In contrast to classic methods carried out under inert atmospheres with dry volatile organic solvents and often low temperatures, the addition of highly polar organometallic compounds to non-activated imines and nitriles proceeds quickly, efficiently, and chemoselectively with a broad range of substrates at room temperature and under air with water as the only reaction medium. Secondary amines and tertiary carbinamines are furnished in yields of up to and over 99 %. The significant solvent D/H isotope effect observed for the on-water nucleophilic additions of organolithium compounds to imines suggests that the on-water catalysis arises from proton transfer across the organic-water interface. The strong intermolecular hydrogen bonds between water molecules may play a key role in disfavoring protonolysis, which occurs extensively in other protic media such as methanol. This work lays the foundation for reshaping many fundamental s-block metal-mediated organic transformations in water.

We report the first transition metal catalyst-and ligand-free conjugate addition of lithium tetraorganozincates (R4ZnLi2) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R4ZnLi2 provide access to valuable nitroalkanes in up to 98% yield under mild conditions (0 °C) and short reaction time (30 min). This is particularly remarkable when employing nitroacrylates and -nitroenones, where despite the presence of other electrophilic groups, selective 1,4 addition to the C=C is preferred. Structural and spectroscopic studies confirmed the formation of tetraorganozincate species in solution, the nature of which has been a long debated issue, and allowed to unveil the key role played by donor additives on the aggregation and structure of these reagents. Thus, while chelating N,N,N',N'-tetramethylethylenediamine (TMEDA) and (R,R)-N,N,N',N'-tetramethyl-1,2-diaminocyclohexane (TMCDA) favour the formation of contacted-ion pair zincates, macrocyclic Lewis donor 12-crown-4 triggers an immediate disproportionation process of Et4ZnLi2 into equimolar amounts of solvent-separated Et3ZnLi and EtLi.

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Since the start of SARS-CoV-2 pandemic, clusters in hospital settings have been described worldwide. Therefore, healthcare workers (HCWs) are considered as a group at high risk of SARS-CoV-2 infection [1]. In Italy, in FebruaryeMay 2020, 119 doctors died because of COVID-19 and globally, in 2020, 91,270 COVID-19 cases were notified among HCWs, with a case-fatality rate of 0.2% [2]. On 27 th December 2020, the Italian Ministry of Health began the immunization campaign against SARS-CoV-2, targeting, as a priority group, HCWs.

A series of novel 1,4-dioxane analogues of the muscarinic acetylcholine receptor (mAChR) antagonist 2 was synthesized and studied for their affinity at M 1 –M 5 mAChRs. The 6-cyclohexyl-6-phenyl derivative 3b , with a cis configuration between the CH 2 N + (CH 3 ) 3 chain in the 2-position and the cyclohexyl moiety in the 6-position, showed p K i values for mAChRs higher than those of 2 and a selectivity profile analogous to that of the clinically approved drug oxybutynin. The study of the enantiomers of 3b and the corresponding tertiary amine 33b revealed that the eutomers are (2 S ,6 S )-(−)- 3b and (2 S ,6 S )-(−)- 33b , respectively. Docking simulations on the M 3 mAChR-resolved structure rationalized the experimental observations. The quaternary ammonium function, which should prevent the crossing of the blood–brain barrier, and the high M 3 /M 2 selectivity, which might limit cardiovascular side effects, make 3b a valuable starting point for the design of novel antagonists potentially useful in peripheral diseases in which M 3 receptors are involved.