Rhodium-catalyzed Reaction Research Articles

Stereoselective rhodium-catalyzed reaction of allenes with organoboronic reagents for diversified branched 1,3-alkadienes.

The terminalisoprene unit, as the simplest branched 1,3-diene unit, exists in a wide range of natural products and bioactive molecules. Herein, we report a stereoselective rhodium-catalyzed reaction of allenes with readily available methyl pinacol boronic ester, providing a straightforward approach to isoprene derivatives with a very high E-stereoselectivity. Its synthetic potential has been illustrated by a concise synthesis of natural product schinitrienin. Such a protocol can be easily extended to aryl and alkenyl boronic reagents affording 2-aryl or -alkenyl substituted 1,3-dienes, which are also of high importance in organic synthesis but remain challenging for their selective synthesis, with a remarkable stereoselectivity. A series of deuterium-labeling experiments indicate a unique mechanism, which involves reversible β-H elimination as well as hydrometalation and isomerization of the allylic rhodium species.

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor.

A novel Rh-catalyzed one-pot homo-coupling reaction of aryl Grignard reagents was achieved. The reaction with bromobenzenes having an electron-donating group or a halogen substituent gave the corresponding homo-coupling products in good yields, although the reaction using heterocyclic or aliphatic bromides scarcely proceeded. A Rh(III)-bis(aryl) complex, which might be formed from RhCl(PPh3)3 and the aryl Grignard reagents, plays an important role in giving the homo-coupling products in this reaction. Furthermore, we applied the reaction to the synthesis of a novel inhibitor for integrins which is critical for several diseases.

Amplifying enantioselectivity in asymmetric transformations using heterogeneous chiral single-rhodium-site catalyst with sustained catalytic activity

Rhodium-catalyzed asymmetric reactions have played a pivotal role in the synthesis of functional chiral molecules. However, the ambiguous mechanism involving several plausible catalytically active species, the potential for catalyst deactivation and the need for constant reusability remain key challenges. Heterogeneous chiral Rh catalysts are highly desirable, but their performance has been hampered by low density and stability of catalytically active sites. Herein, we have devised a versatile methodology for fabricating highly efficient and robust chiral heterogeneous single-Rh-site catalysts by direct polymerization. The successful anchoring of single Rh-ligand species, the amplification of enantioselective inductive ability and the uniform distribution of atomic Rh sites within the resulting polymer matrix are identified as crucial factors contributing to their exceptional catalytic performance via comprehensive characterization and controlled experiments. In contrast to the corresponding homogeneous analogues, these chiral single-Rhodium-site catalysts exhibit outstanding performance, yielding enhanced enantioselectivity and broad applicability, even accommodating various functional groups. Remarkably, these results are achieved with just half catalyst dosage. Furthermore, their industrial potential is demonstrated through successful utilization in continuous flow processes and robust batch recycling. In future, we aim to expand the horizons of heterogeneous chiral single-metal-site catalysis, and bring us a step closer to practical asymmetric synthesis.

Rhodium(II)-Catalyzed Asymmetric Cyclopropanation and Desymmetrization of [2.2]Paracyclophanes.

Chiral [2.2]paracyclophane derivatives are of considerable interest because of their potential in asymmetric catalysis and the development of chiral materials. This study describes the scope of rhodium-catalyzed reactions of aryldiazoacetates with [2.2]paracyclophanes. The reaction with the parent [2.2]paracyclophane resulted in cyclopropanation at two positions, the ratio of which is catalyst-controlled. Because of the strain in the system, one of the cyclopropanes exists primarily as the norcaradiene structure, whereas the other preferentially exists as the cycloheptatriene conformer. In contrast, the reaction with [3.3]paracyclophane results in benzylic C-H functionalization. The reactions with substituted [2.2]paracyclophanes using chiral catalysts can result in either kinetic resolution or desymmetrization. The Rh2(S-p-PhTPCP)]4-catalyzed reaction of monosubstituted paracyclophanes results in kinetic resolution with a selectivity (s) factor of up to 20, whereas reactions on C2v-symmetric disubstituted [2.2]paracyclophanes with Rh2(S-TPPTTL)4 [TPPTTL = 2-(1,3-dioxo-4,5,6,7-tetraphenylisoindolin-2-yl)-3,3-dimethylbutanoate] results in effective desymmetrization to form cycloheptatriene-incorporated paracyclophanes in 78-98% ee.

Synthesis of fused oligosiloles by rhodium-catalyzed stitching reaction and subsequent remote conjugate dehydration

Abstract A new synthetic method for π-conjugated fused oligosiloles has been developed by combining a rhodium-catalyzed stitching reaction and subsequent remote conjugate elimination. Aromatization-driven 1,8-, 1,10-, or 1,12-dehydration was successfully utilized and up to 3 silole units were consecutively fused in a π-conjugated manner. The structural change upon conjugate elimination was confirmed by using X-ray crystallographic analysis, and the optical and electrochemical properties of a series of newly synthesized fused oligosiloles were also examined.

Rhodium-catalyzed ring-opening reactions of heterobicyclic akenes with heteroarene nucleophiles: an experimental and computational investigation

We present an experimental and computational investigation into the rhodium-catalyzed ring-opening reactions of heterobicyclic alkenes with heteroarene nucleophiles. The reaction provides a facile route to trans-substituted dihydronaphthalen-1-ol and 1-amino-dihydronaphthalene products in up to a 95% yield as a single diastereomer. This reaction is 100% atom-economic and offers C–C bond formation without prior functionalization of the coupling partners. The mechanism and origins of selectivity were probed with density functional theory (DFT) at the MN15/Def2-TZVPP level of theory. The energetic barriers between iridium- and rhodium-catalyzed pathways were compared via DFT. Additionally, the reactivity and energetic barriers across diverse heterobicyclic alkenes and heteroarenes were calculated to unveil their relative reactivity.

Mechanistic Studies on Rhodium-Catalyzed Chemoselective Cycloaddition of Ene-Vinylidenecyclopropanes: Water-Assisted Proton Transfer.

Rhodium-catalyzed cycloaddition reactions are a powerful tool for the construction of polycyclic compounds. Combined experimental and DFT studies were used to investigate the temperature-controlled chemoselectivity of cationic rhodium-catalyzed intramolecular cycloaddition reactions of ene-vinylidenecyclopropanes. After a series of mechanistic studies, it was found that trace amounts of water in the reaction system play an important role in generating the product with endo double bond located on a five-membered ring and revealed that trace amounts of water in the reaction system, including the rhodium catalyst, substrate and solvent, were sufficient to promote the formation of the product with endo double bond located on a five-membered ring, and additional water could not further accelerate the reaction. DFT calculation results show that the addition of water indeed significantly lowers the energy barrier of the proton transfer step, making the formation of the product with endo double bond located on a five-membered ring more likely to occur and confirming the rationality of water-assisted proton transfer occurring in the selective access to the product with endo double bond located on a five-membered ring.

Synthesis of Thiophene-Fused Siloles through Rhodium-Catalyzed Trans-Bis-Silylation

Rhodium-catalyzed reactions of 3-ethynyl-2-pentamethyldisilanylthiophene derivatives (1a–1c) have been reported. At 110 °C, compounds 1a–1c reacted in the presence of a rhodium complex catalyst, yielding thiophene-fused siloles (2a–2c) through intramolecular trans-bis-silylation. To understand the production of 2a from 1a, the mechanism was investigated using density functional theory (DFT) calculations.

Rhodium-catalyzed enantioselective in situ C(sp3)−H heteroarylation by a desymmetrization approach

A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C−H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne. The reaction results in chiral indoles containing all-carbon quaternary stereocenters under atmospheric conditions, with a wide range of substrates exhibiting good enantioselectivity (44 examples). Mechnism and DFT studies show that the stereocontrol is reasonably achieved through the collaborative control of a large silicon substituted chiral ligand and C−H···π, LP···π interactions between aryl rings of the carboxylate group and the substrate. Control experiments demonstrate that Rh-aryl bond formation via in situ nucleophilic cyclization is more critical for reaction efficiency than via C−H activation of the nucleophilic cyclization byproduct.

Rhodium-Catalyzed [3+2]-Cycloaddition of in-situ Generated Nitrile Ylides with Nitrosoarenes.

Herein we report the rhodium-catalyzed one-pot three-component reaction of diazo compounds, nitriles, and nitrosoarenes to construct 2,5-dihydro-1,2,4-oxadiazole derivatives. Mechanistic studies indicate that the transformation may proceed through the formation of nitrile ylides intermediates, which then undergo [3+2]-cycloaddition with nitrosoarenes. The strategy exhibits several synthetic advantages, including operational simplicity, good functional group tolerance, and scalability.

Rh(III)-catalyzed regioselective C(sp2)-H alkenylation of isoquinolones with methoxyallene: A facile access to aldehyde-bearing isoquinolones.

A simple and rapid access to isoquinolone aldehyde scaffolds has been established by a rhodium-catalyzed reaction between isoquinolone and methoxyallene that forges alkenylation in an explicit regioselective manner. Herein, methoxyallene serving as an acrolein equivalent results in execution of this unique functionalization. Furthermore, the compatibility with complex molecules underscores the significance of this developed protocol. The mechanistic proposal for this regioselective transformation was consistent with kinetic studies and several control reactions.

Rhodium-catalyzed formal four-component reaction with hypervalent iodine diazoesters, alcohols, and isatins for the synthesis of multi-functionalized oxindoles

A novel Rh(ii)-catalyzed formal four-component reaction involving hypervalent iodine diazoesters, alcohols, and isatins was effectively established as an efficient process to produce multi-functionalized oxindoles in good to high yields.

Mechanistic Investigation of the Rhodium-Catalyzed Transfer Hydroarylation Reaction Involving Reversible C-C Bond Activation.

Carbon-carbon (C-C) bonds are ubiquitous but are among the least reactive bonds in organic chemistry. Recently, catalytic approaches to activate C-C bonds by transition metals have demonstrated the synthetic potential of directly reorganizing the skeleton of small molecules. However, these approaches are usually restricted to strained molecules or rely on directing groups, limiting their broader impact. We report a detailed mechanistic study of a rare example of catalytic C-C bond cleavage of unstrained alcohols that enables reversible ketone transfer hydroarylation under Rh-catalysis. Combined insight from kinetic analysis, in situ nuclear magnetic resonance (NMR) monitoring, and density functional theory (DFT) calculations supports a symmetric catalytic cycle, including a key reversible β-carbon elimination event. In addition, we provide evidence regarding the turnover-limiting step, the catalyst resting state, and the role of the sterically encumbered NHC ligand. The study further led to an improved catalytic system with the discovery of two air-stable precatalysts that showed higher activity for the transformation in comparison to the original conditions.

Rhodium/Ming-Phos-catalyzed asymmetric annulation reaction of silacyclobutanes with terminal alkynes

Asymmetric ring-expansion reactions of silacyclobutanes (SCBs) with alkynes have evolved as one of the powerful protocols for the construction of silicon-stereogenic compounds. However, the achievement of highly enantioselective annulation of SCBs with terminal alkynes remains a challenge. Herein, we report a rhodium-catalyzed asymmetric annulation reaction of SCBs with terminal alkynes, which relies on the newly identified chiral sulfinamide phosphine ligand Ming-Phos. This catalytic system exhibits unique effects under mild conditions, leading to the direct synthesis of structurally diverse chiral silacycles in moderate to good yields with high enantioselectivities (up to 95% ee).

Dynamic Kinetic Resolution of Indole-Based Sulfenylated Heterobiaryls by Rhodium-Catalyzed Atroposelective Reductive Aldol Reaction.

A highly enantio- and diastereoselective dynamic kinetic resolution (DKR) of configurationally labile 3-aryl indole-2-carbaldehydes is described. The DKR proceeds via a Rh-catalyzed intermolecular asymmetric reductive aldol reaction with acrylate esters, with simultaneous generation of three stereogenic elements. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a transient Lewis acid-base interaction (LABI) between the formyl group and a thioether moiety strategically located at the ortho' position. The atropisomeric indole products present a high degree of functionalization and can be further converted to a series of axially chiral derivatives, thereby expanding their potential application in drug discovery and asymmetric catalysis.

Rhodium-catalyzed ring-opening reaction of indole-directed arenes with azabenzonorbornadienes

Rhodium-catalyzed ring-opening reaction of indole-directed arenes with azabenzonorbornadienes

Rhodium-catalyzed ring-opening reactions of heterobicyclic alkenes with heteroarene nucleophiles

We present a rhodium-catalysed ring-opening reaction of heterobicyclic alkenes with indole and pyrrole nucleophiles, resulting in 1,2-disubstitued trans-dihydronaphthalene cores in up to a 95% yield as a single diastereomer. The Rh-catalysed reaction demonstrated tolerance for a broad scope of nucleophiles as well as various heterobicyclic alkenes. Notably, the reaction was successful with substrates that previously performed poorly or failed under iridium catalysis. This reaction is 100% atom-economic and offers C–C bond formation without prior functionalization of the coupling partners.

Mechanistic snapshots of rhodium-catalyzed acylnitrene transfer reactions.

Rhodium acylnitrene complexes are widely implicated in catalytic C-H amidation reactions but have eluded isolation and structural characterization. To overcome this challenge, we designed a chromophoric octahedral rhodium complex with a bidentate dioxazolone ligand, in which photoinduced metal-to-ligand charge transfer initiates catalytic C-H amidation. X-ray photocrystallographic analysis of the Rh-dioxazolone complex allowed structural elucidation of the targeted Rh-acylnitrenoid and provided firm evidence that the singlet nitrenoid species is primarily responsible for acylamino transfer reactions. We also monitored in crystallo reaction of a nucleophile with the in situ generated Rh-acylnitrenoid, providing a crystallographically traceable reaction system to capture mechanistic snapshots of nitrenoid transfer.

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids.

Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem-stamp strategy for the construction of the key isoprene unit, which consists of two steps: one-carbon extension of aldehydes to the alkenyl boronates by the boron-Wittig reaction and the rhodium-catalyzed reaction of alkenyl boronates with 2,3-allenols to yield enals. This chem-stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, β-carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3-allenols, creation of new non-natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

Rhodium-catalyzed Doyle-Kirmse rearrangement reactions of sulfoxoniun ylides

Doyle-Kirmse rearrangement reactions have received continuous attention as an important method for constructing complex chemical structures. Herein, we disclosed an efficient rhodium-catalyzed Doyle-Kirmse rearrangement reaction, which can simultaneously construct CC bonds and CX (X = S/Se) bonds using sulfoxonium ylides as starting materials to obtain sulfur- or selenium-containing compounds. This strategy is characterized by the safer and greener carbene precursor, high yields and broad substrate scope, possessing a wide range of application.