Hydride Source Research Articles

Germanium Hydride Catalyzed Selective Hydroboration and Cyanosilylation of Ketones

AbstractTwo new examples of β‐diketiminate or NacNac analogues, i. e., conjugated bis‐guanidinate (CBG) stabilized low valent germanium chloride (1) and germanium hydride (2) complexes, are reported. Deprotonation of LH upon treatment with n‐BuLi and an in situ generated LLi further treated with GeCl2⋅dioxane afforded LGeCl in 79 % yield. Compound 1 reacted with hydride source NaHBEt3 in toluene, afforded Ge (II) hydride (2) in 76 % yield. Both compounds 1 and 2 were characterized by NMR and mass spectroscopic methods. Further, germanium hydride catalyzed hydroboration and cyanosilylation of a wide range of ketones have been investigated. Control reactions suggest hydroboration reactions occurred via insertion and Ge−O/B−H bond metathesis pathways. It is worthy of mentioning that, in the case of hydroboration of ketones, reducible groups such as alkene, alkyne, halide, ester, nitro, and heterocycles were untouched. Furthermore, compound 2 was employed for the reduction of carbonate, formate, and anhydride substrates via the hydroboration technique.

Iridium(triNHC)-Catalyzed Transfer Hydrogenation of Glycerol Carbonate without Exogenous Reductants

The iridium(Ir) (triNHC = tri-N-heterocyclic carbene)-catalyzed transfer hydrogenation of glycerol carbonate (GC) is described in the absence of additional hydride sources. The described reduction provides a sustainable route to produce industrially-valuable formate and lactate with high turnover numbers (TONs). The bimetallic Ir(I) involving triNHC carbene ligands exhibits high TONs, and the reaction mechanism, including the bimetallic Ir(triNHC) catalyst, is proposed based on mechanistic studies.

The Influence of Silane Steric Bulk on the Formation and Dynamic Behavior of Silyl Palladium Hydrides

Silanes play a versatile role in catalytic transformations, acting as hydride sources, transmetalation reagents, and starting materials in the synthesis of highly valued organosilicon compounds and polymers. Their use in catalysis with palladium is widespread, commonly proposed to proceed via oxidative addition of Si–H to Pd(0); however, little is known about this fundamental reaction. Here, we show that the formation of silyl palladium hydride complexes (dcpe)PdH(SiR3), which exist in equilibrium with starting materials [(μ-dcpe)Pd]2 (dcpe = dicyclohexyl(phosphino)ethane) and tertiary silanes HSiR3 in solution, is dependent on the steric profile of the silanes employed. A lower Keq is observed with increasing steric encumbrance at silicon, correlating well with each substituent’s Charton value, and van’t Hoff analyses show the reaction with sterically congested silanes to be less thermodynamically favorable. Variable temperature kinetics studies likewise reveal a preference for unhindered silanes as determined by Charton and Eyring analyses. On the other hand, the intramolecular ligand exchange of H/SiR3 on the formed complexes is unaffected by silane steric bulk. Together, the energetic parameters derived for each of these steps reveal that thermodynamic factors are primarily responsible for favoring (silyl)Pd(H) formation with less sterically bulky silanes. These results present the first systematic study on the role of silane steric effects in oxidative addition of Si–H to Pd(0) and help to inform organosilicon chemistry with late transition metals.

Iron-Catalyzed H/D Exchange of Primary Silanes, Secondary Silanes, and Tertiary Siloxanes.

A synthetic study into the catalytic hydrogen/deuterium (H/D) exchange of 1° silanes, 2° silanes, and 3° siloxanes is presented, facilitated by iron-β-diketiminato complexes (1a and 1b). Near-complete H/D exchange is observed for a variety of aryl- and alkyl-containing hydrosilanes and hydrosiloxanes. The reaction tolerates alternative hydride source pinacolborane (HBpin), with quantitative H/D exchange. A synthetic and density functional theory (DFT) investigation suggests that a monomeric iron-deuteride is responsible for the H/D exchange.

Sustainable Production of Reduced Phosphorus Compounds: Mechanochemical Hydride Phosphorylation Using Condensed Phosphates as a Route to Phosphite.

In pursuit of a more sustainable production of phosphorous acid (H3PO3), a versatile chemical with phosphorus in the +3 oxidation state, we herein report that condensed phosphates can be employed to phosphorylate hydride reagents under solvent-free mechanochemical conditions to furnish phosphite (HPO32–). Using potassium hydride as the hydride source, sodium trimetaphosphate (Na3P3O9), triphosphate (Na5P3O10), pyrophosphate (Na4P2O7), fluorophosphate (Na2PO3F), and polyphosphate (“(NaPO3)n”) engendered phosphite in optimized yields of 44, 58, 44, 84, and 55% based on total P content, respectively. Formation of overreduced products including hypophosphite (H2PO2–) was identified as a competing process, and mechanistic investigations revealed that hydride attack on in-situ-generated phosphorylated phosphite species is a potent pathway for overreduction. The phosphite generated from our method was easily isolated in the form of barium phosphite, a useful intermediate for production of phosphorous acid. This method circumvents the need to pass through white phosphorus (P4) as a high-energy intermediate and mitigates involvement of environmentally hazardous chemicals. A bioproduced polyphosphate was found to be a viable starting material for the production of phosphite. These results demonstrate the possibility of accessing reduced phosphorus compounds in a more sustainable manner and, more importantly, a means to close the modern phosphorus cycle.

Hexamethyldisilazane Lithium (LiHMDS)-Promoted Hydroboration of Alkynes and Alkenes with Pinacolborane.

Lithium-promoted hydroboration of alkynes and alkenes using commercially available hexamethyldisilazane lithium as a precatalyst and HBpin as a hydride source has been developed. This method will be appealing for organic synthesis because of its remarkable substrate tolerance and good yields. Mechanistic studies revealed that the hydroboration proceeds through the in situ-formed BH3 species, which acts to drive the turnover of the hydroboration of alkynes and alkenes.

Nickel-Catalyzed anti-Markovnikov Hydrodifluoroalkylation of Unactivated Alkenes.

An efficient Ni-catalyzed hydrodifluoroalkylation of unactivated alkenes with bromodifluoroacetate by using PhSiH3 as hydride source was developed. The transformation affords aliphatic difluorides with anti-Markovnikov regioselectivity. A wide range of highly remote alkenes, simple alkenes, drug molecules, commercially available CF2 precursors, and even nonfluorinated substrates are competent in this reaction under mild conditions, demonstrating the practicability of the strategy. Moreover, mechanistic studies indicated that the difluoroalkyl radical might be a key intermediate to this transformation.

Multifunctional Catalytic Properties of Pd/CNT Catalysts for 4‐Nitrophenol Reduction

AbstractCarbon nanotubes are arousing real interest in catalysis, either as catalyst support or as catalyst itself. In this work, the influence of CNT doping (O, N, S) on the catalytic performance of CNT and Pd/CNT catalysts have been investigated in the reduction of 4‐nitrophenol both under H2 or using NaBH4 as a hydride source. The morphology, composition, particle size and crystallinity of the materials were investigated by various techniques including HRTEM, STEM, XPS, Raman spectroscopy and XRD. Among the CNT carbocatalysts, only N‐CNT is active for 4‐nitrophenol reduction at room temperature, and only in the presence of NaBH4. As far as supported Pd catalysts are concerned, the nature of the support influences the Pd nanoparticle location (confinement), the Pd nanoparticles/Pd single atoms ratio and the extent of H‐spillover, three catalyst features that directly affect the catalytic activity. The best combination of Pd nanoparticles/Pd single atoms ratio, H‐spillover and confinement for 4‐nitrophenol reduction using NaBH4, is found in Pd/O‐CNT catalysts, while for reactions performed under H2, Pd/N‐CNT presents the best combination.

Density functional theory investigation of Ru(II) and Os(II) asymmetric transfer hydrogenation catalysts.

Transition metal ions have a unique ability to organise and control the steric and electronic effects around a substrate in the active site of a catalyst. We consider half-sandwich Ru(II) (Noyori-type) and Os(II) sulfonyldiamine 16-electron active catalysts [Ru/Os(η6-p-cymene)(TsDPEN-H2)], where TsDPEN is N-tosyl-1,2-diphenylethylenediamine containing S,S or R,R chiral centres, which catalyse the highly efficient asymmetric transfer hydrogenation of aromatic ketones to chiral alcohols using formic acid as a hydride source. We discuss the recognition of the prochiral ketone acetophenone by the catalyst, the protonation of a ligand NH and transfer of hydride from formate to the metal, subsequent transfer of hydride to one enantiotopic face of the ketone, followed by proton transfer from metal-bound NH2, and regeneration of the catalyst. Our DFT calculations illustrate the role of the two chiral carbons on the N,N-chelated sulfonyldiamine ligand, the axial chirality of the π-bonded p-cymene arene, and the chirality of the metal centre. We discuss new features of the mechanism, including how a change in metal chirality of the hydride intermediate dramatically switches p-cymene coordination from η6 to η2. Moreover, the calculations suggest a step-wise mechanism involving substrate docking to the bound amine NH2 followed by hydride transfer prior to protonation of the O-atom of acetophenone and release of the enantio-pure alcohol. This implies that formation and stability of the M-H hydride intermediate is highly dependent on the presence of the protonated amine ligand. The Os(II) catalyst is more stable than the Ru(II) analogue, and these studies illustrate the subtle differences in mechanistic behaviour between these 4d6 and 5d6 second-row and third-row transition metal congeners in group 8 of the periodic table.

A cascade reaction of indolyl-migratory isocyanide insertion, scaffold rearrangement and redox-neutral event with isocyanide as a C(sp3)H-N synthon efficiently constructs indolylisoindolinones.

Herein, we report a Pd(0)-catalyzed cascade reaction of intramolecular indolyl isocyanide-insertion, isocyanide-initiated scaffold-rearrangement with indolyl migration and redox-neutral process, which affords an efficient access to indolylisoindolinones. Isocyanide as a C(sp3)H-N synthon and the alkyl motif of isocyanide as a hydride source have been explored for the first time.

Synthesis and characterization of rare-earth metallate amido complexes bearing the 2-amidate-functionalized indolyl ligand and their application in the hydroboration of esters with pinacolborane.

The reactions of 2-amidate-functionalized indolyl proligand 2-(2,6-iPr2C6H3NHCO)C8H5NH (H2L) with [(Me3Si)2N]3RE(μ-Cl)Li(THF)3 were studied leading to the synthesis and characterization of a series of novel discrete trinuclear rare-earth metallate amido complexes containing the anion [{η1:(μ2-η1:η1):η1-LREN(SiMe3)2}3(μ3-Cl)]- and cation Li+(THF)4 (RE = Y(1a), Nd (1b), Sm (1c), Gd (1d), Dy (1e), Er (1f), and Yb (1g)) in good yields by silylamine elimination. All of the complexes were characterized by spectroscopic methods, elemental analyses and single-crystal X-ray diffraction, and complexes 1a and 1c were additionally characterized by NMR spectroscopy. As proof of principle of their activity, these complexes were used as precatalysts for the hydroboration of esters using HBpin as the hydride source displaying high activity under neat and room temperature conditions. As a result, the ligand, ionic and multinuclear cooperative effects on catalytic activity were observed.

Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes.

Despite the enormous developments in asymmetric catalysis, the basis for asymmetric induction is largely limited to the spatial interaction between the substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between two aryl groups without a directing group or electronic manipulation. Here we address this challenge by using a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With versatile 2-indole imine methide as the platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π–π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.

Iron(0) tricarbonyl η4-1-azadiene complexes and their catalytic performance in the hydroboration of ketones, aldehydes and aldiminesviaa non-iron hydride pathway

Six iron(0) tricarbonyl complexes (1a-f) with a η4-1-azadiene moiety were prepared and their performance in the hydroboration of unsaturated organic compounds was investigated. All the complexes exhibit catalytic activity towards hydroboration of ketones, aldehydes and aldimines with pinacolborane (HBpin) as a hydride source to lead to secondary alcohols, primary alcohols, and secondary amines, respectively, after hydrolysis of the hydroboration products. Of the iron(0) tricarbonyl complexes, complex 1e is the most robust one and was employed throughout the catalytic investigation. Its preference towards the three types of substrates is as follows: aldimines > aldehydes ≫ ketones. In total, 24 substrates were examined for the catalytic hydroboration reactivity and generally, isolation yields ranging from 40% to 95% were achieved. Mechanistic investigation suggests that the catalytic hydroboration of the substrates proceeds via intramolecular hydride transfer without going through an Fe-H intermediate. As indicated by 1H NMR spectroscopic monitoring, the substrates and the borane agent bind to the iron centre and the imine N atom, respectively, which facilitates the hydride transfer by activating the B-H bond and polarizing the double bond of the substrates.

Nickel-Catalyzed Enantioselective Hydroboration of Vinylarenes.

The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.

Regioselective Hydroalkylation of Vinylarenes by Cooperative Cu and Ni Catalysis

AbstractDisclosed here is a dual copper and nickel catalytic system with a silyl hydride source for promoting the linear selective hydroalkylation of vinylarenes. This carbon–carbon bond‐forming protocol is applied to couple a variety of functionalized vinylarenes with alkyl halides applying a nickel(II) NNN pincer complex in the presence of an NHC‐ligated copper catalyst. This combination allows for a 1 mol % loading of the nickel catalyst leading to turnover numbers of up to 72. Over 40 examples are presented, including applications for pharmaceutical diversification. Labeling experiments demonstrated the regioselectivity of the reaction and revealed that the copper catalyst plays a crucial role in enhancing the rate for formation of the reactive linear alkyl nickel complex. Overall, the presented work provides a complimentary approach for hydroalkylation reactions, whilst providing a preliminary mechanistic understanding of the cooperativity between the copper and nickel complexes.

Regioselective Hydroalkylation of Vinylarenes by Cooperative Cu and Ni Catalysis.

Disclosed here is a dual copper and nickel catalytic system with a silyl hydride source for promoting the linear selective hydroalkylation of vinylarenes. This carbon-carbon bond-forming protocol is applied to couple a variety of functionalized vinylarenes with alkyl halides applying a nickel(II) NNN pincer complex in the presence of an NHC-ligated copper catalyst. This combination allows for a 1 mol % loading of the nickel catalyst leading to turnover numbers of up to 72. Over 40 examples are presented, including applications for pharmaceutical diversification. Labeling experiments demonstrated the regioselectivity of the reaction and revealed that the copper catalyst plays a crucial role in enhancing the rate for formation of the reactive linear alkyl nickel complex. Overall, the presented work provides a complimentary approach for hydroalkylation reactions, whilst providing a preliminary mechanistic understanding of the cooperativity between the copper and nickel complexes.

Precatalyst‐Enabled Selectivity: Enantioselective NiH‐Catalyzed anti‐Hydrometalative Cyclization of Alkynones to Endo‐ and Heterocyclic Allylic Alcohols

AbstractA highly enantioselective NiH‐catalyzed hydrocyclization of alkynones with unparalleled anti‐ and endocyclic selectivities is described. The choice of the precatalysts has significant influence in tuning the regio‐ and enantioselectivity. Using Ni(OTs)2/Phox as a precatalyst and (EtO)2MeSiH as a hydride source, an array of enantioenriched O‐, N‐, and S‐containing heterocyclic tertiary allylic alcohols are obtained in 24–81 % yields with 80:20–99:1 er. Mechanistic investigations and synthetic application are also carried out. This study represents an efficient access to a set of allylic alcohols that are unable to access by the state‐of‐the‐art coupling reactions.

Precatalyst-Enabled Selectivity: Enantioselective NiH-Catalyzed anti-Hydrometalative Cyclization of Alkynones to Endo- and Heterocyclic Allylic Alcohols.

A highly enantioselective NiH-catalyzed hydrocyclization of alkynones with unparalleled anti- and endocyclic selectivities is described. The choice of the precatalysts has significant influence in tuning the regio- and enantioselectivity. Using Ni(OTs)2 /Phox as a precatalyst and (EtO)2 MeSiH as a hydride source, an array of enantioenriched O-, N-, and S-containing heterocyclic tertiary allylic alcohols are obtained in 24-81 % yields with 80:20-99:1 er. Mechanistic investigations and synthetic application are also carried out. This study represents an efficient access to a set of allylic alcohols that are unable to access by the state-of-the-art coupling reactions.

Selective Reduction of Aromatic Alkynes Catalyzed by Palladium with Formic Acid as the Hydride Source

Background: Transfer hydrogenation methods that employ non-H2 hydrogen sources have evolved as an attractive alternative for conventional hydrogenation approaches. Objective: In this study, we aimed at developing optimized conditions to induce the selective transfer hydrogenation reduction of aromatic alkynes catalyzed by PdCl2(PPh3)2 and using formic acid as the hydride source. Methods: The effect of various reaction parameters, such as the nature and amount of the catalyst, the H-donor/base couple, reaction time and temperature, and the nature of the solvent on the outcome of the alkyne reduction were investigated. Results: The reduction of the alkyne can be chemoselectively controlled by adjusting the reaction conditions. Among the tested catalysts, PdCl2(PPh3)2 was the most suitable, with 2% of the catalyst being the optimal amount. While the reduction was successful in different solvents of different polarities, THF was selected as the solvent of choice. The reduction of diphenylacetylene yielded the alkene both at 50°C and 80°C. When testing the optimized conditions on the reduction of 4- phenyl-3-butyne-2-one, quantitative partial reduction to the corresponding α,β-unsaturated ketone was obtained at 50°C, while the saturated ketone was produced as the major product at 80°C. Conclusion: The chemoselective reduction of aromatic alkynes was performed successfully with complete conversion using 2% PdCl2(PPh3)2 as a catalyst, formic acid/NEt3 as the H-donor/base couple, THF as the solvent, at 50°C and 80°C.

Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines

Hydroalkylation, the direct addition of a C(sp3)–H bond across an olefin, is a desirable strategy to produce valuable, complex structural motifs in functional materials, pharmaceuticals, and natural products. Herein, we report a reliable method for accessing α-branched amines via nickel-catalyzed hydroalkylation reactions. Specifically, by using bis(cyclooctadiene)nickel (Ni(cod)2) together with a phosphine ligand, we achieved a formal C(sp3)–H bond insertion reaction between olefins and N-sulfonyl amines without the need for an external hydride source. The amine not only provides the alkyl motif but also delivers hydride to the olefin by means of a nickel-engaged β–hydride elimination/reductive elimination process. This method provides a platform for constructing chiral α-branched amines by using a P-chiral ligand, demonstrating its potential utility in organic synthesis. Notably, a sulfonamidyl boronate complex formed in situ under basic conditions promotes ring-opening of the azanickellacycle reaction intermediate, leading to a significant improvement of the catalytic efficiency.