Suzuki couplings ligand-free

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

Palladacycles [17] have been established as important class of catalysts, an unusual phosphine-free sulfur containing catalyst was introduced by Zim [18] et al. A phosphinite based palladacycle [19] proved to be very efficient in Suzuki coupling reactions. An N,P-Ligand type was synthesized by Kocovsky [20] et al. Tridentate pincer ligands [21] have been proved use-fill in the Heck reaction. Recent developments regarding Heck (22] and Suzuki [23] reactions have been reviewed by Fu and Littke. A new catalyst especially suitable for Heck couplings has been introduced by Beller [24] et al. 

Scheme 15.4 Synthesis of biphenyl compounds via ligand-free Suzuki coupling.

However, efforts were also directed to the development of phosphine-free catalysts. For example, the ligand-free Pd(OAc)2 promoted Suzuki reaction in water was reported using microwave heating. In this way, a low palladium loading (0.4 mol.%) was required and the cross coupling proceeded quickly (5-10 min reaction time), using boronic acids and aryl iodides, bromides and chlorides. 

A ligand-free Suzuki coupling protocol indicates employment of Pd(OAc)2 in PEG-400, in which nanoparticles of Pd are generated in situ. More conventionally, NaOMe is used as a base for coupling at room temperature. Under certain coupling reaction conditions reduction of nitro group(s) also occurs, ... 

Finally, the Suzuki-Miyaura reaction, which has become one of the most versatile and important reactions for the construction of C-C bonds, could be performed in a continuous flow process under ligand-free conditions [43]. The PASSfiow reactor is suited for the coupling of 4-iodoacetophenone and other aryl halides with arylboronic acid to yield the corresponding diaryls within 3 h without formation of homocoupling by-products (Scheme 15). After collecting... 

Instead of aryl halides, arenediazonium salts are also excellent arylating agents in the Suzuki coupling, although more hindered arylboronic acids did not react The reaction is catalysed by several sources of ligand-free palladium such as Pd(OAc)2, Pd2(dba)3 and Pd/C at room temperature in dioxane without any added base [98]. Use of potassium aryl trifluoroborate salts also allowed the introduction of more sterically hindered aryl groups [99]. 

Besides the study on Suzuki cross-coupling reactions (Scheme 5) in the ionic liquid 1,3-di-n-butyl-imidazolium tetrafluoroborate ([BBIM][BF4]) catalyzed by palladium prepared in situ in a cleaning bath, Srinivasan and co-workers reported ligand-free Pd-catalyzed couplings between aryl halides and terminal alkyne ... 

New labeled stilbene derivatives, such as ris-3,5-dimethoxy-4 -[ C]methoxystilbene, as-3,4, 5-trimethoxy-3 -[ C]methoxystilbene, trans-3,5-dimethoxy-4 -[ C]methoxys-tilbene, trans-3,4, 5-trimethoxy-3 -[ CJmethoxystilbene, cis-3,5-dimethoxy-4 -[ F] fluorostilbene, and trans-3,5-dimethoxy-4 -[ F]fluorostilbene, were designed and synthesized [94]. The synthesis of ( )-tris-0-methylresveratrol and ( )-3,5-dimethox-ystilbene via the Miyaura-Suzuki coupling was described [95]. This reaction has been carried out in air without solvent/substrate purification and in the absence of additional free ligand. Figure 1.18 shows a scheme of deoxyschweinfurthin synthesis accomplished in Ref [96]. 

Isolated examples of Suzuki couplings of aryl chlorides performed under phosphine- and NHC-ligand-free or heterogeneous conditions have been reported, although most of these are limited to activated, electron-deficient aryl chlorides [68]. For example. Sun and Sowa have recently described the application of heterogeneous palladium on charcoal to Suzuki reactions of activated aryl chlorides with phenylboronic (Equation 2.38) [69]. 

The cross-coupling of boron compounds with aryl or alkenyl halides (Suzuki coupling) was used for the preparation of polycyclic aromatic compounds in a biphasic reaction medium. For example, 2-bromobenzonitrile and 4-methylphenylboronic acid gave 4-methyl-2"-cyanobiphenyl in good jdeld with Pd/TPPTS catalyst at 80°C in a toluene-ethanol-aqueous Na2C03 solvent mixture (Scheme 37). The product, isolated by phase separation, was free of metal or ligand impurities and the catalyst could be recycled in the aqueous phase (208). 

A facile surfactant-mediated Heck and Suzuki coupling procedure in water has been developed nsing ligand-free Pd catalysts. The procedure which involves nanometric palladinm colloids is operationally simple, environmentally benign, and synthetically as efficient as conventional procednres using organic solvents [21]. 

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