Interrogation of a Sonogashira Cross-Coupling of 8-Bromoguanosine with Phenylacetylene on Amberlite: Evidence for Pd/Cu Ion Binding and Propagation of Pd/Cu Nanoparticles

Abstract

The reactivity of Amberlite (IRA-67) base “heterogeneous” resin in Sonogashira cross-coupling of 8-bromoguanosine 1 with phenylacetylene 3 to give 2 has been examined. Both 1 and 2 coordinate to Pd and Cu ions, which explains why at equivalent catalyst loadings, the homogeneous reaction employing triethylamine base is poor yielding. X-ray photo-electron spectroscopy (XPS) has been used to probe and quantify the active nitrogen base sites of the Amberlite resin, and postreaction Pd and Cu species. The PdCl₂(PPh₃)₂ precatalyst and CuI cocatalyst degrade to give Amberlite-supported metal nanoparticles (average size ∼2.7 nm). The guanosine product 2 formed using the Amberlite Pd/Cu catalyst system is of higher purity than reactions using a homogeneous Pd precatalyst, a prerequisite for use in biological applications.

Keywords:

• Nucleoside
• alkyne
• palladium
• cross-coupling
• inhibition
• catalyst recycling

Acknowledgments

Current affiliation for K. W: School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK. The authors are grateful to the BBSRC (CASE studentship award to A. G. F.), the University of York, and Replizyme Ltd. (Dr. K. Darley) for funding these studies. The authors thank the Royal Society for a generous equipment grant and funding for a research fellowship (I. J. S. F.), and Meg Stark for technical assistance with the electron microscopy.

Notes

^a Atomic% determinations within ± 0.1 atomic%.

^b The Cu content (1.23 wt%) is similar to that observed by elemental analysis (1.28 wt%); the Pd content is slightly higher by XPS (2.84 wt%), as compared to elemental analysis (1.63 wt%).

^c The Pd and Cu content was determined to be < 0.3 wt% by elemental analysis (limit of detection).