Palladium and copper-catalysed arylation of amines, alcohols and thiols, powerful tools for the construction of C-N, C-O and C-S bonds, are typically carried out in organic (and often toxic) solvents. Therefore the use of such a sustainable, benign solvent as water in this context has gained growing attention. This tutorial review presents the most recent advances dealing with palladium and copper-catalysed carbon-heteroatom bond formation performed in total or partial aqueous media. The particular and distinctive features of water which are apparently responsible for the acceleration and greater chemoselectivity of the aqueous protocols will also be discussed.

The synthesis of a series of N,N'-disubstituted indazolone derivatives starting from methyl anthranilates is presented. This general approach features a novel and easy way for access to the target N-heterocycles by formation of a new N-N single bond. The key cyclization step embraces the formation of an N-acylnitrenium intermediate, mediated by the hypervalent iodine reagent PIFA, and its succeeding intramolecular trapping by the amine moiety under rather mild experimental conditions.

Dedicated to the memory of our colleague and friend Prof. Marcial Moreno-Mañas. Abstract:The Suzuki biaryl coupling of a range of electronically dissimilar arylboronic acids and aryl bromides is performed in neat water with excellent to quantitative yields by means of a new CNCpincer palladium catalyst that is soluble in water due to its para-carboxy group. Extremely high turnover numbers and frequencies combined with a remarkable robustness allow an effective catalyst reuse in sustainable conditions.

The hypervalent iodine reagent PIFA promotes the intramolecular electrophilic cyclization of easily accessible alkynylamides and alkynyl carboxylic acids, leading to the formation of pyrrolidinone and lactone skeletons, respectively, in a very efficient way. A synthetic study and a mechanistic proposal for these transformations are presented.

Suzuki-Miyaura biaryl and diarylmethane syntheses via the coupling of arylboronic acids with aryl and arylmethyl bromides are performed in water by means of two new CNC-type palladium pincer complexes. Good to excellent results (including high TON values and extended recycling procedures) are obtained in most cases for a range of electronically dissimilar halides and boronic acids. On the basis of a series of kinetics studies, transmission electron microscopy (TEM), mercury drop tests, and quantitative poisoning experiments, the real role of the latter palladacycles, closely linked to the formation and active participation of palladium nanoparticles, is discussed.