Coupling aryl halides with boronic acids

The Suzuki reaction (the palladium-catalyzed cross-coupling of aryl halides with boronic acids) is arguably one of the most versatile and at the same time also one of the most often used cross-coupling reactions in modern organic synthesis [32], Carrying out high-speed Suzuki reactions under controlled microwave conditions can today be considered almost a routine synthetic procedure, given the enormous literature precedent for this transformation [7]. 

Reaction of aryl halides with boronic acids catalyzed by palladium compounds (Suzuki reaction) is one of the most versatile reactions for selective formation of carbon-carbon bonds. One of the first reports of the application of microwaves to this type of reaction was published by Larhed et al. in 1996 [115]. Subsequently, Varma et al. described the Suzuld-type coupling of boronic acids and aryl halides (Eq. 80) in the presence of palladium chloride and poly(ethylene glycol) (PEG-400) under the action of MW irradiation [116]. The reactions were performed at 100 °C to give the desired coupling products in 50 to 90% yield within 50 s. The coupling reaction can be also conducted under conventional conditions (oil bath, 100 °C), but to achieve similar yields a longer reaction time was needed (15 min). It was found that addition of KE affords better yields. 

One of the earliest reports on use of a phosphonium salt as an IL in such a process was that of Kaufmann and co-workers (9). In this work, the use of tri-butyl(hexadecyl)phosphonium bromide as a recyclable medium for the palladium-mediated Heck coupling of aryl halides with acrylate esters was reported (9). While these reactions proceeded without the use of an additive ligand, elevated temperatures (100 °C) were required and the process was most efficient only with more activated aryl halides [Eq. (1)]. More recently, the use of trihexyl(tetradecyl)-phosphonium chloride (Cyphos IL 101) has been reported as a useful medium for the Suzuki cross-coupling of aryl halides with boronic acid derivatives [Eq. (2)] [10]. In this process, a soluble palladium precursor such as Pd2(dba)3-CHCl3 was dissolved in the phosphonium salt, forming a dark orange solution. This solution was stable in the absence of oxygen for an extended period of time and could be... 

The Suzuki coupling reaction is a powerful tool for carbon-carbon bond formation in combinatorial library production.23 Many different reaction conditions and catalyst systems have been reported for the cross-coupling of aryl triflates and aromatic halides with boronic acids in solution. After some experimentation, we found that the Suzuki cleavage of the resin-bound perfluoroalkylsulfonates proceeded smoothly by using [l,l -bis (diphenylphosphino)ferrocene]dichloropalladium(II), triethylamine, and boronic acids in dimethylformamide at 80° within 8 h afforded the desired biaryl compounds in good yields.24 The desired products are easily isolated by a simple two-phase extraction process and purified by preparative TLC to give the biaryl compounds in high purity, as determined by HPLC, GC-MS, and LC-MS analysis. 

The first copper-mediated C—S coupling of aiyl boronic acids with alkyl thiols was reported in the presence of an organic base, pyridine (Scheme 20.54) [163]. Copper complexes, Cul-neocuproine [164], Cul-ethylene glycol [165], Cul-bipyridine/air [166], and CuSO -l,10-phenanthroUne/O, [167], have been subsequently explored for the coupling of aryl halides and boronic acids with... 

The original cross-coupling reactions of aryl and vinyl halides with boronic acid coupling partners have been extensively developed since their inception. Over the past few years several interesting adaptions have expanded the scope of the original coupling protocol, below are just a few recent examples of systems that have harnessed the Suzuki-Miyaura protocol to access enantio-enriched coupling products. 

Pd(PhCN)2Cl2 has also been demonstrated to be a good catalyst in the Suzuki coupling reaction of aryl or 1-aUcenyl halides with boronic acids. Usually, AsPh3 is used as the ligand, and the addition of Ag20 or base is also necessary (eq 20). ... 

Cellulose is a natural biopolymer, which is biodegradable, environmentally safe, widely abundant, inexpensive, and easy to handle [57]. Cellulose and its derivatives are widely used in chemical and bio-chemical applications and also as supports for the synthesis of organic molecules [58]. Interestingly, the cellulose fibers also act as a nanoreactor for the stabilization of metal nanoparticles [59]. However, its use as a support for catalytic applications is not well explored. Recently, Choplin and coworkers reported cellulose as the support for water soluble Pd(OAc>2/5 TPPTS system in the Trost-Tsuji allylic alkylation reaction [60]. To corroborate the above concept in the cross coupling of aryl halides and boronic acids, we reported A-arylation of imidazoles with aryl halides using a cellulose-supported Cu(0) catalyst (CELL-Cu(O) [61]. The prepared catalyst was well characterized using various instrumental techniques. For example, the X-ray diffraction pattern of CELL-Cu(O) catalyst clearly indicates the presence of Cu (111) and Cu (200) phases which are attributed to Cu(0) [46]. Further, the high resolution XPS narrow scan spectrum of the fresh CELL-Cu(O) catalyst shows a Cu 2p3/2 peak at 932.72 ev, which is attributed to Cu (0) [22]. 

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 overall mechanism is closely related to that of the other cross-coupling methods. The aryl halide or triflate reacts with the Pd(0) catalyst by oxidative addition. The organoboron compound serves as the source of the second organic group by transmetala-tion. The disubstituted Pd(II) intermediate then undergoes reductive elimination. It appears that either the oxidative addition or the transmetalation can be rate-determining, depending on reaction conditions.134 With boronic acids as reactants, base catalysis is normally required and is believed to involve the formation of the more reactive boronate anion.135... 

Suzuki coupling)A palladium-catalyzed substitution that couples an aryl or vinyl halide with a alkyl, aryl, or vinyl boronic acid or boronate ester, (p. 794)... 

Water-soluble palladium(O) complexes have also been used as homogeneous catalysts in aqueous-solution alkylation reactions. The particular complex that has been used is Pd(TPPMS>3. Aryl or heteroaromatic halides can be coupled with aryl or vinyl boronic acids, alkynes, alkenes, or dialkyl phosphites with this palladium(0) complex. This complex in aqueous solution can also be used for the coupling of alkynes with unprotected iodonucleotides, iodonucleosides, and iodoamino acids (133). 

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