Water‐Soluble Pd‐Imidate Complexes as Versatile Catalysts for the Modification of Unprotected Halonucleosides

Modification of unprotected nucleosides has been attracting continuous interest, since these building blocks themselves and their phosphate‐upgraded corresponding nucleotides have shown a plethora of uses in fields like biochemistry or pharmacy. Pd‐catalyzed cross‐coupling reactions, conducted in water or its mixtures with polar organic solvents, have frequently been the researchers' choice for the functionalization of the purine/pyrimidine base of the unprotected nucleosides. In this scenario, the availability of hydrophilic ligands and its water‐soluble palladium complexes has markedly set the pace of the advances. The approach of our group to the synthesis of such complexes, Pd‐imidates specifically, has faced critical stages, namely the jump to synthesize water soluble complexes from our experience working in conventional solvents, the preparation of phosphine free complexes and the overall goal of getting catalytic systems able to work close to room temperature. The continuous feedback with Kapdi's group, experienced in the chemistry of nucleosides, has produced over the last decade the interesting results in both fields presented here. Three generations of neutral and anionic water‐soluble palladium complexes act as versatile catalysts for the modification of unprotected halonucleosides.