Carbonylative Cyclization Research Articles

Palladium-Catalyzed Carbonylative Synthesis of Polycyclic 3,4-Dihydroquinolin-2(1H)-one Scaffolds Containing Perfluoroalkyl and Carbonyl Units.

A palladium-catalyzed one-pot two-step radical mediated carbonylative cyclization of 1,7-enynes with perfluoroalkyl iodides and Mo(CO)6 has been developed for the construction of polycyclic 3,4-dihydroquinolin-2(1H)-one scaffolds. This method realizes a facile synthesis of various polycyclic 3,4-dihydroquinolin-2(1H)-one derivatives containing perfluoroalkyl and carbonyl units in high yields. Moreover, modifications of several bioactive molecules were demonstrated using this protocol.

Carbonylative Synthesis of Fused Quinoxalinones via Palladium-Catalyzed Cascade Cyclization of 2-Heteroaryl Iodobenzene and NaN3

A facile and straightforward approach for the synthesis of fused quinoxalinones via palladium-catalyzed cascade carbonylative cyclization of 2-heteroaryl iodobenzene and NaN3 has been achieved. The transformation might undergo cascade carbonylation, formation of acyl azide, a Curtius rearrangement, and an intramolecular cyclization sequence. The obtained heterocycle products can be easily transformed into other structurally diverse valuable compounds, which demonstrates the synthetic utility of the developed protocol.

Synthesis of β-Lactams by Palladium-Catalyzed Carbonylative Cyclization of Methylarenes and Imines

Key words aldimines - carbon monoxide - C–H bond activation - β-lactams - palladium catalysis

A long-lifetime aqueous organic redox flow battery utilizing multi-redox anolyte

High-volumetric-capacity and long-lifetime aqueous organic redox flow batteries (AORFBs) have received considerable attention for electrochemical energy storage. Here, we report a six-electron transfer π-conjugated heteroaromatic hexaazatrinaphthalene tricarboxylic acid (HATNTA) as a promising anolyte for AORFBs. HATNTA, synthesized by a straightforward and scalable one-step condensation reaction of cyclic carbonyl molecules, can undergo a reversible three-step six-electron redox process of -0.69, -0.87, and -0.94 V (versus Ag/AgCl) at pH=14. The redox reactions of HATNTA are unveiled by combining ultraviolet-visible spectrophotometry and density functional theory calculations. When paired with ferrocyanide catholyte, HATNTA-based AORFB with 1.5 M electron concentration exhibits high open-circuit voltage of 1.24 V, impressive specific capacity of 37.2 Ah L−1, high output power density of 238 mW cm−2 and superior cycling stability with a capacity fade rate of 0.021% per cycle. The outstanding battery performance substantiates that multi-redox HATNTA breaks a novel pathway to develop advanced AORFBs for large-scale energy storage.

Palladium-Catalyzed Carbonylative Synthesis of Amide-Containing Indolo[2,1-a]isoquinolines from Alkene-Tethered Indoles and Nitroarenes

In this new procedure, amide-containing indolo[2,1-a]isoquinoline scaffolds were prepared by palladium-catalyzed carbonylative cyclization of alkene-tethered indoles with nitroarenes. By using Mo(CO)6 as the CO source and reductant and nitroarenes as the nitrogen source, this reaction produced various amide-containing indolo[2,1-a]isoquinoline derivatives in good yields in general. Furthermore, the late-stage modifications of bioactive molecules using this protocol were demonstrated as well.

Palladium-catalyzed four-component cascade carbonylative cyclization to access carbonyl-bridged bisheterocycles

We developed a palladium-catalyzed four-component carbonylative cyclization of alkenyl-tethered aryl iodides, trifluoroacetimidoyl chlorides and propargyl amines for the construction of carbonyl-bridged bisheterocycles.

Difluoroalkylative carbonylation of alkenes to access carbonyl difluoro-containing heterocycles: convenient synthesis of gemigliptin

Fluorinated heterocycles play a vital role in pharmaceutical and agrochemical industries. Hence, rapid and efficient construction of fluorinated heterocycles remains highly demanded. Herein, a difluoroalkylative carbonylative cyclization of unactivated alkenes and ethylene gas enabled by palladium catalysis has been developed for the first time toward the synthesis of α-carbonyl difluoro-modified glutarimides. This procedure can also be applied to the synthesis of GeMigliptin which is a medicine approved for the treatment of type 2 diabetes mellitus.

Palladium-Catalyzed Chemodivergent Carbonylation of ortho-Bromoarylimine to Biisoindolinones and Spiroisoindolinones.

We herein report a palladium-catalyzed carbonylative cyclization reaction of ortho-bromoarylimines that allows for the chemodivergent synthesis of functionalized biisoindolinones and spirocyclic isoindolinones. Either product could be selectively obtained by switching the reaction temperatures and ligands, and the biisoindolinone products could be afforded facilely with catalyst loadings as low as 0.05 mol %. Further transformation of the biisoindolinone product is also described, which represents a novel and concise approach to the biisoindoline diamine ligand.

Recyclable Palladium-Catalyzed Carbonylative Cyclization of Aryl Iodides and 2-Hydroxyacetophenones towards Flavones

AbstractA highly efficient heterogeneous palladium-catalyzed carbonylative cyclization of aryl iodides and 2-hydroxyacetophenones is developed. The reaction proceeds efficiently in DMSO at 120 °C under 3 bar of carbon monoxide by using 2 mol% of an MCM-41-immobilized bidentate phosphine palladium complex [MCM-41-2P-Pd(OAc)2] as the catalyst and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base, providing a general, efficient and practical approach for the assembly of a wide variety of flavones in mostly good to high yields from readily available starting materials. This supported palladium catalyst can be easily recovered via centrifugation of the reaction mixture and recycled more than nine times without any significant loss of its catalytic efficiency.

Palladium-catalyzed carbonylative cyclization of alkene-tethered indoles with phenols or arylboronic acids: Construction of carbonyl-containing indolo[2,1-a]isoquinoline derivatives

A novel palladium-catalyzed carbonylative cyclization of alkene-tethered indoles with phenols or arylboronic acids is described, which provides a facile approach to access indolo[2,1-a]isoquinoline scaffolds. This method employs benzene-1,3,5-triyl triformate (TFBen) as the CO surrogate for the incorporation of a carbonyl group into indolo[2,1-a]isoquinoline scaffolds, and a variety of carbonyl-containing indolo[2,1-a]isoquinoline derivatives are prepared in good yields.

Palladium-catalyzed domino carbonylative cyclization to access functionalized heterocycles

A novel palladium-catalyzed domino carbonylative cyclization of alkene-tethered indole derivatives with alkyne-tethered nucleophiles has been developed, which provides a straightforward and efficient platform for the rapid construction of functionalized heterocycles. By using benzene-1,3,5-triyl triformate (TFBen) as the CO source, this domino reaction proceeded smoothly with the consecutive formation of three CC bonds and one C-X bond to furnish a variety of biologically relevant indolo[2,1-a]isoquinoline-indole and indolo[2,1-a]isoquinoline-dihydrobenzofuran derivatives in good yields.

Palladium-Catalyzed Domino Carbopalladation/Carbonylative Cyclization: Synthesis of Heterocycles bearing Oxindoles and 3-Acylbenzofuran/3-Acylindole Moieties

A novel and straightforward methodology for palladium-catalyzed carbopalladation-initiated domino carbonylative cyclization to construct bisheterocycles has been established. With TFBen as an efficient and convenient CO source, the protocol is capable of generating oxindole and 3-acylbenzofuran/3-acylindole moieties from the corresponding N-(o-iodoaryl)acrylamides and o-alkynylphenols/o-alkynylanilines with the formation of three C-C bonds and one C-O/C-N bond in a single one-step operation. A wide range of bisheterocycles bearing oxindoles and 3-acylbenzofurans/3-acylindoles were prepared in moderate to excellent yields with good functional group tolerance.

Theoretical study on the mechanism of the carbonylation cyclization of 1,5-diynes with hydrosilanes

The carbonylation cyclization of unstaturated hydrocarbons with hydrosilanes is an appealing strategy for the construction of valuable silicon-containing carbonyl compounds. Despite significant advances, the detailed mechanistic investigations on these reactions are still scarce. Herein, density functional theory (DFT) calculations are carried out to provide mechanistic insights into Rh-catalyzed carbonylative cyclization of 1,5-diyne with triethylsilane. The calculated results indicate that (1) In the silylrhodation process, distinguished from the classical Chalk−Harrod mechanism and the modified Chalk−Harrod mechanism, H atom on the Rh center first transfers to CO ligand to yield a aldehyde group. Then the terminal alkyne of 1,5-diyne inserts into Rh−Si bond to form C−Si bond. With the subsequent H atom retransfer to Rh center, β-(E)-silyl-substituted enyne can be obtained. (2) In the CO insertion process, internal alkyne prior to CO ligand coordinates to the Rh center. (3) The yielded metallacyclohexanone intermediate undergoes H-transfer and C−C cyclization steps rather than direct C−C cyclization forming the η3-binding intermediate. Finally, after the reductive elimination, the product (1E,3Z)-1-pentylidene-3-[(triethylsilyl)methylidene]indan-2-one is formed. The computational results demonstrate that H-transfer is the rate-determining step.

Activated carbon fibers supported palladium as efficient and easy-separable catalyst for carbonylative cyclization of o-alkynylphenols with nitroarenes: Facile construction of benzofuran-3-carboxamides

Heterogeneous catalytic processes have a number of advantages over conventional chemical synthesis, such as lower catalyst loading and easier catalyst recyclability. Activated carbon fibers (ACFs) can be readily prepared and used in most organically reactive environments due to its excellent high temperature resistance and chemical stability. Herein, a heterogeneous activated carbon fibers supported palladium (Pd/ACFs) catalyzed carbonylative cyclization of o-alkynylphenols with nitroarenes has been developed for the rapid construction of 3-carbonyl-benzo[b]furan scaffolds. By employing nitroarenes as the nitrogen source, Mo(CO)6 as both the CO surrogate and the reductant, the reaction afforded a variety of 3-carbonyl-benzo[b]furan derivatives in good to excellent yields.

Cobalt-catalyzed carbonylative cyclization of N-(2-Vinylphenyl)nicotinamides to access (NH)-quinolin-2(1H)-ones

A cobalt-catalyzed carbonylative cyclization of N-(2-vinylphenyl)picolinamides for the construction of (NH)-quinolin-2(1H)-one scaffolds has been developed. In this reaction, various free (NH)-quinolin-2(1H)-ones were produced in good yields (up to 92%) by employing benzene-1,3,5-triyl triformate (TFBen) as the CO source and picolinamide as the traceless directing group. Moreover, several synthetic transformations of the obtained (NH)-quinolin-2(1H)-ones were performed and a facile and rapid access to the core skeleton of Tipifarnib was realized to demonstrate the utility of this protocol.

Supported palladium-catalyzed carbonylative cyclization of 2-bromonitrobenzenes and alkynes to access quinolin-4(1H)-ones

A palladium supported on graphitic carbon nitride (Pd/g-C3N4) catalyzed carbonylative cyclization of 2-bromonitrobenzenes and alkynes has been developed for the expedite construction of quinolin-4(1H)-one scaffolds. By using a low loading heterogeneous palladium catalyst, Mo(CO)6 as both the CO surrogate and the reductant, and nitroarenes as the nitrogen source, the reaction proceeded well to give a variety of quinolin-4(1H)-ones in good to excellent yields.

Nickel-Catalyzed Enantioselective C(sp 3 )–H Arylation of Ketones with Aryl Ethers via Selective C Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

Nickel-Catalyzed Enantioselective C(sp ³ )–H Arylation of Ketones with Aryl Ethers via Selective C _Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

Additive-Controlled Divergent Synthesis of Indole and 4H-Benzo[d][1,3]oxazine Derivatives: Palladium-Catalyzed Carbonylative Cyclization of 2-Alkynylanilines and Benzyl Chlorides.

A palladium-catalyzed divergent carbonylative synthesis of indoles and 4H-benzo[d][1,3]oxazines from 2-alkynylanilines and benzyl chlorides with benzene-1,3,5-triyl triformate (TFBen) as the CO source has been developed. The reaction using AlCl3 as the additive produced various indoles in high yields, while a series of 4H-benzo[d][1,3]oxazines was achieved in moderate yields with AcOH as the additive.

Tandem [5 + 1]/[8 + 2] cycloaddition reactions involving phosphiranes and tropones: facile access to 6,5,7-fused tricyclic skeletons

Tandem [5 + 1] carbonyl cyclization/[8 + 2] cycloaddition reactions of phosphiranes and tropones were developed as a straightforward method to access 6,5,7-fused tricyclic scaffolds.

Palladium-catalyzed carbonylative synthesis of indole-3-carboxamides from 2-ethynylanilines and nitroarenes

A facile and straightforward approach for the expedite construction of indole-3-carboxamide skeletons via a palladium-catalyzed carbonylative cyclization of 2-ethynylanilines with nitroarenes has been developed.