Coupling aryl halides with boronic

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 direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls. The synthesis of biaryls was readily carried out in the same flask when the first coupling of aryl halide with diboron was followed by the next reaction with another halide or triflate [240]. The protocol offered a direct and efficient method for the synthesis of the boronic ester in the solid-phase that hitherto met with little success using classical methodology (Scheme 44). The solid-phase boronate (106, 107) [243] was quantitatively obtained by treating a polymer-bound haloarene with the diboron. The subsequent coupling with haloarenes furnished various biaryls. The robot synthesis or the parallel synthesis on the surface of resin is the topic of further accounts of the research. 

Suzuki and Stille couplings. For coupling of aryl chlorides with arylboronic acids the catalytic system contains (CyjPjjPdClj, CsF in NMP. co-Arylalkanoic acids are prepared by coupling of aryl halides with carboxylic esters bearing a 9-BBN substituent at the other terminus, and saponification. A biaryl synthesis from two different aryl halides is accomplished with in situ boronate formation which depends on the (dppfjPdClj catalyst. For access to aryl boronates either the coupling of aryl triflates with bis(pinacolato)diboron" or that of aryl iodides with pinacolborane may be employed. 

Palladium acetate is better than PdCl2(dppf) in terms of cost and catalyst removal and effectively catalyzes the cross-coupling of a wide variety of aryl halides with bis(pinaco-lato)diboron to form the corresponding boronates. These boronates can be conveniently isolated or used in situ for Suzuki cross-coupling reactions with aryl halides to provide biaryls [189b]. 

In this manner, unprotected nucleosides can be coupled to boronic acids in moderate yields. In the Stille coupling reaction, the palladium catalyst formed in situ from PdCl2 and four equivalents of TPPMS was used effectively to couple various aryl halides with R groups on RSnCl3 (Eq. 3) [16]. The use of this catalyst improved the yield and reproducibility compared to the use of PdCl2 alone. The So-nogashira coupling of alkynes with aryl halides is an additional route for the formation of sp—sp2 bonds. The use of this water-soluble phosphine with Pd(OAc)2... 

The use of this catalyst in Suzuki coupling reactions has also been successful. The coupling of various aryl halides with alkenyl borates and boronic acids has been achieved to afford products in good yields (Eq. 6) [19]. One of the advantages of this system concerns the mild reaction conditions that are employed. There have been very few reports involving nickel as the metal center in CCBF. In one... 

Cross-coupling reactions have also been examined in water using amphiphilic PS-PEG resin-supported palladium complexes. Palladium-catalyzed coupling of aryl halides with aryl(or alkenyl)boronic acids (the so-called Suzuki-Miyaura coupling) took place in aqueous alkaline solution in the presence of polymeric catalyst 59 at 25 °C to give the biaryls in excellent yields [90,... 

Figure 13.19 Coupling of aryl halides with vinyl boronic acids.

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. 

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