Transition-metal complexes and purified ketoreductases work together in eutectic mixtures for the synthesis of enantiopure secondary alcohols.

Despite their ubiquitous presence in synthesis, the use of polar organolithium reagents under environmentally benign conditions constitutes one of the greatest challenges in sustainable chemistry. Their high reactivity imposes the use of severely restrictive protocols (e.g., moisture‐ and oxygen‐free, toxic organic solvents, inert atmospheres, low temperatures, etc.). Making inroads towards meeting this challenge, a new air‐ and moisture‐compatible organolithium‐mediated methodology for the anionic polymerization of different olefins (e.g., styrenes and vinylpyridines) was established by pioneering the use of deep eutectic solvents (DESs) as an eco‐friendly reaction medium in this type of transformation. Fine‐tuning of the conditions (sonication of the reaction mixture at 40 °C in the absence of protecting atmosphere) along with careful choice of components of the DES [choline chloride (ChCl) and glycerol (Gly) in a 1:2 ratio] furnished the desired organic polymers (homopolymers and random copolymers) in excellent yields (up to 90 %) and low polydispersities (IPD 1.1–1.3). Remarkably, the in situ‐formed polystyril lithium intermediates exhibited a great resistance to hydrolysis in the eutectic mixture 1ChCl/2Gly (up to 1.5 h), hinting at an unexpected high stability of these otherwise highly reactive organolithium species in these unconventional reaction media. This unique stability can be exploited to create well defined block‐copolymers.

Edging closer towards developing air and moisture compatible polar organometallic chemistry, the chemoselective and ultrafast addition of a range of aryllithium reagents to nitriles has been accomplished by using glycerol as a solvent, at ambient temperature in the presence of air, establishing a novel sustainable access to aromatic ketones. Addition reactions occur heterogeneously ("on glycerol conditions"), where the lack of solubility of the nitriles in glycerol and the ability of the latter to form strong intermolecular hydrogen bonds seem key to favouring nucleophilic addition over competitive hydrolysis. Remarkably, PhLi exhibits a greater resistance to hydrolysis working "on glycerol" conditions than "on water". Introducing glycerol as a new solvent in organolithium chemistry unlocks a myriad of opportunities for developing more sustainable, air and moisture tolerant main-group-metal-mediated organic synthesis.

The combination of the metal-catalyzed cycloisomerization of alkynes containing a tethered nucleophile as substituent in aqueous media (followed by the spontaneous hydrolysis, hydroalkoxylation, or aminolysis of the transiently formed five-membered heterocycles) with the subsequent enantioselective ketone bioreduction (mediated by KREDs) has been achieved. The overall transformations, which formally involve a three-step one-pot reaction, provide a variety of enantiopure valuable molecules (e.g., 1,4-diols, lactones, and γ-hydroxy-carbonyl compounds (carboxylic acids, esters, and amides)) with high conversions and enantioselectivities and under mild reaction conditions, disclosing the concept of integrated metal-catalyzed cycloisomerizations of alkynes and enzymatic catalysis in water.

Transition-metal complexes and polarised organometallic reagents play together in Deep Eutectic Solvents.

Cycloisomerisation reactions of γ-alkynoic acids can be conveniently performed in the eutectic mixture 1ChCl/2Urea at room temperature, under air and in the absence of co-catalysts by using a novel iminophosphorane–Au(i) complex.

In memory of Prof. Victor Snieckus, a leading authority in organolithium chemistry and directed ortho-metalation reactions.Fast addition of highly polar organometallic reagents (RMgX/ RLi) to cyclic carbonates (derived from CO 2 as a sustainable C1 synthon) has been studied in 2-methyltetrahydrofuran as a green reaction medium or in the absence of external volatile organic solvents, at room temperature, and in the presence of air/moisture. These reaction conditions are generally forbidden with these highly reactive main-group organometallic compounds. The correct stoichiometry and nature of the polar organometallic alkylating or arylating reagent allows straightforward synthesis of: highly substituted tertiary alcohols, β-hydroxy esters, or symmetric ketones, working always under air and at room temperature. Finally, an unprecedented one-pot/ two-step hybrid protocol is developed through combination of an Al-catalyzed cycloaddition of CO 2 and propylene oxide with the concomitant fast addition of RLi reagents to the in situ and transiently formed cyclic carbonate, thus allowing indirect conversion of CO 2 into the desired highly substituted tertiary alcohols without need for isolation or purification of any reaction intermediates.

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