Chemoselective homologative preparation of trisubstituted alkenyl halides from carbonyls and carbenoids.

The chemoselective synthesis of trisubstituted alkenyl halides (Cl, Br, F, I) starting from ketones and aldehydes and lithium halocarbenoids is reported. Upon forming the corresponding tetrahedral intermediate adduct, followed by the addition of thionyl chloride, a selective E2-type elimination is triggered, furnishing the targeted motifs. The transformation takes place under full chemocontrol: various sensitive functionalities ( ester, nitrile, nitro, or halogen groups) can be placed on the starting materials, thus documenting a wide reaction scope, as well as the application of the technique to biologically active substances.

Novel alpha6 preferring GABA-A receptor ligands based on loreclezole.

The family of GABA-A receptors contains nineteen mammalian subunits from which pentameric, GABA gated anion channels are assembled. The subunit encoded by the GABRA6 gene is highly expressed in the cerebellum and the receptors to which it contributes have recently been demonstrated to be a promising candidate as a novel drug target. Here we examined a series of loreclezole derivatives for potentially selective action at α6β3γ2 receptors with the help of computational methods and functional testing with the two-electrode voltage clamp technique.

Application of Biobased Solvents in Asymmetric Catalysis.

The necessity of more sustainable conditions that follow the twelve principles of Green Chemistry have pushed researchers to the development of novel reagents, catalysts and solvents for greener asymmetric methodologies. Solvents are in general a fundamental part for developing organic processes, as well as for the separation and purification of the reaction products. By this reason, in the last years, the application of the so-called green solvents has emerged as a useful alternative to the classical organic solvents.

Straightforward synthesis of bench-stable heteroatom-centered difluoromethylated entities controlled nucleophilic transfer from activated TMSCHF.

The commercially available and experimentally convenient (bp 65 °C) difluoromethyltrimethylsilane (TMSCHF) is proposed as a valuable difluoromethylating transfer reagent for delivering the CHF moiety to various heteroatom-based electrophiles. Upon activation with an alkoxide, a conceptually intuitive nucleophilic displacement directly furnishes in high yields the bench-stable analogues.

Direct and straightforward transfer of C1 functionalized synthons to phosphorous electrophiles for accessing gem-P-containing methanes.

The direct transfer of different α-substituted methyllithium reagents to chlorinated phosphorous electrophiles of diverse oxidation state (phosphates, phosphine oxides and phosphines) is proposed as an effective strategy to synthesize geminal P-containing methanes. The methodology relies on the efficient nucleophilic substitution conducted on the P-chlorine linkage. Uniformly high yields are observed regardless the specific nature of the carbanion employed: once established the conditions for generating the competent nucleophile (LiCHHal, LiCHHal, LiCHCN, LiCHSeR etc.

Taking advantage of lithium monohalocarbenoid intrinsic α-elimination in 2-MeTHF: controlled epoxide ring-opening to halohydrins.

The intrinsic degradative α-elimination of Li carbenoids somehow complicates their use in synthesis as C1-synthons. Nevertheless, we herein report how boosting such an α-elimination is a straightforward strategy for accomplishing controlled ring-opening of epoxides to furnish the corresponding β-halohydrins. Crucial for the development of the method is the use of the eco-friendly solvent 2-MeTHF, which forces the degradation of the incipient monohalolithium, due to the very limited stabilizing effect of this solvent on the chemical integrity of the carbenoid.

Chemoselective Homologation-Deoxygenation Strategy Enabling the Direct Conversion of Carbonyls into ()-Halomethyl-Alkanes.

The sequential installation of a carbenoid and a hydride into a carbonyl, furnishing halomethyl alkyl derivatives, is reported. Despite the employment of carbenoids as nucleophiles in reactions with carbon-centered electrophiles, sp-type alkyl halides remain elusive materials for selective one-carbon homologations. Our tactic levers on using carbonyls as starting materials and enables uniformly high yields and chemocontrol.

Highly chemoselective difluoromethylative homologation of iso(thio)cyanates: expeditious access to unprecedented α,α-difluoro(thio)amides.

The new motif - α,α-difluoromethyl thioamide - has been assembled starting from isothiocyanate (as thioamide precursor) and a formal difluoromethyl-carbanion generated from commercially available TMSCHF2. Upon proper activation of this reagent with potassium tert-amylate, the high-yielding transfer of the difluorinated nucleophile takes place under high chemocontrol. Various sensitive functionalities (e.

Direct and Chemoselective Synthesis of Tertiary Difluoroketones via Weinreb Amide Homologation with a CHF-Carbene Equivalent.

The homologation of Weinreb amides into difluoromethylketones with a formal nucleophilic CHF transfer agent is reported. Activating TMSCHF with potassium amylate enables a convenient access to the difluorinated homologation reagent, which adds to the acylating partners. The high chemoselectivity showcased in the presence of variously multifunctionalized Weinreb amides, jointly with uniformly high yields, enables the strategy of general applicability without requiring any stabilization element for the putative carbanion.

Chemoselective reduction of isothiocyanates to thioformamides mediated by the Schwartz reagent.

Thioformamides are easily prepared - under full chemocontrol - through the partial reduction of isothiocyanates with the in situ generated Schwartz reagent. The high electrophilicity of the starting materials enables the straightforward addition of the hydride ion, thus constituting a reliable and high-yielding method for obtaining variously functionalized thioformamides. Sensitive chemical groups to the reduction conditions such as nitro, ester, alkene, azo, azide and keto groups do not interfere with the chemoselectivity of the process.

Potential for the detection of molecular complexes and determination of interaction geometry by 2DIR: application to protein sciences.

The ability to detect molecular complexes and determine their geometries is crucial to our understanding of all biological phenomena, including protein structures and functions. We recently demonstrated that a novel 2DIR technique, EVV 2DIR spectroscopy, can be used for this purpose. In this paper, we evaluate the potential utility of the method for the analysis of protein composition, structure and function.

A novel fluorescence-based method in forensic science for the detection of blood in situ.

Full DNA profiles can be generated from just a few cells; however these profiles can be contaminated from other cell types present at the crime scene. We report here on the development of an immunofluorescent technique to spatially locate human-specific blood in situ and also on the ability of this technique to detect individual leukocytes and the DNA contained within them. Four monoclonal mouse anti-human antibodies were evaluated; anti-glycophorin A to detect erythrocytes and anti-CD45, anti-myeloperoxidase (MPO) and anti-histone H1 to detect the nucleated leukocytes.