Biaryls aryl halides/triflates with aromatic

The Pd-catalyzed intramolecular coupling of aryl halides or triflates with aromatic rings to give biaryl compounds offers useful synthetic methods. Intramolecular aryla-tion of benzene derivatives was reported first by Ames. Cyclization of 102, catalyzed by Pd(OAc)2 in the presence of DBU, is an example [23]. Pyrimido[4,5-fe]indole was prepared by intramolecular arylation of 4-anilino-5-iodopyrimidine 103 in 86 % yield in the presence of Pd(OAc>2, PPh3 and AcONa in DMF [24]. Cyclization of the monobrominated diarylpyrazole 104 afforded pyrazolo[l,5-/]phenanthridine in 65 % yield in the presence of phosphine-free Pd(OAc>2, Bu NBr, LiCl and K2CO3 in DMF at 110°C [25]. 

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. 

The synthesis of unsymmetrical biaryls 8 from two monoaryl species involves the coupling of a metallated aromatic molecule 6 with an aryl halide or triflate 4 under the action of palladium(O) catalysis. The reaction involves a catalytic cycle in which palladium(O) inserts into the C-halogen bond via an oxidative addition to generate an arylpalladium(II) species 5 (Scheme 10.18). This undergoes a trans-metallation with the metallated component, producing a biarylpalladi-um(II) complex 7. The biaryl product is formed by reductive elimination. In the process, Pd(0) is regenerated and this can then react with a second molecule of aryl halide. Pd(0) is therefore a catalyst for the reaction. 

Symmetrical or unsymmetrical biaryls are efficiently produced by the Pd(Ph3P)4 catalyzed cross-coupling of aryl halides or aryl triflates (I,Br > OTf in terms of rate of reaction ) with a variety of metalated aromatics such as arylboronic acids, arylstannanes, ... 

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