Reduction Of Functional Groups Research Articles

Palladium-Catalyzed Site-Selective Hydrogenation of Unactivated Alkenes Directed by 8-Aminoquinoline Amides.

We have developed a method for the site-selective hydrogenation of unactivated alkenes using 8-aminoquinoline amide as the directing group. For unactivated alkenes with two C-C double bonds, Daugulis's 8-aminoquinoline amide facilitated the site-selective hydrogenation of the desired C-C double bond, producing a product in which one C-C double bond was reduced. Site-selective reduction methodologies using intramolecular directing groups are expected to contribute significantly to the synthesis of molecules with multiple reducible functional groups in the future.

Molybdenum‐Catalyzed Direct Synthesis of Pyrroles from Nitroarenes with Glycols as Reductants

A molybdenum‐catalyzed synthesis of N‐(hetero)aryl pyrroles directly from inexpensive and commonly available (hetero)nitroarenes via reduction with pinacol and annulation with 1,4‐dicarbonyls or cyclobutane‐1,2‐diols has been described. The process does not require an inert atmosphere and tolerates the presence of air and water. This non‐noble catalytic system shows high chemoselectivity, allowing a diverse range of potentially reducible functional groups such as alkynes, alkenes, halogens, cyano, and carbonyls. Moreover, this strategy enables the reuse of a waste byproduct as reactant, facilitating the formation of challenging 1,4‐dicarbonyls from accessible cyclobutane‐1,2‐diols used as reducing agents.

Stable and Versatile Pd Precursors for the Preparation of Robust Pd Catalysts under Continuous-Flow.

The chemical and engineering communities require the development of versatile precursors that can be used to synthesize robust catalysts to achieve global sustainability. To meet this demand, we developed a new Pd precursor for incorporating fine Pd metal into supports in a highly efficient manner. An atmospherically stable Pd precursor (Pd-80) was prepared by the thermally promoted aerobic oxidation of tetrakis(triphenylphosphine)palladium. The physical properties of Pd-80 were investigated using NMR spectroscopy, SEM, XPS, solvent-relaxation NMR spectroscopy, and dynamic light scattering (DLS) experiments. We also prepared a cordierite-supported Pd catalyst (Pd/cordierite) by stirring Pd-80 and cordierite powder in chloroform at room temperature. Pd/cordierite selectively catalyzes the hydrogenation of various reducible functional groups, including alkynes, azides, nitro groups, olefins, CO2Bn, N-Cbz, O-Bn, aromatic ketones, and styrene oxide, in continuous-flow hydrogenation reactions. The Pd/cordierite-catalyzed continuous-flow hydrogenation of nitrobenzene derivatives afforded the corresponding anilines, with catalyst activity maintained for over 250 h of continuous operation and a turnover number (TON) of 61,090 recorded.

Cobalt‐Catalyzed Hydrogenation of Ketones and Aldimines with Ammonia Borane

Efficient hydrogenation of organic compounds employing low‐cost and easy‐to‐synthesize catalysts is highly desirable as the corresponding hydrogenated products have significant importance in pharmaceutical and fine‐chemical industries. Herein, a cobalt(II) complex supported by α‐diimine ligand has been easily prepared by treatment of anhydrous CoCl2 with diimine, which can catalyze the hydrogenation of unsaturated bond with ammonia borane as the hydrogen source. A variety of ketones and aldimines bearing diverse functional groups can be reduced to corresponding alcohols and amines in moderate to excellent yields at ambient conditions. It is noteworthy that several readily reducible functional groups such as nitro and cyano are tolerated under the standard reaction conditions. Furthermore, the gram‐scale reaction has been successfully carried out and the procedure could be handled easily, which both make this methodology general and practical.

Activating Methanol for Chemoselective Transfer Hydrogenation of Chalcones Using an SNS-Ruthenium Complex

AbstractMethanol is gaining popularity as a transfer-hydrogenating agent in catalytic reduction reactions because of its bulk-scale production and inexpensive nature. Current research interests include the utilization of methanol as a safe and sustainable hydrogen source for chemical synthesis and drug development. In particular, the chemoselective reduction of α,β-unsaturated ketones is of great interest because of their prevalence in many natural products. We investigated the potential application of acridine-derived SNS-Ru pincer complexes in methanol activation for chemoselective reduction of chalcones. Our developed catalytic system showed broad substrate tolerance, including substrates containing reducible functional groups. Control experiments and postsynthetic applications are also highlighted.

Manganese‐Catalyzed Chemoselective Direct Hydrogenation of α,β‐Epoxy Ketones and α‐Ketoamides at Room Temperature

AbstractChemoselective hydrogenation of α,β‐epoxy ketones and α‐ketoamides is achieved at room temperature (25 °C) using 2.0 bar H2 and a pincer‐ligated Mn(I) catalyst that provides synthetically valuable α‐hydroxy epoxides and α‐hydroxy amides. This protocol applies to a wide range of alkyl‐ and aryl‐substituted α,β‐epoxy ketones, including terpenes (α‐ionone, nootkatone, and R‐carvone)‐ and steroids (testosterone and progesterone)‐derived epoxy ketones, and tolerates H2 sensitive functionalities, such as halides, acetyl, nitrile, nitro, epoxide, alkenyl and alkynyl groups. Additionally, α‐ketoamides bearing reducible functional groups, including acetyl and diazo benzene, were untouched under this protocol and selectively converted to α‐hydroxy amides. A preliminary mechanistic study highlighted the metal‐ligand cooperative H2 activation process.

Air-Stable Arene Manganese Complexes as Catalysts for the Syngas-Assisted Direct Reductive Amination, Cyanation of Aldehyde, and CO2 Fixation by Epoxide with High Functional Groups Tolerance.

Manganese complexes [(arene)Mn(CO)3]+ were prepared in one step from arenes and Mn(CO)5Br. They were found to be efficient catalysts in the carbonyl cyanation with TMSCN, CO2 fixation by epoxides, and direct reductive amination in the presence of syngas. The amination reaction tolerated various reducible functional groups. The synergy of carbon monoxide and hydrogen in syngas provides high efficiency of the catalytic system. The developed protocols do not require an inert atmosphere, and the catalysts can be handled in air.

Nickel‐Catalyzed Efficient Transfer Hydrogenation of Ketones

AbstractAn efficient and versatile synthesis of alcohols via transfer hydrogenation from ketones with isopropanol, utilizing [Ni(6,6′‐(OH)2‐2,2′‐bpy)][Br2] under alkaline conditions, has been documented. It was noteworthy that many readily reducible or labile functional groups such as nitro, cyano, and halide, within the same molecular framework, did not undergo any change under the standard reaction conditions. Furthermore, the gram scale transfer hydrogenation reaction was successfully carried out with good yield using a common route with only a single purification by column chromatography.

Assessment of abiotic reduction rates of organic compounds by interpretable structural factors and experimental conditions in anoxic water environments

For organic contaminants in lake sediments, aquifers, and anaerobic bioreactors, their reduction is one of the primary transformation paths in these anoxic water environments. A simple model is introduced to predict pseudo-first order rate constants (kobs) for the abiotic reduction of organic compounds featuring diverse reducible functional groups. It utilizes the largest experimental dataset of –log kobs, encompassing 59 organic compounds (278 data points). Unlike available complex quantitative structure–activity relationship (QSAR) methods, the novel approach requires both experimental conditions and structural parameters. In comparison to one of the available general QSAR methods, the new model demonstrates favorable performance. The average absolute deviation (AAD), absolute maximum deviation (ADmax), average absolute relative deviation (AARD%), and R-squared (R2) values of the estimated outputs for 54/5 training/test data sets of the new model are 0.641/1.761, 1.761/1.417, 20.52/83.87, and 0.797/0.949, respectively. On the other hand, the available general comparative QSAR method shows the AAD: 1.311/2.301, ADmax: 3.795/3.732, AARD%: 641.0/821.2, and R2: 0.003/0.447. For the test set, AAD, AARD%, ADmax, and R2 values for the new/comparative models are 0.649/2.403, 62.20/190.5, 1.215/3.732 and 0.974/0.789, respectively. In summary, the new model offers a straightforward approach for the manual calculation of –log kobs, demonstrating excellent goodness-of-fit, reliability, precision, and accuracy.

Chemoselective hydrogenation of nitroarenes over highly active 3D-COF derived Co-nanocarbon catalyst

This study unveils a novel approach by efficiently loading earth-abundant cobalt onto a covalent organic framework (COF) for catalyzing the hydrogenation of nitroarenes to aryl amines. The synthesized Co@NC650 nanocomposites exhibit enhanced graphitization and catalytic performance, attributed to synergistic interactions between cobalt and the carbon matrix. The Co@NC650 The resulting material is thoroughly characterized using techniques such as PXRD, XPS, FE-SEM, TEM, and FT-IR. Utilizing this synthesized catalyst, a chemoselective reduction of nitroarenes to corresponding amines is demonstrated under relatively mild conditions, employing molecular hydrogen as sole reductant without any additives or bases. The methodology delivers high yields and exhibits tolerance towards wide range of functional groups. The chemoselective hydrogenation is achieved even in the presence of other potentially reducible functional groups such as ketones, carboxylic acids, amides, sulphonamides, and chalcones. Selected examples showcasing the synthesis of biologically important amines are presented. Furthermore, the proposed catalyst demonstrates reusability without any loss of activity.

Molybdenum trioxide as a newer diversified economic catalyst for the transformation of nitroarenes to arylamine and 5-substituted-1H-tetrazole.

The present work has developed a straightforward, gentle, and effective approach for synthesizing arylamines and 5-substituted-1H-tetrazole derivatives, and among the two tested catalysts, molybdenum trioxide (MoO3) proved to be highly effective. The selective hydrogenation of nitroarenes to arylamines presents a significant challenge due to the complex reaction mechanism and the competitive hydrogenation of other reducible functional groups. It facilitated the transfer hydrogenation of nitrobenzene using hydrazine hydrate-produced amino compounds and enabled the [3 + 2] cycloaddition of sodium azide with aromatic nitriles to yield 5-substituted-1H-tetrazoles. The structure of compound 5-(4-bromophenyl)-1H-tetrazole (5k) was verified through single-crystal X-ray analysis, and the calculation of Green Chemistry Metrics showed the optimal range. Notably, the MoO3 catalyst can be reutilized for up to seven cycles with minimal loss of effectiveness. These attributes make molybdenum trioxide particularly attractive for industrial applications. This methodology offers several advantages over traditional synthetic methods.

Access to carbonyl compounds via the electroreduction of N-benzyloxyphthalimides: Mechanism confirmation and preparative applications

A method to access carbonyl compounds using reductive conditions was evaluated via electrochemical reduction of their corresponding N-benzyloxyphthalimide derivatives (NBOPIs). The mechanism of this originally reported electrochemical reaction was proposed based on DFT calculation and is experimentally confirmed herein, contrasting simulated and experimental cyclic voltammetry data. The reaction scope studied in a preparative scale and using redox sensitive functional groups showed good selectivity and tolerance toward oxidation under the reaction conditions with a moderate to good yield (50–71%). Nevertheless, some restrictions with reducible functional groups, like benzyl-brominated and nitro-aromatic derivatives, were observed. The present approach can be considered a self-sustainable electrochemical catalysis for the synthesis of aromatic carbonylic compounds passing through anion radical intermediates produced by a cathodic reaction.

Selective Transfer Hydrogenation of C=O and Conjugated C=C Bonds Using An NHC-Based Pincer (CNC)MnI Complex in Methanol.

Base metal catalyzed transfer hydrogenation reactions using methanol is highly challenging. Employing a single N-heterocyclic carbene (NHC)-based pincer (CNC)MnI complex, chemoselective single and double transfer hydrogenation of α, β-unsaturated ketones to saturated ketones or alcohols by utilizing methanol as the hydrogen source is disclosed. The protocol was tolerant towards the selective transfer hydrogenation of C=C or C=O bonds in the presence of several other reducible functional groups and led to the synthesis of several biologically relevant molecules and natural products. Notably, this is the first report of a Mn-catalyzed transfer hydrogenation of carbonyl groups with methanol. Several control experiments, kinetic studies, Hammett studies, and density functional theory (DFT) calculations were carried out to understand the mechanistic details of this catalytic process.

Cobalt Nickel Bimetallic Nanocatalyst Supported on g‐C3N4 for Selective Hydrogenation of α,β‐Unsaturated Carbonyls and Nitroarenes

AbstractDesigned CoNi bimetallic catalysts on various supports were synthesized and tested for selective hydrogenation reactions. Amongst these, the newly developed CoNi@gC3N4 nanocatalyst demonstrated a unique reactivity profile. It was found to be most effective for selective hydrogenation of various chalcone derivatives and nitroarenes in the presence of other reducible functional groups such as halo, carbonyl, benzyl ether, cyclopropane, and isolated alkenes. The prepared bimetallic catalyst has advantages over the reported methods in terms of catalytic activity under mild conditions, selectivity, and reusability. The catalyst CoNi@gC3N4 has ability to selectively reduce nitro functional group to amine and allows formation of quinolines.

Abiotic Reduction of Organic and Inorganic Compounds by Fe(II)-Associated Reductants: Comprehensive Data Sets and Machine Learning Modeling.

Iron-associated reductants play a crucial role in providing electrons for various reductive transformations. However, developing reliable predictive tools for estimating abiotic reduction rate constants (logk) in such systems has been impeded by the intricate nature of these systems. Our recent study developed a machine learning (ML) model based on 60 organic compounds toward one soluble Fe(II)-reductant. In this study, we built a comprehensive kinetic data set covering the reactivity of 117 organic and 10 inorganic compounds toward four major types of Fe(II)-associated reductants. Separate ML models were developed for organic and inorganic compounds, and the feature importance analysis demonstrated the significance of resonance structures, reducible functional groups, reductant descriptors, and pH in logk prediction. Mechanistic interpretation validated that the models accurately learned the impact of various factors such as aromatic substituents, complexation, bond dissociation energy, reduction potential, LUMO energy, and dominant reductant species. Finally, we found that 38% of the 850,000 compounds in the Distributed Structure-Searchable Toxicity (DSSTox) database contain at least one reducible functional group, and the logk of 285,184 compounds could be reasonably predicted using our model. Overall, the study is a significant step toward reliable predictive tools for anticipating abiotic reduction rate constants in iron-associated reductant systems.

A constructive synthetic approach for reduction of nitro heterocyclics- characterization and degradation studies

A novel synthetic approach was proposed for a metal free reduction of nitro aromatic compounds to the resultant amines by sodium dithionite. A series of nitro compounds containing various reducible functional groups were chemoselectively reduced in good to excellent yield. Instantaneously some of the products are chemically degraded and all are characterized by spectral methods.

Reductive coupling of nitroarenes with carboxylic acids - a direct route to amide synthesis.

A straightforward and selective way for the preparation of amides from nitroarenes and carboxylic acids using carbon monoxide as a reductant was developed. This protocol does not require any non-gaseous additives, thus simplifying product isolation. Aliphatic carboxylic acid was modified in the presence of aromatic ones, and reducible functional groups such as CC, Ar-Br, and R-NO2 were saved.

Aluminium-Catalyzed Selective Hydroboration of Esters and Epoxides to Alcohols: C-O Bond Activation.

In this work, the molecular aluminium dihydride complex bearing an N, N'-chelated conjugated bis-guanidinate (CBG) ligand is used as a catalyst for reducing a wide range of aryl and alkyl esters with good tolerance of alkene (C=C), alkyne (C≡C), halides (Cl, Br, I and F), nitrile (C≡N), and nitro (NO2 ) functionalities. Further, we investigated the catalytic application of aluminium dihydride in the C-O bond cleavage of alkyl and aryl epoxides into corresponding branched Markovnikov ring-opening products. In addition, the chemoselective intermolecular reduction of esters over other reducible functional groups, such as amides and alkenes, has been established. Intermediates are isolated and characterized by NMR and HRMS studies, which confirm the probable catalytic cycles for the hydroboration of esters and epoxides.

Efficient Base‐Catalyzed Hydrosilylation of Tertiary Amides to Aldehydes

AbstractA chemoselective catalytic reduction of tertiary amides to aldehydes is reported. The catalytic system KOtBu/(EtO)2MeSiH has been found to be highly active in the conversion of tertiary amides to silylated hemiaminals, which after acidic work‐up yields the respective aldehydes under mild conditions. The use of amides containing α‐protons in this catalytic reaction resulted in elimination to furnish enamines characterized by 1H‐NMR. This mild and selective process is compatible with nitriles, ethers, amines, and heterocyclic functionalities. However, competition experiments revealed poor tolerance for easily reducible functional groups, such as esters, ketones, and aldehydes. This transition metal‐free strategy presents a cheap and readily available process for the efficient reduction of tertiary amides to the corresponding aldehydes.

Aluminum-catalyzed selective hydroboration of carbonyls and dehydrocoupling of alcohols, phenols, amines, thiol, selenol, silanols with HBpin

A popular N, N’-chelated NacNac analogue, i.e., conjugated bis-guanidinate (CBG) stabilized aluminum dihydride LAlH2(1) [L = {(ArHN)(ArN)–CN–C=(NAr)(NHAr)}; Ar = 2,6-Et2-C6H3], demonstrates excellent catalytic hydroboration of a wide array of carbonyls with pinacolborane (HBpin) under neat conditions with good tolerance of reducible functional groups such as alkyl, alkene, halide, nitrile, nitro, ester, amide, and heteroaryl. In addition, we investigated complex 1 catalyzed cross-dehydrocoupling (CDC) of alcohols, phenols, amines, thiol, selenol, and silanols with HBpin under mild reaction conditions. Furthermore, several control experiments have been performed to understand the mechanisms in hydroboration and CDC reactions. All corresponding catalytic intermediates have been identified and characterized by 1H and 13C{1H} NMR spectroscopic methods. In contrast to several reports on metal-catalyzed hydroboration of carbonyls, this is the second report for the molecular aluminum catalyzed CDC of organic substrates with HBpin.