Efficient Sonogashira Coupling of Unprotected Halonucleosides in Aqueous Solvents Using Water-Soluble Palladium Catalysts

A variety of applications of C‐alkynylated nucleosides has prompted the continuing development of efficient synthetic methods for their preparation. We report an efficient andenvironmentally benign Sonogashira coupling reaction for alkynylation of unprotected halonucleosides in an aqueous solvent. The combination of Pd(OAc)2, CuI, and TXPTS [trisodium tri(2,4‐dimethyl‐5‐sulfonatophenyl)phosphane] provided an effective catalyst for the alkynylation of 8‐bromopurines and 5‐iodouridine in H2O/CH3CN (1:1) in yields ranging from 42 to 98 %. The combination of Pd(OAc)2, CuI, and TXPTS [trisodium tri(2,4‐dimethyl‐5‐sulfonatophenyl)phosphane] provided a highly active catalyst for the alkynylation of 8‐bromopurines and 5‐iodouridine inH2O/CH3CN in yields ranging from 42 to 98 %. This methodology represents the first example of alkynylation of unprotected 8‐bromoguanosine in an aqueous solvent system.