Synthesis of Tertiary Fluorides through an Acid-Mediated Deoxyfluorination of Tertiary Alcohols.

The combination of methanesulfonic acid and potassium bifluoride is reported for the deoxyfluorination of tertiary alcohols. Under metal-free conditions that use readily available, cheap, and easy-to-handle reagents, a range of tertiary alcohols could be converted into the corresponding fluorides in excellent yields (average yields of 85% for 23 examples). Mechanistic investigation showed that the reaction proceeds at 0 °C, in part, through an elimination/hydrofluorination pathway, but no residual alkenes are observed. The application of these conditions for the fluorination of ether and ester is also demonstrated.

Recent Advances in the Synthesis of Borinic Acid Derivatives.

Borinic acids [R2B(OH)] and their chelate derivatives are a subclass of organoborane compounds used in cross-coupling reactions, catalysis, medicinal chemistry, polymer or optoelectronics materials. In this paper, we review the recent advances in the synthesis of diarylborinic acids and their four-coordinated analogs. The main strategies to build up borinic acids rely either on the addition of organometallic reagents to boranes (B(OR)3, BX3, aminoborane, arylboronic esters) or the reaction of triarylboranes with a ligand (diol, amino alcohol, etc.). After general practical considerations of borinic acids, an overview of the main synthetic methods, their scope and limitations is provided. We also discuss some mechanistic aspects.

Correction: Amine-borane complex-initiated SF5Cl radical addition on alkenes and alkynes.

[This corrects the article DOI: 10.3762/bjoc.16.256.].

Magnesium-Catalyzed Tandem Dehydrogenation-Dehydrocoupling: An Atom Economical Access to Alkynylboranes.

Owing to the unusual reactivity of sterically hindered amine-borane complexes, a catalytic system based on magnesium salts was designed to perform a tandem dehydrogenation-dehydrocoupling between terminal alkynes and boranes. The reaction is providing pure alkynylboranes within few minutes at room temperature, with only two molecules of hydrogen as a byproduct.

Non-biaryl atropisomerism at the C-B bond in sterically hindered aminoarylboranes.

Sterically hindered aminoarylboranes featuring atropisomerism about the C-B bond were prepared by addition of organomagnesium species onto readily accessible dialkylamine-borane complexes. Some of these aminoarylboranes, isosteres of vinyl styrene derivatives, were resolved by HPLC on the chiral stationary phase. They are the first examples of a non-biaryl type system which display slow rotation about a C-B bond.

Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range.

The store-operated calcium entry, better known as SOCE, forms the main Ca2+ influx pathway in non-excitable cells, especially in leukocytes, where it is required for cell activation and the immune response. During the past decades, several inhibitors were developed, but they lack specificity or efficacy. From the non-specific SOCE inhibitor 2-aminoethyl diphenylborinate (2-APB), we synthetized 16 new analogues by replacing/modifying the phenyl groups. Among them, our compound P11 showed the best inhibitory capacity with a Ki ≈ 75 nM. Furthermore, below 1 µM, P11 was devoid of any inhibitory activity on the two other main cellular targets of 2-APB, the IP3 receptors, and the SERCA pumps. Interestingly, Jurkat T cells secrete interleukin-2 under phytohemagglutinin stimulation but undergo cell death and stop IL-2 synthesis when stimulated in the presence of increasing P11 concentrations. Thus, P11 could represent the first member of a new and potent family of immunosuppressors.

Amine-borane complex-initiated SF5Cl radical addition on alkenes and alkynes.

The SF5Cl radical addition on unsaturated compounds was performed using an air-stable amine-borane complex as the radical initiator. This method showed to be complementary to the classic Et3B-mediated SF5Cl addition on alkenes and alkynes. A total of seven alkene and three alkyne derivatives were tested in the reaction, with yields ranging from 3% to 85%.

Dehydrogenative Silylation of Alcohols Under Pd-Nanoparticle Catalysis.

Pd-nanoparticle-catalyzed dehydrogenative coupling between various hydrosilanes and alcohols was shown to provide silyl ethers in good and reproducible yields. The synthetic methodology is effective for a wide range of simple and bulky silanes and secondary alcohols, while keeping various other functional groups intact. The procedure also exhibits high selectivity for the silylation of primary versus secondary alcohols in 1,2-diols, and allows the successive silylation of alkynols and hydrogenation of the triple bond to afford Z-alkenols in good yields.

Pd@[nBu4][Br] as a Simple Catalytic System for N-Alkylation Reactions with Alcohols.

Palladium nanoparticles, simply and briefly generated in commercial and cheap onium salts using supercritical carbon dioxide, have been found to be an effective catalytic system for additive free N-alkylation reaction using alcohols via cascade oxidation/condensation/reduction steps.

Borylation of unactivated aryl chlorides under mild conditions by using diisopropylaminoborane as a borylating reagent.

The synthesis of arylboronic ester derivatives from aryl chlorides by using aryl(amino)boranes is described. Palladium-catalyzed coupling between aryl chlorides and diisopropylaminoborane leads to the formation of a CB bond under mild conditions. A wide range of functional groups are tolerated, making this method particularly useful for the borylation of functionalized aromatics.

Supercritical synthesis of biodiesel.

The synthesis of biodiesel fuel from lipids (vegetable oils and animal fats) has gained in importance as a possible source of renewable non-fossil energy in an attempt to reduce our dependence on petroleum-based fuels. The catalytic processes commonly used for the production of biodiesel fuel present a series of limitations and drawbacks, among them the high energy consumption required for complex purification operations and undesirable side reactions. Supercritical fluid (SCF) technologies offer an interesting alternative to conventional processes for preparing biodiesel. This review highlights the advances, advantages, drawbacks and new tendencies involved in the use of supercritical fluids (SCFs) for biodiesel synthesis.

Microfluidic synthesis of palladium nanocrystals assisted by supercritical CO2: tailored surface properties for applications in boron chemistry.

On the surface: A library of organic-inorganic hybrid palladium nanocrystals was synthesized using continuous supercritical microfluidic technology. The nanocatalysts show moderate to excellent activities towards C(Ar)-B and C(Ar)-C(Ar) bond-forming reactions, thus illustrating the relationship between surface properties and modulated catalytic activity.

In situ generation of radical initiators using amine-borane complexes for carbohalogenation of alkenes.

Atom transfer radical addition of alkyl halides to alkenes was developed using a low amount of a stable initiator, amine borane complexes. Thanks to a slow hydroboration step, the overall carbohalogenation process leads to good isolated yields.

Using Catalysts To Make Catalysts: Titanium-Catalyzed Hydroamination To Access P,N-Ligands for Assembling Catalysts in One Pot.

Using a diamido-bis(amidate) titanium precatalyst, the hydroamination of alkynylphosphines afforded phosphinoenamine products. After reduction, 2-aminophosphines are prepared in excellent yield and on gram scale. A broad variety of alkynylphosphines and primary amines with different electronic and steric features are tolerated in this sequential transformation, enabling the rapid assembly of a collection of ligands. Additionally, intermediate phosphinoenamines can be used directly as proligands for coordination to transition metals using protonolysis or salt metathesis reactions. These transformations result in easy-to-use one pot protocols to prepare metal P,N-complexes for catalysis or small molecule activation.

MreB drives de novo rod morphogenesis in Caulobacter crescentus via remodeling of the cell wall.

MreB, the bacterial actin-like cytoskeleton, is required for the rod morphology of many bacterial species. Disruption of MreB function results in loss of rod morphology and cell rounding. Here, we show that the widely used MreB inhibitor A22 causes MreB-independent growth inhibition that varies with the drug concentration, culture medium conditions, and bacterial species tested. MP265, an A22 structural analog, is less toxic than A22 for growth yet equally efficient for disrupting the MreB cytoskeleton. The action of A22 and MP265 is enhanced by basic pH of the culture medium. Using this knowledge and the rapid reversibility of drug action, we examined the restoration of rod shape in lemon-shaped Caulobacter crescentus cells pretreated with MP265 or A22 under nontoxic conditions. We found that reversible restoration of MreB function after drug removal causes extensive morphological changes including a remarkable cell thinning accompanied with elongation, cell branching, and shedding of outer membrane vesicles. We also thoroughly characterized the composition of C. crescentus peptidoglycan by high-performance liquid chromatography and mass spectrometry and showed that MreB disruption and recovery of rod shape following restoration of MreB function are accompanied by considerable changes in composition. Our results provide insight into MreB function in peptidoglycan remodeling and rod shape morphogenesis and suggest that MreB promotes the transglycosylase activity of penicillin-binding proteins.

Task specific ionic liquids and task specific onium salts.

Task specific ionic liquids (TSILs), or more generally task specific onium salts (TSOSs), can be defined as an association of a cation and anion, one at least being organic, to which has covalently been attached through a linker a function that confers the assembly a specific task. After presentation of the general concept of TSILs and TSOSs, the different methods of preparation of these compounds are developed. Regarding their applications in chemistry, TSILs and TSOSs can be used as soluble supports for reagents and catalysts in multiphasic reactions, enabling high activity and easy recovery of the supported agent. However, additionally, they can be used as soluble supports for organic synthesis in a similar manner to resins and offer several advantages over traditional methods.

Zirconium-Catalyzed Synthesis of Alkenylaminoboranes: From a Reliable Preparation of Alkenylboronates to a Direct Stereodivergent Access to Alkenyl Bromides.

A simple procedure has been optimized for the preparation of alkenylaminoborane from alkynes using diisopropylaminoborane and HZrCp2Cl. Coupled with a magnesium-catalyzed dehydrogenation, it allowed for the use of air- and moisture-stable diisopropylamine. This synthesis has been extended to a one-pot sequence leading directly to bromoalkenes with controlled stereochemistry. As such, it provides an easy, scalable, cheap process to access alkenylboronates and both (E)- and (Z)-bromoalkenes from commercially available alkynes.

Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics.

We have developed a heterobifunctional all-small molecule PROTAC (PROteolysis TArgeting Chimera) capable of inducing proteasomal degradation of the androgen receptor. This cell permeable PROTAC consists of a non-steroidal androgen receptor ligand (SARM) and the MDM2 ligand known as nutlin, connected by a PEG-based linker. The SARM-nutlin PROTAC recruits the androgen receptor to MDM2, which functions as an E3 ubiquitin ligase. This leads to the ubiquitination of the androgen receptor, and its subsequent degradation by the proteasome. Upon treatment of HeLa cells with 10microM PROTAC for 7h, we were able to observe a decrease in androgen receptor levels. This degradation is proteasome dependent, as it is mitigated in cells pre-treated with 10microM epoxomicin, a specific proteasome inhibitor. These results have implications for the potential study and treatment of various cancers with increased androgen receptor levels.

Carbinol derivatives via rhodium-catalyzed addition of potassium trifluoro(organo)borates to aldehydes.

Reaction of potassium aryltrifluoroborates with aldehydes, in the presence of a rhodium catalyst, afforded carbinol derivatives in high yields under mild aqueous conditions; this efficient reaction proved to be general, allowing the production of highly hindered diarylmethanols and aliphatic aldehydes were also reactive under these conditions.