Borrowing Hydrogen Research Articles

Mechanistic Elucidation of an Alcohol Oxidation Reaction Promoted by a Nickel Azophenolate Complex

Borrowing hydrogen (BH) reactions by base metals have attracted significant focus with a perspective in green and sustainable chemistry. In a BH reaction, dehydrogenation of the alcohol motifs is a fundamental step, where several well-established catalysts exhibit metal–ligand cooperativity. We showcase here that the redox noninnocence of the azophenolate backbone in an earth-abundant nickel catalyst drives the alcohol dehydrogenation by a radical pathway. Detailed mechanistic probation including saturation kinetics supports the binding of the substrate alcohol to the nickel center. Thermodynamic data derived from such analysis also proves the azophenolate hemilability to pave the further steps. An Eyring analysis quantifies the kinetic barrier associated with a crucial hydrogen atom transfer step that is driven by the azo radical. Furthermore, both Hammett correlation and linearity in Evans–Polanyi plot implicate that C–H abstraction by radical mechanism as the rate-determining step. The overall mechanism offered by the azophenolate catalyst closely resembles the galactose oxidase-based copper phenoxide chemistry.

Synthesis of 1,4-Diazacycles by Hydrogen Borrowing.

We report the syntheses of 1,4-diazacycles by diol-diamine coupling, uniquely made possible with a (pyridyl)phosphine-ligated ruthenium(II) catalyst (1). The reactions can exploit either two sequential N-alkylations or an intermediate tautomerization pathway to yield piperazines and diazepanes; diazepanes are generally inaccessible by catalytic routes. Our conditions tolerate different amines and alcohols that are relevant to key medicinal platforms. We show the syntheses of the drugs cyclizine and homochlorcyclizine in 91% and 67% yields, respectively.

Recent Developments in Manganese, Iron and Cobalt Homogeneous Catalyzed Synthesis of Primary Amines via Reduction of Nitroarenes, Nitriles and Carboxamides

AbstractThe preparation of primary amines attracts huge attention in the molecular synthetic community. Indeed, amines play a crucial role in chemistry as they are important substructures in a huge amount of drug molecules, agrochemicals, dyes and molecular materials. Compared to stoichiometric reductions using metal hydride based reagents, the catalyzed reduction of nitroarenes, nitriles and carboxamides appears to be an attractive option, mainly when associated to first row transition metals such as manganese, iron, or cobalt. In this short review, we illustrate the progress achieved in homogeneous hydrogenation, hydrogen transfer, hydrogen borrowing and hydrosilylation of nitroarenes, nitriles and carboxamides.magnified image

Iridium-Catalyzed Enantioconvergent Borrowing Hydrogen Annulation of Racemic 1,4-Diols with Amines.

We present an enantioconvergent access to chiral N-heterocycles directly from simple racemic diols and primary amines, through a highly economical borrowing hydrogen annulation. The identification of a chiral amine-derived iridacycle catalyst was the key for achieving high efficiency and enantioselectivity in the one-step construction of two C-N bonds. This catalytic method enabled a rapid access to a wide range of diversely substituted enantioenriched pyrrolidines including key precursors to valuable drugs such as aticaprant and MSC 2530818.

Carbonyl Allylation and Crotylation: Historical Perspective, Relevance to Polyketide Synthesis, and Evolution of Enantioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer Processes.

The evolution of methods for carbonyl allylation and crotylation of alcohol proelectrophiles culminating in the design of iodide-bound ruthenium-JOSIPHOS catalysts is prefaced by a brief historical perspective on asymmetric carbonyl allylation and its relevance to polyketide construction. Using gaseous allene or butadiene as precursors to allyl- or crotylruthenium nucleophiles, respectively, new capabilities for carbonyl allylation and crotylation have been unlocked, including stereo- and site-selective methods for the allylation and crotylation of 1,3-diols and related polyols.

C-Alkylation by Phenalenyl-Based Moleculeviaa Borrowing Hydrogen Pathway

The present study demonstrates the first transition-metal-free catalytic C-alkylation via a borrowing hydrogen pathway for the α-alkylation of ketone, synthesis of substituted quinoline, and 9-monoalkylation of fluorene. With applications on diversification of biologically active molecules and gram-scale synthesis, a preliminary investigation of the reaction mechanism has been carried out, suggesting a radical-mediated borrowing hydrogen pathway.

Methanol as a Potential Hydrogen Source for Reduction Reactions Enabled by a Commercial Pt/C Catalyst

Catalytic reduction reactions using methanol as a transfer hydrogenating agent is gaining significant attention because this simple alcohol is inexpensive and produced on a bulk scale. Herein, we report the catalytic utilization of methanol as a hydrogen source for the reduction of different functional organic compounds such as nitroarenes, olefins, and carbonyl compounds. The key to the success of this transformation is the use of a commercially available Pt/C catalyst, which enabled the transfer hydrogenation of a series of simple and functionalized nitroarenes-to-anilines, alkenes-to-alkanes, and aldehydes-to-alcohols using methanol as both the solvent and hydrogen donor. The practicability of this Pt-based protocol is showcased by demonstrating catalyst recycling and reusability as well as reaction upscaling. In addition, the Pt/C catalytic system was also adaptable for the N-methylation and N-alkylation of anilines via the borrowing hydrogen process. This work provides a simple and flexible approach to prepare a variety of value-added products from readily available methanol, Pt/C, and other starting materials.

1,4-d-Sorbitan: A Promising Biobased-Platform for the Synthesis of Chiral Amines.

The regio- and diastereoselective synthesis of chiral amines derived from 1,4-d-sorbitan has been developed via the borrowing hydrogen reaction using a cooperative catalysis between an achiral iridium catalyst and diphenylphosphoric acid. The different reactivities of the four hydroxyl groups on the 1,4-d-sorbitan scaffold have also been highlighted.

Identifying active sites at the Cu/Ce interface for hydrogen borrowing reactions

The interface between metal sites and metal oxides sometimes acts as the real active site, but the identification of its structure and function in catalysis is still elusive. Here, we demonstrate that Lewis acid-base pairs (LPs) at the interface of Cu/CeO2 catalyst display outstanding catalytic performance on the hydrogen borrowing reaction under base free conditions. Characterizations disclose that LPs consist of Lewis acidic Cu(I) and Lewis basic surface oxygen (Osurf), where the Cu(I) species are formed by electron transfer between the interfacial Cu and Ce {e.g., Ce(III) + Cu(II) ↔ Ce(IV) + Cu(I)} and Osurf species are simultaneously created by surface oxygen mobility. The Cu(I)-H and Osurf-H intermediates are generated by reacting hydride (H-) and proton (H+) from CH and OH cleavage with Lewis acidic Cu(I) and Lewis basic Osurf, respectively. The combination of control experiments, deuterium isotope studies and DFT calculations reveals that the Cu(I)-H and Osurf-H intermediates are spatially isolated by LPs and prefer to transfer to CN bonds rather than forming H2 molecules, leading to outstanding selectivity towards the desired N-alkyl amine.

Asymmetric Ruthenium-Catalyzed Carbonyl Allylations by Gaseous Allene via Hydrogen Auto-Transfer: 1° vs 2° Alcohol Dehydrogenation for Streamlined Polyketide Construction.

Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols 2a-2r with the gaseous allene (propadiene) 1a to form enantiomerically enriched homoallylic alcohols 3a-3r with complete atom-efficiency. Using formic acid as reductant, aldehydes dehydro-2a and dehydro-2c participate in reductive C-C coupling with allene to deliver adducts 3a and 3c with comparable levels of asymmetric induction. Deuterium labeling studies corroborate a mechanism in which alcohol dehydrogenation triggers allene hydroruthenation to form transient allylruthenium-aldehyde pairs that participate in carbonyl addition. Notably, due to a kinetic preference for primary alcohol dehydrogenation, chemoselective C-C coupling of 1°,2°-1,3-diols occurs in the absence of protecting groups. As illustrated by the synthesis of C7-C15 of spirastrellolide B and F (7 vs 17 steps), C3-C10 of cryptocarya diacetate (3 vs 7 or 9 steps), and a fragment common to C8'-C14' of mycolactone F (1 vs 4 steps) and C22-C28 marinomycin A (1 vs 9 steps), this capability streamlines type I polyketide construction.

Hydrogenation of C=N bonds on TiO2 surface: The effect of the Cu2O/TiO2 p-n heterojunction photocatalyst

As a widely used semiconductor photocatalyst, TiO2 has been explored in organic compounds hydrogenation. In this study, the hydrogenation of C=N bonds on the surface of TiO2 was accomplished for the first time utilizing Cu2O/TiO2 type-II (p-n) heterojunction. The probe reactions, hydrogenation of N-benzylphenylamine with benzyl alcohol, and N-methylation of amines with methanol exhibited that the hydrogenation of C=N bonds on TiO2 surface can be achieved through borrowing hydrogen reaction (BH, alcohols as hydrogen source). Additionally, the BH reaction rate could be improved by adding external H+ to the reaction system. The catalytic activity of Cu2O/TiO2 was discovered to remain at an efficient level even after six reaction cycles.

N-Heterocyclic Carbene-Supported Nickel-Catalyzed Selective (Un)Symmetrical N-Alkylation of Aromatic Diamines with Alcohols

The "borrowing hydrogen" (BH) approach for the N-alkylation of phenylenediamines using alcohols as coupling partners is highly challenging due to the selectivity issue of the generated products. Furthermore, the development of base-metal systems that can potentially substitute precious metals with competitive activity is a major challenge in BH catalysis. We present herein an efficient protocol for the N,N'-di-alkylation of aromatic diamines using an in situ-generated Ni-NHC complex from NiCl2 and the ligand L1, which gave access to a wide range of N,N'-di-alkylated orthophenylene diamines (rather than the generally observed benzimidazole derivatives), meta- and para-phenylene diamines along with 2,6-diamino pyridine derivatives in good to excellent yields. Moreover, the catalyst system was also successful in the derivatization of a clinically important drug molecule, Dapsone. Notably, the present protocol could be applied effectively to synthesize unsymmetrically substituted N,N'-di-alkylated diamines via sequential alkylation and is the first report in the base-metal system to the best of our knowledge. Diverse control experiments including the deuterium incorporation studies suggest that the present protocol proceeds via a BH sequence.

Synthesis and structure of Pd(II) pincer complexes: catalytic application in β-alkylation of secondary alcohols involving sequential dehydrogenation of alcohols via the borrowing hydrogen approach.

Herein, we report an efficient and sustainable approach for the selective synthesis of ketones by palladium pincer catalyzed β-alkylation of secondary alcohols with aromatic primary alcohols via the borrowing hydrogen (BH) approach for the first time. A set of new Pd(II) ONO pincer complexes was synthesized and characterised by elemental analysis and spectral techniques (FT-IR, NMR and HRMS). The solid-state molecular structure of one the complexes was corroborated by X-ray crystallography. A range of α-alkylated ketone derivatives (25 examples) was obtained in excellent yields up to 95% through sequential dehydrogenative coupling of secondary and primary alcohols with 0.5 mol% catalyst loading with a substoichiometric amount of the base. Control experiment studies were carried out for the coupling reactions which revealed that the reaction involves an aldehyde, a ketone and chalcone intermediates, and eventually established the borrowing hydrogen strategy. Gratifyingly, this protocol is simple and atom economical, with water/hydrogen as byproducts. In addition, large-scale synthesis also demonstrated the synthetic usefulness of the present protocol.

Efficient β-alkylation of secondary alcohols to α-substituted ketones catalyzed by functionalized Ir complexes via borrowing hydrogen in water

Highly efficient and selective alkylation via borrowing hydrogen in water was achieved with a functional Ir complex bearing an amidate ligand. The significant cooperation effect of the ligand on the high efficiency and selectivity was demonstrated.

Transition metal-catalysis in interrupted borrowing hydrogen strategy.

In recent times, the transition metal-catalyzed borrowing hydrogen (BH) and interrupted borrowing hydrogen (IBH) strategies have attracted much attention and represent atom- and step-economic processes to access diverse building blocks via various C-C and C-heteroatom bond-forming reactions. The advantages of these approaches include (i) use of feedstock chemicals, (ii) high atom economy, (iii) no pre-activation of the substrates, and (iv) producing water as the only by-product. In this context, several synthetic strategies have been developed in this regime for the past few decades. To the best of our knowledge, no review article describes the important concepts of interrupted borrowing hydrogen (IBH) reaction. This review article highlights the recent advances in the IBH strategy and its application in sustainable chemical synthesis, particularly C-C bond formation using methanol as a C1 source, synthesis of 3,3'-bisindolylmethanes (3,3'-BIMs), α-branched ketones/diketones, and regioselective alkylation of N-heterocycles.

Enantioconvergent transformations of secondary alcohols through borrowing hydrogen catalysis.

Direct substitution of readily available alcohols is recognized as a key research area in green chemical synthesis. Starting from simple racemic secondary alcohols, the achievement of catalytic enantioconvergent transformations of the substrates will be highly desirable for efficient access to valuable enantiopure compounds. To accomplish such attractive yet challenging transformations, the strategy of the enantioconvergent borrowing hydrogen methodology has proven to be uniquely effective and versatile. This review aims to provide an overview of the impressive progress made on this topic of research that has only thrived in the past decade. In particular, the conversion of racemic secondary alcohols to enantioenriched chiral amines, N-heterocycles, higher-order alcohols and ketones will be discussed in detail.

Ligand effect of cyclometallated iridium(iii) complexes on N-alkylation of amines in hydrogen borrowing reactions.

Dinuclear iridium complexes with the general formula (C^N)2Ir(μ-Cl)2Ir(C^N)2 (C^N = bidentate ligand with carbon and nitrogen donor atoms) were prepared and used in catalytic systems for N-alkylation of amines through the hydrogen borrowing pathway. Triphenylphosphine derivatives were used as auxiliary in catalytic systems to provide excellent conversion of amines to N-alkylation products in yields ranging from 57% to 100%. The catalytic ability of the catalyst depends on the structure of its coordination ligands, including bidentate ligands (C^N) and triphenylphosphine derivatives. These catalytic systems adopt an environmentally friendly and sustainable reaction process through a hydrogen self-transfer strategy, using readily available alcohols as alkylating agents without the need for bases, solvents, and other additives, showing potential in the synthetic and pharmaceutical industries.

Ligand-Promoted [Pd]-Catalyzed α-Alkylation of Ketones through a Borrowing-Hydrogen Approach.

A new class of palladium complexes bearing bidentate 2-hydroxypyridine based ligands have been prepared and fully characterized. The applications of these new complexes towards ketone alkylation reactions with alcohols through a metal-ligand cooperative borrowing-hydrogen (BH) process were demonstrated.

Chemodivergent coupling of azoarenes with benzyl alcohols via a borrowing hydrogen strategy using a well-defined nickel catalyst

A chemodivergent protocol for the (de)hydrogenative coupling of azoarenes with benzyl alcohol is described via the NN bond activation using an inexpensive and well-defined nickel catalyst.

Ruthenium-catalysed N-alkylation of anilines with primary carbohydrate alcohols via borrowing hydrogen strategy.

Ruthenium-catalysed N-alkylation of anilines with sugar derivatives proceeded via the borrowing hydrogen strategy. Primary carbohydrate alcohols were successfully applied to N-alkylation of aniline derivatives to give the corresponding aminosugars in high yields.