Regioselective Hydroformylation Research Articles

Regioselective hydroformylation with subnanometre Rh clusters in MFI zeolite

Regioselective hydroformylation with subnanometre Rh clusters in MFI zeolite

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.

Regioselective hydroformylation of propene catalysed by rhodium-zeolite.

Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than99% regioselectivity to n-butanal and more than99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.

Synergistic effect between monophosphine species for regioselective hydroformylation of olefin with CO2

CO2 as a substitute for CO in hydroformylation is promising for alleviating greenhouse effect. Phosphine ligand has a significant impact on the regioselectivity of olefin hydroformylation with CO2. Compared with complex and expensive bisphosphine ligands, easily available and inexpensive monophosphine ligands are potential for widespread application especially in industrial hydroformylation. However, the regioselectivity of monophosphine ligand catalysts is still unsatisfactory. Herein, we proposed synergistic effect existing in two types of monophosphine species, which was copolymerized in a concise manner. The single-atom catalysts (Rh-POL-PPO&PPh3) obtained through such a strategy, are efficient for olefins/CO2 hydroformylation with high regioselectivity (l/b = 18.4) and conversion (94.9 %), which is comparable to diphosphine ligand. The characterization and DFT calculations reveal that high hydroformylation regioselectivity is attributed to the synergistic effect between two monophosphine species, which endows the catalyst with better configuration of active sites, and can promote the association of Rh with the terminal carbon of olefin.

Pd-Catalyzed Regioselective Hydroformylation of Olefins with HCO2H and Its Derivatives.

An effective Pd-catalyzed regioselective hydroformylation process with N-formylsaccharin or 2,4,6-trichlorophenyl formate along with formic acid is described. Linear aldehydes can be obtained in up to 83% yield and >20:1 l/b ratio. The reaction is operationally simple without the need for external CO and H2.

Operando characterization of rhodium catalyst degradation in hydroformylation

Kinetic studies combined with DFT calculations revealed degradation of catalyst to Rh-carbonyl clusters is responsible for the loss of regioselectivity in hydroformylation.

Metal–organic framework ZIF-8 loaded with rhodium nanoparticles as a catalyst for hydroformylation

Porous metal–organic framework ZIF-8 materials containing incorporated rhodium (Rh@ZIF-8) and rhodium chloride (RhCl3@ZIF-8) nanoparticles were obtained and tested as a catalytic reaction vessel in the reactions of hydroformylation of 1-decene and styrene. Catalytic tests with Rh@ZIF-8 showed that the selectivity and conversion of the hydroformylation reaction depended on the size of the substrate molecule. The incorporation of catalytic nanoparticles into the pores of a metal–organic framework opens up new possibilities for regioselective hydroformylation.

Confinement of atomically dispersed Rh catalysts within porous monophosphine polymers for regioselective hydroformylation of alkenes

Precisely controlling the regioselectivity with monophosphine ligand is a long-standing challenge in hydroformylation. Herein, we describe the one-pot encapsulation of single-atom Rh catalysts within porous monophosphine polymers for regioselective heterogeneous hydroformylation of alkenes. The optimized catalyst (Rh@POP-PTBA-HA-50) shows remarkable enhancement of regioselectivity compared with the combination of Rh(CO)2(acac) and monophosphine ligand (PTBA), and the linear aldehyde selectivity increases from 62% to 92%. In addition, this catalyst shows excellent catalytic activity (one run TON at least 60,000) and good stability. Detailed studies reveal that the encapsulation of atomically dispersed Rh catalysts within porous monophosphine polymers may endow the catalysts with high regioselectivity, while the encirclement of metal active species by abundant but dispersive phosphine ligand would strengthen the stability of the catalysts through multiple-sites-coordination. The present study provides meaningful insights for designing heterogeneous catalysts with good regioselectivity, and merging the advantages of homogeneous and heterogeneous catalysis.

Synthesis of rac-[formula omitted]-aryl propionaldehydes via branched-selective hydroformylation of terminal arylalkenes using water-soluble Rh-PNP catalyst

This work detailed the preparation of a class of water-soluble PNP ligands that differed by the nature of the substitute on phenyl ring of ligands. These ligands were incorporated into water-soluble rhodium-PNP complex catalysts that were used to regioselective hydroformylation of a series of terminal arylalkenes, providing efficient access to rac-α-aryl propionaldehydes in good to excellent yield (up to 97%) and branched-regioselectivity (up to 40:1 b/l ratio). Furthermore, gram-scale and diverse synthetic transformation demonstrated synthetic application of this methodology for non-steroidal antiinflammatory drugs.

Phosphorus coordinated Rh single-atom sites on nanodiamond as highly regioselective catalyst for hydroformylation of olefins

Single-atom Rh catalysts present superior activity relative to homogeneous catalyst in olefins hydroformylation, yet with limited success in regioselectivity control. In the present work, we develop a phosphorus coordinated Rh1 single-atom catalyst with nanodiamond as support. Benefiting from this unique structure, the catalyst exhibits excellent activity and regioselectivity in hydroformylation of arylethylenes with wide substrate generality, i.e., with high conversion (>99%) and high regioselectivity (>90%), which is comparable with the homogeneous counterparts. The coordination interaction between Rh1 and surface phosphorus species is clarified by 31P solid-state NMR and X-ray absorption spectroscopy (XAS). Rh single atoms are firmly anchored over nanodiamond through Rh-P bonds, guaranteeing good stability in the hydroformation of styrene even after six runs. Finally, by using this catalyst, two kinds of pharmaceutical molecules, Ibuprofen and Fendiline, are synthesized efficiently with high yields, demonstrating a new prospect of single-atom catalyst in pharmaceutical synthesis.

Micellar Catalysis for Sustainable Hydroformylation

AbstractIt is here reported a fully sustainable and generally applicable protocol for the regioselective hydroformylation of terminal alkenes, using cheap commercially available catalysts and ligands, in mild reaction conditions (70 °C, 9 bar, 40 min). The process can take advantages from both micellar catalysis and microwave irradiation to obtain the linear aldehydes as the major or sole regioisomers in good to high yields. The substrate scope is largely explored as well as the application of hydroformylation in tandem with intramolecular hemiacetalization thus demonstrating the compatibility with a broad variety of functional groups. The reaction is efficient even in large scale and the catalyst and micellar water phase can be reused at least 5 times without any impact in reaction yields. The efficiency and sustainability of this protocol is strictly related to the in situ transformation of the aldehyde into the corresponding Bertagnini's salt that precipitates in the reaction mixture avoiding organic solvent mediated purification steps to obtain the final aldehydes as pure compounds.

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.

Chemo- and regioselective hydroformylation of alkenes with CO2/H2 over a bifunctional catalyst

Combining CO2 and H2 for chemo- and regioselective hydroformylation of alkenes has been realized. The key to success is the use of a bifunctional Rh/PTA catalyst, which can ingeniously combine efficient CO2 hydrogenation and hydroformylation.

Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures.

Native to the Asia-Pacific region and widely applied in traditional Chinese medicine, the genus Daphniphyllum has produced over 330 known Daphniphyllum alkaloids. Investigations into these alkaloids have shown an exceptional range of interesting bioactivities. Challenging and caged polycyclic architectures and the promising biological profiles make Daphniphyllum alkaloids intriguing synthetic targets. Based on their backbones, these alkaloids can be categorized into 13-35 structurally distinct subfamilies. In addition to our work, almost 30 impressive total syntheses of Daphniphyllum alkaloids from seven subfamilies, namely, daphniphylline-type, secodaphniphylline-type, daphnilactone A-type, bukittinggine-type, daphmanidin A-type, calyciphylline A-type, and calyciphylline B-type alkaloids, have been reported by 11 research groups. However, many Daphniphyllum alkaloid subfamilies remain inaccessible by chemical synthesis.In this Account, we summarize our recent endeavors in the total synthesis of Daphniphyllum alkaloids commencing from simple chiral bicyclic synthons. Daphniphyllum alkaloids with diversified skeletons from four different subfamilies, namely, calyciphylline A-type, daphnezomine A-type, bukittinggine-type, and yuzurimine-type alkaloids, have been achieved. Furthermore, the tricyclic core structure of daphniglaucin C-type alkaloids daphnimacropodines was also synthesized. First, we describe a 14-step synthesis of calyciphylline A-type alkaloid (-)-himalensine A, which features a mild Cu-mediated nitrile hydration, an intramolecular Heck reaction to assemble the pivotal 2-azabicyclo[3.3.1]nonane moiety, and a Meinwald rearrangement to introduce the critical oxidative state into the skeleton. We then introduce the synthesis of daphnezomine A-type alkaloid dapholdhamine B, which possesses a unique aza-adamantane core. This target molecule was fabricated using key reactions including Huang's amide-activation-annulation. An unexpected radical detosylation during the synthesis of dapholdhamine B further inspired an ambitious radical cyclization cascade strategy, which eventually led to an efficient total synthesis of bukittinggine-type alkaloid (-)-caldaphnidine O. This highly chemo-, regio-, and stereoselective radical reaction cascade also shed light on the synthetic strategy of other alkaloids with caged structures. We next describe the first total synthesis of yuzurimine-type alkaloid (+)-caldaphnidine J. The key steps in our approach include a Pd-catalyzed regioselective hydroformylation and a novel Swern oxidation/ketene dithioacetal Prins reaction cascade. The work has achieved the first synthesis of a member of the largest subfamily of Daphniphyllum alkaloids. Finally, we show our efforts toward the total synthesis of daphniglaucin C-type alkaloids. Overall, we hope that the interesting strategies and synthetic methods demonstrated in our efforts could inspire a wide variety of additional applications to natural product synthesis.

Regioselective Hydroformylation of Internal and Terminal Alkenes via Remote Supramolecular Control.

Regioselective catalytic transformations using supramolecular directing groups are increasingly popular as it allows for control over challenging reactions that may otherwise be impossible. In most examples the reactive group and the directing group are close to each other and/or the linker between the directing group is very rigid. Achieving control over the regioselectivity using a remote directing group with a flexible linker is significantly more challenging due to the large conformational freedom of such substrates. Herein, we report the redesign of a supramolecular Rh-bisphosphite hydroformylation catalyst containing a neutral carboxylate receptor (DIM pocket) with a larger distance between the phosphite metal binding moieties and the DIM pocket. For the first time regioselective conversion of internal and terminal alkenes containing a remote carboxylate directing group is demonstrated. For carboxylate substrates that possess an internal double bond at the Δ-9 position regioselectivity is observed. As such, the catalyst was used to hydroformylate natural monounsaturated fatty acids (MUFAs) in a regioselective fashion, forming of an excess of the 10-formyl product (10-formyl/9-formyl product ratio of 2.51), which is the first report of a regioselective hydroformylation reaction of such substrates.

Rh-catalyzed highly regioselective hydroformylation to linear aldehydes by employing porous organic polymer as a ligand.

In this work, we developed a new structural porous organic polymer containing biphosphoramidite unit, which can be used as a solid bidentate phosphorous ligand for rhodium-catalyzed solvent-free higher olefins hydroformylation. The resultant catalyst demonstrated unprecedently high regioselectivity to linear aldehydes and could be readily recovered for successive reuses with good stability in both catalytic activity and regioselectivity.

Heterogeneous Ligand-Free Rhodium Oxide Catalyst Embedded within Zeolitic Microchannel to Enhance Regioselectivity in Hydroformylation

This work reported the heterogeneous rhodium oxide catalyst encapsulated within microporous silicalite-1 (S-1) zeolite (Rh2O3@S-1) through epitaxial growth of S-1 seeds pre-anchored with rhodium sp...

A domino reaction for generating \u03b2-aryl aldehydes from alkynes by substrate recognition catalysis

The development of universal catalyst systems that enable efficient, selective, and straightforward chemical transformations is of immense scientific importance. Here we develop a domino process comprising three consecutive reaction steps based on the strategy of supramolecular substrate recognition. This approach provides valuable β-aryl aldehydes from readily accessible α-alkynoic acids and arenes under mild reaction conditions, employing a supramolecular Rh catalyst containing an acylguanidine-bearing phosphine ligand. Furthermore, the synthesis of a key intermediate of Avitriptan using this protocol is accomplished. The first step of the reaction sequence is proved to be the regioselective hydroformylation of α-alkynoic acids. Remarkably, molecular recognition of the ligand and the substrate via hydrogen bonding plays a key role in this step. Control experiments indicate that the reaction further proceeds via 1,4-addition of an arene nucleophile to the unsaturated aldehyde intermediate and subsequent decarboxylation.

Efficient Stereoselective Synthesis of a Key Chiral Aldehyde Intermediate in the Synthesis of Picolinamide Fungicides

A highly stereoselective and efficient synthesis of (4S,5S,6S)-6-(benzyloxy)-5-phenoxy-4-propoxyheptanal, a key intermediate for syntheses of picolinamide fungicides, is described in this report. The synthesis features a scalable allylpropyl ether preparation, an efficient synthesis of the C1–C3 anti,syn-(S,S,S) stereotriad via a highly diastereoselective allylboration, and Cu-catalyzed phenylation of a sterically hindered secondary alcohol with BiPh3(OAc)2 followed by highly regioselective hydroformylation with the formation of a linear aldehyde. Excellent overall route efficiency was achieved (six steps and 39% yield) starting from readily available and inexpensive (S)-ethyl lactate.

Rational Redesign of a Regioselective Hydroformylation Catalyst for 3‐Butenoic Acid by Supramolecular Substrate Orientation

AbstractRational design of ligands for regioselective transformations is one of the long pursuing targets in the field of transition metal catalysis. In the current contribution, we report OrthoDIMphos (L2), a ligand that was designed for regioselective hydroformylation of 3‐butenoic acid and its derivatives. The previously reported ParaDIMphos (L1) based hydroformylation catalyst was very selectively producing the linear aldehyde when substrates were bound in its pocket via hydrogen bonding. However, the distance between the binding site and the rhodium center was too large to also address 3‐butenoic acid and its derivatives. We therefore designed OrthoDIMphos (L2) as new ligand which has a shorter distance between the DIM‐receptor and the catalytic center. The OrthoDIMphos (L2) based catalyst displays high regioselectivity in the hydroformylation of 3‐butenoic acid and challenging internal alkene analogue (l/b up to 84, TON up to 630), which cannot be achieved with the ParaDIMphos (L1) catalyst. Detailed studies show that the OrthoDIMphos (L2) based catalyst forms a dimeric structure, in which the two ligands coordinate to two different rhodium metals. Substrate binding to the DIM‐receptor is required to break up the dimeric structure, and as only the monomeric analogue is a selective catalyst, the outcome of the reaction is dependent on substrate concentration used in catalysis.