Rh-catalyzed Reaction Research Articles

Rh-Catalyzed Three-Component Reaction of Diazo Compounds

Key words diversity-oriented synthesis - multicomponent reaction - aza-Michael addition - intramolecular aldol reaction - rhodium

Intramolecular Transannulation of Alkynyl Triazoles via Alkyne–Carbene Metathesis Step: Access to Fused Pyrroles

An intramolecular Rh-catalyzed transannulation reaction of alkynyl triazoles has been developed. This method allows efficient construction of various 5,5-fused pyrroles, including tetrahydropyrrolo and spiro systems. The method demonstrates excellent functional group compatibility. A rhodium carbene-alkyne metathesis mechanism is proposed for this transformation.

Rhodium(III) Catalyzed and Uncatalyzed Kinetic Spectrophotometric Oxidation of Amodiaquine Hydrochloride With Chloramine-T in Presence of Alkaline Buffer: A Mechanistic Chemistry

Amodiaquine hydrochloride (AQ) is a 4-aminoquinoline derivative commonly used to prevent and treat malaria. Sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) is a well-known oxidizing agent. In rhodium(III) chloride (Rh(III)) catalyzed oxidation, the rate law is -d[CAT] / dt = k [CAT]o [AQ]o [OH–]–x [Rh(III)]y and it takes the form -d[CAT]/dt = k [CAT]o[AQ]o[OH–]–x for uncatalyzed reaction, where x and y are less than unity. The rate constants revealed that the Rh(III) catalyzed reactions are about five fold faster than the uncatalyzed reactions. The catalytic constant (KC) and activation parameters with respect to Rh(III) catalyst have been deduced.

ChemInform Abstract: Synthesis of Bridged Polycyclic Ring Systems via Carbene Cascades Terminating in C—H Bond Insertion.

AbstractThe Rh‐catalyzed reaction of cyclic alkynyl diazoacetates leads to different bridged products.

Synthetic studies on the icetexones: enantioselective formal syntheses of icetexone and epi-icetexone

Two strategies for the synthesis of the icetexane diterpenoids icetexone and epi-icetexone that rely on Ga(III)-catalyzed cycloisomerization of alkynyl indene substrates to yield fused [6-7-6] tricycles have been explored. In the first approach, access to a tricycle bearing a gem-dimethyl group paved the way for explorations of C–H functionalization of one of the methyl groups in close proximity to a hydroxyl-directing group. This approach was ultimately unsuccessful and led only to ring cleaved products. In the second approach, an alkynyl indene substrate bearing a cyano substituent was utilized, which was effective in providing a functional handle to access the icetexone subclass of diterpenoids. A key epoxide opening/diazene rearrangement sequence was utilized to complete a formal synthesis of icetexone and epi-icetexone, which is discussed in detail. Furthermore, the cyano-containing substrate has been prepared in enantioenriched form using a Rh-catalyzed conjugate addition reaction, which now provides a route to the enantioselective synthesis of these natural products.

ChemInform Abstract: Rhodium‐Catalyzed Asymmetric 1,4‐Additions, in Water at Room Temperature, with In‐Flask Catalyst Recycling.

Using the newly introduced designer surfactant polyethyleneglycol ubiquinol sebacate (PQS), as the platform for micellar catalysis, nonracemic BINAP has been covalently attached and rhodium(I) inserted to form PQS-BINAP-Rh. This species, the first example of a nonracemically-ligated transition metal catalyst-tethered amphiphile, can be utilized for Rh-catalyzed asymmetric conjugate addition reactions of arylboronic acids to acyclic and cyclic enones. These are performed in water at room temperature, while the catalyst can be recycled without its removal from water in the reaction vessel.

Stereoselective synthesis of short benzyl malonyl peptides

A Rh-catalyzed addition reaction on non symmetric dehydro alanine retro-peptides is the key step in the reported three-step strategy for the diastereoselective synthesis of differently functionalized benzyl malonyl peptides (74% overall yield).

Rhodium‐Catalyzed Asymmetric 1,4‐Additions, in Water at Room Temperature, with In‐Flask Catalyst Recycling

Using the newly introduced designer surfactant polyethyleneglycol ubiquinol sebacate (PQS), as the platform for micellar catalysis, nonracemic BINAP has been covalently attached and rhodium(I) inserted to form PQS-BINAP-Rh. This species, the first example of a nonracemically-ligated transition metal catalyst-tethered amphiphile, can be utilized for Rh-catalyzed asymmetric conjugate addition reactions of arylboronic acids to acyclic and cyclic enones. These are performed in water at room temperature, while the catalyst can be recycled without its removal from water in the reaction vessel.

Rh-catalyzed intermolecular reactions of cyclic α-diazocarbonyl compounds with selectivity over tertiary C-H bond migration.

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C-H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X-H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described.

Application of chiral tetrahydropentalene ligands in rhodium-catalyzed 1,4-addition of (E)-2-phenylethenyl- and (Z)-propenylboronic acids to enones

Chiral tetrahydropentalenes (3aR,6aR)-1 have been prepared and used as ligands in the Rh-catalyzed 1,4-addition of 1-alkenylboronic acids to cyclic enones 5. It has been discovered that the stereochemistry of the reaction was controlled by the steric properties of the aryl groups in 1 rather than their electronic nature. In the vinylation with (E)-2-phenylethenylboronic acid 5, ligands (3aR,6aR)-1 provided enantioselectivity up to 87% ee and gave high yields of ethenylketones 6 in the presence of 1 (6.6mol%). The configuration of all ketone products obtained with (3aR,6aR)-1 is (S). Rh-catalyzed reaction of cyclopentenone 4a and (Z)-propenylboronic acid 7 in the presence of ligands (3aR,6aR)-1 yielded at 50°C an inseparable mixture of (Z)- and (E)-ketones 8 with (Z)-8 as the major product and both in only moderate enantiomeric excess.

Rh-Catalyzed Three-Component Tandem Reaction to Pyrrolidines

Rh-Catalyzed Three-Component Tandem Reaction to Pyrrolidines

Total synthesis of laulimalide: synthesis of the northern and southern fragments.

The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru-catalyzed alkene-alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn-catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh-catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six-membered ring, over a seven. The use of an electron-deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading.

Rh–IndOlefOx catalyzed conjugate addition/Heck-type coupling of organoboronics to a lactam or a lactone

Four indole-olefin-oxazoline (IndOlefOx) ligands were synthesized and evaluated in Rh-catalyzed reactions between organoboronics and a lactam or a lactone. In addition to the expected conjugate addition products, the formation of significant amounts of Heck-type products was observed. The scope and limitations of these reactions were investigated.

Rh-catalyzed intramolecular sp2 C–H bond difluoromethylenation

A new Rh-catalyzed intramolecular coupling reaction of a CF(2)Br group with a 2-aryl of indole or pyrrole via C-H bond activation is presented. This reaction represents a new way of incorporating difluoromethylene groups into organic compounds. Preliminary mechanistic studies suggest that this reaction might not occur via a conventional free radical pathway.

Rhodium-Catalyzed Trapping of Oxonium Ylides with Michael Acceptors

Multicomponent reactions are a powerful means to generate high levels of molecular complexity from relatively simple and readily available starting materials. Transition-metal catalysis is especially useful for these types of processes and catalyst control has the ability to rapidly create chiral products from achiral reactants. The authors disclose a diastereoselective Rh-catalyzed multicomponent reaction for the synthesis of produce α-hydroxy esters.

Catalytic Asymmetric Intramolecular Hydroacylation with Rhodium/Phosphoramidite–Alkene Ligand Complexes

Give me a P: An asymmetric intramolecular Rh-catalyzed hydroacylation reaction of pent-4-enals for the preparation of functionalized cyclopentanones in good yield and high enantioselectivity is described (see scheme, DCE=dichloroethane). This process uses rhodium complexes featuring novel modular phosphoramidite–alkene ligands and achiral phosphine coligands.

Three-Component Polycondensation of Bis(diazoketone) with Dicarboxylic Acids and Cyclic Ethers: Synthesis of New Types of Poly(ester ether ketone)s

New types of poly(ester ether ketone)s 3 and 8 were prepared by three-component polycondensation of bis(diazoketone) 1 with a variety of dicarboxylic acids 2 and THF or THP catalyzed by Rh2(OAc)4. THF was ring-opened and incorporated into almost every carboxyl O–H of 2 via simultaneous insertion together with a diazocarbonyl-derived carbene, resulting in the formation of a unique poly(ester ether ketone) framework. On the other hand, when THP was used as a cyclic ether, insertion of carbene alone into the carboxyl O–H (normal insertion) competes with the simultaneous insertion of THP and carbene, and the ratio of the two modes of insertion depends on the kind of 2 employed. The mode and selectivity of the propagation were confirmed by conducting Rh-catalyzed model reactions of diazoacetophenone 4 with 4-tert-butylbenzoic acid 5 in THF and THP.

ChemInform Abstract: Enantioselective Synthesis of Axially Chiral Hydroxy Carboxylic Acid Derivatives by Rhodium‐Catalyzed [2 + 2 + 2] Cycloaddition.

AbstractThe Rh‐catalyzed reaction of 2‐methoxynaphthalene substituted propynoates with 1,6‐ and 1,7‐diynes is found to provide biaryls and teraryls in good yields with high regio‐ and enantioselectivity.

ロジウム錯体触媒によるヒドロアシル化反応―分子内反応から分子間反応への展開―

Rh-catalyzed hydroacylation reaction can be classified into intramolecular reaction (cyclization) and intermolecular reaction. The intramolecular hydroacylation of 4-pentenals by Rh-complex was clarified about 40 years ago. Intramolecular hydroacylation by Rh-complex has been developed into catalytic reaction, enantioselective reaction, and medium-ring formation reaction. At the beginning, however, Rh-catalyzed intermolecular hydroacylation reaction did not proceed because of decarbonylation side reaction, but, the chelation of aldehyde having an additional functional group suppressed the decarbonylation, and the Rh-catalyzed intermolecular hydroacylation reaction using the chelation of aldehyde proceeded. Especially, the double chelation of both salicylaldehyde and diene promoted the intermolecular hydroacylation under mild reaction conditions. The Rh-catalyzed intermolecular hydroacylation has been developed into diastereoselective and enantioselective reactions.

The Vinyl Moiety as a Handle for Regiocontrol in the Preparation of Unsymmetrical 2,3‐Aliphatic‐Substituted Indoles and Pyrroles

Rh-catalyzed reactions of anilides (I) or methyl-2-acetamidoacrylate (VI) with various enynes proceed with excellent regioselectivity to furnish 2-alkenyl indoles and pyrroles, respectively.