Arylation arylboronic acids

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... 

Wittig reagents. Magnesium generation from alkylphosphonium sj Arylboronic acids.Aryl hahe ultrasonication. Hydrolysis of the reac Pinacols." A simple method presence of NH Cl. 

Arylboronic acids.Aryl halides, alkyl borates, and magnesium in THF react under ultrasonication. Hydrolysis of the reaction mixtures provides arylboronic acids. 

In the presence of a Pd catalyst, CIPd[P(Cf,Hvinyl iodide couples with mctalatcd aromatics, particularly arylzinc chloride or arylboronic acids. Aryl Grignard reagents, however, couple in very low yield. The resulting C-aryl glucals can be converted to C-aryl glycosides by functionalization of the enol ether double bond.2... 

Olofsson and coworkers have developed several efficient one-pot syntheses of diaryliodonium salts [385-390], A general and universal procedure provides both symmetrical and unsymmetrical diaryliodonium triflates 272 from both electron-deficient and electron-rich arenes 271 and aryl iodides 270 using mCPBA as the oxidant and trifiic acid (Scheme 2.78) [385-387]. The electron-rich diaryliodonium tosylates are prepared similarly using toluenesulfonic acid instead of trifiic acid as the additive [387]. Symmetrical diaryliodonium triflates can be synthesized by a modified one-pot procedure from iodine, arenes, mCPBA and trifiic acid under similar conditions [374,375]. A similar procedure based on a one-pot reaction of arylboronic acids, aryl iodides, mCPBA and BF3 -Et20 has been used for regioselective synthesis of unsymmetrical diaryliodonium tetrafiuoroborates [388,389]. In a further improvement of this approach, a range of... 

Aqueous TlOH solution, which produces highly insoluble salts similar to the barium base, completes the coupling reaction of mesitylboronic acid with iodobenzene within 30 min at room temperature (Table 2 and the procedure in the text)." However, this excellent base for mesitylboronic acid, unfortunately, does not work well for other less substituted arylboronic acids. Aryl- and 1-alkenylboronic acids transmetallate to thallium salts. 

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). 

The more utilitarian means for installing an aryl substituent in position 4 onto the 2(5//)-furanone ring, the Suzuki-type cross-coupling of arylboronic acid with... 

Aryl-5-oxo-1,2,3,5-tetrahydropyrido[ 1,2,3-i/e]quinoxaline-6-carboxy-mides were prepared from 7-chloro derivatives and arylboronic acids in the presence of Na2C03, diphenylphosphinated divinylbenzene-crosslinked polystyrene and Pd(PPh3)4 catalyst. 7-Chloro derivatives were obtained from 7-hydroxy derivatives by heating in POCI3 at 50°C for 3 h (01MIP12). 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

The optimal reaction conditions were applied with 59d in the addition of various aryl boronic acids and potassium trifluoroborates to several cyclic and acyclic enones (Fig. 8). Arylboronic acids added to cyclic enones in high yields (89-97%) and with good to excellent selectivities (85-98% ee). Under these conditions, the potassium trifluoroborate reagents reacted at faster rates, but with slightly lower selectivities (83-96% ee). The reactions of acyclic enones with aryl boron reagents gave also excellent yields (83-96%). 

The MH-type reaction of silanols and organotin compounds with olefins via a Pd(II)-mediated pathway has been reported by Hiyama and co-workers. Based on this pathway, a plausible MH-type reaction mechanism with arylboronic acids was presented in Fig. 26. According to this mechanism, the aryl unit migrated to... 

The facile arylation of aldehydes with arylboronic acid has prompted the exploration of asymmetric versions of this reaction. However, this field has been scarcely explored and only few examples have been reported in the literature, with moderate results. The first diastereoselective example was described by Ftirstner and coworkers. By reacting the Gamer aldehyde 15 with phenylboronic acid under their set of experimental conditions (i.e. RhClj-SH O, IPr HCl) (Scheme 7.4) [21], the secondary alcohol was obtained in higher selectivity than that observed in the addition of phenylmagnesium bromide reported by Joullie (de = 94% versus 66%), with the anti isomer as the major compound [29]. 

So far, there is only one report describing the use of chiral NHC-metal complexes in catalytic asymmetric arylation of imines. This was achieved by using C -symmetric cationic NHC-Pd diaquo complex 20 (Scheme 7.6) [38]. The arylation of a variety of A-tosylimines with different arylboronic acids was carried out under mild conditions. The presence of electron-withdrawing or electron-donating substituents on both partners did not seem to affect the reaction and the corresponding chiral diarylamines were obtained in good to excellent yields and high enantiomeric excess. 

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). 

Arylation of alkynes via addition of arylboronic acids to alkynes represents an attractive strategy in organic synthesis. The first addition of arylboronic acids to alkynes in aqueous media catalyzed by rhodium was reported by Hayashi et al.89 They found that rhodium catalysts associated with chelating bisphosphine ligands, such as 1,4-Ws(diphenyl-phosphino)butane (dppb) and 1,1 -/ E(diphenylphospliino)fcrroccnc... 

Table 4 Reaction of an or/Ao-substitutcd aryl iodide with an arylboronic acid in the presence of K2C03, Pd(OAc)2 and norbornene.3...

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