This review highlights recent advances in metal- and biocatalyzed transformations, in the synthesis of APIs and other biologically active compounds, when employing deep eutectic solvents and water as environmentally responsible solvents.

Grignard and organolithium reagents undergo smooth nucleophilic additions to γ-chloroketones “on water”.

The first application of Deep Eutectic Solvents (DESs) in the asymmetric bioreduction of ketones has been accomplished for purified ketoreductases (KREDs). The performance of the biocatalysts was enhanced by increasing the percentage of neoteric solvent in DES-buffer mixtures. At a buffer content of 50% (w/w) and even 20% (w/w), the combination of either choline chloride (ChCl)/glycerol (Gly) (1 : 2) or ChCl/sorbitol (1 : 1) proved to be most effective for achieving up to >99% conversion and up to >99% enantiomeric excess of the corresponding secondary alcohols. Moreover, this reaction medium was used to perform the first example of a chemoenzymatic cascade process in DES-buffer mixtures, namely the ruthenium-catalysed isomerisation of racemic allylic alcohols coupled with a further enantioselective bioreduction, in both sequential and concurrent modes.

Ortho-Lithiation/functionalization of diaryltetrahydrofurans proceeds well with t-BuLi both in Et₂O and cyclopentyl methyl ether and, remarkably, also in protic eutectic mixtures.