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: jarterbu@nmsu.edu

Abstract
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.