Suzuki ligand free

Solvent-free microwave-assisted Suzuki reaction on AI2O3 as soHd support using KF as base has also been described in the hterature by Villemin [38] (Scheme 20). Ligand-free Pd(OAc)2 was used as a precatalyst. In a reaction... 

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. 

TBAB = tetrabutylammonium bromide Scheme 6.12 Ligand-free Suzuki reactions using TBAB as an additive. 

Scheme 2.10 Ligand free Suzuki reaction in water.

Leadbeater and Marco also undertook to optimise the reaction conditions for ligand-free Suzuki reactions in water using both aryl bromides and chlorides. Comparisons between reactions performed under microwave irradiation and oil-bath heating led to the conclusion that the yields were identical or better with oil baths when aryl bromides were used as aryl precursors. However, comparisons between microwave and oil-bath heating with aryl chlorides as starting material clearly favoured the microwave technique38. 

Leadbeater, N.E. and Marco, M., Ligand-free palladium catalysis of the Suzuki reaction in water using microwave heating, Org. Lett., 2002,4, 2973-2976. 

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... 

Scheme 15 Ligand-free palladium-catalyzed Suzuki-Miyaura reactions in the PASSflow reactor (first percentage refers to degree of transformation yields in parentheses refer to purified products)...

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 ... 

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]. 

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]. 

Bhattacharya S, Srivastava A, Sengupta S (2005) Remarkably facile Heck and Suzuki reactions in water using a simple cationic surfactant and ligand-free palladium catalysts. Tetrahedron Lett 46(20) 3557-3560... 

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