Chemoselective Reduction Research Articles

Asymmetric synthesis of \u03b3-branched amines via rhodium-catalyzed reductive amination

Amines bearing γ-stereocenters are highly important structural motifs in many biologically active compounds. However, reported enantioselective syntheses of these molecules are indirect and often require multiple steps. Herein, we report a general asymmetric route for the one-pot synthesis of chiral γ-branched amines through the highly enantioselective isomerization of allylamines, followed by enamine exchange and subsequent chemoselective reduction. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents, which allows for a rapid and modular synthesis of many chiral γ-branched amines. To demonstrate the synthetic utility, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity.

Mechanistic and kinetic insights of reduction of indophenol by sodium borohydride: A theoretical study to explore the effect of solvent and counter ion

NaBH4 finds plethora of applications in organic synthesis due to its unique capability of chemo-selective reduction of carbonyl functional group. Present work is focussed to explore the energetically feasible reaction pathway for reduction of indophenol by sodium borohydride. Our calculations suggest following reaction steps for reduction of indophenol. The reduction reaction is initially driven via an asynchronous nucleophilic attack of borohydride ion on carbonyl group of indophenol. Intermediate generated is subjected to concurrent, hydroxyl ion assisted, proton abstraction followed by protonation of nucleophilic rich site on the molecule. Finally, reduction process undergoes completion by hydrolysis. Potential energy surface suggest that initial step of the reduction reaction is a rate determining step (RDS). More importantly, the synergistic effect of solvent and counter ion was observed to increase the electrophilicity of carbonyl carbon and thereby assisting in lowering energy barrier of RDS. This, in turn, enhances the reaction rate significantly.

Ruthenium-Catalyzed Asymmetric Reduction of Isoxazolium Salts: Access to Optically Active Δ4-Isoxazolines

A tethered MsDPEN-ruthenium catalyst reduces a series of isoxazolium salts, affording optically active Δ4-isoxazolines in moderate to good yields and enantioenrichment. The redundancy of heating or high pressures allowed for chemoselective reduction with no subsequent heterocyclic ring opening. Our results reinforce our understanding of the workings of these Noyori-class catalysts.

Inexpensive and rapid hydrogenation catalyst from CuSO4/CoCl2 — Chemoselective reduction of alkenes and alkynes in the presence of benzyl protecting groups

The simple reduction of a number of alkenes and alkynes was performed with a typical reaction time of 20 min using a copper-cobalt catalytic system. The reduction did not cleave benzyl protecting groups which are usually vulnerable to catalytic hydrogenation reactions. The catalyst can be prepared in situ by reduction of the inexpensive precursor salts CuSO4 and CoCl2 with NaBH4. Sodium borohydride was also used as an easily handled hydrogen source for the catalytic reductions. No pressure, heating or inert atmosphere is required and purification/catalyst removal is achieved using extraction procedures, making this approach simple and efficient.

Synthesis of Mesoporous γ-Alumina-Supported Co-Based Catalysts and Their Catalytic Performance for Chemoselective Reduction of Nitroarenes

Mesoporous γ-alumina (γ-MA)-supported cobalt oxides (Co3O4) with large surface areas and narrow pore size distributions were first prepared through one-pot hydrolysis of metal nitrates. The obtained Co3O4/γ-MA materials were impregnated with a water-ethanol solution of 1,10-phenanthroline, followed by treatment at 700 °C in N2 atmosphere, generating Co-NC/γ-MA catalysts containing N-doped graphitic carbon (NC). The Co-NC/γ-MA catalysts maintained the mesoporous structure of γ-MA, and Co3O4 was reduced to metallic Co nanoparticles highly dispersed in the γ-MA frameworks. Metallic Co species had a strong interaction with NC in the matrices, avoiding the surface oxidation of Co particles. The Co-NC/γ-MA catalysts exhibited superior catalytic activity and quantitatively reduced a variety of functionalized nitroarenes to the corresponding arylamines with hydrazine hydrate in ethanol at near room temperature, affording yields of >99%. The recycling test of 2-chloronitrobenzene as a model reaction showed no detectable change in catalyst performance after 10 cycle reactions.

Surfactant‐Induced Preparation of Highly Dispersed Ni‐Nanoparticles Supported on Nanocrystalline ZrO2for Chemoselective Reduction of Nitroarenes

AbstractMetal‐support interaction plays crucial role in heterogeneous catalysis, stabilizing the active metal species during catalysis. We report here the successful preparation of highly dispersed nickel nanoparticles supported ZrO2nanocrystals, which showed excellent performance toward catalytic reduction of nitroarenes to their corresponding amines, where metal‐support interaction plays the key role in enhancing the activity and stability of catalyst. The catalyst was synthesized by a single step hydrothermal method using CTAB (cetyltrimethyl ammonium bromide) as a structure‐ directing agent and PVP (Polyvinylpyrrolidone) as capping agent. Prepared catalyst was characterized by BET‐surface area, Inductively coupled plasma atomic emission spectroscopy (ICP‐AES), X‐ray diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Temperature programmed reduction (TPR), X‐ray photoelectron spectroscopy (XPS), Fourier transform infra‐red (FT‐IR) spectroscopy, RAMAN spectroscopy, Thermogravimetric analysis (TGA‐DTA), UV‐vis spectroscopy and Extended X‐ray absorption fine structure (EXAFS) analysis. Results obtained from XRD and TPR analysis of 4.9% Ni‐ZrO2, support the presence of highly dispersed and subtle Ni (below 5 nm) nanoparticles supported on nanocrystalline ZrO2. Prepared 4.9 wt% Ni‐ZrO2catalyst showed 100% conversion ofp‐nitrophenol with >99% selectivity top‐aminophenol in aqueous medium at 60 °C, in presence of molecular H2(1.0 MPa). Superior activity of 4.9% Ni‐ZrO2was due to presence of very small (below 5 nm), uniformly distributed, highly dispersed nickel nanoparticle having good metal‐support interaction. Prepared 4.9% Ni‐ZrO2catalyst was recycled up to eight successive runs without any significant loss in catalytic activity.

Stabilization of NaBH4 in Methanol Using a Catalytic Amount of NaOMe. Reduction of Esters and Lactones at Room Temperature without Solvent-Induced Loss of Hydride.

Rapid reaction of NaBH4 with MeOH precludes its use as a solvent for large-scale ester reductions. We have now learned that a catalytic amount of NaOMe (5 mol %) stabilizes NaBH4 solutions in methanol at 25 °C and permits the use of these solutions for the reduction of esters to alcohols. The generality of this reduction method was demonstrated using 22 esters including esters of naturally occurring chiral γ-butyrolactone containing dicarboxylic acids. This method permits the chemoselective reductions of esters in the presence of cyano and nitro groups and the reductive cyclization of a pyrrolidinedione ester to a fused five-membered furo[2,3-b]pyrrole and a (-)-crispine A analogue in high optical and chemical yields. Lactones, aliphatic esters, aromatic esters containing electron-withdrawing groups, and heteroaryl esters are reduced more rapidly than aryl esters containing electron-donating groups. The 11B NMR spectrum of the NaOMe-stabilized NaBH4 solutions showed a minor quartet due to monomethoxyborohydride (NaBH3OMe) that persisted up to 18 h at 25 °C. We postulate that NaBH3OMe is probably the active reducing agent. In support of this hypothesis, the activation barrier for hydride transfer from BH3(OMe)- onto benzoic acid methyl ester was calculated as 18.3 kcal/mol.

Catalyst-free chemoselective conjugate addition and reduction of α,β-unsaturated carbonyl compounds via a controllable boration/protodeboronation cascade pathway

A transition-metal-catalyst-free method provides a useful and eco-friendly tool for the chemoselective conjugate addition and reduction of α,β-unsaturated carbonyl compounds.

Chemoselective amide reductions by heteroleptic fluoroaryl boron Lewis acids.

The heteroleptic borane catalyst (C6F5)2B(CH2CH2CH2)BPin is found to hydrosilylatively reduce amides under mild conditions. Simple tertiary amides can be reduced using Me2EtSiH, whereas tertiary benzamides required a more reactive secondary silane, Et2SiH2, for efficient reduction. The catalytic system described exhibits exceptional chemoselectivity in the reduction of oligoamides and tolerates functionalities which are prone to reduction under similar conditions.

Unravelling 2-aminoquinazolin-4(3H)-one as an organocatalyst for the chemoselective reduction of nitroarenes

A novel, green and transition metal-free reduction of nitroarenes has been explored. 2-Aminoquinazolin-4(3H)-one and its derivatives have been first time investigated as hydrogen bonding organocatalysts for the activation of hydrazine hydrate to reduce nitroarenes.

Chemoselective reduction of heteroarenes with a reduced graphene oxide supported rhodium nanoparticle catalyst

Rhodium nanoparticles immobilized on reduced graphene oxide catalyze the selective hydrogenation of N- and O-containing heteroarenes.

Selective ligand-free cobalt-catalysed reduction of esters to aldehydes or alcohols

Activated cobalt metal salts are effective and versatile catalysts for the chemoselective reduction of esters to aldehydes or alcohols through hydrosilylation reaction.

Green synthesis & catalytic study of sucrose stabilized Pd nanoparticles in reduction of nitro compounds to useful amines

An efficient chemoselective reduction of aromatic nitro compounds to corresponding amino analogues was achieved using palladium/sucrose (Pd/S) nanoparticles as an eco friendly catalyst, a green approach formate in ethanol at RT. The reductions are fruitfully carried out in presence of various other reducible functional groups such as halo, alkoxy, carbonyl, and cyanide etc. The reactions are worthy and high yielding (100%).

2-Phenyl-2,3-dihydrobenzo[d]thiazole: A Mild, Efficient, and Highly Active in situ Generated Chemoselective Reducing Agent for the One-Pot Synthesis of 5-Monoalkylbarbiturates in Water

A metal- and catalyst-free reductive alkylation protocol for the one-pot synthesis of 5-monoalkylbarbiturates from barbituric acids and aldehydes using the in situ generated chemoselective reducing agent 2-phenyl-2,3-dihydrobenzo[d]thiazole from 2-aminothiophenol and benzaldehyde is described. The notable advantages of the protocol are operational simplicity, mild reaction conditions, high yield, short reaction time, and simple workup and purification process which make it highly attractive.

Total Synthesis of (-)-Himalensine A.

The first enantioselective synthesis of (-)-himalensine A has been achieved in 22 steps. The synthesis was enabled by a novel catalytic, enantioselective prototropic shift/furan Diels-Alder (IMDAF) cascade to construct the ACD tricyclic core. A reductive radical cyclization cascade was utilized to build the B ring, and end-game manipulations featuring a molecular oxygen mediated γ-CH oxidation, a Stetter cyclization to access the pendant cyclopentenone, and a highly chemoselective lactam reduction delivered the natural product target.

Chemoselective Reductive Heterocyclization by Controlling the Binomial Architecture of Metal Particles and Acid–Base Properties of the Support

2,1-Benzisoxazoles have been selectively synthesized through reductive heterocyclization of 2-nitroacylarenes using Pt-supported nanoparticles. The reaction involves a cascade process in which the first step is the reduction of the nitro group into hydroxylamine followed by heterocyclization through the nucleophilic attack of the hydroxylamine group to the carbonyl of the acyl group and further dehydration. The reaction was performed on Pt/C, Pt/TiO2, and Pt/MgO using hydrogen as the reducing agent under mild reaction conditions. The results showed that Pt/MgO was the most active and selective catalyst. The study of the influence of the crystal size of the metal on the activity and selectivity, combined with the reaction mechanism examined by in situ Fourier transform infrared spectroscopy of the adsorbed reactant, showed that the maximum activity and selectivity to the target compound can be achieved by controlling the architecture of metal particles and acid–base properties of the support. The effect of...

Chemoselective Reduction of Nitro and Nitrile Compounds with Magnetic Carbon Nanotubes-Supported Pt(II) Catalyst under Mild Conditions

Multi-walled carbon nanotubes (MWNTs) decorated with Fe3O4 nanoparticles have been prepared using a coprecipitation technique and were surface modified using poly(citric acid) (PC) dendrimer. These PC-functionalized magnetic carbon nanotubes (MWCNT/MA@PC) have been used as a novel support for Pt(II) complex immobilized as magnetic nanocatalyst (MWCNT/MA@PC/Pt(II)). The morphology and structural features of the magnetic nanocatalyst were characterized using different microscopic and spectroscopic techniques, including FT-IR, TEM, EDX, BET, XRD, TGA, ICP, and VSM. The nitro and nitrile groups in aromatic and aliphatic compounds containing various reducible substituents, such as carboxylic acid, ketone, aldehyde, and halogen, are selectively reduced to the corresponding amines in water as a eco-friendly solvent with excellent yields by employing NaBH4 in the presence of MWCNT/MA@PC/Pt(II). In addition, the Pt(II) magnetic nanocatalyst can be simply separated from the mixture of reactants by using an external...

Efficient and Convenient Reduction of Organic Carbonyl Compounds to their Corresponding Alcohols by Zn(BH4)2/Charcoal in THF

Zn(BH4)2 (0.5-1.5 mmol) in the presence of charcoal (1 mmol) reduces a variety of organic carbonyl compounds such as aldehydes, ketones, acyloins, α-diketones and α,β-unsaturated carbonyl compounds to their corresponding alcohols. Reduction reactions were carried out in THF at room temperature in high to excellent yields. The chemoselective reduction of aldehydes over ketones was successfully accomplished with this reducing system. In addition, regioselectivity and exclusive 1,2-reduction of conjugated carbonyl compounds to their corresponding allylic alcohols was also performed in in high to excellent yields with this reducing system.

Chemoselective Reduction: Xanthates as Traceless Precursors of Polyfunctionalized α,α-Dichloroketones.

The use of BEt3·H2O has allowed the chemoselective reductive dexanthylation in the presence of the very fragile α,α-dichloroketone motif. This has solved a major hurdle in our approach to this important, but hitherto grossly understudied, family of compounds and opened access to a number of very useful synthetic transformations.

Synthesis and Analysis of Bacterial Folate Metabolism Intermediates and Antifolates.

The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.