ABSTRACT
An efficient strategy for the preparation of spirocyclic indole-N-oxide compounds through a Rh(III)-catalyzed [4 + 1] spiroannulation reaction of N-aryl nitrones with 2-diazo-1,3-indandiones as C1 synthons under extremely mild conditions is presented. From this reaction, 40 spirocyclic indole-N-oxides were easily obtained in up to 98% yield. In addition, the title compounds could be successfully used for the construction of structurally intriguing maleimide-containing fused polycyclic scaffolds via a diastereoselective 1,3-dipolar cycloaddition reaction with maleimides.
ABSTRACT
We report herein an efficient and practical strategy for the preparation of 5H-phthalazino[1,2-b]quinazolin-8(6H)-one derivatives through a t-BuOK-catalyzed intramolecular hydroamination reaction of functionalized quinazolinones under extremely mild reaction conditions. A variety of quinazolinone substrates are well tolerated to furnish the corresponding products in good to high yields via an exclusive 6-exo-dig cyclization process. The present protocol has the advantages of readily obtainable starting materials, broad substrate scope, and high regio- and stereoselectivity.
ABSTRACT
A rhodium-catalyzed formal [4 + 5] annulation reaction of 2-arylindoles with quinone monoacetals for the selective preparation of bridged nine-membered carbocyclic and heterocyclic compounds is developed. When 2-aryl substituted indoles are employed, this annulation reaction affords bridged nine-membered carbocyclic compounds with excellent indolyl C3 selectivity. On the other hand, with 2-aryl-3-substituted indoles as the substrates, bridged nine-membered heterocyclic compounds are exclusively formed via N1 annulation. Further transformations of the obtained products into new bridged compounds showcase the synthetic potential of this protocol.
ABSTRACT
A novel and practical procedure for the preparation of isoindolo[2,1- b]isoquinoline-7-carboxylate derivatives through a Rh(III)-catalyzed oxidative [4 + 1] cycloaddition of isoquinolones with diazoketoesters followed by an in situ deacylation reaction is disclosed. Intriguingly, the title compounds could be easily converted into isoindolo[2,1- b]isoquinolin-5(7 H)-ones via de-esterification, which are rosettacin analogues and frequently found in various natural alkaloids and synthetic drug molecules.
ABSTRACT
A simple and practical procedure for the selective preparation of 3 H-indol-3-one and indolo[1,2- c]quinazoline derivatives through copper-catalyzed aerobic oxygenation and intramolecular cyclization reactions of 2-(2-amidoaryl)-1 H-indoles in the presence of acid has been disclosed. Interestingly, the reaction outcomes are exclusively dependent on the reaction medium employed. With DMF as the solvent, the amide moiety of indole substrates could act as an auxiliary to enable the indole's oxygenation reaction with molecular oxygen from air as the oxidant to give 3 H-indol-3-one derivatives in a highly selective manner. On the other hand, when the reactions were performed in 1,4-dioxane, the amide moiety switched to participate in an intramolecular indolyl N1-cyclization to afford indolo[1,2- c]quinazolines as the predominating products.
ABSTRACT
An efficient and facile protocol for the synthesis of quinazolinone-fused tetracyclic compounds through an iodine-mediated one-pot cascade reaction of 2'-bromoacetophenones with 2-aminobenzohydrazides or 2-aminobenzamides is reported. With 2-aminobenzohydrazides as the substrates, the reaction gave 5H-quinazolino[3,2-b]cinnoline-7,13-diones in moderate to good yields under metal-catalyst-free conditions. With 2-aminobenzamides as the substrates and CuBr as the catalyst, on the other hand, it afforded tryptanthrin derivatives with good efficiency. Mechanistically, the formation of the tetracyclic systems is initiated by iodination and oxidation of 2'-bromoacetophenones followed by a cascade procedure consisting of cyclocondensation, aromatization and intramolecular cyclization of the in situ formed 2-bromoarylglyoxals with 2-aminobenzohydrazides or 2-aminobenzamides, respectively.
Subject(s)
Acetophenones/chemistry , Benzamides/chemistry , Heterocyclic Compounds, 2-Ring/chemical synthesis , Hydrazines/chemistry , Iodine/chemistry , Quinazolines/chemical synthesis , Heterocyclic Compounds, 2-Ring/chemistry , Molecular Structure , Quinazolines/chemistryABSTRACT
A practical and highly efficient procedure for the selective preparation of 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-diones through a palladium-catalyzed one-pot three-component cascade reaction of 2-aminobenzamides with 2-bromobenzaldehydes and carbon monoxide under atmospheric pressure has been developed. This cascade reaction, in which four new C-C/C-N bonds and two new rings are simultaneously constructed, is triggered by a cyclocondensation of 2-aminobenzamides with 2-bromobenzaldehydes, followed by a Pd-catalyzed cyclocarbonylation of the in situ formed 2,3-dihydroquinazolin-4(1H)-ones with CO (1 atm). Compared with the existing methods, the present protocol has the advantages of readily available starting materials, broad substrate scope, structural diversity of products, and free of high-pressure equipment.
ABSTRACT
Novel and selective synthetic approaches toward indole derivatives via copper-catalyzed one-pot multicomponent cascade reactions of 1-bromo-2-(2,2-dibromovinyl)benzenes with aldehydes and aqueous ammonia are presented. Intriguingly, the concentration of ammonia, the molar ratio of reagents, and the structural features of the aldehyde substrate serve as key factors in controlling the selective formation of 3-cyano-1H-indoles, 9H-pyrimido[4,5-b]indoles, or 9H-pyrido[2,3-b]indoles. Compared with literature procedures, the synthetic approaches reported herein have advantages such as readily available starting materials, mild reaction conditions, and divergent reaction patterns toward different products with easily tunable selectivity.
ABSTRACT
Highly selective and convenient synthesis of indolo[1,2-c]quinazolines and 11H-indolo[3,2-c]quinolines through copper-catalyzed one-pot cascade reactions of 2-(2-bromoaryl)-1H-indoles with aldehydes and aqueous ammonia has been achieved. Notably, the regioselectivity was easily controlled by tuning the reaction conditions. Compared with literature methods, the present protocol features easily controlled selectivity, readily available starting materials, good functional group tolerance, and simple operation procedures.
ABSTRACT
A simple and practical procedure for the preparation of C5-(isoxazol-3-yl)-pyrimidine nucleosides through 1,3-dipolar cycloaddition of the in situ formed C5-nitrile oxide substituted pyrimidine nucleosides with various terminal alkynes is presented. Compared with literature procedures, this new method has advantageous features such as readily available and inexpensive starting materials, simple procedure without using expensive transition metal catalyst, and broad scope of substrates. By employing this method, 30 nucleoside analogues were prepared in moderate yields. Biological studies on these C5-(isoxazol-3-yl)-pyrimidine nucleosides showed that most of them exhibited significant in vitro antileishmanial activity.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Leishmania donovani/drug effects , Pyrimidine Nucleosides/chemical synthesis , Pyrimidine Nucleosides/pharmacology , Animals , Antiprotozoal Agents/chemistry , Drug Design , Humans , Isoxazoles/chemical synthesis , Isoxazoles/chemistry , Isoxazoles/pharmacology , Leishmaniasis/drug therapy , Pyrimidine Nucleosides/chemistry , Structure-Activity RelationshipABSTRACT
A novel series of isoxazoline benzoxaborole small molecules was designed and synthesized for a structure-activity relationship (SAR) investigation to assess the ectoparasiticide activity against ticks and fleas. The study identified an orally bioavailable molecule, (S)-3,3-dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol (38, AN8030), which was long lasting in dogs (t1/2=22 days). Compound 38 demonstrated 97.6% therapeutic effectiveness within 24 h of treatment, with residual efficacy of 95.3% against American dog ticks (Dermacentor variabilis) on day 30% and 100% against cat fleas (Ctenocephalides felis) on day 32 after a single oral dose at 50 mg/kg in dogs.
Subject(s)
Boron Compounds/chemistry , Dog Diseases/drug therapy , Drug Discovery , Ectoparasitic Infestations/drug therapy , Isoxazoles/chemical synthesis , Administration, Oral , Animals , Boron Compounds/administration & dosage , Boron Compounds/pharmacology , Dog Diseases/parasitology , Dogs , Isoxazoles/administration & dosage , Isoxazoles/chemistry , Isoxazoles/pharmacology , Molecular Structure , Structure-Activity Relationship , Time FactorsABSTRACT
A one-pot procedure for the synthesis of 3-alkynylpyridines via a zinc-mediated tandem reaction of nitriles with propargyl bromides under extremely mild reaction conditions has been developed. This reaction exhibits high efficiency, broad substrate scope, and good functional group tolerance. In addition, the 3-alkynylpyridines obtained herein were found to be versatile and convenient intermediates for the preparation of fused-heterocyclic compounds with potential biological and material interests.
Subject(s)
Alkynes/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Nitriles/chemistry , Pargyline/analogs & derivatives , Pyridines/chemical synthesis , Zinc/chemistry , Alkynes/chemistry , Catalysis , Heterocyclic Compounds/chemistry , Molecular Structure , Pargyline/chemistry , Pyridines/chemistryABSTRACT
A practical and efficient synthesis of pyrazolo[1,5-c]quinazolines and 5,6-dihydropyrazolo[1,5-c]quinazolines, including several spiro compounds, through copper-catalyzed tandem reaction of 5-(2-bromoaryl)-1H-pyrazoles with carbonyl compounds and aqueous ammonia under air has been developed. Compared with literature methods toward pyrazolo[1,5-c]quinazoline derivatives, the synthetic method reported in this paper has the advantages of readily available and inexpensive starting materials and reagents, broad scope of substrates, and mild reaction conditions.
Subject(s)
Ammonia/chemistry , Copper/chemistry , Ketones/chemistry , Pyrazoles/chemistry , Quinazolines/chemical synthesis , Catalysis , Molecular Structure , Pyrazoles/chemical synthesis , Quinazolines/chemistry , Water/chemistryABSTRACT
In the title compound, C(13)H(12)O(2), the dihedral angle between the pyran-one and phenyl rings is 57.55â (9)°. In the crystal, the mol-ecules are linked by π-π stacking inter-actions between the parallel pyran-one rings of neighboring mol-ecules with distances of 3.5778â (11)â Å and 3.3871â (11)â Å between the planes. C-Hâ¯O interactions also occur.
ABSTRACT
The title compound, C(12)H(13)ClN(2)O(2), crystallizes with two independent but very similar mol-ecules (A and B) in the asymmetric unit. The pyrazole ring in each mol-ecule has an envelope conformation. The dihedral angle between the pyrazole ring mean plane and the benzene ring is 86.07â (14)° in A and 85.99â (14)° in B. In the crystal, the A and B mol-ecules are linked via a pair of O-Hâ¯O hydrogen bonds, forming dimers. These dimers are further linked via C-Hâ¯O inter-actions to form -A-B-A-B- chains propagating along the c-axis direction.
ABSTRACT
Rhodium-catalyzed substrate-tunable oxidative annulation and spiroannulation reactions of 2-arylindoles with benzoquinone leading to 9H-dibenzo[a,c]carbazol-3-ols and new spirocyclic products are reported. Intriguingly, with 2-aryl-substituted indoles, benzoquinone could act as a C2 synthon to afford dibenzo[a,c]carbazoles. On the contrary, when 2-aryl-3-substituted indoles were used, benzoquinone switched to act as a C1 synthon to furnish spirocyclic compounds. In addition, further transformations of the obtained products demonstrate the synthetic utility of the present protocol.
ABSTRACT
Rh(III)-catalyzed site-selective oxidative spirocyclization reactions of isoquinolones with α-diazo-1,3-indandiones leading to three kinds of spiro compounds by employing isoquinolones with different structural features or tuning the reaction parameters are presented. In addition, a plausible catalytic cycle is proposed on the basis of control experimental results and density functional theory calculations. Finally, the diverse transformations of the spiro products into other complex skeletons demonstrate the synthetic utility of this protocol.
ABSTRACT
[reaction: see text] The gold-catalyzed cyclization reactions of 2-oxo-3-butynoic esters or disubstituted-1,2-diones with a variety of nucleophiles are described, which offer an efficient and straightforward route to substituted 3(2H)-furanones under mild reaction conditions. The Au(III) catalysts are also highly effective in the hydration of these activated alkynes.
ABSTRACT
A highly efficient and regioselective synthetic route to 6 H-isoindolo[2,1-a]indol-6-ones and indeno[1,2-b]indol-10(5 H)-ones through the Pd-catalyzed cyclocarbonylation of 2-(2-bromoaryl)indoles under atmospheric CO pressure has been achieved. Notably, the regioselectivity of the reaction was exclusively dependent on the structural characteristics of the indole substrates. With N-unsubstituted indoles as the starting materials, the reaction afforded 6H-isoindolo[2,1-a]indol-6-ones in good-to-excellent yields. On the other hand, with N-substituted indoles as the substrates, the reaction gave indeno[1,2-b]indol-10(5 H)-ones in a highly regioselective manner.
ABSTRACT
An efficient synthesis of diversely substituted quinazolines and 1,2,3,4-tetrahydroquinazolines through copper-catalyzed tandem reactions of the readily available 2-bromobenzyl bromides, aldehydes, and aqueous ammonia or amines has been developed. By using ammonia and simple aliphatic amines as the nitrogen source, the present method provides a versatile and practical protocol for the synthesis of quinazolines and 1,2,3,4-tetrahydroquinazolines.