Borohydride Reagents Research Articles

A Radical Strategy for the Alkylation of Amides with Alkyl Halides by Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis.

Amide alkylation is a fundamental process in organic chemistry. However, the low nucleophilicity of amides means that divergent coupling with alkyl electrophiles is often not achievable. To circumvent this reactivity challenge, individual amine synthesis followed by amidation with standard coupling agents is generally required. Herein, we demonstrate a radical solution to this challenge by using an amine-borane complex and copper catalysis under oxidative conditions. While borohydride reagents are generally used as reducing agents in ionic chemistry, their conversion into amine-ligated boryl radicals diverts their reactivity toward halogen-atom transfer. This enables the conversion of alkyl halides into the corresponding alkyl radicals for amide functionalization via copper catalysis. The process is applicable to the N-alkylation of primary amides employing unactivated alkyl iodides and bromides, and it was also showcased in the late-state functionalization of both complex amide- and halide-containing drugs.

Kit-based synthesis of 2-deoxy-2-[18F]-fluoro-D-sorbitol for bacterial imaging.

Clinically available imaging tools for diagnosing infections rely on structural changes in the affected tissues. They therefore lack specificity and cannot differentiate between oncologic, inflammatory and infectious processes. We have developed 2-deoxy-2-[18F]fluoro-D-sorbitol (18F-FDS) as an imaging agent to visualize infections caused by Enterobacterales, which represent the largest group of bacterial pathogens in humans and are responsible for severe infections, often resulting in sepsis or death. A clinical study in 26 prospectively enrolled patients demonstrated that 18F-FDS positron emission tomography (PET) was safe, and could detect and localize infections due to drug-susceptible or multi-drug-resistant Enterobacterales strains as well as differentiate them from other pathologies (sterile inflammation or cancer). 18F-FDS is cleared almost exclusively through renal filtration and has also shown potential as a PET agent for functional renal imaging. Since most PET radionuclides have a short half-life, maximal clinical impact will require fast, on-demand synthesis with limited infrastructure and personnel. To meet this demand, we developed a kit-based solid phase method that uses commercially and widely available 2-deoxy-2-[18F]fluoro-D-glucose as the precursor and allows 18F-FDS to be produced and purified in one step at room temperature. The 18F-FDS kit consists of a solid-phase extraction cartridge packed with solid supported borohydride (MP-borohydride), which can be attached to a second cartridge to reduce pH. We evaluated the effects of different solid supported borohydride reagents, cartridge size, starting radioactivity, volumes and flow rates in the radiochemical yield and purity. The optimized protocol can be completed in <30 min and allows the synthesis of 18F-FDS in >70% radiochemical yield and >90% radiochemical purity.

Green Synthesis of Ge1−xSnx Alloy Nanoparticles for Optoelectronic Applications

Compositionally controlled, light-emitting, group IV semiconductor nanomaterials have potential to enable on-chip data communications and infrared (IR) imaging devices compatible with the complementary metal−oxide−semiconductor (CMOS) technology. The recent demonstration of a direct band gap laser in Ge-Sn alloys opens avenues to the expansion of Si-photonics. Ge-Sn alloys showed improved effective carrier mobility as well as direct band gap behavior at Sn composition above 6–11%. In this work, Ge1−xSnx alloy nanoparticles with varying Sn compositions from x = 0.124 to 0.178 were prepared via colloidal synthesis using sodium borohydride (NaBH4), a mild and non-hazardous reducing reagent. Successful removal of the synthesized long-alkyl-chain ligands present on nanoparticles’ surfaces, along with the passivation of the Ge-Sn nanoparticle surface, was achieved using aqueous (NH4)2S. The highly reactive surface of the nanoparticles prior to ligand exchange often leads to the formation of germanium oxide (GeO2). This work demonstrates that the (NH4)2S further acts as an etching reagent to remove the oxide layer from the particles’ surfaces. The compositional control and long-term stability will enable the future use of these easily prepared Ge1−xSnx nanoalloys in optoelectronic devices.

Metal-Rich Metallaboranes: Synthesis, Structures and Bonding of Bi- and Trimetallic Open-Faced Cobaltaboranes

Synthesis, isolation, and structural characterization of unique metal rich diamagnetic cobaltaborane clusters are reported. They were obtained from reactions of monoborane as well as modified borohydride reagents with cobalt sources. For example, the reaction of [Cp*CoCl]2 with [LiBH4·THF] and subsequent photolysis with excess [BH3·THF] (THF = tetrahydrofuran) at room temperature afforded the 11-vertex tricobaltaborane nido-[(Cp*Co)3B8H10] (1, Cp* = η5-C5Me5). The reaction of Li[BH2S3] with the dicobaltaoctaborane(12) [(Cp*Co)2B6H10] yielded the 10-vertex nido-2,4-[(Cp*Co)2B8H12] cluster (2), extending the library of dicobaltadecaborane(14) analogues. Although cluster 1 adopts a classical 11-vertex-nido-geometry with one cobalt center and four boron atoms forming the open pentagonal face, it disobeys the Polyhedral Skeletal Electron Pair Theory (PSEPT). Compound 2 adopts a perfectly symmetrical 10-vertex-nido framework with a plane of symmetry bisecting the basal boron plane resulting in two {CoB3} units bridged at the base by two boron atoms and possesses the expected electron count. Both compounds were characterized in solution by multinuclear NMR and IR spectroscopies and by mass spectrometry. Single-crystal X-ray diffraction analyses confirmed the structures of the compounds. Additionally, density functional theory (DFT) calculations were performed in order to study and interpret the nature of bonding and electronic structures of these complexes.

The first hydride-Meisenheimer adduct of electron-deficient 3-nitronaphthalimide: application to colorimetric borohydride determination.

The first hydride-Meisenheimer adduct of 3-nitronaphthalimide was used for the colorimetric borohydride assay. To explain the regioselectivity of the adduct, the reaction enthalpies of the two most plausible Meisenheimer adducts were obtained via computational calculation. Using the adduct formation, the assay of borohydride reagents was successfully conducted.

ChemInform Abstract: Radical Reactions of Borohydrides

AbstractReview: [58 refs.

Reduction of Weinreb amides to aldehydes under ambient conditions with magnesium borohydride reagents

Chloromagnesium dimethylaminoborohydride (ClMg+ [H3BNMe2]−, MgAB) is an analogue of the versatile lithium dialkylaminoborohydrides (LAB reagents), prepared by the reaction of dimethylamine-borane with methylmagnesium chloride. MgAB is a partial reducing agent for Weinreb amides under ambient conditions and is complementary to the commonly utilized lithium aluminum hydride (LiAlH4) and diisobutylaluminum hydride (DIBAL) reagents, while exhibiting enhanced chemoselectivity. To prevent over-reduction, the aldehyde products are readily isolated in good yields by forming the sodium bisulfite adducts. Aldehyde products can both be stored and later used as the bisulfite adducts, or can be regenerated from the bisulfite adducts by treatment with aqueous formaldehyde.

A twist on facial selectivity of hydride reductions of cyclic ketones: twist-boat conformers in cyclohexanone, piperidone, and tropinone reactions.

The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin–Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not with a bulky hydride (lithium triisopropylborohydride).

Unusual Aluminum Hydride-mediated Reduction of N-(γ- or δ-Oxoacyl)oxazolidinone

Abstract Reduction of N-(γ-oxoacyl)oxazolidinone with a borohydride reagent, such as NaBH4 or LiBEt3H, resulted in formation of the corresponding lactone or lactol. In contrast, when an aluminum hydride reagent was used instead of a borohydride reagent, reduction of N-(γ- or δ-oxoacyl)oxazolidinone proceeded unexpectedly to give not the corresponding lactone or lactol, but a tetrahydrofuran or tetrahydropyran derivative, respectively, containing an oxazolidino group.

Poly(n-butyl-4-vinylpyridinium) borohydride as a new stable and efficient reducing agent in organic synthesis

Sodium borohydride is stabilized on poly(n-butyl-4-vinylpyridinium) chloride, and it is used as an efficient and regenerable polymer-supported borohydride reagent for the reduction of a variety of carbonyl compounds, such as aldehydes, ketones, α,β-unsaturated carbonyl compounds, α-diketones, and acyloins.

Poly(1,4-butyl-bis-vinylpyridinium) borohydride as a new stable and efficient reducing agent in organic synthesis

The unstable sodium borohydride is stabilized on modified poly(4-vinylpyridinium), and it is used as an efficient and regenerable polymer-supported borohydride reagent for the reduction of a variety of carbonyl compounds, such as aldehydes, ketones, α,β-unsaturated carbonyl compounds, α-diketones and acyloins, in good to excellent yields.

NMR Studies of Structure–Reactivity Relationships in Carbonyl Reduction: A Collaborative Advanced Laboratory Experiment

An upper-division laboratory project has been developed as a collaborative investigation of a reaction routinely taught in organic chemistry courses: the reduction of carbonyl compounds by borohydride reagents. Determination of several trends regarding structure–activity relationship was possible because each student contributed his or her results to an overall data set in a situation similar to a research environment. The students learned to use 1H NMR techniques for in situ kinetic determinations and collaborated with classmates to develop a complete theory for structure–activity effects in the kinetics of this fundamental organic reaction.

ChemInform Abstract: Free Radical Mediated Hydroxymethylation Using CO and HCHO

AbstractReview: 36 refs.

Free Radical-mediated Hydroxymethylation Using CO and HCHO

Tin-free radical hydroxymethylations of haloalkanes using CO and HCHO as a C1 unit proceed efficiently in the presence of borohydrides as radical mediators. In the approach using CO, the formation of aldehydes by radical carbonylation and their subsequent reduction by hydrides lead to alcohols. On the other hand, the use of formaldehyde is more straightforward, in which the key reaction is alkyl radical addition to formaldehyde to give alkoxy radical, which abstracts hydrogen from borohydride reagents. The cascade sequences were observed in the reaction of cholesteryl bromide with HCHO, which displays the diverse applications of HCHO in radical chemistry.

Stereoselective Reduction of 2‐Hydroxy Ketones towards syn‐ and anti‐1,2‐Diols

AbstractStereoselective reduction of 2‐hydroxy ketones should in principle give access to syn‐ and anti‐1,2‐diols. anti‐1,2‐Diols are accessible in a highly selective way using zinc borohydride [Zn(BH4)2] under chelation control (dr&gt;20:1). Diastereoselective reduction of unprotected or even protected 2‐hydroxy ketones towards syn‐1,2‐diols could be achieved only with moderate selectivity of dr≤5:1. Even when using sterically demanding protecting groups and/or polymer‐supported borohydride reagents high selectivity could not be achieved. A new ionic liquid‐dependent borohydride reduction method, although highly attractive with respect to reaction engineering, resulted in only moderate to good selectivity. An efficient two‐step biocatalytic method for the synthesis of syn‐1,2‐diols is described. The method relies on the whole‐cell Pichia glucozyma‐catalyzed stereoselective reduction of the unprotected (R)‐2‐hydroxy ketones (dr&gt;10:1). The latter are accessible through thiamine diphosphate‐dependent enzyme‐catalyzed synthesis starting from simple aldehydes. Thus, biocatalytic transformations enable a process which is hardly accessible through present non‐enzymatic methods.

Unsymmetrical RPNPR′ pincer ligands and their group 10 complexes

Two new unsymmetrical (R)PNP(R')-type pincer ligands based on a bis(tolyl)amine framework have been synthesized and characterized by a variety of techniques, including X-ray crystallography. These ligands have been coordinated to Ni, Pd, and Pt precursors to provide a number of well-characterized group 10 halides. Conversion of these metal halides to metal hydrides was accomplished using borohydride reagents, or by direct interaction of the ligand with the zerovalent metal precursor. The insertion of oxygen into these hydrides in an attempt to prepare metal hydroperoxides has been examined; however, we were unable to obtain stable and isolable hydroperoxide species.

ChemInform Abstract: 3,3-Dimethyl-7-methylenecycloocta-1,5-dione, a Versatile Building Block for the Preparation of Substituted Cyclooctadienones and δ- Valerolactones.

Abstract De Mayo reaction of dimedone with allene results in the formation of 3,3-dimethyl-7-methylenecycloocta-1,5-dione 6 together with the corresponding head-to-tail adduct 5 which spontaneously dimerizes to the hetero Diels-Alder adduct 7 . Reduction of 6 together with sodium borohydride or Grignard reagents affords the transannular hemiketals 9 which can easily be isomerized (DBU) to their conjugated analogues 10 . Depending on the substrate chosen ( 9 or 10 , the substituent R and the applied reaction conditions, an acid-catalyzed rearrangement of these hemiketals leads to the cyclooctadienones 12 in either pure form or in admixture with δ-valerolactones 11 or substituted cyclohexenones.

SYNTHESIS AND ANTIPLASMODIAL ACTIVITY TESTING OF (1)-N-(4-METHOXYBENZYL)-1,10-PHENANTHROLINIUM BROMIDE

Synthesis of (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide from 1,10-phenanthroline monohydrate and 4-methoxybenzaldehyde as starting material and evaluation of its antiplasmodial activities have been carried out. The 4-methoxybenzyl alcohol was prepared from 4-methoxy-benzaldehyde using sodium borohydride (NaBH4) reagent and ethanol absolute solution. The mixture was refluxed for 3 h. To yield colorless dilution compound with 90.41 % in efficiency. Furthermore, bromination of 4-methoxybenzyl alcohol with phosphorus bromide (PBr3) was conducted by refluxing for 3 h. The product of this reaction was yellow liquid of 4-methoxybenzyl bromide, 79.03% yield and 95.34 % purity. The final step of reaction was benzylation of 1,10-phenanthroline monohydrate with 4-methoxybenzyl bromide reagent. It was conducted by refluxing in aceton for 8 h at 55 oC. The yield of the reaction was (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide (77.63%). It is pink solid form, and its melting point is 192-193 oC. Identification of the product was carried out by means of GC-MS, IR and 1H-NMR spectrometers. The in vitro antiplasmodial activity on chloroquine-resistant Plasmodium falciparum FCR-3 strain and chloroquine sensitive P. falciparum D10 strain for (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide were determined by microscopic method. The result showed that after 72 h incubation, it has IC50 0.93±0.02 µM and 1.21±0.09 µM, respectively. Keywords: 1,10-phenanthroline, (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide, 4 methoxybenzaldehyde, antiplasmodial activities

Recent development and improvement for boron hydride-based catalytic asymmetric reduction of unsymmetrical ketones

Catalytic asymmetric reduction of prochiral ketones with hydrides such as boranes and borohydrides is one of the simplest and the most convenient methods for obtaining chiral alcohols. This tutorial review describes the most significant advances recently achieved for enhancing the enantioselectivity and practicability of the reduction using this methodology. The review covers the development of new homogeneous and/or immobilized catalysts for asymmetric reduction using borane or borohydride reagents and practical improvement of the well-known oxazaborolidine (OAB)-catalysed reduction through developing more stable, cost effective and recoverable OABs, scalable and environmental friendly borane sources, and one-pot procedures for the reduction.

Selective Reduction of 7-Demethylsinomenine

Abstract Several borohydride reagents: sodium borohydride, sodium cyanoborohydride, soudium acetoxyborohydride and soudium triacetoxyborohydride were screened, respectively, for the reduction of 7-demethylsinomenine, which was an α,β-dicarbonyl compound derived from sinomenine. Highly regio- and stereo-selectivity was acquired when sodium cyanoborohydride or NaBH(OAc) 3 was used. The product was structurally confirmed as 7R configuration by NMR, X-ray crystal diffraction analysis. Some preliminary discussion was also made on the mechanism of the selective reduction.