Serena Monticelli

A Robust, Eco‐Friendly Access to Secondary Thioamides through the Addition of Organolithium Reagents to Isothiocyanates in Cyclopentyl Methyl Ether (CPME)

The nucleophilic addition of widely available and variously functionalized organolithium reagents to isothiocyanates represents a straightforward, high-yielding, one-pot method to access secondary thioamides. The simple reaction conditions required and the broad scope (>50 cases examples) makes it a robust and reliable method to access both simple and complex thioamides, including enantiopure ones. Noxious and unpleasant-smelling sulfurating agents, usually employed in the literature established methods, are avoided during the whole synthetic procedure thus, rendering the protocol highly attractive, also for sustainability aspects.

Eco-friendly chemoselective N-functionalization of isatins mediated by supported KF in 2-MeTHF

A sustainable, efficient method for the chemoselective N-functionalization of isatins based on the use of KF-Celite in 2-methyltetrahydrofuran is reported. Notably, the protocol allows reactions with a wide range of electrophiles such as alkyl halides, isocyanates and Michael acceptors.

Recent advancements on the use of 2-methyltetrahydrofuran in organometallic chemistry

Since the introduction of 2-methyltetrahydrofuran as an useful alternative to the classical tetrahydrofuran, there has been a continuous interest in the synthetic community operating at academic and industrial towards it. In particular, the much higher stability that basic organometallic reagents display in 2-methyltetrahydrofuran makes it suitable for processes involving such sensitive species including asymmetric transformations. The easy formation of an azeotropic mixture with water, the substantial immiscibility with water, and the fact it derives from natural sources (corncobs or bagasse), allow to consider it in agreement with the Anastas’ Geen Chemistry principles. In this minireview, selected examples of its employment in organometallic transformations ranging from carbanions to radical and transition metal-catalyzed processes are provided.Graphical abstract

Design, Synthesis, and Pharmacological Evaluation of Novel β2/3 Subunit-Selective γ-Aminobutyric Acid Type A (GABAA) Receptor Modulators

Subunit-selective modulation of γ-aminobutyric acid type A receptors (GABAAR) is considered to exert fewer side effects compared to unselective clinically used drugs. Here, the β2/3 subunit-selective GABAAR modulators valerenic acid (VA) and loreclezole (LOR) guided the synthesis of novel subunit-selective ligands with simplified structures. We studied their effects on GABAARs expressed in Xenopus laevis oocytes using two-microelectrode voltage clamp technique. Five compounds showed significantly more efficacious modulation of GABA-evoked currents than VA and LOR with retained potency and selectivity. Compound 18 [( E)-2-Cyano-3-(2,4-dichlorophenyl)but-2-enamide] induced the highest maximal modulation of GABA-induced chloride currents ( Emax: 3114 ± 242%), while 12 [( Z)-3-(2,4-dichlorophenyl)but-2-enenitrile] displayed the highest potency (EC50: 13 ± 2 μM). Furthermore, in hippocampal neurons 12 facilitated phasic and tonic GABAergic inhibition, and in vivo studies revealed significantly more potent protection against pentylenetetrazole (PTZ)-induced seizures compared to VA and LOR. Collectively, compound 12 constitutes a novel, simplified, and subunit-selective GABAAR modulator with low-dose anticonvulsant activity.

Fluoroiodomethane: A versatile CH2F Source

Vittorio Pace received his Ph.D. in Chemical Sciences from the Complutense University of Madrid in 2010. After post-doctoral training at Vienna, Manchester, and Stockholm, he obtained a tenure track position at the University of Vienna. In 2016 he received the Habilitation in Pharmaceutical Chemistry from the University of Vienna and in 2017 the Habilitation for Full Professor of Organic Chemistry.

Diethylaluminium Azide: A Versatile Reagent in Organic Synthesis

The unique properties of diethylaluminium azide – arising from the Lewis acid aluminium and the nucleophilicity of the azide – make it a versatile reagent in organic synthesis. Ring-opening of epoxides, Michael-type additions, synthesis of acyl azides, and functionalizations of fullerene C60 will be discussed. Among the recently described uses of the reagent, particular attention will be devoted to the powerful Sedelmeier’s method to access 1H-tetrazol starting from nitriles.

A practical guide for using lithium halocarbenoids in homologation reactions

Lithium halocarbenoids are versatile reagents for accomplishing homologation processes. The fast α-elimination they suffer has been considered an important limitation for their extensive use. Herein, we present a series of practical considerations for an effective employment in the homologation of selected carbon electrophiles.Graphical abstract

Cyclopentyl Methyl Ether: an Elective Eco-Friendly Ethereal Solvent in Classical and Modern Organic Chemistry

Abstract Solvents represent one of the major contributions to the environmental impact of fine‐chemical synthesis. As a result, the use of environmentally friendly solvents in widely employed reactions is a challenge of vast real interest in contemporary organic chemistry. Within this Review, a great variety of examples showing how cyclopentyl methyl ether has been established as particularly useful for this purpose are reported. Indeed, its low toxicity, high boiling point, low melting point, hydrophobicity, chemical stability towards a wide range of conditions, exceptional stability towards the abstraction of hydrogen atoms, relatively low latent heat of vaporization, and the ease with which it can be recovered and recycled enable its successful employment as a solvent in a wide range of synthetic applications, including organometallic chemistry, catalysis, biphasic reactions, oxidations, and radical reactions.

Recent advances in the synthesis and reactivity of spiro-epoxyoxindoles

Spiro-epoxyoxindoles containing an unsubstituted methylene fragment in the oxirane ring are excellent building blocks in organic synthesis due to the high reactivity conferred by the three-membered oxygenated cycle. In this minireview, a concise survey of the methods of their synthesis and examples of reactivity with carbon and nitrogen nucleophiles is presented, with a particular focus on the stereochemical aspects. The review covers the literature for the last twenty years.