Synthesis, X-ray characterization and DFT analysis of dicyanidoaurate telluronium salts: on the importance of charge assisted chalcogen bonds.

In this manuscript we report the synthesis and X-ray characterization of two cyanidoaurate telluronium salts, namely (3-fluorophenyl)(methyl)(phenyl)telluronium dicyanidoaurate [(3-F-Ph)(Me)(Ph)Te][Au(CN)2] (1) and methyldiphenyltelluronium dicyanidoaurate [(Me)(Ph)2Te][Au(CN)2] (2). In the solid state, the tellurium atom establishes three concurrent and directional chalcogen bonds (ChBs) with the adjacent anions, in both compounds. These charge-assisted ChBs (CAChBs) have been analyzed using DFT calculations and several computational tools. The MEP surface analysis discloses the existence of three σ-holes at the Te-atoms capable of establishing strong CAChBs with the counter-ions. In addition, significant charge transfer from the lone pair orbital at the N-atom of the anion to the antibonding σ*(Te-C) orbital of the cation is observed in some cases.

Strigolactones as Broad-Spectrum Antivirals against ß-Coronaviruses through Targeting the Main Protease Mpro.

The current SARS-CoV-2 pandemic and the likelihood that new coronavirus strains will emerge in the immediate future point out the urgent need to identify new pan-coronavirus inhibitors. Strigolactones (SLs) are a class of plant hormones with multifaceted activities whose roles in plant-related fields have been extensively explored. Recently, we proved that SLs also exert antiviral activity toward herpesviruses, such as human cytomegalovirus (HCMV). Here we show that the synthetic SLs TH-EGO and EDOT-EGO impair ß-coronavirus replication including SARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Interestingly, in silico simulations suggest the binding of SLs in the SARS-CoV-2 main protease (Mpro) active site, and this was further confirmed by an in vitro activity assay. Overall, our results highlight the potential efficacy of SLs as broad-spectrum antivirals against ß-coronaviruses, which may provide the rationale for repurposing this class of hormones for the treatment of COVID-19 patients.

One-Pot, Telescoped Alkenylation of Amides via Stable Tetrahedral Intermediates as Lithium Enolate Precursors.

A mild and efficient telescoped procedure for the stereoselective alkenylation of simple, non-activated amides using LiCH2SiMe3 and carbonyl compounds as surrogates of alkenyllithium reagents is reported. Our methodology relies on the formation of stable tetrahedral intermediates, which, upon collapse into highly reactive lithium enolates in a solvent-dependent fashion, allows for the assembly of α,ß-unsaturated ketones in a single synthetic operation with high stereoselectivity.

A Mild, Efficient and Sustainable Tetrahydropyranylation of Alcohols Promoted by Acidic Natural Deep Eutectic Solvents.

A straightforward protocol to promote the tetrahydropyranylation of alcohols, using for the first time bioinspired acidic natural deep eutectic solvents (NADESs) as non-innocent reaction media under mild reaction conditions, was reported. This approach enables the preparation of several tetrahydropyranyl (THP) ethers starting from primary, secondary and tertiary alcohols in short reaction times and with high levels of chemoselectivity, working under air and without the need of additional catalyst. The sustainability of the methodology was further highlighted by its scalability and the easy recyclability of the NADES, allowing multigram preparations of THP ethers without any loss of the catalytic activity of the reaction media up to ten recycling steps. Telescoped, one-pot tetrahydropyranylation/nucleophilic acyl substitution transformations using the same eutectic mixture were also demonstrated.

Design of a New Chiral Deep Eutectic Solvent Based on 3-Amino-1,2-propanediol and Its Application in Organolithium Chemistry.

A chiral glycerol derivative, namely 3-amino-1,2-propanediol, was employed for as the hydrogen bond donor (HBD) in the design of a new deep eutectic solvent (DES) with choline chloride acting as the hydrogen bond acceptor (HBA). The novel mixture was characterized and unambiguously classified as a DES. Furthermore, its synthetic usefulness was demonstrated in the room-temperature n-butyllithium-addition under air to carbonyl compounds and benzyl chloride. In some cases, pure products (100% conversion) were obtained by a simple extractive work-up in up to 72% isolated yield, thus suggesting the potential practical usefulness of this procedure as a green alternative to the classical Schenk procedure in volatile organic solvents for the synthesis of tertiary alcohols. The chirality of the HBD, bearing an interesting basic primary amino group, is an intriguing feature currently under investigation for further exploitation.

Chemo- and Regioselective Anionic Fries Rearrangement Promoted by Lithium Amides under Aerobic Conditions in Sustainable Reaction Media.

A straightforward and efficient protocol to promote the metalation/anionic Fries rearrangements of O-aryl carbamates, using for the first time a lithium amide as metalating agent under aerobic/ambient-friendly reaction conditions, is reported. This approach enables the sustainable preparation of salicylamide derivatives with high levels of chemoselectivity within ultrafast reaction times, working at room temperature in the presence of air/moisture, and using environmentally responsible cyclopentyl methyl ether as a solvent. Furthermore, the regioselective manipulation of O-2-tolyl carbamates has been accomplished using interchangeably alkyllithiums or lithium amides, with an unexpected beneficial contribution from the employment of biorenewable protic eutectic mixtures as non-innocent reaction media.

A Fast and General Route to Ketones from Amides and Organolithium Compounds under Aerobic Conditions: Synthetic and Mechanistic Aspects.

We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.

Lateral lithiation in deep eutectic solvents: regioselective functionalization of substituted toluene derivatives.

The heteroatom-directed lateral lithiation of functionalized toluenes in a choline chloride-based eutectic mixture is reported. The metalations proceed within ultrafast reaction times, with a broad substrate and electrophile scope. The directing groups provide a rapid and high regioselective access to functionalized aromatic derivatives of remarkable synthetic value.

Directed ortho-metalation-nucleophilic acyl substitution strategies in deep eutectic solvents: the organolithium base dictates the chemoselectivity.

Directed ortho metalation (DoM) or nucleophilic acyl substitution (SNAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki-Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents.