Palladium-catalyzed Intramolecular Coupling Research Articles

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Microwave-Assisted Synthesis of 2-Methyl-1H-indole-3-carboxylate Derivatives via Pd-Catalyzed Heterocyclization

Indole moiety is well-known as a superlative framework in many natural products and synthetic pharmaceuticals. Herein, we report an efficient procedure to synthesize a series of functionalized 2-methyl-1H-indole-3-carboxylate derivatives from commercially available anilines properly functionalized by different electron-withdrawing and -donating groups through a palladium-catalyzed intramolecular oxidative coupling. The conversion of a variety of enamines into the relevant indole was optimized by exposing the neat mixture of reactants to microwave irradiation, obtaining the desired products in excellent yields and high regioselectivity. The synthesized compounds were confirmed by 1H and 13C spectroscopic means as well as by high-resolution mass spectrometry.

General and practical intramolecular decarbonylative coupling of thioesters via palladium catalysis

We report a general and practical palladium-catalyzed intramolecular decarbonylative coupling of thioesters via C–S bond cleavage, decarbonylation and C–S bond reformation.

Total Synthesis of the Monomeric Unit of Lomaiviticin A.

The architecturally symmetrical and synthetically challenging marine natural products lomaiviticins A and B present alluring synthetic targets due to their molecular complexity, potent antitumor properties, and natural scarcity. Herein, we report the total synthesis of the fully glycosylated monomeric unit of lomaiviticin A, monolomaiviticin A. The retrosynthetically derived synthetic strategy relied on an intramolecular palladium-catalyzed coupling reaction to complete the tetracyclic aglycon scaffold and gold-promoted glycosylations to install the synthetically challenging α- and β-glycoside moieties of the target molecule. This accomplishment paves a path for the eventual total synthesis of lomaiviticins A and B and opens opportunities for biological investigations within this family of compounds.

Palladium-catalyzed intramolecular dehydrogenative coupling of BH and OH: synthesis of carborane-fused benzoxaboroles.

A Pd-catalyzed intramolecular dehydrogenative coupling of BH and OH for the construction of cage B-O bonds has been developed, leading to a new class of 1,3- and 1,4-o-carboranobenzoxaborole derivatives. This represents a new route to C,B-carborane-fused heterocycles.

From Isocyanides to Iminonitriles via Silver-mediated Sequential Insertion of C(sp3)-H Bond.

SummaryHeterocycles are prevalent constituents of many marketing drugs and biologically active molecules to meet modern medical challenges. Isocyanide insertion into C(sp3)–H bonds is challenging especially for the construction of quaternary carbon centers. Herein, we describe an efficient strategy for the synthesis of α-iminonitrile substituted isochromans and tetrahydroisoquinolines (THIQs) with quaternary carbon centers through silver-triflate-mediated sequential isocyanide insertion of C(sp3)–H bonds, where isocyanide acts as the crucial “CN” and “imine” sources. The produced α-iminonitriles have extensive applications as valuable synthetic building blocks for pharmacologically interesting heterocycles. This protocol could be further applied for the synthesis of iminonitrile-decorated phenanthridines and azapyrene. Interestingly, a remarkable aggregation-induced emission (AIE) effect was first observed for an iminonitrile-decorated pyrene derivative, which may open a particular area for iminonitrile applications in materials science.

Nitrogen-Centered Concave Molecules with Double Fused Pentagons.

Distinctive concave compounds bearing a nitrogen core and double fused pentagons were synthesized with a palladium-catalyzed intramolecular coupling of 1-chloro-8 H-indolo[3,2,1- de]acridine as the key step. Structural analysis confirmed the formation of bowl-shaped molecules. Experimental characterizations and theoretical calculations reveal the incorporation of nitrogen is crucial to alleviate the pentagon fusing strain, as well as in property regulation.

Synthesis of imidazopyridine-fused indoles via one-pot sequential Knoevenagel condensation and cross dehydrogenative coupling.

A simple and efficient strategy for the synthesis of imidazopyridine-fused indoles has been developed that involves one-pot sequential Knoevenagel condensation of readily available active methylene azoles with N-substituted-1H-indole-3-carboxaldehydes or N-substituted-1H-indole-2-carboxaldehydes followed by palladium-catalyzed intramolecular cross dehydrogenative coupling reaction. A series of 36 derivatives was prepared by using this strategy. The products were obtained in moderate to excellent (32-94%) yields and showed broad substrate scope with tolerance of various functional groups and was amiable for gram scale preparation without problems.

Synthesis of Substituted Benzo[b]thiophenes via Sequential One-Pot, Copper-Catalyzed Intermolecular C–S Bond Formation and Palladium-Catalyzed Intramolecular Arene–Alkene Coupling of Bis(het)aryl/alkyl-1,3-monothiodiketones and o-Bromoiodoarenes

A new, convergent, one-pot synthesis of 2,3-substituted benzo[b]thiophenes from readily available 1,3-bis(het)aryl-1,3-monothiodiketones and o-bromoiodoarenes involving a sequential copper-catalyzed intermolecular C-S coupling followed by palladium-catalyzed intramolecular arene-alkene coupling of in situ generated β-(o-bromoaryl)thiovinylketones has been described. Synthesis of a few thieno- and furano-fused 2-(het)aroylethylidenethiochromenes via intramolcular direct C-H (het)arylation of β-(o-bromoaryl)thioenones carrying 2-thienyl/furyl groups under different palladium-catalyzed conditions has also been reported.

Palladium-Catalyzed Intramolecular Cross-Dehydrogenative Coupling: Synthesis of Fused Imidazo[1,2-a]pyrimidines and Pyrazolo[1,5-a]pyrimidines.

A palladium-catalyzed intramolecular dehydrogenative coupling reaction was developed for the synthesis of fused imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a]pyrimidines. The developed protocol provides a practical approach for the synthesis of biologically important substituted pyrimidines from easily available substrates, with a broad substrate scope under mild reaction conditions.

Palladium-Catalyzed Decarboxylative Synthesis of Arylamines

A novel approach has been developed for the synthesis of arylamines via the palladium-catalyzed intramolecular decarboxylative coupling (IDC) of aroyloxycarbamates, obtained in situ by reacting aryl carboxylic acids with hydroxycarbamates. The reaction offers facile access to structurally diverse arylamines with the site-specific formation of the C(sp2)-N bond under mild conditions.

Concise Total Synthesis of Nannocystin A.

Nannocystin A, a structurally unique 21-membered macrocyclic depsipeptide with low nanomolar inhibitory activity against elongation factor 1A, was synthesized according to a strategy involving the vinylogous Mukaiyama aldol reaction, Sharpless epoxidation, olefin metathesis, the Mitsunobu reaction, and a palladium-catalyzed intramolecular Suzuki coupling of a highly complex cyclization substrate. The overall synthesis is efficient and paves the way for preparation of analogues for drug development efforts.

(Invited) Synthesis of Nitrogen-Embedded Buckybowl and Its Strong Association Behavior with C60

Curved π-conjugated molecules have attracted considerable interest because of their unique properties originating from their curved π surface. Besides their figurative beauty, the curved psurface generates unique functions such as chiroptical properties, anisotropic electron transitions, and dynamic motion in solution and solid states. However, the synthesis of such distorted molecules requires harsh conditions, which hamper an easy access to heteroatom-containing curved π-systems. Buckybowls represent important curved π-conjugated molecules, which can be precursors for the bottom-up synthesis of fullerenes and nanotubes. The nitrogen-embedded bowl-shaped molecules have been sought as model compounds for azafullerenes and nitrogen-doped carbon nanotubes. However, the synthesis of buckybowls with internal nitrogen atoms has been still challenging. Here we report the synthesis of a π-extended azacorannulene with nitrogen in its center. The oxidation of 9-aminophenanthrene provides tetrabenzocarbazole, which is converted to the azabuckybowl through palladium-catalyzed intramolecular coupling reaction. The structure was unambiguously elucidated by X-ray diffraction analysis, showing its bowl-shaped conformation. The electron-donating nature and curved π surface of the azabuckybowl enable its tight association with C60 in solution and solid states. The titration experiments with C60 by electronic absorption and emission spectroscopic analysis indicate the presence of intermolecular charge-transfer interaction between them. In addition, high charge carrier mobility was observed for the azabuckybowl/C60 assembly in solid state. This new compound would be a novel molecular entity in the field of curved π systems as fullerene hosts, anisotropic π donors, and precursors to nitrogen-containing nanocarbon materials. Figure 1

ChemInform Abstract: Access to Biaryl Sulfonamides by Palladium‐Catalyzed Intramolecular Oxidative Coupling and Subsequent Nucleophilic Ring Opening of Heterobiaryl Sultams with Amines

Abstractor NaOEt

Palladium-catalyzed regioselective intramolecular coupling of o-carborane with aromatics via direct cage B-H activation.

Palladium-catalyzed intramolecular coupling of o-carborane with aromatics via direct cage B-H bond activation has been achieved, leading to the synthesis of a series of o-carborane-functionalized aromatics in high yields with excellent regioselectivity. In addition, the site selectivity can also be tuned by the substituents on cage carbon atom.

Access to biaryl sulfonamides by palladium-catalyzed intramolecular oxidative coupling and subsequent nucleophilic ring opening of heterobiaryl sultams with amines.

The installation of sulfonamide pharmacophores on heterobiaryls has successfully been executed by a previously unknown palladium-catalyzed intramolecular oxidative coupling in N-arylsulfonyl heterocycles followed by novel ring opening of heterobiaryl sultams with amine nucleophiles. The protocol has a wide scope of substrates warranting broad applications in the synthesis of heterobiaryls containing an o-sulfonyl or carboxyl functional group.

Palladium-catalyzed intramolecular oxidative coupling involving double C(sp(2))-H bonds for the synthesis of annulated biaryl sultams.

The palladium-catalyzed intramolecular oxidative coupling described herein involves a double C(sp(2))-H bond functionalization in sulfonanilides, providing a workable access to biaryl sultams annulated into a six-membered ring that are otherwise difficult to obtain by literature methods. The other synthetic applications of this protocol including the synthesis of biaryl sultams containing a seven-membered ring and analogous sultones are also presented.

Mechanism and Substrate-Dependent Rate-Determining Step in Palladium-Catalyzed Intramolecular Decarboxylative Coupling of Arenecarboxylic Acids with Aryl Bromides: A DFT Study

The mechanism of palladium-catalyzed intramolecular decarboxylative coupling of arenecarboxylic acids with aryl bromides has been studied computationally with the aid of density functional theory. Full free-energy profiles have been computed for all ether- and amine-containing substituted substrates. The calculations indicate that the rate-determining step is indeed substrate dependent, as reflected in free energy profiles; the oxidative addition, decarboxylation, or reductive elimination step can become the rate-determining step for the full catalytic cycle due to the different substituents on the substrates. In addition, we also demonstrate the preference of NCH3- over NH-containing amine substrates for the decarboxylation process. The calculations are in good agreement with the experimental observations.

Facile Access to 3‐Acylindoles through Palladium‐Catalyzed Addition of Indoles to Nitriles: The One‐Pot Synthesis of Indenoindolones

Well-connected: The palladium-catalyzed addition of indoles to nitriles affords 3-acylindoles. The reaction proceeds with high selectivity, wide substrate scope, broadly available starting materials, and an operationally simple procedure. Combination with the palladium-catalyzed intramolecular oxidative coupling of 3-indolylarylketone gives access to indenoindolones in a one-pot synthesis.

Synthesis of benzopyrano[4,3-b](N-arylsulfonyl)indoles and benzopyrano[3,4-b](N-arylsulfonyl)indoles via intramolecular palladium-catalyzed aryl–aryl coupling reaction

A series of benzopyrano[3,4-b](N-arylsulfonyl) indole derivatives and benzopyrano[4,3-b](N-arylsulfonyl) indole derivatives were synthesized from 2- or 3-methylindole via intermolecular S( N )2 reaction and subsequent intramolecular palladium-catalyzed aryl-aryl coupling reaction for the first time. It was suggested that, besides using the Fischer cyclization, benzopyrano[4,3-b]indoles and benzopyrano[3,4-b]indoles could also be prepared via intermolecular S( N )2 reaction and sequential intramolecular palladium-catalyzed coupling reaction.