Hydroaminomethylation Reaction Research Articles

A Cooperative Rh/Co‐Catalyzed Hydroaminomethylation Reaction for the Synthesis of Terpene Amines

AbstractAn original bimetallic catalytic system based on Rh(I) and Co(0) in glycerol is described for the synthesis of biomass‐derived amines through the tandem hydroaminomethylation reaction of terpenes, such as (R)‐limonene, β‐pinene and camphene. Under optimized conditions, this multicatalytic system is highly chemoselective (avoiding hydrogenations of substrates and aldehyde‐based intermediates, and aldol condensations), exhibiting good‐to‐excellent regioselectivity towards linear amines. From a mechanistic viewpoint, cobalt mainly boosts the reductive amination, while rhodium shows a foremost role in the hydroformylation step. Regarding the nature of the organometallic species, catalytically inactive metal nanoparticles have been identified at the end of the reaction, proving the homogeneous nature of the bimetallic catalytic system.

Mechanistic kinetic modeling of the rhodium-catalyzed tandem hydroaminomethylation of 1-decene in a thermomorphic solvent system

For a more resource-efficient production of amines the homogeneously catalyzed tandem hydroaminomethylation reaction is of large relevance. The kinetics of the sulfoxantphos‑rhodium-catalyzed hydroaminomethylation of 1-decene were studied exploiting a thermomorphic solvent system. Focus was a mechanistic kinetic description of the enamine hydrogenation as the final step in the tandem reaction. Based on proposing a catalytic cycle and applying the Christiansen mathematics, a mechanistic rate model was derived and parameterized. The mechanistic model was able to describe the experimental observations in a broad range of operation conditions including pressure and temperature perturbations providing the basis for process design and optimization.

An alternative non-redox Ni(I) pathway in hydroaminomethylation: A theoretical perspective

Herein, we report a theoretical investigation on the nickel-catalyzed hydroaminomethylation reaction of alkyne with imine. In this work, an alternative Ni(I) mechanism, without a redox reaction, was proposed by DFT calculations. The mechanism based on these calculations is favorable compared with the previously proposed redox Ni(0)-Ni(II) pathway. A Ni(I)-amino complex is considered to be the active species, which can be obtained from hydrogen transfer between an imine-coordinated Ni(0) complex and an amine. A Meerwein-Ponndorf type hydride transfer takes place between an amino group and a coordinated alkyne. Then an imine insertion affords Ni(I)-allylamino. Proton transfer with the approaching imine yields the hydroaminomethylation product and regenerates the Ni(I)-amino active species. Throughout the catalytic cycle, the oxidative state of Ni remains at +1. Furthermore, AIM analysis shows that the dissociation of the amine ligand to provide a vacancy would lead to a higher free-energy barrier for the Ni(0)-Ni(II) pathway.

Interrupted Intramolecular Hydroaminomethylation of N-Protected-2-vinyl Anilines: Novel Access to 3-Substitued Indoles or Indoline-2-ols.

A new synthetic alternative to the synthesis of 3-methyl indoles and 3-methyl indoline-2-ols with an excellent atomic economy is presented in this study. It is demonstrated that the intramolecular interrupted hydroaminomethylation (HAM) reaction is a powerful tool for the formation of these compounds, which exhibit wide-ranging biological activity. Several N-Protected-2-vinyl anilines were synthesized and involved in the reaction producing the corresponding 3-methylindole or 3-methyl indoline-2-ol depending on the nature of the N-protecting groups.

Sequential hydroaminomethylation/Pd-catalyzed hydrogenolysis as an atom efficient route to valuable primary and secondary amines

The facile synthesis of valuable primary and secondary amines is reported using a sequential procedure of hydroaminomethylation and Pd-catalyzed hydrogenolysis. The hydroaminomethylation reaction was catalyzed by a cationic Rh(I) iminopyridyl complex and the N-alkylated benzylamines were produced with high chemoselectivity, albeit as mixtures of linear and branched products. Performing the hydrogenolysis reaction using 10% Pd/C, provided access to valuable primary and secondary amines which have applications in the surfactant, pharmaceutical and polymer industries.

Continuous co-product separation by organic solvent nanofiltration for the hydroaminomethylation in a thermomorphic multiphase system

While homogeneous catalysts can be used to efficiently produce intermediate and specialty chemicals, the separation of the precious catalyst from products, by-products or co-products can be a major challenge. Consequently, novel processes need to be developed to effectively separate and reuse the active catalyst, while avoiding accumulation of the various reaction products. Therefore, this work presents the development and demonstration of a hybrid, continuous reaction and separation process for the catalytic auto-tandem hydroaminomethylation (HAM) reaction. Herein, long-chain alkenes are converted to valuable higher aliphatic amines with high atom economy, while producing only water as co-product. Since the HAM is a rhodium-catalyzed reaction, a thermomorphic multiphase system is used as an integrated catalyst recycling strategy, which is further combined with a membrane-based separation of the co-product via organic solvent nanofiltration. Based on initial screening of various membranes and investigation on the water influence on the phase separation after the reactor, the full process for the HAM of 1-decene with diethylamine with separation of the co-product water was operated continuously for 75 h in a miniplant. The continuous operation of the process successfully demonstrated stable process operation, avoiding a steady accumulation of water while maintaining high catalyst rejection between 97% and 99.3%. The overall leaching of rhodium was kept below 3% of the total amount supplied. This corresponds to a loss of only 11 mg of catalyst per kg of product.

The Hydrogenation Problem in Cobalt‐based Catalytic Hydroaminomethylation

AbstractThe hydroaminomethylation (HAM) reaction converts alkenes into N‐alkylated amines and has been well studied for rhodium‐ and ruthenium‐based catalytic systems. Cobalt‐based catalytic systems are able to perform the essential hydroformylation reaction, but are also known to form very active hydrogenation catalysts, therefore we examined such a system for its potential use in the HAM reaction. Thus, we have quantum‐chemically explored the hydrogenation activity of [HCo(CO)3] in model reactions with ethene, methyleneamine, formaldehyde, and vinylamine using dispersion‐corrected relativistic density functional theory at ZORA‐BLYP‐D3(BJ)/TZ2P. Our computations reveal essentially identical overall barriers for the catalytic hydrogenation of ethene, formaldehyde, and vinylamine. This strongly suggests that a cobalt‐based catalytic system will lack hydrogenation selectivity in experimental HAM reactions. Our HAM experiments with a cobalt‐based catalytic system (consisting of Co2(CO)8 as cobalt source and P(n‐Bu)3 as ligand) resulted in the formation of the desired N‐alkylated amine. However, significant amounts of hydrogenated starting material as well as alcohol (hydrogenated aldehyde) were always formed. The use of cobalt‐based catalysts in the HAM reaction to selectively form N‐alkylated amines seems therefore not feasible. This confirms our computational prediction and highlights the usefulness of state‐of‐the‐art DFT computations for guiding future experiments.

Glycerol Boosted Rh-Catalyzed Hydroaminomethylation Reaction: A Mechanistic Insight.

We report a Rh-catalyzed hydroaminomethylation reaction of terminal alkenes in glycerol that proceeds efficiently under mild conditions to produce the corresponding amines in relatively high selectivity towards linear amines, moderate to excellent yields by using a low catalyst loading (1 mol % [Rh], 2 mol % phosphine) and relative low pressure (H2 /CO, 1:1, total pressure 10 bar). This work sheds light on the importance of glycerol in enabling enamine reduction via hydrogen transfer. Moreover, evidence for the crucial role of Rh as chemoselective catalyst in the condensation step has been obtained for the first time in the frame of the hydroaminomethylation reaction by precluding deleterious aldol condensation reactions. The hydroaminomethylation proceeds under a molecular regime; the outcome of catalytically active species into metal-based nanoparticles renders the catalytic system inactive.

Alkylation of Amines Via Tandem Hydroaminomethylation Using Imino-Pyridine Complexes of Rhodium as Catalyst Precursors

Novel cationic Rh(I) imino-pyridine complexes were evaluated as catalyst precursors in the hydroaminomethylation of 1-octene in conjunction with both primary (aniline and benzylamine) and secondary amines (piperidine). These complexes were found to be highly efficient catalysts in mediating a one-pot hydroaminomethylation reaction. High chemoselectivities towards the target secondary and tertiary amines were obtained depending on the reaction components.

Copper-Catalyzed Asymmetric Formal Hydroaminomethylation of Alkenes with N,O-Acetals to Access Chiral β-Stereogenic Amines: Dual Functions of the Copper Catalyst

Chiral amines are synthetically versatile intermediates used for the preparation of a wide range of biologically active compounds and drugs. Compared with the well-developed synthesis of α-stereoge...

Hydroaminomethylation reaction as powerful tool for preparation of rhodium/phosphine-functionalized nanomaterials. Catalytic evaluation in styrene hydroformylation

This paper describes a new efficient synthetic methodology to prepare Rh/phosphine functionalized carbon nanotubes and iron oxide magnetic nanoparticles via hydroaminomethylation reaction. These hybrid nanomaterials were fully characterized and evaluated in rhodium catalyzed styrene hydroformylation. The iron oxide magnetic nanoparticle based catalyst demonstrated high activity and selectivity for branched aldehydes, displaying easy recovery by magnetic separation without loss of activity in consecutive cycles.

Tandem Hydroaminomethylation Reaction to Synthesize Amines from Alkenes.

In the context of atom economy and low environmental impact, synthesis of amines by an efficient catalytic process is of great importance to produce these building blocks for fine chemical industry. The one-pot hydroaminomethylation of alkenes is a tandem reaction which involves three successive steps under CO/H2 pressure to perform the catalyzed hydroformylation of the alkene into the corresponding aldehyde followed by its condensation with a N-H function and the catalyzed hydrogenation of the imine/enamine intermediate into the corresponding saturated amine. Rhodium and more recently ruthenium complexes have been designed to combine high conversions of the reactants and chemoselectivity in the expected amines with high regioselectivity in either the linear or the branched amine. The coordination sphere of the metal according to the presence of ligands, temperature, CO/H2 partial pressures, and nature of the solvent is essential for complying with these selectivity requirements. The rate of the hydroformylation step needs to be fast with regard to the hydrogenation step. The role of amines in the coordination sphere and water, presumably in the second sphere, on the mechanism requires some more studies. Similarly, the enantioselective synthesis of amine is not yet achieved directly and interrupted processes or use of asymmetric organo-catalyzed reductive amination are efficient synthetic ways for producing chiral amines. The separation of the catalyst from the organic products by biphasic or (semi-) heterogeneized systems and its recycling have been demonstrated in many cases. The present review provides a report of the state of the art in this autotandem hydroaminomethylation catalysis and should open prospects in the design of less expensive and abundant metal complexes for reaching at low cost similar and even superior performances.

Catalyst recycling in the hydroaminomethylation of methyl oleate: A route to novel polyamide monomers

This article describes the development of an effective thermomorphic multicomponent solvent (TMS) system for the production of branched polyamide monomers. In this system, methyl oleate, a renewable from fats and oils, and a functionalized amine are used as starting materials in a tandem catalytic reaction, which merges different reaction steps into a single preparative step. This particular TMS system consisted of a heptane/acetonitrile solvent mixture and made reusing the precious rhodium catalyst possible in three recycle runs. A constant yield of 61–65% was obtained for each run due to low‐catalyst leaching. Fortunately, the catalyst system does not require any additional phosphorous ligands and allows high yields. A scale‐up for the production of 10–11 g of the desired product in each run was realized. Subsequent hydrogenation of the product directly provided an amine ester, which is a valuable polyamide monomer.Practical applications: A method was developed to enable access to primary amines via hydroaminomethylation and hydrogenation. The product, a nitrile ester, is a valuable intermediate for polyamide monomers. This nitrile ester was successfully hydrogenated to an amine ester, which features a potential polyamide monomer directly. A catalyst recycle of the homogeneous rhodium complex within the hydroaminomethylation of methyl oleate and an amino nitrile was successfully carried out, enabling constant homogeneous catalyst activity over the course of three recycle runs. A scale‐up to obtain 10–11 g of the hydroaminomethylation product was realized.A general method is described for the conversion of methyl oleate within a hydroaminomethylation reaction. The catalyst can be recovered and reused. Valuable polyamide intermediates were obtained.

Rhodium/Yanphos-Catalyzed Asymmetric Interrupted Intramolecular Hydroaminomethylation of trans-1,2-Disubstituted Alkenes.

The first interrupted asymmetric hydroaminomethylation reaction was developed. The challenging trans-1,2-disubstituted olefins were employed as substrates, and a series of valuable chiral pyrrolidinones and pyrrolidines were obtained in high yields with high regioselectivities and excellent enantioselectivities. Several synthetic transformations were conducted, demonstrating the high synthetic utility of our method. A creative route for the synthesis of vernakalant and Enablex was also developed.

ChemInform Abstract: Synthesis of 4‐Aryl‐2,3‐dihydropyrroles via Rh‐Catalyzed Intramolecular Hydroamino‐Methylation Reaction.

The rhodium-catalyzed intramolecular hydroaminomethylation reaction, generating 4-aryl-2,3-dihydropyrroles, has been developed. Triphenylphosphine has been proved to be the excellent ligand to prepare the dihydropyrrole derivatives in up to 99% yield. This procedure provides an efficient and simple alternative route to synthesize 4-aryl-2,3-dihydropyrrole derivatives only in one step.

Synthesis of 4-aryl-2,3-dihydropyrroles via Rh-catalyzed intramolecular hydroamino-methylation reaction

The rhodium-catalyzed intramolecular hydroaminomethylation reaction, generating 4-aryl-2,3-dihydropyrroles, has been developed. Triphenylphosphine has been proved to be the excellent ligand to prepare the dihydropyrrole derivatives in up to 99% yield. This procedure provides an efficient and simple alternative route to synthesize 4-aryl-2,3-dihydropyrrole derivatives only in one step.

Rhodium exchanged ETS-10 and ETS-4: Efficient heterogeneous catalyst for hydroaminomethylation

Rhodium exchanged titanosilicates (ETS-10 and ETS-4) were synthesized and found to be efficient and stable catalysts for hydroaminomethylation reaction. The catalyst was highly active and selective towards amine product within lower reaction time of 4h. 1-Hexene and pyrrolidine were taken as representative substrates for parametric variations using Rh-ETS-10. The increase in pyrrolidine ratio gave some significant information showing a decrease in conversion with increased selectivity. The reason may be the competition between pyrrolidine and 1-hexene for coordination sites in rhodium and which prevents the beta-hydride elimination. The ratios of H2 and CO have influenced hydroaminomethylation and the best performance was in the CO:H2 ratio of 1:4 under the studied conditions. The initial rate of formation of amine was double than that of isomerization of 1-hexene. The Rh cluster like complex was formed on treating the catalyst with syn gas. A homogenous–heterogeneous dual nature of Rh was found during hydroaminomethylation. The catalyst was effectively recycled for three times without much loss in its activity and selectivity.

Hydroaminomethylation of Styrene Catalyzed by Rhodium Complexes Containing Chiral Diphosphine Ligands and Mechanistic Studies: Why Is There a Lack of Asymmetric Induction?

Various chiral diphosphine ligands (P–P) have been introduced in the coordination sphere of neutral or cationic rhodium complexes, and the generated species catalyze efficiently the hydroaminomethylation reaction of styrene with piperidine. The diphospholane ligand family is particularly adapted to this tandem reaction leading to the branched amine with good chemo- and regioselectivity. We analyzed in detail the main reasons why the reaction proceeds with no enantioselectivity. Catalytic and HP-NMR experiments reveal the presence of the [Rh(H)(CO)2(P–P)] species as the resting state. DFT calculations allow us to elucidate the mechanism of the hydrogenation of the branched (Z) or (E)-enamine. From the [Rh(H)(CO)(P–P)] active species, the coordination of the two enamine isomers, the hydride transfer, the H2 activation, and then the final reductive elimination follow similar energetic pathways, explaining the lack of enantioselectivity for the present substrates. Analysis of the energy-demanding steps highlights the formation of the active species as crucial for this rate-limiting hydrogenation reaction.

Thermoregulated phase-transfer rhodium nanoparticle catalyst for hydroaminomethylation of olefins

Rh nanoparticles used as catalysts for hydroaminomethylation reaction is reported for the first time. An efficient and recyclable Rh nanoparticle catalyst stabilized by thermoregulated ligand Ph2P(CH2CH2O)nCH3 (n = 16) was studied for the hydroaminomethylation of olefins in the aqueous/1-butanol biphasic system through thermoregulated phase-transfer catalysis, which allows not only for a homogeneous catalytic reaction, but also for an easy biphasic separation. Under the optimized conditions, the conversion of 1-octene and the product amine selectivity were as high as 99% and 97%, respectively. After reaction, the Rh nanoparticle catalyst can be separated from products by simple phase separation and recycled directly for the next run.

Interplay between Cationic and Neutral Species in the Rhodium‐Catalyzed Hydroaminomethylation Reaction

The reactivity of [Rh(CO)(2){(R,R)-Ph-BPE}]BF(4) (2) toward amine, CO and/or H(2) was examined by high-pressure NMR and IR spectroscopy. The two cationic pentacoordinated species [Rh(CO)(3) {(R,R)-Ph-BPE}]BF(4) (4) and [Rh(CO)(2)(NHC(5)H(10)){(R,R)-Ph-BPE}]BF(4) (8) were identified. The transformation of 2 into the neutral complex [RhH(CO)(2){(R,R)-Ph-BPE}] (3) under hydroaminomethylation conditions (CO/H(2), amine) was investigated. The full mechanisms related to the formation of 3, 4 and 8 starting from 2 are supported by DFT calculations. In particular, the pathway from 2 to 3 revealed the deprotonation by the amine of the dihydride species [Rh(H)(2)(CO)(2){(R,R)-Ph-BPE}]BF(4) (6), resulting from the oxidative addition of H(2) on 2.