Suzuki resin-bound aryl halide

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. 

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. 

The biarylphosphines 10 also reacted with the chloromethylated PS resin under basic conditions to give the PS-supported biarylphosphines 11 and 12 (Scheme 5) [38]. The resin-bound biaryl(dialkyl)phosphines 11 and 12 were the ligands designed for use in the palladium-catalyzed amination and Suzuki-Miyaura coupling of aryl halides, especially those of aryl chlorides. 

In general, Suzuki reactions with immobilized aryl halides (Table 9) appear to be more successful then with polymer-bound boronic acids (Table 10). A recent report describes the use of solid-supported arylboronic acids in a resin-to-resin Suzuki coupling (RRTR Suzuki strategy) (Table 9, entry 40). 

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