Applications of Boronic Acids in Selective C-C and C-N Arylation of Purines

J. Jacob Strouse, Marjan Ješelnik, and Jeffrey B. Arterburn*
Department of Chemistry & Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88003 U.S.A. E-mail:

Substituted purine derivatives have broad biomedical value as therapeutics, and have attracted great interest as molecular tools and probes for investigating biological systems. The modification of purines with aryl or heteroaryl substituents dramatically alters conformational preferences, the steric profile, and hydrogen-bonding capacity. The development of new methods for metal-mediated coupling with aryl or heteroaryl halide substrates has greatly expanded the range of synthetically accessible arylpurine derivatives. Arylboronic acids have proven to be extremely effective reagents for the synthesis of arylpurine compounds. Arylboronic acids are stable, versatile, and readily available reagents for metal-mediated C-C and C-N coupling reactions. Coupling reactions resulting in C-C bond formation are catalyzed by palladium and nickel catalysts at positions C2, C6, and C8. Copper mediated N-arylation occurs at positions N1, N2’, N7, and N9. These methods are also applicable using solid supported purine substrates. Successful coupling involves careful optimization of catalyst, ligand, base, solvent, and reaction temperature. These methods provide convenient access to structurally unique arylpurine derivatives with applications in drug discovery and chemical biology.

Key words:C-C coupling, C-N coupling, Aryl-Purine Derivatives