagonists, a new class of antihypertensive drugs (Bernhagen, 1998). 

A one-pot process to form 1,3,4-substituted pyrazoles 25 by Suzuki coupling of arylboronic acids to chromone 24, followed by condensation with hydrazine has been reported <06JCO286>. The synthesis of 3 or 5-o-hydroxyphenol-4-benzylpyrazoles has been accomplished by treatment of 3-benzylchromones, 3-benzylflavones and their 4-thiochromone analogs with hydrazine hydrate in hot pyridine <06EJO2825>. 

A parallel synthesis of a library of 2-aryl-6-chlorobenzothiazoles 112 involves a regioselective palladium-catalyzed Suzuki coupling reaction of 2,6-dichlorobenzothiazole 111 with arylboronic acids (1.1 equiv) under microwave irradiation <06TL3091>. When excess phenylboronic acid is used, Pd(PPh3)4 still provides 2-phenyl-6-chlorobenzothiazole exclusively, while 2-dicyclohexylphosphinobiphenyl 113 generates 2,6-diphenylbenzothiazole as the major product. 

Table 9 Reaction of arylboronic acids with 3,5-dihalo-1,2,4-triazole derivatives under Suzuki coupling conditions (Equation 25)...

The Suzuki coupling has been utilized to craft (Toctasubstituted tetramesitylporphyrins using various arylboronic acids [62], and Schluter has adopted this reaction to prepare phenyl-pyrrole mixed polymers 75 [63]. The BOC group is easily removed by heating [64] and polymers with molecular weights of up to 23,000 were synthesized. These polymers are potentiaEy interesting for their electrical and nonlinear optical properties [65]. 

In the course of their successful syntheses of the marine alkaloids nortopsentins A-D, Kawasaki and co-workers were able to prepare selectively boronic acid 103 from 1 -(tert-butyldimethylsilyl)-3,6-dibromoindole (102) and effect Suzuki couplings to give 3-arylindoles 104 in good yields [117]. Complementary to this chemistry is the direct Pd-catalyzed reaction of 102 with arylboronic acids to give 6-aryl-3-bromoindoles 105 [117]. 

Martin effected the synthesis of several 3,5-diarylated indoles by a tandem Stille-Suzuki sequence [131]. The latter reaction involves exposure of 3-(3-pyridyl)-5-bromo-l-(4-toluenesulfonyl)indole with arylboronic acids (aryl = 3-thienyl, 2-furyl, phenyl) under typical conditions to give the expected products in 86-98% yield [131], Carrera engaged 6- and 7-bromoindole in Pd-catalyzed couplings with 4-fluoro- and 4-methoxyphenylboronic acids to prepare 6- and 7-(4-fluorophenyl)indole (90% and 74% yield) and 6-(4-methoxyphenyl)indole (73% yield) [29]. Banwell and co-workers employed 7-bromoindole in a Suzuki coupling with 3,4-dioxygenated phenylboronic acids en route to the synthesis of Amaryllidaceae alkaloids [132], Yields of 7-arylated indoles are 93-99%. Moody successfully coupled 4-bromoindole... 

The medicinal importance of 2-aryltryptamines led Chu and co-workers to develop an efficient route to these compounds (130) via a Pd-catalyzed cross-coupling of protected 2-bromotryptamines 128 with arylboronic acids 129 [137]. Several Suzuki conditions were explored and only a partial listing of the arylboronic acids is shown here. In addition, boronic acids derived from naphthalene, isoquinoline, and indole were successfully coupled with 128. The C-2 bromination of the protected tryptamines was conveniently performed using pyridinium hydrobromide perbromide (70-100%). 2-Phenyl-5-(and 7-)azaindoles have been prepared via a Suzuki coupling of the corresponding 2-iodoazaindoles [19]. 

Indolyltriflates have been used in Suzuki couplings by Mdrour [138, 139]. Thus, the readily available l-(phenylsulfonyl)indol-2-yl triflate (131) smoothly couples with arylboronic acids in 65-91% yield. Similarly, Pd-catalyzed cross-coupling of phenylboronic acid with l-benzyl-2-carbomethoxyindol-3-yl triflate affords the 3-phenyl derivative (62% yield) [139]. 

Three-component assembly of allenes, organic halides and arylboronic acids has been reported in which Suzuki coupling of a Jt-allylpalladium complex with an orga-noboronic acid is utilized (Scheme 16.26) [31], Addition of phosphorus ligands to the reaction mixture greatly decreases either the product yields or E/Z ratios. The decrease in E/Z ratio may be explained based on the fact that donor ligands readily promote anti-syn rearrangement of a Jt-allylpalladium species via a cr-allylpalladium intermediate. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

An N-heterocyclic carbene ligand, formed from l,3-bis-(2,4,6-trimethylphenyl)-3//-imidazol-l-ium chloride and cesium carbonate, with dipalladium tris(dibenzylideneacetone) gave excellent yields (93-96% yields) in the Suzuki coupling of 2-chloropurines and arylboronic acids in anhydrous dioxane <2001TL8751>. The combination of an imidazolium-carbene and nickel(O) bis(cyclooctadiene) formed a catalyst capable of insertion into the C-F bond of 6-fluoropurine nucleosides (Scheme 35) <20050L1149>. 

The Suzuki coupling of aryl halides was also extended to tosylates recently. Benzothiazole 5-tosylate reacted with m-xylene-2-boronic acid (6.13.) to give the coupled product in 94% yield using palladium acetate and a stericly congested biphenyl based phosphine ligand as catalyst.17 Another class of less commonly utilised cross-coupling partners are methyltio derivatives. In the presence of a copper salt, which activates the carbon-sulphur bond, 2-methyltio-benzotiazol coupled readily with a series of arylboronic acids.18... 

The synthesis of pyrone derivatives attracted attention due to their synthetic potential. In an illustrative example Cho and co-workers studied the Suzuki-coupling of 3,5-dibromo-2-pyrone with arylboronic acids (8.9.). Under regular conditions the aryl group is introduced selectively into the more electron deficient 3-position, while in the presence of an equimolar amount of copper(I) iodide the coupling is diverted selectively into the 5-position (N.B. drop of the reaction temperature from 50 °C to ambient temperature negated the effect of copper and led to 3-arylation). The way copper effects the coupling is still unclear, but it was successfully used in the preparation of a range of 5-aryl-2-pyrons.17... 

Resin-bound benzylic thioethers can be converted into sulfonium salts by S-alkyla-tion with triethyloxonium tetrafluoroborate. These sulfonium salts react with palladium ) complexes to yield benzylpalladium complexes, which undergo Suzuki coupling with arylboronic acids (Entry 7, Table 3.48),... 

In the Suzuki reaction, an aryl iodide or synthetic equivalent thereof is coupled with an arylboronic acid or a borane, again using palladium(O) as the catalyst. This reaction is usually used to prepare biaryls, and few examples have been reported of the solid-phase synthesis of alkenes by means of a Suzuki coupling (Table 5.8). 

C-Arylation of indoles can be accomplished by means of palladium-catalyzed coupling reactions, such as the Suzuki coupling (Entry 7, Table 15.7) or Stille coupling with resin-bound 2-bromoindoles [88] or 5-bromoindoles [75]. 2-Iodoindoles have been prepared on polystyrene by iododesilylation of 2-silylindoles with NIS (Entry 8, Table 15.7), and these can be C-arylated with arylboronic acids [73]. 

Palladium catalysts have been found which are effective in the Suzuki coupling reaction of arylboronic acids with aryl chlorides carrying electron-withdrawing groups.73 Biaryls may also be synthesized by cross-coupling of arylboronic acids with arenediazonium salts.74,75 There has been a report of the polymer-bound palladium-catalysed Suzuki coupling of aryl triflates with organoboron compounds.76 Arylbor-onates may themselves be synthesized by the palladium-catalysed reactions of... 

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