Sila-Morita−Baylis−Hillman Reaction of Arylvinyl Ketones: Overcoming the Dimerization Problem

Arylvinyl ketones, under Morita−Baylis−Hillman (MBH) reaction conditions, produce a mixture of dimerization products. We propose a solution to this problem: a sila-MBH reaction. This cascade reaction involves addition of phosphine catalyst to arylvinyl ketones, trapping of the forming β-silylenolate with aldehyde, followed by a 1,3-Brook rearrangement to give the Si-MBH adducts in good to excellent yields

Dual Role of Alkynyl Halides in One-Step Synthesis of Alkynyl Epoxides

Dual Role of Alkynyl Halides in One-Step Synthesis of Alkynyl Epoxide

Can Polarization of Triple Bond in Tolanes Be Deduced from ¹³C NMR Shifts? Re-evaluation of Factors Affecting Regiochemistry of the Palladium-Catalyzed Hydrostannation of Alkynes

Polarization of the triple bond in a series of differently substituted ortho- and para-tolanes has been studied by NMR and computational methods in order to examine if 13C NMR data can be effectively used for the assessment of electronic polarization of a triple bond in diarylacetylenes. DFT calculations of both natural charges and NMR properties revealed that chemical shifts concur with effective charges on sp-carbon atoms in para-tolanes, whereas in ortho-analogues magnetic anisotropy complicates the analysis making 13C NMR data inapplicable for ascribing triple bond polarization. The obtained information was used to reevaluate factors affecting the regiochemistry of the Pd-catalyzed hydrostannation of the triple bond in tolanes. Computational study on the polarization of triple bonds taken together with the experimental data on hydrostannation of various mono- and disubstituted tolanes bearing para- and ortho-substituents demonstrated that the regioselectivity of hydrostannation is governed by a combination of electronic and steric factors. In para-tolanes, the electronic effect prevails and α- and β-vinylstannanes are obtained predominantly for substrates with electron-withdrawing and electron-donating groups, respectively. In the ortho-series, steric factors dominate over electronics and α-isomers are produced with high selectivity regardless of the substituents' nature. However, it was found that in disubstituted “push−pull” tolanes steric control of an ortho-group can be overruled by the very strong electronic effect of an electron-withdrawing substituent in para-position

Highly Diastereo- and Regioselective Transition Metal-Catalyzed Additions of Metal Hydrides and Bimetallic Species to Cyclopropenes: Easy Access to Multisubstituted Cyclopropanes

The first highly efficient, diastereo- and regioselective transition metal-catalyzed addition of metal hydrides (stannanes, silanes, and germanes) and bimetallic species (ditins and silyltins) to cyclopropenes has been developed. It was shown that the addition across the double bond of cyclopropenes is generally controlled by steric factors and proceeds from the least hindered face. This methodology represents a powerful and atom-economic approach toward a wide variety of highly substituted stereodefined cyclopropylmetals, useful building blocks unavailable by other methods

Sila Morita−Baylis−Hillman Reaction of Cyclopropenes

The first example of sila-Morita-Bayis-Hillman reaction between 1-silylcyclopropenes and carbonyl compounds has been demonstrated. This novel phosphine-catalyzed transformation features a 1,3-Brook rearrangement/elimination cascade and provides convenient access to a variety of 1-(silyloxymethyl)cyclopropenes, which are not easily available via traditional methods

Additional file 1: Table S1. of Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice

Primer sequences for qPCR. Primers were custom designed and validated by PrimerDesign Ltd. (Southampton, UK). Figure S1. The effect of a low dose of LPS on locomotor activity at 24 and 48 h post-challenge in naïve mice. Naïve animals were subjected to a single dose of LPS (0.1 or 0.5 mg/kg) or vehicle injection and were tested at 24 or 48 h post-injection. (A) Neither the resting time was unaltered by the treatment in the TruScan open field nor (B) rearing in the novel cage test for the total number of rear. (C–E) Aggressive behaviour was also unaltered. Data are mean ± SEM, two-way ANOVA throughout. Figure S2. (A, B) Body weight in the chronic stress experiment. Experimental groups were balanced upon baseline mean values of body weight measured 7 days prior the start of the chronic stress experiment and LPS challenge. Mice exposed to chronic stress had a significant reduction in body weight as compared with baseline measurements (*p < 0.05, pairwise t test). Chronically stressed mice injected either with vehicle or LPS had similar mean body weight prior the LPS challenge. (C–E) Sucrose preference. Experimental groups were balanced upon baseline mean values of sucrose preference when evaluated 7 days prior the experiment chronic stress procedure and LPS challenge. Experimental groups had similar mean measures of sucrose and water intake. (p > 0.05, one-way ANOVA and post hoc Tukey test; see the text). (F) Naïve and stressed animals (10 days) were challenged with a single dose of LPS (0.1 mg/kg) or vehicle (saline) and tested 24 h thereafter in a novel cage test for total number of rears (see the text). Data are mean ± SEM. No differences between the groups were observed. Figure S3. (A–C) Baseline behaviour in a resident-intruder test. Experimental groups were balanced upon baseline mean scores of behaviours in a resident-intruder test that were studied 7 days prior the experimental chronic stress procedure and LPS challenge. Mice had similar mean measures of (A) latency to attack, (B) number of attack and (C )duration of crawl over behaviour. (p > 0.05, one-way ANOVA and post hoc Tukey test; see the text). (D) The latency to attack after the chronic stress was not significantly altered

Development of an Optimized Process for the Liver-Targeted Triantennary <i>N</i>‑Acetylgalactosamine Ligand

Development of a scalable process for N-acetylgalactosamine (GalNAc) ligand 1 is discussed. Multikilogram-scale synthesis of the GalNAc ligand is achieved in four reaction steps, where each step is characterized via factorial design of experiments (DoE) and first-principles experiments. The reactions tolerate a wide range of input parameters without generating critical impurities, and noncritical impurities are removed or reduced via aqueous washes and organic extractions. The GalNAc ligand can be isolated as an off-white amorphous solid via lyophilization or spray drying