Hydride Reduction Research Articles

Quick Access to Protoberberine and Tetrahydroprotoberberine Derivatives/Analogues with One-Pot Sequential Isochromenylium-Mediated Annulation.

A one-pot access to the protoberberine and tetrahydroprotoberberine scaffold has been developed from easily available primary amine-functionalized o-alkynylbenzaldehydes. The core skeleton of protoberberine was afforded via in situ generation of isochromenylium by Ag(I) catalysis, subsequent cyclization to isoquinolinium, and final hydride reduction by a continuous operation procedure. The newly developed step-economic protocol shows excellent regio- and stereoselectivity and is capable of achieving those previously unavailable derivatives/analogues with electron-deficient substituents, providing a robust tool for medicinal investigations of protoberberines and derivatives.

Zirconium Hydride Catalysis Initiated by Tetrabutylammonium Fluoride.

In our drug discovery campaigns to target the oncogenic drivers of cancers, the demand for a chemoselective, stereoselective and economical synthesis of chiral benzylamines drove the development of a catalytic zirconium hydride reduction. This methodology uses the inexpensive, bench stable zirconocene dichloride, and a novel tetrabutylammonium fluoride activation tactic to catalytically generate a metal hydride under ambient conditions. The diastereo- and chemoselectivity of this reaction was tested with the preparation of key intermediates from our discovery programs and in the scope of sulfinyl ketimines and carbonyls relevant to medicinal chemistry and natural product synthesis. A preliminary mechanistic investigation conducted into the role of tetrabutylammonium fluoride indicates that formation of a zirconocene fluoride occurs to initiate catalysis. The implications of this convenient activation approach may provide expanded roles for zirconium hydrides in catalytic transformations.

Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

Reduction of CO to Methanol with Recyclable Organic Hydrides.

The reaction steps for the selective conversion of a transition metal carbonyl complex to a hydroxymethyl complex that releases methanol upon irradiation with visible light have been successfully quantified in acetonitrile solution with dihydrobenzimidazole organic hydride reductants. Dihydrobenzimidazole reductants have been shown to be inactive toward H2 generation in the presence of a wide range of proton sources and have been regenerated electrochemically or photochemically. Specifically, the reaction of cis-[Ru(bpy)2(CO)2]2+ (bpy = 2,2'-bipyridine) with one equivalent of a dihydrobenzimidazole quantitatively yields a formyl complex, cis-[Ru(bpy)2(CO)(CHO)]+, and the corresponding benzimidazolium on a seconds time scale. Kinetic experiments revealed a first-order dependence on the benzimidazole hydride concentration and an unusually large kinetic isotope effect, inconsistent with direct hydride transfer and more likely to occur by an electron transfer-proton-coupled electron transfer (EΤ-PCET) or related mechanism. Further reduction/protonation of cis-[Ru(bpy)2(CO)(CHO)]+ with two equivalents of the organic hydride yields the hydroxymethyl complex cis-[Ru(bpy)2(CO)(CH2OH)]+. Visible light excitation of cis-[Ru(bpy)2(CO)(CH2OH)]+ in the presence of excess organic hydride was shown to yield free methanol. Identification and quantification of methanol as the sole CO reduction product was confirmed by 1H NMR spectroscopy and gas chromatography. The high selectivity and mild reaction conditions suggest a viable approach for methanol production from CO, and from CO2 through cascade catalysis, with renewable organic hydrides that bear similarities to Nature's NADPH/NADP+.

Electroreductive Synthesis of Nickel(0) Complexes**

AbstractOver the last fifty years, the use of nickel catalysts for facilitating organic transformations has skyrocketed. Nickel(0) sources act as useful precatalysts because they can enter a catalytic cycle through ligand exchange, without needing to undergo additional elementary steps. However, most Ni(0) precatalysts are synthesized with stoichiometric aluminum–hydride reductants, pyrophoric reagents that are not atom‐economical and must be used at cryogenic temperatures. Here, we demonstrate that Ni(II) salts can be reduced on preparative scale using electrolysis to yield a variety of Ni(0) and Ni(II) complexes that are widely used as precatalysts in organic synthesis, including bis(1,5‐cyclooctadiene)nickel(0) [Ni(COD)2]. This method overcomes the reproducibility issues of previously reported methods by standardizing the procedure, such that it can be performed anywhere in a robust manner. It can be transitioned to large scale through an electrochemical recirculating flow process and extended to an in situ reduction protocol to generate catalytic amounts of Ni(0) for organic transformations. We anticipate that this work will accelerate adoption of preparative electrochemistry for the synthesis of low‐valent organometallic complexes in academia and industry.

Reduction Performance and Mechanism of Liquid Terminated-Carboxyl Fluoroelastomers Using Unitary or Binary Metal Hydride Reduction Systems

Reduction Performance and Mechanism of Liquid Terminated-Carboxyl Fluoroelastomers Using Unitary or Binary Metal Hydride Reduction Systems

Electron and hydrogen atom donor photocatalysts in situ generated from benzimidazolium salts and hydride reagents

Photocatalytic systems consisting of 2-substituted benzimidazoliums (BI+–R, R = polycyclic aryl, triarylamine or phenyl-sulfate) and stoichiometric hydride donor reagents were developed. Light emitting diode irradiation of these photocatalysts in the presence of NaBH4 or picoline borane promotes desulfonylation reactions of an N-sulfonyl indole, N-sulfonyl amide and α-sulfonyl ketone. Absorption spectroscopic and redox potential measurements as well as density functional theory calculations were carried out to gain mechanistic information. Benzimidazolines (BIH–R), generated in situ by hydride reduction of BI+–R, serve as both an electron and hydrogen atom donor photocatalysts in these reductive desulfonylation reactions, which contrasts to ordinary reducing photocatalysts that simply donate electrons.

Topotactic Transition: A Promising Opportunity for Creating New Oxides

AbstractTopotactic transition is a structural phase change in a matrix crystal lattice mediated by the ordered loss/gain and rearrangement of atoms, leading to unusual coordination environments and metal atoms with rare valent states. As early as in 1990s, low temperature hydride reduction is utilized to realize the topotactic transition. Since then, topological transformations are developed via multiple approaches. Especially, the recent discovery of the Ni‐based superconductivity in infinite‐layer nickelates has greatly boosted the topotactic transition mean to synthesizing new oxides for exploring exotic functional properties. In this review, a detailed and generalized introduction is provided to oxygen‐related topotactic transition. The main body of the review includes four parts: the structure‐facilitated effects, the mechanism of the topotactic transition, some examples of topotactic transition methods adopted in different metal oxides (V, Mn, Fe, Co, Ni) and the related applications. This study is to provide timely and thorough strategies to successfully realize topotactic transitions for researchers who are eager to create new oxide phases or new oxide materials with desired functions.

Syntheses of Tetrahydropyran Type 8,7'-Neolignans Using a Ring-Expansion Reaction and Tetrahydrofuran Type 8,7'-Neolignans to Discover a Novel Phytotoxic Neolignan.

One novel tri-substituted tetrahydropyran type 8,7'-neolignan and its enantiomer with higher enantiomeric excess were synthesized from all cis-tetra-substituted tetrahydrofuran with an iodomethyl group by a hydride or H2 ring-expansion reaction. The normal hydride reductions of C-I bonds of tetra-substituted tetrahydrofurans bearing iodomethyl groups were observed in other 2,3-cis-stereoisomers of tetra-substituted tetrahydrofurans to give tetra-substituted tetrahydrofurans bearing 7,8-cis and 8,7'-neolignan structures. The phytotoxicities of their synthesized compounds were compared with previously synthesized 7,8-trans-8,7'-neolignans bearing tetra-substituted tetrahydrofurans to find out the highest phytotoxic tri-substituted tetrahydropyran type 8,7'-neolignan.

On the Structure–Odor Correlation of Muguet Aldehydes: Synthesis of 3‐(4’‐Isobutyl‐2’‐methylphenyl)propanal (Nympheal) and Four Novel Derivatives from a Hagemann’s Ester

AbstractLilybelle and Biomuguet are currently the only renewable and biodegradable non‐spermotoxic Lilial replacers. Being non‐aromatic, these lack however some of the green, aquatic aspects of Lilial that are present in the captive odorant Nympheal, 3‐(4‐isobutyl‐2‐methylphenyl)propanal, which is not available from renewable resources. Therefore, the influence of the aromatic nucleus on the odor of four new hydrogenated Nympheal derivatives was investigated, which were all accessible from the isobutyl Hagemann’s ester that was synthesized in 75 % yield from isovaleraldehyde with two equivalents of ethyl acetoacetate. The respective Hagemann’s ester was alkylated with 3‐bromopropanal dimethyl acetal and subjected to decarboxylative saponification, followed by hydride reduction and dehydration through the corresponding mesylate to furnish, after deprotection with formic acid, the corresponding exo‐ and endo‐dihydro‐Nympheal derivative. Full or partial hydrogenation of the central acetal‐protected intermediate provided after deprotection the analogous fully saturated analogue or the cyclohexene derivative. The olfactory properties of these four novel Nympheal derivatives are discussed and rationalized by computational olfactophore models.

An Enantiospecific Synthesis of 5-epi-α-Bulnesene.

As a result of its unique fragrance and wider role in traditional medicine, agarwood produced in Aquilaria spp. and certain other trees has been harvested to near extinction as a natural phenomenon. Artificially induced agarwood production in Aquilaria plantations has sated some of the demand although the product quality is variable. Synthetic chemistry may have a role to play in providing sustainable routes to many of the fragrant components identified in agarwood and its smoke when burnt as incense. In this work, we report efforts towards a total synthesis of the guaiane sesquiterpene α-bulnesene, which is found, along with its more fragrant oxidised derivatives, in agarwood. Following the ring-expansion of (R)-carvone using reported procedures, α-butenylation gave a substrate for samarium diiodide mediated reductive cyclisation, the two butenyl epimers of the substrate each leading to a single bicyclic alcohol (24 and 25). Overall homoconjugate hydride reduction of one of these alcohols was achieved by Lewis acid-mediated ionisation and then hydride transfer from triethylsilane to complete an overall seven-step synthesis of 5-epi-α-bulnesene. This new synthesis paves the way for short routes to both α-bulnesene enantiomers and a study of their aerial and enzymatic oxidation products.

Quantitative evaluation of perfluorinated alkanethiol molecular order on gold surfaces.

Self-assembled monolayers (SAMs) of perfluoroalkanethiols [CF3(CF2)xCH2CH2SH (x = 3, 5, 7, and 9)] on gold were characterized by x-ray photoelectron spectroscopy (XPS), near edge x-ray absorption fine structure (NEXAFS), and static time-of-flight secondary ion mass spectrometry (ToF-SIMS). Perfluoroalkanethiols of several chain lengths were synthesized using a known hydride reduction method for transforming commercially available perfluoroalkyliodides to corresponding perfluoroalkanethiols. This strategy provides improved product yields compared to other known routes based on hydrolysis from the common thioacetyl perfluoroalkyl intermediate. Angle-dependent XPS analysis revealed that CF3(CF2)xCH2CH2SH (x = 5, 7, and 9; F6, F8, and F10, respectively) SAMs on gold exhibited significant enrichment of the terminal CF3 group at the outer monolayer surface with the sulfur present as a metal-bound thiolate located at the monolayer-gold interface. XPS of the CF3(CF2)3CH2CH2SH (F4) monolayer revealed a thin film with a significant (>50%) amount of hydrocarbon contamination consistent with poorly organized monolayers, while the longest thiol (F10) showed XPS signals attributed to substantial ordering and anisotropy. ToF-SIMS spectra from all four SAMs contained molecular ions representative of the particular perfluorinated thiol used to prepare the monolayer. NEXAFS methods were used to determine degrees of ordering and average tilt for molecules comprising monolayers. The SAMs prepared from the longest (F10) thiols exhibited the highest degree of ordering with the molecular axis nearly perpendicular to the gold surface. The degree of ordering decreased significantly with decreasing length of the perfluorocarbon tail.

Thermodynamics Evaluation of Selective Hydride Reduction for α,β-Unsaturated Carbonyl Compounds

The selective reduction of α,β-unsaturated carbonyl compounds is one of the core reactions and also a difficult task for organic synthesis. We have been attempting to study the thermodynamic data of these compounds to create a theoretical basis for organic synthesis and computational chemistry. By electrochemical measurement method and titration calorimetry, in acetonitrile at 298 K, the hydride affinity of two types of unsaturated bonds in α,β-unsaturated carbonyl compounds, their single-electron reduction potential, and the single-electron reduction potential of the corresponding radical intermediate are determined. Their hydrogen atom affinity, along with the hydrogen atom affinity and proton affinity of the corresponding radical anion, is also derived separately based on thermodynamic cycles. The above data are used to establish the corresponding "Molecule ID Card" (Molecule identity card) and analyze the reduction mechanism of unsaturated carbonyl compounds. Primarily, the mixture of any carbonyl hydride ions and Ac-tempo+ will stimulate hydride transfer process and create corresponding α,β-unsaturated carbonyl compounds and Ac-tempoH from a thermodynamic point of view.

Bioinspired Formal Synthesis of Pancracine via Selective Hydro­genation of an Indole Derivative

AbstractA bioinspired formal synthesis of the montanine-type Amaryllidaceae alkaloid pancracine through selective hydrogenation of a 3-arylindole derivative is disclosed. The key features of this synthesis include a hexahydroindole synthesis by a chemoselective hydrogenation of an aryl-substituted indole and a diastereoselective silyl hydride reduction of an iminium intermediate generated from an enaminone through Tf2O activation. The eight-step assembly of the 5,11-methanomorphanthridine framework represents a novel and efficient strategy that permits one of the shortest syntheses of pancracine reported so far.

Asymmetric Binary Acid Catalysis: Switchable Enantioselectivity in Enantioselective Conjugate Hydride Reduction.

The exchange of the metal ion from Zr(IV) to Fe(III) leads to a switch in the enantioselectivity of binary acid-catalyzed conjugate hydride reductions. In the presence of Hantzsch ester, γ-indolyl β,γ-unsaturated α-keto esters could be reduced to the desired (S)- or (R)-products, respectively, with good to excellent enantioselectivity (up to 98% ee).

Catalytic Asymmetric Synthesis of C-Chiral Phosphonates

The current review is devoted to the achievements in the development of methods for the catalytic asymmetric synthesis of phosphonates containing a chiral center in the side chain. C-chiral phosphonates are widely represented among natural compounds with various biological activities as insecticides, herbicides, antibiotics, and bioregulators. Synthetic representatives of this class have found practical application as biologically active compounds. The review summarizes methods of asymmetric metal complex catalysis and organocatalysis as applied to such reactions as phospha-aldol reaction, two-component and three-component phospha-Mannich reaction, phospha-Michael reaction, as well as hydrogenation of unsaturated phosphonates and phosphine oxides, ketophosphonates, and iminophosphonates. Methods for the asymmetric hydride reduction of C=X phosphonates (X=O, S, NR) are also discussed in detail. The review presents updated literature reports, as well as original research by the author.

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics.

In this work, the pKa values of 69 polar alkanes (YH2) in acetonitrile were computed using the method developed by Luo and Zhang in 2020, and representative 69 thermodynamic network cards on 22 elementary steps of YH2 and related polar alkenes (Y) releasing or accepting H2 were naturally established. Potential electron reductants (YH-), hydride reductants (YH-), antioxidants (YH2 and YH-), and hydrogen molecule reductants (YH2) are unexpectedly discovered according to thermodynamic network cards. It is also found that there are great differences between YH2 and common hydrogen molecule reductants (XH2), such as Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydro-phenanthridine (PH2), releasing two hydrogen ions to unsaturated compounds. During the hydrogenation process, XH2 release hydrides first, then the oxidation state XH+ release protons. However, in the case of YH2, YH2 release protons first, then YH- release hydrides. It is the differences on acidic properties of YH2 and XH2 that result in the behavioral and thermodynamic differences on YH2 and XH2 releasing two hydrogen ions (H--H+). The redox mechanisms and behaviors of Y, YH-, and YH2 as electron, hydrogen atom, hydride, and hydrogen molecule donors or acceptors in the chemical reaction are reasonably investigated and discussed in this paper using thermodynamics.

Researches on Photofunctional and Photocatalytic Chemistry of Metal Complexes as Core Materials

We found the following new photochemical reactions and photophysical properties of transition metal complexes: (1) photochemical formation of Ru(II) hydride complexes, (2) photochemical ligand substitution reactions of the Re(I)diiminetricarbonyl complexes, and (3) control of photophysical and electrochemical properties of metal complexes by introducing p-p interaction between ligands. Application of these reactions and photophysical properties of transition metal complexes enabled us to synthesize new photofunctional metal-complex oligomers and polymers， and to develop efficient， durable， and highly selective photocatalysts for hydride reduction of NAD(P)+ models and CO2 reduction. We also succeeded construction of new photofunctional hybrids of the metal-complex photocatalysts with various solid materials， i.e. semiconductor-particle photocatalysts， p-type semiconductor electrodes， and mesoporous organosilica， which can drive photocatalytic reduction of CO2 via Z-scheme electron transfer， photocatalytic CO2 reduction by using water as a reductant and visible light as energy， and lightenergy accumulation for photocatalytic CO2 reduction， respectively.

Iminium-substituted 2,3-dihydroisoxazoles: synthesis from acetylenic iminium salts and nitrones, and some transformations

Abstract Iminium-functionalized 2,3-dihydroisoxazoles (4-isoxazolines) were prepared in high yields by [3+2] cycloaddition of N-methyl-C-phenylnitrone and acetylenic iminium salts. Conversion of the very hygroscopic cycloadducts into neutral compounds was achieved by hydrolysis or hydride reduction of the iminium functional group. By a thermal rearrangement, the cycloadducts were converted into 2,3-dihydro-1H-imidazolium salts. With C,N-diphenylnitrone as the reaction partner, the expected cycloadduct, a [(2,3-dihydroisoxazol-4-yl)-1-(phenyl)methylene]-N,N-dimethylammonium triflate, could be prepared at −75°C and was characterized by NMR. This product was found to be thermally unstable above −30°C, being converted into an inseparable product mixture. Basic hydrolysis of this mixture afforded a structurally interesting acyclic enaminone/half-aminal, which is likely derived from a 2,3-dihydro-1,3-oxazole.

Kinetic Control of Anion Stoichiometry in Hexagonal BaTiO3

The cubic oxyhydride perovskite BaTiO3−xHx, where the well-known ferroelectric oxide BaTiO3 is partially hydridized, exhibits a variety of functions such as being a catalyst and precursor for the synthesis of mixed-anion compounds by utilizing the labile nature of hydride anions. In this study, we present a hexagonal version, BaTi(O3−xHx) (x < 0.6) with the 6H-type structure, synthesized by a topochemical reaction using hydride reduction, unlike reported hexagonal oxyhydrides obtained under high pressure. The conversion of cubic BaTiO3 (150 nm) to the hexagonal phase by heat treatment at low temperature (950~1025 °C) using a Mg getter allows the introduction of large oxygen defects (BaTiO3−x; x − 0.28) while preventing the crystal growth of hexagonal BaTiO3, which has been accessible at high temperatures of ~1500 °C, contributing to the increase of the hydrogen content. Hydride anions in 6H-BaTiO3−xHx preferentially occupy face-sharing sites, as do other oxyhydrides.