Rhodium-catalyzed Hydroformylation Research Articles

Microkinetic Molecular Volcano Plots for Enhanced Catalyst Selectivity and Activity Predictions.

Molecular volcano plots, which facilitate the rapid prediction of the activity and selectivity of prospective catalysts, have emerged as powerful tools for computational catalysis. Here, we integrate microkinetic modeling into the volcano plot framework to develop "microkinetic molecular volcano plots". The resulting unified computational framework allows the influence of important reaction parameters, including temperature, reaction time, and concentration, to be quickly incorporated and more complex situations, such as off-cycle resting states and coupled catalytic cycles, to be tackled. Compared to previous generations of molecular volcanoes, these microkinetic counterparts offer a more comprehensive understanding of catalytic behavior, in which selectivity and product ratios can be explicitly determined by tracking the evolution of each product concentration over time. This is demonstrated by examining two case studies, rhodium-catalyzed hydroformylation and metal-catalyzed hydrosilylation, in which the unique insights provided by microkinetic modeling, as well as the ability to simultaneously screen catalysts and reaction conditions, are highlighted. To facilitate the construction of these plots/maps, we introduce mikimo, a Python program that seamlessly integrates with our previously developed automated volcano builder, volcanic.

Integrated techno-economic and life cycle assessment of hydroformylation in microemulsion systems

This paper presents the first integrated techno-economic and life cycle assessment of microemulsion systems being applied for rhodium-catalyzed hydroformylation of long-chain alkenes at industrial scale. The case study describes a projected 150 kt/a production of tridecanal (US gulf coast, 2019). The industrial success of the hydroformylation of short-chain alkenes lies in the continuous recycling of the rhodium-containing water phase. Microemulsion systems can be applied to transfer this concept to long-chain alkenes by overcoming the miscibility gap between the aqueous catalyst phase and the unipolar alkene phase and, moreover, by generating a temperature-induced multi-phase system enabling the immobilization of the catalyst and its continuous recycling, as demonstrated in miniplant operations with dodecene and rhodium/SulfoXantPhos. Customizable simulation models have been developed for scale-up and assessment of the miniplant data. Surprisingly, a profitability-driven sensitivity study indicates a base case optimum at low residence time with low alkene conversion leading to large throughput streams and high raw material purge rates. The comparison to the industrial cobalt-based benchmark system shows an economic advantage regarding net present value (Rh: 68 M$; Co: 62 M$), while about half of the environmental indicators are in favor or equivalent. In a best-case scenario considering zero leaching of expensive rhodium the net present value increases by almost 40% accompanied by a shift to overall lower environmental impacts than the benchmark. In conclusion, the investigated miniplant data suggest microemulsion systems to be competitive when applied in continuous processes at a large scale.

P(V)-Promoted Rh-Catalyzed Highly Regioselective Hydroformylation of Styrenes under Mild Conditions.

Hydroformylation of olefins is widely used in the chemical industry due to its versatility and the ability to produce valuable aldehydes with 100% atom economy. Herein, a hybrid phosphate promoter was found to efficiently promote rhodium-catalyzed hydroformylation of styrenes under remarkably mild conditions with high regioselectivities. Preliminary mechanistic studies revealed that the weak coordination between the Rhodium and the P=O double bond of this pentavalent phosphate likely induced exceptional reactivity and high ratios of branched aldehydes to linear products.

A Tandem Hydroformylation-Organocatalyzed Friedel-Crafts Reaction for the Synthesis of Diindolylmethanes.

Herein, we present an efficient and atom-economic tandem hydroformylation organocatalyzed Friedel-Crafts reaction sequence for the synthesis of diindolylmethanes. Classic syntheses have relied on (Lewis) acid activation of aldehydes, which are often not commercially available and rather sensitive in handling. In contrast, the combination of rhodium-catalyzed hydroformylation and subsequent organocatalytic activation of the in-situ formed aldehydes allows the use of readily available and stable alkenes with various functional groups while avoiding acidic conditions to expand the range of available diindolylmethanes. A broad scope of diindolylmethanes was prepared in yields up to 85 % demonstrates the utility of the presented method.

Exploring the Hurdles in Thermomorphic Multicomponent Systems in the Rhodium-Catalyzed Multiphase Hydroformylation

Exploring the Hurdles in Thermomorphic Multicomponent Systems in the Rhodium-Catalyzed Multiphase Hydroformylation

Rhodium-catalyzed hydroformylation of strained dialkenes: Ligand effect on product selectivity and complex coordination mode

We reported the synthesis of new and easily tunable diphosphine ligands L1-L5 based on bis(1H-indol-3-yl)methane. Strained 2,5-norbornadiene and dicyclopentadiene were used as the substrates to elucidate the relationship between ligand structure and product selectivity in Rh-catalyzed hydroformylation. Details in NMR, HRMS and single-crystal X-ray diffraction revealed that the coordination number and oxidation state could change rapidly upon exposure of RhI-L complexes to air. More importantly, the special structure of ligand which led to intramolecular methylene C–H oxidative addition to metal center could facilitate the hydroformylation reaction in an unexpected way.

Unexpected selectivities in transition metal-catalyzed hydroformylation of vinyl-substituted cavitands

Platinum- and rhodium-catalyzed hydroformylation reactions were performed on tetra(vinyl)cavitand skeletons. Instead of obtaining a statistical mixture of products, the reactions proceeded with high ‘tetra-selectivities’, that is, all four vinyl groups were either hydrogenated or transformed to the branched or linear aldehydes via hydroformylation. Based on these exceptionally high chemo- and regioselectivities, a cooperation between all the four catalytic reaction centers was supposed.

Review of Calixarene-Derivatives in Transition Metal Chemistry

The survey depicts the combination of large-scale monodentate phosphites in response to PCl3/NEt3 with p-tert-butyl calix[4]-(OH)3-OR, where R contains an oxygen-containing substituent (R = CH2P(O)Ph2, -CH2CO2Et, -CH2C(O)NEt2, -CH2CH2OMe). These funnel-shaped calissarenes have a phosphorus particle bridging three phenolic oxygen atoms, and are incredibly steady in NaOH-aqueous arrangement due to the cone point being more noteworthy than 180°. Upon response with transition metal particles, these phosphites shape either P monodentate complexes or expansive P,O chelate complexes including the oxygen atom of the R group. The reactivity of four different ligands in the rhodium-catalyzed hydroformylation of octene was examined. The general trend is that a bulkier phosphite ligand leads to a slower reaction rate. The ligand-to-base ratios ranged from 1.4 to 3.6, and the highest straight aldehyde selectivity was observed when the carboxylate group was CH2CO2Et.

Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis, Characterisation and Application in Rhodium-Catalysed Hydroformylation

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)2(acac), was attested by 31P NMR, which presented a doublet in the range of δ = 120 ppm, with a 1J(103Rh-31P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm−1 and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.

Construction of a quaternary stereogenic center by asymmetric hydroformylation: a straightforward method to prepare chiral α-quaternary amino acids.

The construction of chiral quaternary carbon stereocenters has been a long-standing challenge in organic chemistry. Particularly, α-quaternary amino acids that are of high importance in biochemistry still lack a straightforward synthetic method. We here reported a hydroformylation approach to access chiral quaternary stereogenic centers, which has been a long-standing challenge in transition metal catalysis. α,β-Unsaturated carboxylic acid derivatives undergo hydroformylation with a rhodium catalyst to generate an α-quaternary stereocenter under mild conditions. By using this method, a variety of chiral α-quaternary amino acids could be synthesized with satisfactory enantioselectivity. In-depth investigation revealed that the regioselectivity is dramatically influenced by the electronic properties of the substituents attached to the target C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> C bond. By applying NMR and DFT analyses, the chiral environment of a rhodium/Yanphos complex was depicted, based on which a substrate-catalyst interaction model was proposed.

Synthesis of diols from jojoba oil via rhodium-catalyzed reductive hydroformylation: a smart way to access biobased polyurethanes

Diol was synthesised from Jojoba oil ester by a recyclable catalytic system and was used for biobased polyurethane synthesis.

Selective Rhodium-Catalyzed Hydroformylation of Terminal Arylalkynes and Conjugated Enynes to (Poly)enals Enabled by a π-Acceptor Biphosphoramidite Ligand.

The hydroformylation of terminal arylalkynes and enynes offers a straightforward synthetic route to the valuable (poly)enals. However, the hydroformylation of terminal alkynes has remained a long-standing challenge. Herein, an efficient and selective Rh-catalyzed hydroformylation of terminal arylalkynes and conjugated enynes has been achieved by using a new stable biphosphoramidite ligand with strong π-acceptor capacity, which affords various important E-(poly)enals in good yields with excellent chemo- and regioselectivity at low temperatures and low syngas pressures.

Synthesis of the Lipophilic Amine Tail of Abediterol Enabled by Multiphase Flow Transformations

The development of a continuous-flow sequence for the synthesis of an important drug candidate precursor is reported. Abediterol is a β2-adrenoceptor agonist that has undergone phase IIa clinical trials for the treatment of respiratory disease. A flow sequence is developed for the preparation of the lipophilic amine tail portion of abediterol. The sequence comprises of a phase-transfer-catalyzed liquid/liquid O-alkylation, a rhodium-catalyzed hydroformylation, and a ruthenium-catalyzed reductive amination. The reactions were optimized separately within continuous-flow environments to identify important parameter effects. The strongly basic O-alkylation operates with greater than 90% conversion within a 23 min residence time. The hydroformylation uses 1 mol % Rh(acac)(CO)2 (acac = acetylacetone) as a catalyst and 6 mol % Xantphos as a ligand with 1.1 equiv of hydrogen and carbon monoxide. The optimized O-alkylation and hydroformylation telescoped flow process was successfully operated over 6 h. The protocol is shown to be high yielding for the desired linear aldehyde (75% gas chromatography yield, ∼2.5 g/h). The sequence requires a solvent switch prior to the reductive amination. The final step is a high-pressure (40 bar) and high-temperature (150 °C) Ru-catalyzed reductive amination using ammonia and hydrogen to afford the amine tail. The solution yield for the formation of the amine tail was 78%. The yield of the reductive amination with an unoptimized isolation was 50%, resulting in an overall isolated yield for the three-step sequence of 38%. This compares favorably against the batch yield of 26% using a different synthetic route.

Rhodium-Catalyzed Regioselective Hydroformylation of Alkynes to α,β-Unsaturated Aldehydes Using Formic Acid.

A rhodium-catalyzed hydroformylation of alkynes with formic acid was developed. The method provides α,β-unsaturated aldehydes in high yield and E-selectivity without the need to handle toxic CO gas.

Solvent effects in hydroformylation of long-chain olefins

With the increasing concern about climate change, a transformation of chemical processes from petrochemicals towards renewable, sustainable feedstock is indispensable. This transition, however, requires a careful assessment of the transferability of kinetic and thermodynamic data and reaction mechanisms. Here, the rhodium-catalyzed hydroformylation reaction of a long chain olefin (1-decene) from renewable resources with synthesis gas (CO/H2) is investigated. The bidentate phosphite ligand (BiPhePhos) shows a high degree of selectivity towards the desired n-aldehyde. This selectivity can be rationalized by kinetic discrimination at the branching point, i.e. the transition state of the hydride insertion step. Formation of the iso-aldehyde is kinetically and thermodynamically discriminated. The complex multi-step reactions of the desired hydroformylation reaction pathway with respect to the side-reactions such as olefin isomerization and hydrogenation are elucidated in detail. The solvent effects of a mixed polar/non-polar thermomorphic solvent system (DMF/dodecane) on chemical equilibria and activation energies were investigated using the COSMO-RS solvent model. Solvent screening for the overall rate-determining step gives a perspective as to solvent control of the process.

AutodE: Automated Calculation of Reaction Energy Profiles- Application to Organic and Organometallic Reactions.

Calculating reaction energy profiles to aid in mechanistic elucidation has long been the domain of the expert computational chemist. Here, we introduce autodE (https://github.com/duartegroup/autodE), an open-source Python package capable of locating transition states (TSs) and minima and delivering a full reaction energy profile from 1D or 2D chemical representations. autodE is broadly applicable to study organic and organometallic reaction classes, including addition, substitution, elimination, migratory insertion, oxidative addition, and reductive elimination; it accounts for conformational sampling of both minima and TSs and is compatible with many electronic structure packages. The general applicability of autodE is demonstrated in complex multi-step reactions, including cobalt- and rhodium-catalyzed hydroformylation and an Ireland-Claisen rearrangement.

Hydroformylation of olefins using redox-active rhodium(I) alpha-diimine-cored aryl ether metallodendrimers

Rhodium(I) poly(aryl ether)-based, core-functionalised alpha-diimine metallodendrimers were investigated as catalyst precursors in the rhodium-catalysed hydroformylation of terminal olefins, 1-octene and styrene. The electronic environment across the metallodendrimer series was probed using cyclic voltammetry. The electrochemical behaviour of the metallodendrimers show irreversible and quasi-reversible electrochemical behaviour in the range 0.0–2.0 V at a scan rate of 100 mV s−1. All the catalyst precursors (C1-C6) gave excellent conversions of the respective substrates with good chemoselectivity under the investigated conditions. In general, the higher dendritic catalysts C5 and C6 gave better regioselectivity, favouring linear aldehydes.

Rh-Catalyzed Asymmetric Hydroaminomethylation of α-Substituted Acrylamides: Application in the Synthesis of RWAY.

The successful rhodium-catalyzed asymmetric hydroformylation and hydroaminomethylation of α-substituted acrylamides is described using 1,3-phosphite-phosphoramidite ligands based on a sugar backbone. A broad scope of chiral aldehydes and amines were afforded in high yields and excellent enantioselectivities (up to 99%). Furthermore, the synthetic potential of this method is demonstrated by the single-step synthesis of the brain imaging molecule RWAY.

Sequential catalytic carbonylation reactions for sustainable synthesis of biologically relevant entities

The sustainable synthesis of highly functionalised formylcarboxamide compounds with biological relevance is reported through a sequential aminocarbonylation/hydroformylation approach. The optimisation of palladium-catalysed aminocarbonylation of iodoaromatic substrates, using allylamine as nucleophile was first performed, with molybdenum hexacarbonyl as alternative CO source versus gaseous carbon monoxide. The combination of microwave irradiation with molybdenum hexacarbonyl allowed to selectively prepare a set of N-heterocyclic-based allylcarboxamides. Subsequent rhodium-catalysed hydroformylation of the allylcarboxamide intermediates led to the preparation of new pyridine, pyrazoline and chalcone derivatives containing both carboxamide and formyl moieties.

Highly Efficient 1-Octene Hydroformylation at Low Syngas Pressure: From Single-Droplet Screening to Continuous Flow Synthesis

We present a reconfigurable flow chemistry strategy for facile transition between accelerated screening and continuous synthesis of linear aldehydes through homogeneous rhodium-catalyzed hydroformylation of alkenes. The intensified mass and heat transport rates of the utilized membrane-based flow reactor enable access to safe and desirable reaction conditions (i.e., 50 psig syngas pressure) while providing high chemoselectivity and regioselectivity of the produced aldehydes. Additionally, by conducting hydrogen–deuterium scrambling experiments, we propose a reaction mechanism for the highly efficient hydroformylation reaction in flow.