Regioselective Hydrogenation Research Articles

Anchoring Frustrated Lewis Pair Active Sites on Copper Nanoclusters for Regioselective Hydrogenation.

In recent years, the concept of Frustrated Lewis Pairs (FLPs), which consist of a combination of Lewis acid (LA) and Lewis base (LB) active sites arranged in a suitable geometric configuration, has been widely utilized in homogeneous catalytic reactions. This concept has also been extended to solid supports such as zeolites, metal oxide surfaces, and metal/covalent organic frameworks, resulting in a diverse range of heterogeneous FLP catalysts that have demonstrated notable efficiency and recyclability in activating small molecules. This study presents the successful immobilization of FLP active sites onto the surface of ligand-stabilized copper nanoclusters with atomic precision, leading to the development of copper nanocluster FLP catalysts characterized by high reactivity, stability, and selectivity. Specifically, thiol ligands containing 2-methoxyl groups were strategically designed to stabilize the surface of [Cu34S7(RS)18(PPh3)4]2+ (where RSH = 2-methoxybenzenethiol), facilitating the formation of FLPs between the surface copper atoms (LA) and ligand oxygen atoms (LB). Experimental and theoretical investigations have demonstrated that these FLPs on the cluster surface can efficiently activate H2 through a heterolytic pathway, resulting in superior catalytic performance in the hydrogenation of alkenes under mild conditions. Notably, the intricate yet precise surface coordination structures of the cluster, reminiscent of enzyme catalysts, enable the hydrogenation process to proceed with nearly 100% selectivity. This research offers valuable insights into the design of FLP catalysts with enhanced activity and selectivity by leveraging surface/interface coordination chemistry of ligand-stabilized atomically precise metal nanoclusters.

Phosphine-Built-In Porous Organic Cage Supported Ultrafine Pd Nanoclusters Enable Highly Efficient and Regioselective Hydrogenation of Epoxides

Phosphine-Built-In Porous Organic Cage Supported Ultrafine Pd Nanoclusters Enable Highly Efficient and Regioselective Hydrogenation of Epoxides

Microwave-initiated Quick Synthesis of Magnetically-separable Ru/Ni@N-CNT Catalysts for Regioselective Hydrogenation of Quinoline

Microwave-initiated Quick Synthesis of Magnetically-separable Ru/Ni@N-CNT Catalysts for Regioselective Hydrogenation of Quinoline

Rigid confined space in frustrated Lewis pair/MOF catalyst: Highly regioselective reduction of α, β-unsaturated carbonyl compounds

The regioselective hydrogenation of α, β-unsaturated carbonyl compounds is an extremely important transformation. However, its development is hampered by a lack of precise and efficient catalysts. In this work, triggered by the steric hindrance and confinement capacity of the catalyst, we designed a novel catalyst FLP/MIL-101(Cr), with the bulky frustrated Lewis pair (FLP) of PPh3 and B(C6F5)3 immobilized in NH2-MIL-101(Cr). In the well-tailored FLP/MIL-101(Cr), the promoted selective reduction behaviors were realized, with cinnamyl alcohol selectivity up to 99 % and the complete substrate conversion in cinnamyl aldehyde reduction. Experimental characterizations and theoretical calculations indicated that the CN bond and π-π stacking interaction between FLP and the organic ligand of MIL-101(Cr) implemented and reinforced a rigid structure. Compared with homogeneous FLP, the special nano-space in FLP/MIL-101(Cr) catalyst benefits the selective reduction behavior towards the unsaturated bond with the smaller steric hindrance in α,β-unsaturated carbonyl compounds. As expected, FLP/MIL-101(Cr) showed good stabilities of skeleton structure and catalytic performance. This contribution provides an ingenious strategy to design FLP heterogeneous catalysts and represents its utilization possibility in selective reduction.

Investigation of the Biosynthetic Mechanism of Bipentaromycin Featuring an Unprecedented Cyclic Head-to-Tail Dimeric Scaffold.

Bipentaromycins are heterodimeric aromatic polyketides featuring two distinctive 5/6/6/6/5 pentacyclic ring systems and exhibit antibacterial activities. However, their overall biosynthetic mechanism, particularly the mechanism for early-stage modifications, such as hydrogenation and methylation, and late-stage dimerization, remains unknown. Herein, by integrating heterologous expression, isotope labeling, gene knockout and complementation, and computational modeling, we determined the biosynthetic origin of the skeleton, identified the enzymes involved in stereo-/regioselective hydrogenation and methylation, and provided new mechanistic insights into the dimerization. This work not only deciphers the biosynthetic mechanism of bipentaromycins but also provides new strategies for creating biologically active dimeric pharmacophores for drug discovery and development.

Single-palladium-atom catalyst nestled in nine-atom gold “bowl” for regioselective hydrogenation

Achieving the goal of “catalysts by design” has long been a major dream for chemists. In the September issue of Chem , Shen et al. describe the design of a single-atom catalyst (SAC) consisting of a single palladium atom nestled in a 9-atom gold bowl for achieving regioselective hydrogenation of dienes. Achieving the goal of “catalysts by design” has long been a major dream for chemists. In the September issue of Chem , Shen et al. describe the design of a single-atom catalyst (SAC) consisting of a single palladium atom nestled in a 9-atom gold bowl for achieving regioselective hydrogenation of dienes.

Regioselective hydrogenation of alkenes over atomically dispersed Pd sites on NHC-stabilized bimetallic nanoclusters

<h2>Summary</h2> A catalyst containing atomically dispersed Pd sites on N-heterocyclic carbene (NHC)-stabilized Au nanoclusters, with the precise formula of PdAu₉(NHC^Bn)₇X₂ (NHC^Bn is dibenzylbenzimidazolin-2-ylidene, X is Br or Cl), has been developed for the regioselective hydrogenation of alkenes. Each Pd site is encircled by an Au₉ ring protected by seven NHC and two halide ligands. Such an encirclement arrangement and open stereochemical framework endow the single Pd atom with the power to activate molecular hydrogen and catalyze the hydrogenation of alkenes efficiently. Interestingly, it otherwise exhibits much lower activity toward the crowded alkenes, owing to the inherent and highly stringent steric requirement of NHC ligands, as also visualized by the theory. As such, these clusters are demonstrated to be a highly efficient (653 h⁻¹ of turnover frequency) and highly selective (97%) catalyst in the regioselective hydrogenation of linalool, an important synthetic perfume and a key intermediate in the synthesis of vitamin A.

Regioselective Hydrogenation of Polycyclic Aromatic Hydrocarbons and Olefins Catalyzed by Magnesium‐Activated Chromium Complexes

AbstractReplacing precious metals with the first‐row transition metals having abundant earth reserves in organic synthesis is in line with the sustainable development of chemistry. In this study, the regioselective hydrogenation of polycyclic aromatic hydrocarbons (PAHs) and olefins had been simply realized with a low‐valent Cr‐catalyst from CrCl2 and diketimine, which was in situ reduced by magnesium. Results showed that unilateral cyclic hydrogenation of many PAHs could be achieved with this catalyst under mild conditions, which was a convenient and efficient method for the synthesis of partially saturated polycyclic aromatic hydrocarbons.

Manganese catalyzed enantio- and regioselective hydrogenation of α,β-unsaturated ketones using an imidazole-based chiral PNN tridentate ligand

The enantioselective 1,2-reduction of α,β-unsaturated ketones has been achieved using a chiral pincer Mn catalyst. A series of PNN tridentate ligands containing benzimidazole groups were designed with ferrocene as the backbone, which coordinated with Mn to form the active catalyst. This mild process represents a general method to access chiral allyl alcohols with high catalytic activity (up to 9500 TON) and high enantioselectivity (66–86% ee). Furthermore, this catalytic system provides a novel synthesis of key pharmaceutical intermediates of cannabidiol.

Accelerating Chemo- and Regioselective Hydrogenation of Alkynes over Bimetallic Nanoparticles in a Metal–Organic Framework

Selective semihydrogenation of alkynes has been a long-term and significant target, yet it remains a great challenge. Herein, bimetallic nanoparticles in a metal–organic framework (MOF), i.e., CuPd...

Kinetics and mechanisms of homogeneous catalytic reactions. Part 16. Regioselective hydrogenation of quinoline catalyzed by dichlorotris(triphenylphosphine)ruthenium(II)

The complex RuCl2(PPh3)3 (1) showed to be an efficient and regioselective precatalyst for the hydrogenation of quinoline (Q) to 1,2,3,4-tetrahydroquinoline (THQ) at P = 5.0–6.5 at m and T = 140−167 °C. This reaction showed to be first order on catalyst concentration and fractional order on dissolved hydrogen concentration (1.84). However, different to other Ru, Os, Rh and Ir precatalysts, the reaction showed an inverse fractional order on Q concentration (-0.44). The rate law may be written as: r = {KoK1k2/(Ko + [Q]+ KoK1[H2])}[Ru][H2]2. Coordination chemistry and theoretical DFT studies allowed us to propose a detailed catalytic cycle for this reaction. Under the hydrogenation conditions, the ruthenium precursor 1 is totally transformed to RuCl2(κN-Q)2(PPh3)2 (3) and subsequently to RuHCl(κN-Q)2(PPh3)2 (4) by heterolytic addition of H2. Complex 4 reversibly dissociates a Q ligand to generate RuHCl(κN-Q)(PPh3)2, which was proposed as the catalytically active species (CAS) entering to the catalytic cycle. The reversible addition of hydrogen yields a species containing a κN-1,2-dihydroquinoline (κN-DHQ) ligand (possibly through the coordination of hydrogen, migration of hydride to the N atom of Q ligand and posterior DHQ reductive elimination); this species suffers a change of coordination mode from κN- to an olefin-like η2-DHQ. Posteriorly, the addition of a second molecule of H2, considered the rate-determining step, generates a THQ species (probably through migration of hydride to C3 of DHQ ligand followed by the heterolytic addition of hydrogen). The cycle is completed by the substitution of the THQ ligand by a new Q molecule, therefore regenerating the CAS.

Analysis of the aerobic biodegradation of glucocorticoids: Elucidation of the kinetics and transformation reactions

Glucocorticoids (GCs) are one of the most prescribed pharmaceutical classes worldwide. They have reached the focus as environmental pollutants in the current scientific research, due to their potential risks to aquatic organisms even in the lower ng L−1 range. The objective of this study was to determine the kinetic behavior of selected GCs and to identify their main transformation products (TPs) in lab scaled biodegradation experiments. Therefore, we analyzed the removal of 13 GCs in aerated incubation experiments with activated sludge taken from a German municipal wastewater treatment plant (WWTP) as inoculum. For all steroids, an exponential decrease of the concentrations was observed, which was modelled by pseudo-first order kinetics. Overall, the rate constants kbiol. ranged from 0.07 L gss−1 d−1 (triamcinolone acetonide) to 250 L gss−1 d−1 (prednisolone). These results emphasize the broad variation in the biodegradability and recalcitrance of certain GCs. The selection of the studied GCs enabled a deduction of microbiological stability related to functional groups. Based on the identified TPs, a variety of enzymatically mediated reactions were postulated. Moreover, the identified TPs are characterized by an intact steroid core structure. Thus residual endocrine activity cannot be ruled out. The main observed reactions were regioselective hydrogenation of carbon double-bonds, degradation of the steroid C17 side-chain, ester hydrolysis and oxidative hydroxylation. In total, 41 TPs were tentatively identified and 22 of them were unambiguously confirmed via reference standards. Additionally, 12 TPs were detected in the effluents of municipal WWTPs and, to the best of our knowledge, the occurrence of eight of these TPs has been shown for the first time. These TPs might significantly contribute to the detected residual endocrine activities in the aquatic environments. Therefore, there is a strong need for efficient removal strategies, in particular for persistent steroid hormones with elevated potencies.

Phosphine‐Catalyzed [4+1] Cycloadditions of Allenes with Methyl Ketimines, Enamines, and a Primary Amine

AbstractUnprecedented phosphine‐catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N‐based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one‐pot access to cyclopentenoyl enamines and imines, or (chiral) γ‐lactams through two geminal C−C bond or two C−N bond formations, respectively. Several P‐based key intermediates including a 1,4‐(bis)electrophilic α,β‐unsaturated ketenyl phosphonium species have been detected by 31P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram‐scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively.

Phosphine-Catalyzed [4+1] Cycloadditions of Allenes with Methyl Ketimines, Enamines, and a Primary Amine.

Unprecedented phosphine-catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N-based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one-pot access to cyclopentenoyl enamines and imines, or (chiral) γ-lactams through two geminal C-C bond or two C-N bond formations, respectively. Several P-based key intermediates including a 1,4-(bis)electrophilic α,β-unsaturated ketenyl phosphonium species have been detected by 31 P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram-scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively.

Construction of Spirofused Tricyclic Frameworks by NHC-Catalyzed Intramolecular Stetter Reaction of a Benzaldehyde Tether with a Cyclic Enone.

Various benzaldehyde tethers with a cyclic enone were prepared from commercially available 2-hydroxybenzaldehydes via a three-step sequence involving triflate formation, Sonogashira cross-coupling, and regioselective hydrogenation. These substrates were then exposed to an N-heterocyclic carbene, whereupon intramolecular Stetter reaction proceeded smoothly to give various spirofused tricyclic 1,4-diketones in 30-87% yields. Furaldehyde and nicotinaldehyde derivatives also participated in the reaction under the Stetter conditions.

Iron-catalysed regioselective hydrogenation of terminal epoxides to alcohols under mild conditions

The reduction of epoxides has been recognized as an important method for the synthesis of alcohols using stoichiometric amounts of metal hydride reducing agents. However, homogeneous catalysis-enabled hydrogenation processes with molecular hydrogen remain scarce. Here, we present a general methodology for the synthesis of primary alcohols in high yields, selectively and under mild conditions, from aliphatic and aromatic epoxides. Crucial for the hydrogenation of terminal epoxides is the presence of an Fe(BF4)2.6H2O/tetraphos catalyst system. Compared to existing methods, which make use of noble metals, the presented protocol shows broad substrate scope and good functional group tolerance. The generality of this is showcased by transformation of various natural products, including steroids, terpenoids, sesquiterpenoids and drug derivatives, which give the desired alcohols in moderate to excellent yields. Mechanistic studies confirm the distinct feature of the catalyst system, which is active for Meinwald rearrangement of epoxides as well as for carbonyl hydrogenations. Primary alcohols are known for their broad application in life sciences and the chemical industry. Now, Beller and colleagues present a regioselective, iron-catalysed hydrogenation of aliphatic and aromatic epoxides as a general route to primary alcohols under mild conditions

Regioselective Hydrogenation of a 60-Carbon Nanographene Molecule toward a Circumbiphenyl Core.

Regioselective peripheral hydrogenation of a nanographene molecule with 60 contiguous sp2 carbons provides unprecedented access to peralkylated circumbiphenyl (1). Conversion to the circumbiphenyl core structure was unambiguously validated by MALDI-TOF mass spectrometry, NMR, FT-IR, and Raman spectroscopy. UV–vis absorption spectra and DFT calculations demonstrated the significant change of the optoelectronic properties upon peripheral hydrogenation. Stimulated emission from 1, observed via ultrafast transient absorption measurements, indicates potential as an optical gain material.

Regioselective Hydrogenation of Itaconic Acid to γ-Isovalerolactone by Transition-Metal Nanoparticle Catalysts.

Current methods for hydrogenation of bio-derived itaconic acid (IA) lead to a mixture of isomeric lactone products. Transition-metal nanoparticles (TM-NPs), in situ-generated through thermolysis of TM(0) (Ru, Fe, W, Cr) carbonyls, in particular Ru-NPs, were found to catalyze regioselective hydrogenation of IA by syngas (2 H2 /CO) into γ-isovalerolactone (GiVL) in approximately 70 % isolated yield. Key sustainability features of this new route include: a one-pot direct transformation of bio-renewable IA into value-added GiVL selectively, use of inexpensive and renewable syngas in aqueous solution, and development of a supported recyclable NP catalyst system, Al2 O3 -Ru-NPs.

Catalytic Transfer Hydrogenation Using Biomass as Hydrogen Source.

We developed an operationally simple method for the direct use of biomass-derived chemical entities in a fundamentally important process, such as hydrogenation. Various carbohydrates, starch, and lignin were used for stereoselective hydrogenation. Employing a transition metal catalyst and a novel catalytic system, the reduction of alkynes, alkenes, and carbonyl groups with high yields was demonstrated. The regioselective hydrogenation to access different stereoisomers was established by simple variations in the reaction conditions. This work is based on an unprecedented catalytic system and represents a straightforward application of biomass as a reducing reagent in chemical reactions.

Ir-Catalyzed Asymmetric and Regioselective Hydrogenation of Cyclic Allylsilanes and Generation of Quaternary Stereocenters via the Hosomi-Sakurai Allylation.

A number of cyclic dienes containing the allylsilane moiety were prepared by a Birch reduction and subjected to iridium-catalyzed regioselective and asymmetric hydrogenation, which provided chiral allylsilanes in high conversion and enantiomeric excess (up to 99 % ee). The compounds were successively used in the Hosomi-Sakurai allylation with various aldehydes employing TiCl4 as Lewis acid, providing adducts with two additional stereogenic centers in excellent diastereoselectivity.