Aryl with arylboronic acids

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]. 

The conditions developed by Chan and Lam <1998TL2933, 1998TL2941> can also be applied to pyrroles and indoles for N-arylation with arylboronic acids in the presence of cupric acetate and either triethylamine or pyridine at room temperature <1999T12757>. The use of microwave heating makes Ullman N-arylations of pyrroles and indoles a practical proposition <2003TL4217>. 

Scheme 6.13 The in situ generation of N-Boc imines from a-carbamoyl sulfone derivatives followed by their enantioseiective arylation with arylboronic acids, as described by Ellman s group [18b].

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). 

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 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]. 

These ligands afford high yields of cross-coupling products in the highly sterically burdened reactions of aryl bromides with arylboronic acids when both contain substituents in the ortho- (or equivalent) positions, although drastic reaction conditions are required (110). 

Catalysts can also be immobilized through nonphosphine ligands. A new type of immobilized Pd° complex with a macrocyclic triolefin ligand (L30) has been successfully used for simple crosscoupling reactions of aryl iodides and allyl bromide with arylboronic acids, in both aqueous and anhydrous media.498... 

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. 

Another example involves dioxygen-promoted regioselective oxidative Heck aryla-tions of electron-rich alkenes with arylboronic acids (Scheme 4.12c). For this, two types of microwave reactors have been used. In a single-mode instrument (1 mmol run 25 mL vessel), the Heck arylation was performed by first pre-pressurizing the... 

The same research group additionally presented further investigations on fluor-ous-phase palladium-catalyzed carbon-carbon couplings [93]. Fluorinated aryl octyl-sulfonates were reacted in slight excess with arylboronic acids under microwave con-... 

Miura reported a 1,4-shift of rhodium in the reaction of norbornene with arylboronic acids (Scheme 3) where rhodium moves from an alkyl sp2-carbon to an aryl sp2-carbon, and the arylrhodium species further reacts with another molecule of norbornene.30 Polyalkylated phenyls are obtained in good yields. Cesium fluoride facilitates the transmetallation, generating the phenylrhodium complex which then coordinates to the -face of norbornene. 

Arylative cyclization of alkynals with arylboronic acids is catalyzed by rhodium-diene complexes and even proceeds enantioselectively in the presence of a chiral diene (Equation (48)).399... 

Simiraly, alkynones undergo arylative cyclization with arylboronic acids in the presence of a rhodium catalyst (Equation (49)).400 When acetylenic /3-keto esters are employed as shown in Equation (50), arylative cyclization (formation of cyclobutanols) and subsequent, facile acid-catalyzed bond cleavage take place to give <5-keto esters.401 Ring expansions of cyclic [3-keto esters are also possible according to this reaction. 

Recently, the groups of Fu and Buchwald have coupled aryl chlorides with arylboronic acids [34, 35]. The methodology may be amenable to large-scale synthesis because organic chlorides are less expensive and more readily available than other organic halides. Under conventional Suzuki conditions, chlorobenzene is virtually inert because of its reluctance to oxidatively add to Pd(0). However, in the presence of sterically hindered, electron-rich phosphine ligands [e.g., P(f-Bu)3 or tricyclohexylphosphine], enhanced reactivity is acquired presumably because the oxidative addition of an aryl chloride is more facile with a more electron-rich palladium complex. For... 

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