Borrowing Hydrogen Research Articles

B(C6F5)3-catalyzed β-C(sp3)-H alkylation of tertiary amines with 2-aryl-3H-indol-3-ones.

The β-C-H functionalization of amines is one of the most powerful tools for the synthesis of saturated nitrogen-containing heterocycles in organic synthesis. However, the β-C-H functionalization of amines via redox-neutral addition with cyclic-ketimines is still unprecedented. Herein, the β-C-H functionalization of tertiary amines is described, providing the corresponding 1,3-diamines containing the indolin-3-one moiety in high yields via the B(C6F5)3-catalyzed borrowing hydrogen strategy. According to the experimental results, a possible catalytic cycle has been proposed to rationalize the process of this reaction. Notably, the β-C-H alkylation of amines is external oxidant- and transition-metal-free, which makes a significant contribution to promoting economical chemical synthesis.

N-coordinated Ru(ii) catalyzed solvent freeN-alkylation of primary amines with alcohols through borrowing hydrogen strategy

The catalytic efficacy of N-coordinated Ru(ii)-complexes has been examined forN-alkylation of amines in a benign and solvent-free conditions. Electron deficient [Ru-1] led to superior catalytic conversion due to Metal Ligand Cooperation.

TiO2 (P25) nanoparticle catalyzed C-alkylation and quinoline synthesis via the borrowing hydrogen method

TiO2 (P25) nanoparticle catalyzed C-alkylation and quinoline synthesis via the borrowing hydrogen method.

K2S2O8 promoted metal-free direct C-alkylation of acetophenones with alcohols.

Herein, we report a metal-free synthetic methodology for the C-alkylation of acetophenones following a hydrogen borrowing-like pathway using the commercially available inorganic oxidant K2S2O8 in conjunction with KOtBu. This study articulates the potential of K2S2O8 in fast initiation of the oxidation of benzyl alcohols to develop an atom-economical, easy, and more efficient methodology for the C-alkylation of various acetophenones and synthesis of a variety of substituted quinolines. Experimental data from control experiments, literature and characterization of intermediates through spectroscopic techniques support the proposed plausible mechanism.

Discovering the role of N-heterocyclic carbene as hydrogen borrowing organocatalyst: metal-free, directN-alkylation of amines with benzyl alcohols

A highly sustainable, bench-stable, inexpensive, non-toxic and commercially available N-heterocyclic carbene based hydrogen borrowing organocatalyst for the direct N-alkylation of amines with alcohols is reported.

S-Alkylation of dithiocarbamates via a hydrogen borrowing reaction strategy using alcohols as alkylating agents.

Herein, we report an operationally simple, environmentally benign and scalable approach towards the synthesis of S-benzyl/alkyl dithiocarbamates via a hydrogen borrowing reaction between alcohols and dithiocarbamate anions catalyzed using a hydroxyapatite-supported copper nano-catalyst. This strategy has a broad substrate scope and offers high yields of products using inexpensive and readily available alcohols as starting materials. The catalyst was prepared by easy and straightforward methods and analyzed by several analytical techniques, e.g., FESEM, HR-TEM, BET, XRD, EDS, and XPS, demonstrating the anchoring of Cu nanoparticles on hydroxyapatite in the zero oxidation state.

Zinc(II) and Cadmium(II) Salphen Catalyzed Alkylation Reactions to Form α-Alkylated Ketones

The zinc (II) and cadmium (II)-salphen catalyzed α-alkylation of ketones with primary alcohols is reported. Various α-alkylated ketones were obtained in good yields through a borrowing hydrogen strategy by using 1 % of catalysts and a catalytic amount of NaOH (10 mol%) as the base under air atmosphere. All synthesized compounds were characteized by 1H and 13C NMR.

α-Methylation of Ketones and Indoles Catalyzed by a Manganese(I) PCNHCP Pincer Complex with Methanol as a C1 Source

Acceptorless alcohol dehydrogenation is a powerful reaction in sustainable synthesis. When combined in a tandem reaction with dehydrogenative coupling or hydrogen borrowing, acceptorless dehydrogenation can be used for the environmentally benign construction of C–C, C–N, and C–O bonds. While many of these reactions rely on using precious metals, in the past decade the use of earth-abundant metals has become more prevalent. If a green and renewable feedstock could be introduced as well, the sustainability of the acceptorless dehydrogenation could further be increased. Methanol would be such a substrate and could serve as a renewable C1 source when used for the methylation of a wide variety of substrates. Herein, we report the efficient manganese-catalyzed α-methylation of ketones and indoles. The manganese catalyst is based on a PCNHCP pincer platform containing a rare central carbene donor. The reaction supports a diverse set of functional groups, occurs at moderate temperatures (110 °C), and provides the corresponding methylated ketones and indoles in excellent yields. In contrast to previously reported mechanisms, the herein reported mechanism does not depend on metal–ligand cooperativity but rather proceeds via (i) a metal-based mechanism featuring a manganese hydride or (ii) via a ligand-centered mechanism where a manganese-carbonyl acts as catalytic center, depending on the used additive.

Coding Synthetic Chemistry Strategies for Furan Valorization into Bacterial Designer Cells.

Following a synthetic chemistry blueprint for the valorization of lignocellulosic platform chemicals, this study showcases a so far unprecedented approach to implement non-natural enzyme modules in vivo. For the design of a novel functional whole cell tool, two purely abiotic transformations, a styrene monooxygenase-catalyzed Achmatowicz rearrangement and an alcohol dehydrogenase-mediated borrowing hydrogen redox isomerization, were incorporated into a recombinant bacterial host. Introducing this type of chemistry otherwise unknown in biosynthesis, the cellular factories were enabled to produce complex lactone building blocks in good yield from bio-based furan substrates. This whole cell system streamlined the synthetic cascade, eliminated isolation and purification steps, and provided a high degree of stereoselectivity that has so far been elusive in the chemical methodology.

Economical Access to Diverse Enantiopure Tetrahydropyridines and Piperidines Enabled by Catalytic Borrowing Hydrogen.

We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one-pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3-amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N-protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di- and tri-substituted piperidines, which ranks the topmost frequent N-heterocycle in commercial drugs.

Economical Access to Diverse Enantiopure Tetrahydropyridines and Piperidines Enabled by Catalytic Borrowing Hydrogen

AbstractWe disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one‐pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3‐amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N‐protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di‐ and tri‐substituted piperidines, which ranks the topmost frequent N‐heterocycle in commercial drugs.

Nickel-Catalyzed Direct Synthesis of N-Substituted Indoles from Amino Alcohols and Alcohols.

A one-pot cascade approach for the synthesis of N-substituted indoles from amino alcohols and alcohols under additive and base-free conditions with the liberation of water as the only stoichiometric byproduct is reported. The commercially available bench-stable Ni(OTf)2 salt in combination with 1,2-bis(dicyclohexylphosphino)ethane (dcype) is very effective for this unprecedented catalytic transformation. A broad range of substrates including aromatic and aliphatic primary alcohols, cyclic and acyclic secondary alcohols, and various substituted 2-aminophenyl ethyl alcohols are employed in the reaction conditions to provide a diverse range of N-alkylated indoles. Mechanistic studies revealed that the reaction proceeds through tandem N-alkylation via hydrogen autotransfer followed by the cyclization of N-alkylated alcohol intermediate.

Iridium-, Ruthenium-, and Nickel-Catalyzed C-C Couplings of Methanol, Formaldehyde, and Ethanol with π-Unsaturated Pronucleophiles via Hydrogen Transfer.

In this Perspective, the use of methanol and ethanol as C1 and C2 feedstocks in metal-catalyzed C-C couplings to π-unsaturated pronucleophiles via hydrogen auto-transfer is surveyed. In these processes, alcohol oxidation to form an aldehyde electrophile is balanced by reduction of an π-unsaturated hydrocarbon to form a transient organometallic nucleophile. Mechanistically related reductive couplings of paraformaldehyde mediated by alcohol reductants or formic acid also are described. These processes encompass the first catalytic enantioselective C-C couplings of methanol and ethanol and, more broadly, illustrate how the native reducing ability of alcohols enable the departure from premetalated reagents in carbonyl addition.

Nickel-Catalyzed Sustainable and Selective Alkylation of Alcohols to α-Alkylated Ketones via Borrowing Hydrogen Approach

AbstractHerein, we report a nickel-catalyzed sustainable, environment­-friendly, and economically affordable borrowing hydrogen approach (BHA) for synthesizing various α-alkylated ketones via dehydro­genative coupling of primary and secondary alcohols. Using a well-­defined, air-stable, inexpensive, and easy-to-prepare four-coordinate macrocyclic Ni(II)-catalyst [Ni(MeTAA)] of a tetra-aza macrocyclic ligand (tetramethyltetraaza[14]annulene (H2MeTAA)), a series of α-alkylated ketones were prepared in good yields. A few control reactions, including deuterium-labelling experiments, were performed to unveil the reaction mechanism.

Ruthenium-Catalyzed Butadiene-Mediated Crotylation and Oxazaborolidine-Catalyzed Vinylogous Mukaiyama Aldol Reaction for The Synthesis of C1-C19 and C23-C35 of Neaumycin B.

Neaumycin B is a femtomolar inhibitor of U87 human glioblastoma. Using a newly developed anti-diastereoselective ruthenium-catalyzed butadiene-mediated crotylation of primary alcohol proelectrophiles via hydrogen auto-transfer, as well as a novel variant of the catalytic asymmetric vinylogous Mukaiyama aldol (VMA) reaction applicable to linear aliphatic aldehydes and terminally methylated dienyl ketene acetals, preparation of the key C1-C19 and C23-C35 substructures of neaumycin B is achieved in 12 and 7 steps (LLS), respectively.

Stereo- and Site-Selective Crotylation of Alcohol Proelectrophiles via Ruthenium-Catalyzed Hydrogen Auto-Transfer Mediated by Methylallene and Butadiene.

Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols with methylallene (1,2-butadiene) or 1,3-butadiene to form products of anti-crotylation with good to excellent levels of diastereo- and enantioselectivity. Distinct from other methods, direct crotylation of primary alcohols in the presence of unprotected secondary alcohols is possible, enabling generation of spirastrellolide B (C9-C15) and leucascandrolide A (C9-C15) substructures in significantly fewer steps than previously possible.

Sustainable Amination of Bio-Based Alcohols by Hydrogen Borrowing Catalysis

In this review, we aim to give an overview of the use of the Borrowing Hydrogen (BH) methodology with bio-based alcohols. This methodology only forms water as a by-product, thus providing a sustainable way to amines, which have a large range of applications. This process is of particular interest when related to biomass due to the high abundance of alcohol functions in natural compounds. However, natural compounds often comprise multiple chemical functions that can change the reactivity of the substrate. This comprehensive review, comprising both homogeneous and heterogeneous catalysts, aims at summarizing the recent advancements in biomass amination for every class of substrate, highlighting the key parameters governing their reactivity and the remaining scientific hurdles. Even though most substrates have successfully been converted into the corresponding amines, reaction selectivity and functional group tolerance still need to be improved.

High Active Palladium Composite and Catalytic Applications on the Synthesis of Substituted Aminopyridine Derivatives Through Borrowing Hydrogen Strategy

High Active Palladium Composite and Catalytic Applications on the Synthesis of Substituted Aminopyridine Derivatives Through Borrowing Hydrogen Strategy

Recent Advances for Alkylation of Ketones and Secondary Alcohols Using Alcohols in Homogeneous Catalysis

AbstractThe alkylation of ketones or secondary alcohols using alcohols as alkylating agents via hydrogen borrowing strategy presents a powerful method for the synthesis of ɑ‐alkylated ketones. In this review, we summarize the progress catalyzed by Ir, Pd, Rh, Ru, Mn, Fe, Co, Ni, and Cu catalysts for the α‐alkylation of ketones with alcohols and cross‐coupling of secondary alcohols with alcohols from 2017 to 2021. A wide range of ketones (aromatic and aliphatic ketones) and alcohols (benzylic and aliphatic primary alcohols, aromatic and aliphatic secondary alcohols, alkenyl alcohols, and diols) are well tolerated. Furthermore, we also discuss current challenges and propose perspectives on the coming development in this filed. The objective of the present review is to give an overview on recent advances for α‐alkylation of ketones with alcohols and β‐alkylation of secondary alcohols with alcohols. Finally, we hope that this review will give inspirations on alkylation of ketones or secondary alcohols with alcohols.magnified image

Late stage modifications of phosphine oxide ligands by iron‐catalyzed hydrogen borrowing reactions

α-Alkylation reaction involving methyldiarylphosphine oxides and (hetero)arylmethanols as the electrophilic partners can be performed using iron based catalyst under hydrogen borrowing conditions. Various (hetero)arylmethanols can be used leading to the corresponding alkyldiarylphosphine oxides with moderate to good yields.