Suzuki reaction—continued

Scheme 4.29 Nucleophilic aromatic substitutions, esterifications, and Suzuki reactions under continuous-flow conditions.

One of the obvious areas where flow chemistry comes into its own is in the arena of catalysed reactions and continuous processing. An excellent example of this is the Suzuki reaction (for recent reviews on the Suzuki Cross-Coupling reaction, see Miura 2004 Beilina et al. 2004 ... 

He, P. and Heswell, S.J. and Fletcher, P.D.I. (2004). Microwave-assisted Suzuki reactions in a continuous flow capillary reactor. Applied Catalysis A General, 274, 111-114. 

Salen-like ligands have also been used to complex, and hence immobilize, a number of metals onto polystyrene and silica for use in a variety of cross-coupling reactions. The salen-palladium complex 32 was used in Suzuki reactions (Figure 4.7). The column containing the immobilized catalyst was heated to 1000 C in a water bath and the reagents were recirculated continuously at a flow rate of 6 pi/min for 5 h, resulting in conversions in the range of 65-75% [154],... 

Another resin-capture approach has been pubhshed in relation to the synthesis of tetrasubstituted ethylenes via Suzuki coupling reactions (Scheme 20) [42, 53]. A 25-member hbrary was synthesized using five alkynes, five aryl halides, and a polymer-bound aryl iodide. The alkynes 55 were converted into bis(boryl)alkenes 56 in solution, and the crude intermediates were used in Suzuki reactions with an excess of aryl halide. When all of the bis(boryl)alkene 56 had been consumed, the aryl iodide resin 59 was added to the reaction mixture and the reaction continued on the solid support. Side products such as 58, arising from a double Suzuki reaction, remained in solution and could be washed away. Compounds 60 were cleaved from the polymer using trifluoroacetic acid and products 61 were obtained in > 90% purity. 

A microwave continuous-flow capillary reactor was capable of local heating of Pd-Si02 and Pd-Al203 catalysts enhancing the rate of the Suzuki reaction to give 70% product yield in 60 s contact time [62]. A thin layer of gold metal on the outside surface enabled effective heating of the reaction mixture. 

The Suzuki-Miyaura coupling reaction is one of the most versatile, chemically robust pathways to form carbon-carbon bonds. It is usually associated with the use of low-hazard reactants and is thus being widely applied in academic and industrial laboratories [46]. Several groups have described results of Suzuki reactions in continuous-flow reactors [40,47-49]. As an example, a simple... 

The patterned amine materials have been used to construct CGC-inspired sites that were evaluated in the catalytic polymerization of ethylene after activation with MAO. The complexes assembled on a porous silica surface using this methodology are more active than previously reported materials prepared on densely-loaded amine surfaces. This increased activity further suggests the isolated, unique nature of the metal centers. Work is continuing in our laboratory to further characterize the nature of the active sites, as well as to obtain more detailed kinetic data on the catalysts. The patterning methodology is also being applied to the creation of immobilized catalysts for small molecule reactions, such as Heck and Suzuki catalysis. 

Baxendale IR, Griffiths-Jones CM, Ley SV, Tranmer GK (2006b) Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations. Chem Eur J 12 4407-4416 Baxendale IR, Deeley J, Griffiths-Jones CM, Ley SV, Saaby S, Tranmer GK (2006c) A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine a new paradigm for molecular assembly. J Chem Soc Chem Commun 2566-2568... 

Leadbeater NE, Pillsbury SJ, Shanahan E, Williams VA (2005) An assessment of the technique of simultaneous cooling in conjunction with microwave heating for organic synthesis. Tetrahedron 61 3565-3585 Lee CKY, Holmes AB, Ley SV, McConvey IF, Al-Duri B, Leeke GA, Santos RCD, Seville JPK (2005) Efficient batch and continuous flow Suzuki crosscoupling reactions under mild conditions, catalysed by polyurea-encapsulated palladium (II) acetate and tetra-n-butylammonium salts. J Chem Soc Chem Commun 2175-2177... 

Baxendale IR, Griffiths-Jones CM, Ley S V, Tranmer GK. Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations. ChemEur J 2006 12 4407-4416. 

Table 4 Suzuki-Miyaura reaction used as a model to demonstrate the optimization of microwave induced continuous flow reactions...

Table 19 Summary of the results obtained for the continuous flow Suzuki-Miyaura reaction using an immobilized Pd (II) catalyst 136...

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