Biaryls, solution-phase combinatorial libraries

Boger DL, Goldberg J, Andersson CM, Solution phase combinatorial synthesis of biaryl libraries employing heterogeneous conditions for catalysis and isolation with size exclusion chromatography for purification, J. Org. Chem., 64 2422-2429, 1999. 

Starting from a mixture of iodoarenes, reductive dimerization in the presence of palladium on charcoal gave access to a library of biaryl derivatives. By using five different iodoarenes, a mixture of 15 biaryls was produced, which were identified clearly by means of HPLC traces (Scheme 49). A novel core suitable for use in solution-phase combinatorial has been prepared using the Stille reaction. ]... 

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. 

In 1996, workers at GlaxoWellcome disclosed the solution-phase preparation of 2-aminothiazole combinatorial libraries [99], Utilizing 20 glass vials and a DPC liquid dispensing robot, they prepared a library of 2500 compounds by this procedure. Also in 1996, Argonaut reported the use of their computer-controlled fluid delivery system for biaryl synthesis via a Suzuki coupling reaction [61],... 

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