Hydride Reagents Research Articles

Modified synthesis of mixed-ligand dinuclear Ru–Ir, Ru–Rh, and Ru–Ru polyhydride-bridged complexes, CpsRuH3ML (Cps = C5Me5 (Cp*), C5tBu3H2 (Cp‡); M = Rh, Ir, Ru; L = C5(CH3)5, C6H6, p-CH3C6H4CH(CH3)2)

Hetero-bimetallic polyhydride clusters exhibit a regio- and chemoselective activation of a substrate. The rational synthetic method for hetero-bimetallic polyhydride complexes using readily available halide complexes is reported. The reaction of hetero-bimetallic Ru–Ir trichloride complex, Cp*Ru(μ-Cl)3IrCp* (5a), in 2-propanol in the presence of a base afforded Cp*Ru(μ-H)3IrCp* (6a) by sequential salt metathesis and β-hydrogen elimination. CpsRu(μ-H)3ML [Cps = Cp*, Cp‡; ML = IrCp*, RhCp*, Ru(p-cymene), Ru(benzene)] were also selectively synthesized by reacting a mixture of CpsRuCl/n and [LM(μ-Cl)Cl]2 via the formation of CpsRu(μ-Cl)3ML. The IrCp*, RhCp*, and Ru(arene) complexes, Cp‡Ru(μ-H)3IrCp* (6b), Cp‡Ru(μ-H)3RhCp* (8), and Cp‡Ru(μ-H)3Ru(arene) (10), were newly synthesized by this method. The reaction mechanism was discussed based on the hetero-bimetallic chloro-hydride intermediates. Absence of main group hydride reagents was responsible for maintaining the hetero-bimetallic structure during the introduction of the hydride ligand, which lead to selective formation of dinuclear mixed-metal trihydride-bridged complexes.

Controlled Reduction of Tertiary Amides to the Corresponding Alcohols, Aldehydes, or Amines Using Dialkylboranes and Aminoborohydride Reagents.

Dialkylboranes and aminoborohydrides are mild, selective reducing agents complementary to the commonly utilized amide reducing agents, such as lithium aluminum hydride (LiAlH4) and diisobutylaluminum hydride (DIBAL) reagents. Tertiary amides were reduced using 1 or 2 equiv of various dialkylboranes. The reduction of tertiary amides required 2 equiv of 9-borabicyclo[3.3.1]nonane (9-BBN) for complete reduction to give the corresponding tertiary amines. One equivalent of sterically hindered disiamylborane reacts with tertiary amides to afford the corresponding aldehydes. Aminoborohydrides are powerful and selective reducing agents for the reduction of tertiary amides. Lithium dimethylaminoborohydride and lithium diisopropylaminoborohydride are prepared from n-butyllithium and the corresponding amine-borane. Chloromagnesium dimethylaminoborohydride (ClMg(+)[H3B-NMe2](-), MgAB) is prepared by the reaction of dimethylamine-borane with methylmagnesium chloride. Solutions of aminoborohydride reduce aliphatic, aromatic, and heteroaromatic tertiary amides to give the corresponding alcohol, amine, or aldehyde depending on the steric requirement of the tertiary amide and the aminoborohydride used.

Flame-Sealed Tube Graphitization Using Zinc as the Sole Reduction Agent: Precision Improvement of EnvironMICADAS 14C Measurements on Graphite Targets

The flame-sealed tube zinc reduction graphitization method has been successfully adapted and optimized for radiocarbon measurements on EnvironMICADAS in the Institute for Nuclear Research of the Hungarian Academy of Sciences, Hertelendi Laboratory of Environmental Studies (ATOMKI HLES). To reduce the cost and treatment time of producing graphite targets from samples of about 1 mg carbon content, we have omitted the titanium hydride (TiH 2 ) reagent and used a decreased amount of zinc as the sole reductant in our new method. These changes have also helped to eliminate methane formation during the graphitization processes as well as to recover higher ion current at the same background level. These conditions have led to improved efficiency in the 14 C measurements; furthermore, the instrument background level remained sufficiently low (<49,000 yr BP). After determining the optimum parameters of the new Zn graphitization method (2.5 mg Fe powder, 15.0 mg Zn powder, 10 hr graphitization at 550°C in heating block, reaction cells with reagent pretreated at 300°C for 1 hr), verification of the accuracy was carried out by the preparation and measurement of IAEA standard samples (C2, C6, C7, C8) with known 14 C activity. The sensitivity of the method for gas contamination was tested and determined by comparing the results to measurements of reserved portions of previously processed real samples. DOI: 10.2458/azu_rc.57.18193

Development of variously functionalized nitrile oxides.

N-Methylated amides (N,4-dimethylbenzamide and N-methylcyclohexanecarboxamide) were systematically subjected to chemical transformations, namely, N-tosylation followed by nucleophilic substitution. The amide function was converted to the corresponding carboxylic acid, esters, amides, aldehyde, and ketone upon treatment with hydroxide, alkoxide, amine, diisobutylaluminium hydride and Grignard reagent, respectively. In these transformations, N-methyl-N-tosylcarboxamides behave like a Weinreb amide. Similarly, N-methyl-5-phenylisoxazole-3-carboxamide was converted into 3-functionalized isoxazole derivatives. Since the amide was prepared by the cycloaddition reaction of ethynylbenzene and N-methylcarbamoylnitrile oxide, the nitrile oxide served as the equivalent of the nitrile oxides bearing a variety of functional groups such as carboxy, alkoxycarbonyl, carbamoyl, acyl and formyl moieties.

Toward the ABCD core of the calyciphylline A-type Daphniphyllum alkaloids: solvent non-innocence in neutral aminyl radical cyclizations

The Daphniphyllum alkaloids remain an attractive target in the synthetic community because of their unique framework and promising biological activities. We have shown that the ABC core of the calyciphylline A-type alkaloids can be rapidly accessed via the tandem cyclization of a neutral aminyl radical with a polarized cyclic olefin. Deuterium labeling experiments and reactions omitting a tin hydride reagent suggest that the solvent is the major source of the terminating hydrogen atom in the cyclization cascade. Incorporation of an internal alkyne in the radical pathway was tolerated in the reaction, and it provided the necessary atoms to enable completion of the D ring of the calyciphylline A-type alkaloids.

Flame-Sealed Tube Graphitization Using Zinc as the Sole Reduction Agent: Precision Improvement of EnvironMICADAS 14C Measurements on Graphite Targets

The flame-sealed tube zinc reduction graphitization method has been successfully adapted and optimized for radiocarbon measurements on EnvironMICADAS in the Institute for Nuclear Research of the Hungarian Academy of Sciences, Hertelendi Laboratory of Environmental Studies (ATOMKI HLES). To reduce the cost and treatment time of producing graphite targets from samples of about 1 mg carbon content, we have omitted the titanium hydride (TiH2) reagent and used a decreased amount of zinc as the sole reductant in our new method. These changes have also helped to eliminate methane formation during the graphitization processes as well as to recover higher ion current at the same background level. These conditions have led to improved efficiency in the 14C measurements; furthermore, the instrument background level remained sufficiently low (&lt;49,000 yr BP). After determining the optimum parameters of the new Zn graphitization method (2.5 mg Fe powder, 15.0 mg Zn powder, 10 hr graphitization at 550°C in heating block, reaction cells with reagent pretreated at 300°C for 1 hr), verification of the accuracy was carried out by the preparation and measurement of IAEA standard samples (C2, C6, C7, C8) with known 14C activity. The sensitivity of the method for gas contamination was tested and determined by comparing the results to measurements of reserved portions of previously processed real samples.

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.

Insight into alcohol reduction by saccharides and their homologues in supercritical water via aldehyde-mediated radical formation

Benzhydrol was directly reduced to diphenylmethane by α-hydroxyaldehydes and dialdehyde, being saccharide degradates, without using a hydride reagent, in supercritical water at 400°C for 10min. A lower-temperature reaction in subcritical water at 300°C primarily generated 1,1,2,2-tetraphenylethane. A plausible reaction pathway was proposed, involving radical formation via the degradation of hemiacetal intermediates derived from benzhydrol and aldehydes.

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).

Hydrogenation of carboxylic acid derivatives with bifunctional ruthenium catalysts

AbstractThis paper focuses on recent advances in the chemistry of bifunctional Ru catalysts with chelate protic amine ligands effective for hydrogenation of polar carbonyl compounds. The rational design of the cooperating amine ligand that adjusts the balance of the electronic factors on the M/NH units in the bifunctional catalysts is crucial to exploit the characteristic catalytic performance with a wide scope and high practicability. These bifunctional molecular catalysts offer a great opportunity to develop new fundamental processes for the straightforward hydrogenation of carboxylic acid derivatives as a powerful alternative for classical reduction using stoichiometric amounts of metal hydride reagents.

Aluminum-stabilized low-spin iron(II) hydrido complexes of 1,4,7-trimethyl-1,4,7-triazacyclononane.

We investigated herein the reactions of (Me3tacn)FeCln (1a: n = 3, 1b: n = 2) with common aluminum hydride reagents and a bulky dihydridoaluminate {Li(ether)2}{Al(OC6H3-2,6-(t)Bu2)}(μ-H)2, which yielded the diamagnetic hydrido complexes 2-4 containing Fe(II) and Al(III). In particular, the use of divalent 1b afforded excellent isolated yields. The structures of 2-4 were determined using spectroscopic and crystallographic analyses. The crystal structures showed distorted octahedral Fe centers and fairly short Fe-Al distances [2.19-2.24 Å]. The structures of cation moiety 2 and neutral complex 4 were further probed using DFT calculations, which indicated a stable low-spin Fe(II) state and strongly electron-donating nature of the (Me3tacn)FeH3 fragment toward the Al(III) center.

Chiral Sulfoxides as Building Blocks for Enantiopure 1,3-Diol Precursors in the Synthesis of Natural Products

1,3-Diol motif is of particular interest due to its prominence within many classes of natural products. In this field, β,δ-diketo sulfoxides are specially attractive because both syn- and anti-1,3-diols can be prepared from these key compounds by two successive high diastereoselective reductions of both carbonyls. Thus, β-carbonyl reduction requires DIBAL-H or the ZnX2/DIBAL-H system. The resulting stereochemistry of the corresponding hydroxyl is fully controlled by the chiral sulfoxide group. Then, the reduction of δ-carbonyl leads to syn or anti 1,3-diols depending on the hydride reagents employed and the stereoselectivity is directed by the newly formed β- hydroxylic center. In this paper, emphasis is given to the use of valuable β,δ-diketo sulfoxides in the total synthesis of selected natural products.

Reactivity and catalytic activity of tert-butoxy-aluminium hydride reagents

The reactivity and catalytic activities of the tert-butoxy aluminium hydride reagents [((t)BuO)xAlH3-x] [x = 1 (1), 2 (2)] and (L)Li[((t)BuO)2AlH2] [L = THF (3), 1,4-dioxane (4)] are investigated. The structural characterisation of the novel compounds 3 and 4 shows that the nature of the hydridic species present is affected dramatically by the donor ligand coordinating the Li(+) cation. Stoichiometric reaction of 1 with pyridine gives [(1,4-H-pyrid-1-yl)4Al](-)[(pyridine)4AlH2](+) (5) while reaction with the amine-borane Me2NHBH3 in the presence of PMDETA [(Me2NCH2CH2)2NMe] affords [(PMDETA)AlH2](+)[(BH3)2NMe2](-) (6). The reagents 1-4 catalyse the dehydrocoupling reaction of the amine-borane Me2NHBH3 into the ring compound [Me2NBH2]2, with the activity decreasing in the order 1≫2∼3 > 4. The greater reactivity of the neutral dihydride 1 provides the potential basis for future catalytic optimisation.

Synthesis, Characterization, and Reactions of Ruthenium(II), -(III), and -(IV) Complexes with Sterically Demanding 1,2,4-Tri-tert-butylcyclopentadienyl Ligands

The reaction of RuCl3·3H2O with 1,3,5-C5(tBu)3H3 afforded a dimeric Ru(III) dichloride complex, [Cp‡RuCl(μ-Cl)]2 (1b; Cp‡ = η5-1,2,4-C5(tBu)3H2). The treatment of 1b with gaseous oxygen afforded the tetravalent ruthenium μ-oxo complex [Cp‡RuCl2]2(μ-O) (2b). The treatment of 2b with a primary or secondary alcohol regenerated 1b with concomitant dehydrogenative oxidation of the alcohol to afford the corresponding aldehyde or ketone, respectively. The treatment of 2b with refluxing 2-propanol or an excess of zinc powder in tetrahydrofuran efficiently afforded a novel dimeric Ru(II) monochloride with a butterfly structure, [Cp‡Ru(μ-Cl)]2 (4), with unsaturated ruthenium centers and high reactivity toward electron-donating reagents. The reaction of 1b with 4 afforded the mixed-valence Ru(III)/Ru(II) complex Cp‡Ru(μ-Cl)3RuCp‡ (7). The treatment of the appropriate precursor 1b or 2b with an excess of a hydride reagent such as LiEt3BH or LiAlH4 afforded the novel dinuclear ruthenium tetrahydride-bridged complex Cp‡Ru(μ-H)4RuCp‡ (9b). The treatment of a mixture of [Cp*Ru(μ3-Cl)]4 and 4 with LiEt3BH afforded the analogous dinuclear ruthenium tetrahydride-bridged complex bearing Cp* (Cp* = η5-C5Me5) and Cp‡ ligands, Cp*Ru(μ-H)4RuCp‡ (9c). The molecular structures of the newly synthesized complexes 1b, 2b, 4, 7, 8b, and 9b,c were determined by X-ray diffraction (XRD) studies. The reaction of 9b with ethylene exclusively afforded a μ-ethylidyne μ-ethylidene complex, Cp‡Ru(μ-CCH3)(μ-CHCH3)(μ-H)RuCp‡ (11), whereas the reaction of 9a with excess ethylene selectively afforded a dinuclear ruthenium diviny ethylene complex, Cp*Ru(μ-CHCH2)2(CH2CH2)RuCp* (10). The difference in the reactivities can be attributed to the difference in the spatial size of the reaction sites rather than their electronic properties such as electron density at the ruthenium centers. Irradiation of 11 with UV light (365 nm) effectively afforded a bis(μ-ethylidyne) complex, Cp‡Ru(μ-CCH3)2RuCp‡ (12). The structures of 11 and 12 were also determined by XRD studies.

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.

New N-substituted sulfinamides of neomenthane series

A reaction of neomenthanethiol with ammonia and N-chlorosuccinimide with subsequent addition of aromatic aldehydes leads to chiral N-arylideneneomenthylsulfenimines, whose oxidation at the sulfur atom gives N-arylideneneomenthylsulfinimines. The reactions of N-arylideneneomenthylsulfinimines with lithium aluminum hydride or Grignard reagents proceed at the imine fragment and lead to the corresponding N-benzylneomenthylsulfinamides.

Copper Acetoacetonate [Cu(acac)2]/BINAP‐Promoted Csp3N Bond Formation via Reductive Coupling of N‐Tosylhydrazones with Anilines

AbstractWe report the the copper(II) acetoacetonate [Cu(acac)2]/BINAP‐catalyzed synthesis of arylamines from N‐tosylhydrazones and anilines. A fine tuning of the reaction conditions was required to accomplish the cross‐coupling successfully, including the ligands effect and the addition of small amounts of water. The characteristic feature of this protocol is its functional group compatibility and its chemoselectivity when various aminophenol derivatives were used. Taking into consideration the interest for this copper‐reductive coupling in which no stoichiometric metal hydride reagent is employed, this can be considered as an alternative to the conventional reductive amination.magnified image

Direct Nucleophilic Addition to N‐Alkoxyamides

While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long-standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N-alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N-alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N-alkoxy group formed a five-membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL-H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter- and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α-trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five- and six-membered lactams, and macrolactams.

ChemInform Abstract: Catalytic Reductive Transformations of Carboxylic and Carbonic Acid Derivatives Using Molecular Hydrogen

AbstractReview: 227 refs.

Catalytic Reductive Transformations of Carboxylic and Carbonic Acid Derivatives Using Molecular Hydrogen

A comprehensive overview on homogeneous catalytic hydrogenation of carboxylic acids and its derivatives as well as carbonic acid derivatives with transition metal-based molecular catalysts is described. Despite the tremendous potential in the hydrogenation of these less electrophilic carbonyl compounds using molecular hydrogen in synthetic organic chemistry, their reduction still relies mostly on the stoichiometric use of metal hydride reagents, such as LiAlH4, NaBH4, and their derivatives. For the past decade, a significant and rapid progress in particularly ester hydrogenation has been achieved by utilization of conceptually new bifunctional molecular catalysts originating from the metal–ligand cooperation effects. The bifunctional-catalyst-promoted hydrogenation using molecular hydrogen is now realized to be a practical tool in synthetic organic chemistry in both academia and industry. The industrial outlook for the present hydrogenation is bright because of its operational simplicity, scope, economic viability, and growing awareness of the need for green chemistry.