Intra- and Intermolecular Cation-π Interactions between Onium Salts and Alkynes/Acetylene: Experimental and Theoretical Insights.

Cation-π interactions between various onium salts, alkynes, and acetylene were studied, taking into account the substituents of the triple bond, the nature of the anions, and the polarity of the solvent, through a combination of MP2 calculations and experiments. In an intramolecular setting, these data (including single-crystal X-ray crystallography) concurred with the stability of folded conformers of alkynyl onium salts, even substituted with electron-withdrawing groups. To examine the contribution of these interactions on the alkyne electronic population, a thorough in silico study was carried out using natural bonding orbital analysis of the conformers.

Organocatalyzed enantio- and diastereoselective isomerization of prochiral 1,3-cyclohexanediones into nonalactones bearing distant stereocenters.

The lactonization of 2-(2-nitrophenyl)-1,3-cyclohexanediones containing an alcohol side chain and up to three distant prochiral elements is reported by isomerization under the mediation of simple organocatalysts such as quinidine. Through a process of ring expansion, strained nonalactones and decalactone are produced with up to three stereocenters in high er and dr (up to 99 : 1). Distant groups, including alkyl, aryl, carboxylate and carboxamide moieties, were examined.

NMR and DFT Studies with a Doubly Labelled N/ Li S-Trifluoromethyl Sulfoximine Reveal Why a Directed ortho-Lithiation Requires an Excess of n-BuLi.

This work shows why it is imperious to use an excess of butyllithium for a directed ortho-lithiation of a trifluoromethyl sulfoximine. The analysis of mixtures of n-BuLi and sulfoximine 1 in THF-d using { H, Li, C, N, F} NMR experiments at low temperatures reveal that a first deprotonation occurs that leads to dimeric and tetrameric N-lithiated sulfoximine (93 : 7). Using an excess n-BuLi (5 equivalents), the second deprotonation on the ortho-position of the aromatic occurs.

Nickel-Catalyzed Electrochemical Cyclization of Alkynyl Aryl Iodide and the Domino Reaction with Aldehydes.

An intramolecular carbometallation of a triple bond promoted by electrochemistry and mediated by nickel catalysis is described. This domino process transforms various aryl halides bearing a propargyl chain into substituted heterocycles in one single operation, with high stereoselectivities and in good to high yields. This reaction, characterized by a cyclic voltammetry set of experiments, proceeds following a -- cyclization process.

Intertwined Analytical, Experimental and Theoretical Studies on the Formation and Structure of a Copper Dienolate.

The reaction of a silyl dienolate, a Cu(II) salt and TBAT yielding the corresponding copper dienolate is addressed. A combined NMR and cyclic voltammetry analysis first highlight the role of TBAT in the Cu(II) to Cu(I) reduction and the structure of the precatalytic species. From these first results a second set of NMR and theoretical studies enable the determination of the structure and the mechanism of formation of the copper dienolate catalytic species.

Accurate measurement of effective Li-Li scalar coupling constants: the NMR missing link for alkyllithium aggregates.

Scalar coupling in organolithium systems can provide access to useful structural and dynamic informations. In this work, we propose a robust method for the accurate measurement of the effective J coupling constant in tetramerics alkyllithium aggregates. This crucial information, unavalaible to date, gives a simple access to various structural factors, including the dynamics, solvation and the operative steric hindrance of alkyl chains.

Ligand effects on coordination properties of organolithium compounds: insights from computational experiments on a "weakened" Li.

A simple numerical experiment is presented which allows tuning the lithium electrophilicity, a parameter strongly affected by the solvent and additives coordination. A series of coordination of Li to carbanions or polydentate nucleophiles is examined showing the potential and the limits of this approach. The results suggest that such a simple trick can be remarkably helpful to model and decipher the effects of solvation on the structure and properties of lithiated organometallic species.

H-bonding vs Protonation of Alkynes in Regioselective Hydroamination Reactions: A Glimpse into the Reactivity of Arylogous Ynolethers and Ynamines.

In this paper is described the competition and transition between hydrogen bonding and protonation of alkynes connected, on one side, to various aromatic rings and to chiral amino ester appendages on the other side. While the first mode of activation induced the cyclization into pyrrolidines, the protonation of the alkyne led preferentially to tetrahydropyridines due to the higher level of the highest occupied molecular orbital (HOMO) of the considered arylogous ynolethers and ynamines. The transition between H-bonding and protonation was observed with the alkyne substituted with 2-methoxyphenyl, for which the cyclization delivered either five- or six-membered rings depending on the temperature of the experiment.

Introduction to chemical warfare agents, relevant simulants and modern neutralisation methods.

Despite international prohibition, some ill-intentioned states and organisations have shown their will and capacity to run chemical weapon programs, and the number of incidents involving chemical warfare agents (CWA) has significantly increased in recent years. Herein, we aimed to offer a clear overview of chemical warfare agents to organic chemists not specialized in this field by (1) introducing the main CWAs and their relevant simulants legally usable in academic laboratories and (2) presenting a selection of recent and soft neutralisation methods, such as organocatalysis and continuous flow, and materials such as metal-organic frameworks and polyoxometalates. These modern approaches offer potential future alternatives to "heavy" decontamination methods.

Total synthesis of spiromastilactone A.

The total synthesis of spiromastilactone A is reported for the first time. A swift strategy is presented that involves a pivotal enantioselective nucleophilic 1,2-alkylation of an aldehyde prepared in four quantitative synthetic steps from commercial 2,4-dihydroxybenzoic acid. This key reaction, which was described very recently by our group and carried out here on a gram scale, involves cheap and easily accessible tricoordinated chiral lithium amido zincates.

Chiral Lithium Amido Aryl Zincates: Simple and Efficient Chemo- and Enantio-Selective Aryl Transfer Reagents.

An enantioselective aryl transfer is promoted using chiral tricoordinated lithium amido aryl zincates that are easily accessible reagents and whose chiral appendage is simply recovered for reuse. The arylation reaction is run in good yields (60 % average on twenty substrates) and high enantiomeric excesses (95 % ee average). This occurs whatever the ortho, meta, or para substituent borne by the substrate and a complete chemoselectivity is observed with respect to the aldehyde function.

Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct.

A straightforward synthetic pathway allowing the access to anti or syn 2-amino-1,3-diol scaffolds is presented. The strategy relies on a diastereoselective organocatalyzed decarboxylative aldol reaction of a N-Boc-hemimalonate that is easily formed from commercial N-Boc-diethyl malonate. Although this method has been optimized previously with the N-Bz-hemimalonate analogue, this key step was reinvestigated with the N-Boc derivative to improve the required reaction time, the yield, and the diastereoselectivity.

Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions: Auto-assembling Reagents Involving a Fully Recyclable Ligand.

A methodology consisting in carrying out enantioselective nucleophilic 1,2-additions (ee values up to 97 %) from cheap, easily accessible, and never described before, chiral lithium amido zincates is presented. These multicomponent reactants auto-assemble when mixing, in a 1:1 ratio, a homoleptic diorganozinc (R Zn) with a chiral lithium amide (CLA). The latter, obtained after a single reductive amination, plays the role of the chiral inductor and is fully recoverable thanks to a simple acid-base wash, allowing being recycled and re-use without loss of stereochemical information.

Synthesis and Identification of Aryl and Alkyl Gem-Dilithium Phosphido-Boranes: A Boost to the Chemistry of Phosphandiides.

The synthesis and identification of unprecedented gem-dianionic phosphorus compounds, that is, gem-dilithium phosphido-boranes Li [RP⋅BH ], with R=Ph or Cy, are reported in THF solution. These were obtained by double deprotonation of the corresponding primary phosphine-borane precursors RPH ⋅BH . Their in-depth structural study, based on multinuclear ( H, Li, Li, B, C, P) mono- and bi-dimensional NMR analyses, indicates a strong influence of the phosphorus substituent on the structure of the gem-dianionic phosphorus structure; a monomeric arrangement was obtained when R=phenyl, whereas a cyclic oligomer was observed for R=cyclohexyl.

Domino Ring Expansion: Regioselective Access to 9-Membered Lactones with a Fused Indole Unit from 2-Nitrophenyl-1,3-cyclohexanediones.

The domino anionic fragmentation of 2-nitrophenyl-1,3-cyclohexanediones containing an electrophilic appendage such as aldehyde and epoxide is disclosed. This reaction, initiated by a series of nucleophiles, involves the generation of an intermediate hydroxylate followed by the regioselective formation and fragmentation of an intermediate lactolate into enolate. This strategy, devoid of any protecting group, enlarges the initial ring and provides an original access to decorated 9-membered lactones with a fused indole unit.

A Combined H/ Li NMR DOSY Strategy Finally Uncovers the Structure of Isopropyllithium in THF.

Despite its common use in synthesis, the structure of isopropylliyhium in THF has never been determined, a dimer being generally proposed but not supported. This paper fills this data gap through a sophisticated NMR study that shows that, in THF at low-temperature, isopropyllithium is in the form of a 1:2 mixture of a trisolvated monomer and a disolvated dimer in equilibrium. The presence of the monomer, never evoked before, together with a hypo-solvation of the dimer hinted by DFT calculations, provides a rational explanation to the remarkable reactivity of this organolithium reagent in ethereal solvents.

Lithium Amide Protected against Hydrolysis by Aggregated Lithium Halides: An MS + DFT Investigation.

Supported by mass spectrometry experiments, DFT computations indicate that the lithium amide of a 3-aminopyrrolidine (lithium benzhydryl(1-benzylpyrrolidin-3-yl)amide, 1-Li) is protected, up to a certain limit, against hydrolysis when it is aggregated with a strongly polar partner such as LiCl, LiBr, or MeLi.

Oxidative Neutralization of Mustard-Gas Simulants in an On-Board Flow Device with In-Line NMR Monitoring.

The fast and effective neutralization of the mustard-gas simulant 2-chloroethyl ethyl sulfide (CEES) using a simple and portable continuous flow device is reported. Neutralization takes place through a fully selective sulfoxidation by a stable source of hydrogen peroxide (alcoholic solution of urea-H O adduct/MeSO H freshly prepared). The reaction progress can be monitored with an in-line benchtop NMR spectrometer, allowing a real-time adjustment of reaction conditions.

Direct Syn Addition of Two Silicon Atoms to a C≡C Triple Bond by Si-Si Bond Activation: Access to Reactive Disilylated Olefins.

A catalytic intramolecular silapalladation of alkynes affords, in good yields and stereoselectively, syn-disilylated heterocycles of different chemical structure and size. When applied to silylethers, this reaction leads to vinylic silanols that undergo a rhodium-catalyzed addition to activated olefins, providing the oxa-Heck or oxa-Michael products, depending on the reaction conditions.

Chiral Lithium Amides: Tuning Asymmetric Synthesis on the Basis of Structural Parameters.

An overview on the structural arrangements adopted by Chiral Lithium Amides (CLAs), alone or in mixed complexes, is presented. These species are important reagents for asymmetric synthesis and understanding their organization is essential to improve their design and the reaction conditions.

"On water" reaction of deactivated anilines with 4-methoxy-3-buten-2-one, an effective butynone surrogate.

Poorly nucleophilic aromatic amines (nitroanilines, chloroanilines, etc.) react readily and selectively with trans-4-methoxy-3-buten-2-one, a convenient, effective and inexpensive surrogate for 3-butyn-2-one, to afford (Z)-enaminones. The efficiency of the reaction mostly lies in the use of water as a solvent, which enhances the reaction rate by a 45 to 200-fold factor with regard to other media.

Flexible Total Synthesis of (±)-Aureothin, a Potent Antiproliferative Agent.

Amenable to late-stage preparation of analogues, a flexible and convergent total synthesis of (±)-aureothin is presented. The strategy was based on a desymmetrization of α,α'-dimethoxy-γ-pyrone by a process combining 1,4-addition and alkylation of vinylogous enolate to stereoselectively reach the backbone of the target. Palladium-catalyzed cyanation of an elaborated and isomerizable E,Z dienyl motif followed by Pinner cyclization enabled the construction of the tetrahydrofuran motif while a first approach based on a late-stage oxidation was unsuccessful.

Direct Carboxylation of Aryl Tosylates by CO2 Catalyzed by In situ-Generated Ni(0).

A novel Ni(0) -catalyzed carboxylation of aryl tosylates with carbon dioxide has been achieved under moderate temperatures and atmospheric pressure. In this procedure, the active Ni(0) species is generated in situ by simply mixing the Ni(0) precatalyst [NiBr2 (bipy)] with an excess of manganese metal. This approach requires neither a glove-box nor the tedious preparation of sophisticated intermediate organometallic derivatives.