Domino Cyclization Research Articles

Synthesis of hybrid polycycles containing fused hydroxy benzofuran and 1H-indazoles via a domino cyclization reaction

A trifluoroacetic acid mediated [3+2] annulation reaction between 5-hydroxy-1H-indazoles – generated in situ – and p-benzoquinones has been reported.

Synthesis of Triazolo- and Oxadiazolopiperazines by Gold(I)-Catalyzed Domino Cyclization: Application to the Design of a Mitogen Activated Protein (MAP) Kinase Inhibitor

An efficient method for the synthesis of [1,2,4]triazolo[4,3- a]piperazine derivatives was established based on a gold(I)-catalyzed domino cyclization of an amidrazone substrate with a terminal alkyne. The amidoxime congeners were converted into [1,2,4]oxadiazolo[4,5- a]piperazine derivatives in the presence of a gold catalyst. The oxadiazolopiperazine is a promising scaffold for the design of novel inhibitors against p38 mitogen activated protein kinase (MAP kinase).

Cp*Co(III)-Catalyzed Regioselective Synthesis of Cyclopenta[ b]carbazoles via Dual C(sp2)-H Functionalization of 1-(Pyridin-2-yl)-indoles with Diynes.

Cp*Co(III)-catalyzed synthesis of cyclopenta[ b]carbazoles from 1-(pyridin-2-yl)-indoles and diynes is developed. This reaction involves dual C-H activation of indoles and domino cyclizations with diynes and has excellent regioselectivity, high efficiency, a broad substrate scope, and tolerance for various functional groups. A series of cyclopenta[ b]carbazole molecular scaffolds are obtained in good to excellent yields.

Heterocyclization and Spirocyclization Processes Based on Domino Reactions of N-Tosylhydrazones and Boronic Acids Involving Intramolecular Allylborylations of Nitriles.

Polycyclic molecules featuring all-carbon quaternary bridgehead centers were synthesized through domino cyclizations between N-tosylhydrazones and boronic acids. Variations of the general cascade have been applied for the preparation of 3-quinuclidinones and related alkaloid-like scaffolds through transannular heterocyclizations. Moreover, the employment of 3-cyanopropyl and 4-cyanobutylboronic acids and α,β-unsaturated N-tosylhydrazones led to spirocycles through unprecedented formal [n+1] cyclizations, including the stereoselective spirocyclization of the Hajos-Parrish ketone. The common feature of all the new reactions described is the creation of an all-carbon quaternary center by formation of two Csp3 -C bonds on the hydrazonic carbon atom. DFT-based calculations suggested the occurrence of cascade processes, which involve a diazo compound carboborylation followed by a 1,3-borotropic rearrangement on an intermediate allylboronic acid and a novel bora-aza-ene cyclization.

ピンポイントフッ素化多環式芳香族炭化水素（F-PAH）：フルオロアルケンの求電子的活性化による合成と性質

On treatment with a cationic Pd(II) catalyst in the presence of BF3·OEt2, 1,1-difluoroalkenes and 1,1,2-trifluoroalkenes underwent Friedel-Crafts-type ring closures (direct activation) to afford pinpoint-monofluorinated and pinpoint-vic-difluorinated phenacenes (F-phenacenes), respectively. Treatment of 1,1-difluoroallenes with an InBr3 catalyst facilitated domino cyclization (indirect activation) leading to the synthesis of F-phenacenes and related F-PAHs. Using the formed F-PAH library, the physical properties of these compounds were investigated. Notably, the HOMO-LUMO energy gaps of F-picenes, consisting of five benzene rings, were smaller than that of the corresponding fluorine-free picene by 0.02-0.26 eV. The HOMO energy levels of F-picenes were lowered by 0.10-0.22 eV, leading to enhanced resistance of these materials to aerial oxidation. 5-Fluoropicene and 13-fluoropicene exhibited p-type semiconducting behavior [5-fluoropicene: 2.8×10−5 cm2/Vs (vacuum deposition); 13-fluoropicene: 6.6×10−2 cm2/Vs(vacuum deposition), 1.3×10−4 cm2/Vs (spin casting)]. The introduction of fluorine substituent(s) into picenes increased their solubilities in organic solvents, which was best exemplified by the much higher solubilities of 6-fluoropicene (5.3 wt%), 6,7-difluoropicene (5.3 wt%), and 13-fluoropicene (3.1 wt%) in THF, compared to that of picene (0.20 wt%)。

Further Studies on the Pyrolytic Domino Cyclization of Stabilized Phosphonium Ylides Bearing an Ortho-Aminophenyl Group.

Four new, stabilized phosphonium ylides containing a 2-(benzyl(methyl)amino)phenyl group have been prepared and characterized and are found, upon pyrolysis under gas-phase flow conditions, to lose Ph3PO and benzyl radicals to afford new heterocyclic products resulting from domino cyclization of both C- and N-centered radicals. Most products arise from processes of the former type and have quinoline, phenanthridine, or ring-fused phenanthridine structures, while in one case, a process of the latter type leads to a benzocarbazole product. The X-ray structure of a 2-(methyl(tosyl)amino)phenyl ylide is also reported.

Flash vacuum pyrolysis of oxo-stabilised phosphonium ylides containing methoxythiophene and methylthiophene groups

Ten new oxo-stabilised phosphonium ylides containing substituted thiophene groups, as well as two deuterium-labelled analogues, are prepared and fully characterised. Upon flash vacuum pyrolysis at 800 °C, the simpler examples undergo extrusion of Ph3PO coupled with domino cyclisation to give thieno[3,2-b]furan and thieno[3,4-b]furan products but the corresponding approach to a thieno[2,3-b]furan fails. One ylide designed to give a thieno[3,4-b]furan instead gives phenylbutadiyne and 2-phenyl-3-vinylthiophene at 725 °C and the mechanism of this unusual process is elucidated by deuterium labelling. Attempts to access more complex heterocyclic products from extended methoxythienyl ylides failed. Two ylides bearing a 3-methyl-2-thienylacryloyl group gave 5-benzylbenzothiophene, 5-(α-methylbenzyl)benzothiophene and fluoreno[3,4-b]thiophene upon FVP at 800 °C and the mechanism was again elucidated by deuterium labelling.

Pyrido[2,3-d]pyrimidines by Domino Cyclization on a Solid Acid Catalyst

Key words domino reaction - cyclization - pyridopyrimidines - nitroalkenes - aldehydes

Copper-Catalyzed Photoinduced Radical Domino Cyclization of Ynamides and Cyanamides: A Unified Entry to Rosettacin, Luotonin A, and Deoxyvasicinone

A general and efficient procedure for the copper-catalyzed photoinduced radical domino cyclization of ynamides and cyanamides providing an efficient access to complex tri-, tetra- and pentacyclic nitrogen heterocycles is reported. Upon visible light irradiation in the presence of catalytic amounts of [(DPEphos)(bcp)Cu]PF6 and an amine, a range of unactivated aryl and alkyl iodides were shown to be smoothly transformed to the corresponding radical species, initiating the radical domino cyclization. This procedure provides a unified entry to rosettacin, luotonin A, and deoxyvasicinone that could be efficiently prepared in a limited number of steps.

Solid acid-catalyzed domino cyclization reaction: regio- and diastereoselective synthesis of pyrido[2,3-d]pyrimidine derivatives bearing three contiguous stereocenters

A highly efficient, operationally simple, green method using a solid acid for regio- and diastereoselective synthesis of pyrido[2,3-d]pyrimidines.

A Gold-Catalyzed Domino Cyclization Enabling Rapid Construction of Diverse Polyheterocyclic Frameworks.

We report herein an efficient gold(I)-catalyzed post-Ugi domino dearomatization/ipso-cyclization/Michael sequence that enables access to libraries of diverse (hetero)arene-annulated tricyclic heterocycles. This process affords novel complex polycyclic scaffolds in moderate to good yields from readily available acyclic precursors with excellent chemo-, regio-, and diastereoselectivity. The power of this strategy has been demonstrated by the rapid synthesis of 40 highly functionalized polyheterocycles bearing indole, pyrrole, (benzo)furan, (benzo)thiophene, pyrazole, and electron-rich arene groups in two operational steps.

A Gold‐Catalyzed Domino Cyclization Enabling Rapid Construction of Diverse Polyheterocyclic Frameworks

AbstractWe report herein an efficient gold(I)‐catalyzed post‐Ugi domino dearomatization/ipso‐cyclization/Michael sequence that enables access to libraries of diverse (hetero)arene‐annulated tricyclic heterocycles. This process affords novel complex polycyclic scaffolds in moderate to good yields from readily available acyclic precursors with excellent chemo‐, regio‐, and diastereoselectivity. The power of this strategy has been demonstrated by the rapid synthesis of 40 highly functionalized polyheterocycles bearing indole, pyrrole, (benzo)furan, (benzo)thiophene, pyrazole, and electron‐rich arene groups in two operational steps.

One-pot synthesis of quinazolin-4(3H)-ones and fused quinazolinones by a palladium-catalyzed domino process

An efficient one-pot synthesis of quinazolin-4(3H)-ones, benzoimidazo[2,1-b]quinazolin-12(6H)-ones and imidazo[2,1-b]quinazolin-5(1H)-ones via a palladium-catalyzed domino process has been developed. The Pd-catalyzed reactions of 2-azidobenzamides 1 with isocyanides 2 produced quinazolin-4(3H)-ones 4 at room temperature by a domino Pd-catalyzed cross-coupling/carbodiimide-mediated cyclization. However, as 2-azido-N-(2-bromophenyl)benzamides 1 were used under heating condition in the presence of Cs2CO3, the benzoimidazo[2,1-b]quinazolin-12(6H)-ones 5 were directly obtained by twice Pd-catalyzed domino cyclization. A domino reogioselective 5-exo-dig intramolecular cyclization reaction of alkynyl-containing azides 6 with isocyanides 2 generated imidazo[2,1-b]quinazolin-5(1H)-ones 9 in 74–93% yields in the presence of catalyst Pd(PPh3)4 and K2CO3.

Synthesis of Indolizine‐Containing Diaryl‐ and Triarylmethanes through a Cu‐Catalyzed Domino Cyclization of 2‐(2‐Enynyl)pyridines

AbstractA Cu‐catalyzed protocol for the synthesis of indolizine‐containing diaryl‐ and triarylmethane derivatives through a 5‐endo‐dig cyclization of 2‐(2‐enynyl)pyridines, followed by a remote addition of nucleophiles, such as hydride and 2‐naphthols, is described.

Versatile Pyrolytic Synthesis of Fused Polycyclic Heteroaromatic Compounds

Thirty-six new stabilised phosphonium ylides designed to undergo thermal loss of Ph3PO and radical domino cyclisation have been prepared and are generally found to undergo the desired reaction under flash vacuum pyrolysis conditions at 850 °C. A wide range of ­tetra- and pentacyclic fused-ring heterocycles, many previously unknown, are thus formed in moderate to high yield in a single step. By using suitably substituted starting materials, substituents such as CH3 and Cl can be installed at various positions in the products. The method has also been demonstrated in a combinatorial mode to generate a small library of twelve fused-ring heterocycles in a single pyrolysis.

Gas-phase domino cyclization of phosphonium ylides leading to the total synthesis of Eustifoline D

Six stabilised phosphonium ylides bearing ortho-benzylaminophenyl and cinnamoyl (or a heterocyclic analogue) groups have been prepared and upon flash vacuum pyrolysis at 800°C were found to undergo cascade cyclization processes to give mainly 3-styrylquinolines but also in some cases ring-fused carbazoles and other fused-ring heterocyclic products. By starting with an appropriate ring-methylated precursor the natural product Eustifoline D was obtained in 19% yield in the pyrolysis in addition to the 3-(2-furylethenyl)quinoline (46%).

Construction of benzo[d]imidazo[2,1-b]thiazole derivatives via a simple multi-component domino cyclization

An operationally simple and highly efficient one-pot multi-component domino cyclization for the preparation of benzo[d]imidazo[2,1-b]thiazole derivatives from 2-amine-benzo[d]thiazoles, 2-oxoaldehyde and cyclic 1,3-dicarbonyl compounds under microwave irradiation has been developed in this work. Formation of the benzo[d]imidazo[2,1-b]thiazole skeleton and its functionalization can proceed smoothly, avoiding the usage of metal catalyst. Furthermore, the procedure provides few intermediates, low energy consumption and simple purification operation.

Microwave‐assisted Three‐component Reactions for Regioselective Synthesis of Functionalized Benzo[e]indoles

Microwave‐assisted three‐component reactions of arylglyoxals with cyclic 1,3‐dicarbonyl compounds and naphthalen‐2‐amine have been established, by which a series of new functionalized benzo[e]indoles with good yields were synthesized. The reaction was easily conducted in HOAc, enabling domino cyclization to construct three new σ‐bonds in a one‐pot operation. Flexible structural modification and broad functional group compatibility as well as mild reaction conditions make this strategy a useful and attractive process of library generation for drug discovery.

L-Proline catalyzed domino cyclization for the green synthesis of novel 1,4-dihydrobenzo[a]pyrido[2,3-c]phenazines

l-Proline has been used as an efficient, reusable, and bifunctional organocatalyst for the one-pot, two-step, five-component synthesis of novel 1,4-dihydrobenzo[a]pyrido[2,3-c]phenazines by the condensation reaction of 2-hydroxynaphthalene-1,4-dione, aromatic 1,2-diamines, aldehydes, ammonium acetate, and ethyl acetoacetate under conventional heating in solvent-free conditions. In this domino transformation, six bonds and two new rings are efficiently formed. High yields, short reaction time (20–30 min), operational simplicity, easy work-up procedure, avoidance of hazardous or toxic catalysts and organic solvents are the main advantages of this green methodology.

Access to Benzo[a]carbazoles and Indeno[1,2-c]quinolines by a Gold(I)-Catalyzed Tunable Domino Cyclization of Difunctional 1,2-Diphenylethynes.

The cyclization order of the difunctional 1,2-diphenylethynes was precisely tuned under the catalysis of gold by changing the nitrogen substitution of the substrates, leading to the facile preparation of benzo[a]carbazole and indeno[1,2-c]quinoline derivatives. The mechanisms of these domino cyclizations were probed by control experiments, and an insight into the selectivity of the cyclization was gained by density functional theory (DFT) calculations. This research represents a unified and common method to access benzo[a]carbazoles and indeno[1,2-c]quinolines.