Aryl boronic acids, palladium catalyzed coupling

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. 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

Several microwave-assisted procedures have been described for soluble polymer-supported syntheses. Polyethylene glycol) (PEG)-supported aryl bromides have been shown to undergo rapid palladium(0)-catalyzed Suzuki couplings with aryl boronic acids in water (Scheme 12.16) [63], The reaction proceeded without organic cosolvent... 

Watanabe reports a new method for the direct conversion of o-choroacetaldehyde N,N-disubstituted hydrazones into 1-aminoindole derivatives 93 by palladium-catalyzed intramolecular ring closure of 92 in the presence of P Bu3 or the bisferrocenyl ligand 94 <00AG(E)2501>. When X = Cl, this cyclizative process can be coupled with other Pd-catalyzed processes with nucleophilic reagents (e.g., amines, azoles, aryl boronic acids) so as to furnish indole derivatives with substituents on the carbocyclic ring. 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

Endothelin receptor antagonists 134 and 135 were prepared from the triflated oxicam derivative 136 (Scheme 18) <1998BMC1447>. Addition of aryl thiol 137 to the position gave product 134. Palladium-catalyzed Suzuki coupling of aryl boronic acid 138 and aryl triflate 136 affords the sulfonamide product 135. 

Li and Yue also reported the intermolecular palladium catalyzed cross coupling reactions of bromo quinoxalines 214 and 216 with aryl boronic acids and heterocyclic stannanes, respectively <99TL4507>. The Suzuki couplings (i.e., 214 215) required the use of a... 

Pyrrolyl- and indolyl-stannanes and -boronic acids, which can be prepared from the corresponding organolithium derivatives, have received increasing use in palladium-catalyzed coupling reactions with aryl halides (Scheme 82) (91S613,92JOC1653). 

Although catalytic amounts of Ag20 have been found to promote the palladium-catalyzed coupling of aryl boronic acids and terminal alkynes, the authors in this case do not attribute the desired reactivity to the formation, and subsequent transmetalla-tion, of a silver acetylide. Rather, it is proposed that the Ag20 activates the alkynylpalladium complex to allow transmetallation from the boronic acid, and that any competing formation of the silver acetylide results in a homocoupling of the alkynes (Scheme 1.55).123... 

In combinatorial chemistry, the reaction times and reaction temperatures required are frequently crucial factors. Microwave irradiation is used to enhance reaction rates [105]. Larhed et al. recently reported that microwave-assisted, palladium-catalyzed coupling of aryl and heteroaryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored to Tenta-Gel S RAM, provides coupling products in excellent yields after a reaction time of just 3.8 minutes (45 W) [106]. The preparative results are summarized in Table 4. 

The Suzuki reaction is a palladium-catalyzed substitution that couples an aryl or vinyl halide with an alkyl, alkenyl, or aryl boronic acid or boronate ester. Many variations on this fundamental reaction are possible, containing a wide variety of functional groups. 

In a seminal paper, Aliprantis and Canary described the use of ESMS for the characterization of catalytic intermediates in the palladium(0)-catalyzed crosscoupling reaction of alkyl halides and aryl boronic acids known as the Suzuki reaction [46]. The now accepted reaction pathway for the Suzuki coupling is out-... 

The palladium-catalyzed coupling of boronic acids (as well as other boron derivatives) with aryl and vinyl halides and psendohalides is known as the Suzuki or Suzuki-Miyaura reaction. Because boron is nontoxic, this reaction has been used in pharmaceutical syntheses. In addition, hydroboration or borate substitution allows for the synthesis of virtually any desired coupling partner. For these reasons, as well as the high yields and functional group compatibility, the Suzuki reaction is the first reaction to consider for carrying out a cross coupling. Representative substrates and catalysts are shown in Scheme 17. The various bases are used to generate four-coordinate boron ate complexes that are more reactive in transmetalation. 

Shi described a palladium(II) catalyzed cross-coupling of electron rich (hetero) arenes with aryl boronic acids (Scheme 22) [45]. A major strategic challenge was avoiding homo-coupling of the aryl boronic acids in the presence of palladium(II). 

Palladium-catalyzed coupling between halogenated nucleosides and ar-ylstannanes containing a boronic acid substituent (see below) in the aryl group proceeds chemoselectively at the C—Sn bond rather than at the C—B bond to give boron-containing nucleosides (166). The methodology... 

Palladium catalyzed cross coupling between 4-iodo substituted pyridines, (55) and (56), and aryl boronic acids, (57) and (58), has been used in syntheses of 1,7-naphthyridine (94JHC(31)11) and P-carboline (Scheme 25) (94TL(35)2003>. 

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