Copper-Catalyzed Annulation Research Articles

Synthesis of 4-fluoroisocoumarins by copper-catalyzed annulation of 2-halobenzoic acids and 2-fluoro-1,3-diketones

Fluorinated heterocycles have been promising in the field of medicinal, agrochemical and materials chemistry due to their unique properties. However, despite the potentially very useful structures of fluorinated isocoumarins, the synthetic method of fluorinated isocoumarins remains a challenging topic. Herein, we describe the synthetic method of fluorinated isocoumarins by tandem coupling-cyclization-deacylation reaction of readily available 2-halobenzoic acids and 2-fluoro-1,3-diketones. This study provides one of the few synthetic methods of fluorinated isocoumarins.

A copper-catalyzed annulation reaction of diazo esters with propargyl amines for the synthesis of 2,5-dihydropyrroles

An efficient protocol for the synthesis of 2,5-dihydropyrroles using diazo esters and propargyl amines has been reported, featuring mild reaction conditions, straightforward operation, the absence of metal ligands, and high atom economy.

Copper-Catalyzed Annulation of Electrophilic Benzannulated Heterocycles with 2-Aminopyridine and 2-Aminoquinoline: Direct Access toward Polyring-Fused Imidazo[1,2-a]pyridines.

We have developed a direct method for the synthesis of polyring-fused imidazo[1,2-a]pyridines via a copper-catalyzed annulation of electrophilic benzannulated heterocycles with 2-aminopyridine and 2-aminoquinoline. From 3-nitroindoles and 2-aminopyridine, we could synthesize tetracenes, viz., indole-fused imidazo[1,2-a]pyridines, and by starting from 2-aminoquinoline, we could generate pentacenes, viz., indolo-imidazo[1,2-a]quinolines. In addition, we could also extend the methodology toward the synthesis of benzothieno-imidazo[1,2-a]pyridines starting from 3-nitrobenzothiophene. Furthermore, the basic photophysical properties of these synthesized heteroacenes were evaluated.

Copper-Catalyzed Annulation-Trifluoromethyl Functionalization of Enynones.

The Cu(I)-catalyzed annulation-halotrifluoromethylation and cyanotrifluoromethylation of enynones have been established, enabling multibond formations of the synthesis of quaternary carbon-centered 1-indanones in moderate to good chemical yields. The reaction of enynones with Togni's reagent and chloro- or bromotrimethylsilane afforded halo- and CF3-containing 1-indenones. However, the addition of K3PO4 as a base into the catalytic system led to forming cyano-anchored (Z)-1-indanones as major stereoisomeric products. This strategy exhibits remarkable compatibility with a wide range of enynones.

Copper-Catalyzed Annulation of O-Acyl Oximes with Cyclic 1,3-Diones for the Synthesis of 7,8-Dihydroindolizin-5(6H)-ones and Cyclohexanone-Fused Furans.

A copper-catalyzed annulation of O-acyl oximes with cyclic 1,3-diones has been developed for the concise synthesis of 7,8-dihydroindolizin-5(6H)-ones and cyclohexanone-fused furans through the substituent-controlled selective radical coupling process. 2-Alkyl cyclic 1,3-diones undergo C-C radical coupling, while 2-unsubstituted cyclic 1,3-diones undergo C-O radical coupling.

Synthesis of Stable N–H Imines with a Benzo[7,8]indolizine Core and Benzo[7,8]indolizino[1,2-c]quinolines via Copper-Catalyzed Annulation of α,β-Unsaturated O-Acyl Ketoximes with Isoquinolinium N-Ylides

A copper-catalyzed annulation of α,β-unsaturated O-acyl ketoximes with isoquinolinium N-ylides has been developed for the concise synthesis of stable N-H imines with a benzo[7,8]indolizine core. When β-(2-bromoaryl)-α,β-unsaturated O-acyl ketoximes are used as the starting materials, a cascade cyclization occurs to afford the benzo[7,8]indolizino[1,2-c]quinolines.

FeCl3-Promoted Facile Synthesis of Multiply Arylated Nicotinonitriles

AbstractMany biologically active nicotinonitriles have been reported to date. Consequently, the development of synthetic methods for multiply arylated/alkylated nicotinonitriles remains a sought-after field of research. In the present work, a new synthetic strategy for multi-substituted nicotinonitriles is described. A FeCl3-promoted condensation–cyclization reaction of an enamino nitrile and α,β-unsaturated ketones proceeded efficiently with a wide range of substrates. It is noteworthy that this method facilitates access to fully and differently substituted nicotinonitriles, including tetra-arylated nicotinonitriles, in only three steps. Using the functionality of the cyano group, the copper-catalyzed annulation reaction of the nicotinonitrile was achieved to yield benzo­[c][2,7]naphthyridin-5(6H)-one.

Cascade Reaction of 2-Naphthols and Azirines: One-Pot Synthesis of C-3 Naphthol-Substituted Benzo[e]indoles.

A copper-catalyzed annulation of 3-aryl-2H-azirines with 2-naphthols has been developed for the rapid assembly of C-3-naphthol-substituted benzo[e]indoles in one pot. This cascade reaction was realized through dearomatic nucleophilic ring opening of azirine, intramolecular cyclization, and oxidative cross-dehydrogenative coupling to furnish the important unreported π-expanded naphthol/benzo[e]indole biaryls.

Copper-Catalyzed Annulation of Indolyl α-Diazocarbonyl Compounds Leads to Structurally Rearranged Carbazoles.

Indolyl α-diazocarbonyl compounds have proven to be effective starting materials for the construction of various 2,3-ring fused indole frameworks. Activation of the diazo functional group under metal catalysis generates a spiro-cyclic indolenine-type intermediate which rearranges to provide two distinct carbazoles upon oxidation. The current study investigates the effects of the catalyst as well as the substituents on the migratory group involved in controlling the selectivity of the rearrangement.

Synthesis of benzofuro- and benzothieno[2,3-c]pyridines via copper-catalyzed [4 + 2] annulation of ketoxime acetates with acetoacetanilide

An efficient copper-catalyzed annulation of ketoxime acetates with acetoacetanilide has been developed for the facile synthesis of benzofuro- and benzothieno[2,3-c]pyridines.

Generation of stereodefined (Z)-3,4-dihydronaphthalen-1(2H)-ones via copper-catalyzed annulation-cyanotrifluoromethylation of 1,7-enynes

A new three-component strategy for the copper-catalyzed annulation–cyanotrifluoromethylation of easily available 1,7-enynes with Togni’s reagent and TMSCN is developed. The reaction proceeds smoothly under mild conditions, providing a rapid and concise access to a wide range of stereodefined (Z)-3,4-dihydronaphthalen-1(2H)-ones with a quaternary carbon center in generally good yields. The protocol enjoys wide substrate scope regarding 1,7-enynes, high functional group tolerance and complete stereoselectivity.

Copper-Catalyzed Modular Assembly of Polyheterocycles.

Easy operation, readily accessible starting materials, and short syntheses of the privileged scaffold indeno[1,2-c]isoquinolinone were achieved by an multicomponent reaction (MCR)-based protocol via an ammonia–Ugi-four component reaction (4CR)/copper-catalyzed annulation sequence. The optimization and scope and limitations of this short and general sequence are described. The methodology allows an efficient construction of a wide variety of indenoisoquinolinones in just two steps.

Copper-Catalyzed Annulation-Cyanotrifluoromethylation of 1,6-Enynes Toward 1-Indanones via a Radical Process.

A new Cu(II)-catalyzed annulation–cyanotrifluoromethylation of 1,6-enynes with Togni's reagent and trimethylsilyl cyanide (TMSCN) has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields. This reaction was performed by using low-cost Cu(OTf)2 as the catalyst and Togni's reagent as both the radical initiator and a CF3 source, providing an efficient protocol for building up an 1-indanone framework with wide functional group compatibility. The reaction mechanism was proposed through a radical triggered addition/5-exo-dig cyclization/oxidation/nucleophilic cascade.

Copper-Catalyzed Annulation of Oxime Acetates with α-Amino Acid Ester Derivatives: Synthesis of 3-Sulfonamido/Imino 4-Pyrrolin-2-ones.

A copper-catalyzed annulation of oxime acetates and α-amino acid ester derivatives for the easy preparation of 4-pyrrolin-2-ones bearing a 3-amino group has been developed. This process features the oxidation of amines with oxime esters as the internal oxidant to produce the active 1,3-dinucleophilic and 1,2-dielectrophilic species concurrently. The subsequent nucleophilic cyclization realizes the efficient construction of 4-pyrrolin-2-one derivatives.

Copper-Catalyzed Annulation Reaction of Alkenes and N-Alkyl(aryl)-1-(methylthio)-2-nitroethenamine: an Approach for the Synthesis of Isoxazole Derivatives

A copper-catalyzed annulation reaction to access a variety of isoxazoles from alkenes and oxazete in situ generated from N-alkyl(aryl)-1-(methylthio)-2-nitroethenamine was reported. A plausible mechanism underlying the formation of the product was proposed, which represented a new approach for the construction of isoxazolines. This reaction was capable of tolerating alkenes bearing various substituents, which showed a relatively broad substrate scope with good functional group compatibility.

Synthesis of 2,3-Ring Fused Pyrroles via Cu-Catalyzed 5-exo-dig Annulation of Alkyne-Tethered Enaminones.

A copper-catalyzed annulation of alkyne-tethered enaminones for the synthesis of 2,3-ring fused pyrroles is reported. The 5-exo-dig cyclization/olefin migration reaction delivers the multisubstituted pyrroles in 59-99% yields with 16 examples. This strategy features easily available starting materials, mild reaction conditions, and a cheap ligand-free copper catalyst. The atom-economic transformation provides a simple access to a variety of synthetic useful pyrroles and their derivatives.

Direct Synthesis of Benzo[ f]indazoles from Sulfonyl Hydrazines and 1,3-Enynes by Copper-Catalyzed Annulation.

A novel and efficient strategy for the direct synthesis of benzo[ f]indazoles via copper-catalyzed cascade reaction of sulfonyl hydrazides with 1,3-enynes under mild conditions has been developed. This method achieves the formation of two C-N bonds and one C-C bond in one pot, providing a series of benzo[ f]indazoles in moderate to good yields with good functional group tolerance and remarkable regioselectivity.

Synthesis of 2,3,5,6-Tetrasubstituted Pyridines via Copper-Catalyzed Domino Oxidative Annulation of 1,3-Dicarbonyl Compounds with Methanol and Ammonium Acetate

Synthesis of 2,3,5,6-Tetrasubstituted Pyridines via Copper-Catalyzed Domino Oxidative Annulation of 1,3-Dicarbonyl Compounds with Methanol and Ammonium Acetate

Synthesis of Organophosphorus Compounds through Copper-Catalyzed Annulation Involving C-O and C-P Bond Formations.

A novel copper(II) trifluoromethanesulfonate-catalyzed, high-efficiency, and atom-economical synthesis of valuable organophosphorus compounds via cascade annulation of propargylic alcohols with diphenylphosphine oxide is described. This protocol, which has a good functional-group compatibility and insensitivity to an ambient atmosphere, provides a simple and direct pathway to the products, organophosphorus compounds, in good yields under mild conditions. The method could be efficiently scaled up to gram scale, thus highlighting a potential application of this methodology.

Copper-Catalyzed Annulation of Tetronic Acids with Azirines: Scope and Mechanism

Key words copper catalysis - annulation - azirines - pyrroles - tetronic acids