Copper-mediated intramolecular aza-Wacker-type cyclization of 2-alkenylanilines toward 3-aryl indoles

A copper-mediated intramolecular aza-Wacker-type cyclization was developed for the direct and efficient synthesis of 3-aryl indoles using 2-alkenylanilines in moderate to good yields with good functional group compatibility. This strategy shows the high efficiency, operational simplicity as well as broad substrate scope.     

Properties of 2,3-dihydro-imidazolo[1,2-a]pyridines. (Review)

Published data on the physical and chemical characteristics of 2,3-dihydroimidazo[1,2-a]pyridines to 1998 are reviewed.Riga Technical University, Riga, Latvia; e-mail: mara@ktf.rtu.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1011–1027, August, 2000.     

Synthesis of 2-(hetero)arylthieno[2,3-b] or [3,2-b]pyridines from 2,3-dihalopyridines, (hetero)arylalkynes,and Na2S. Further functionalizations

A simple and efficient three-step methodology is described for the first time for the synthesis of 2-(hetero)arylthieno[2,3-b] or [3,2-b]pyridines. The first step is a Sonogashira coupling from 3-bromo-2-chloropyridine or 2-bromo-3-chloropyridine with several (hetero)arylalkynes to obtain the corresponding 2- or 3-chloro(hetero)arylethynylpyridines. These were cyclized by treatment with Na₂S affording the expected 2-(hetero)arylthienopyridines. As an improvement, these reactions were also performed in one-pot, without the isolation of the Sonogashira product, giving the thienopyridines in similar or better yields, reducing significantly the reaction time after the addition of Na₂S. Further functionalizations were achieved in the thienopyridine system either by bromination in the thiophene ring or chlorination in the pyridine ring via a N-oxide intermediate, allowing metal-catalyzed coupling reactions and/or nucleophilic substitutions. The functionalization of some substituents is also possible and as an example a 1,3-diarylurea was obtained from the reaction of an aniline derivative with an arylisocyanate.     

A Base-Mediated Approach Towards Dihydrofuro[2,3-b]Benzofurans from 2-Nitrobenzofurans and 1,3-Dicarbonyls

A straight-forward approach for the synthesis of a dihydrofuro[2,3-b]benzofuran derivatives has been achieved through a base-mediated Michael addition of 1,3-dicarbonyls to 2-nitrobenzofurans followed by intramolecular cyclization. A variety of 1,3-dicarbonyls, including cyclic as well as trifluoromethylated ones, have been subjected to react with 2-nitrobenzofurans under optimal conditions, and the respective dihydrofuro[2,3-b]benzofurans could be accessed in moderate to excellent yields.     

Interaction of 4,5-diphenyl-2,3-dihydro-2,3-pyrroledione with ethoxycarbonylmethylenetriphenylphosphorane: synthesis and crystal structure of 4,5-diphenyl-Z-2-ethoxycarbonylmethylene-2,3-dihydro-3-pyrrolone

1-Unsubstituted 4,5-diphenyl-2,3-dihydro-2,3-pyrroledione interacts with ethoxycarbonyl-methylenetriphenylphosphorane regioselectively to give 4,5-diphenyl-Z-2-ethoxycarbonyl-methylene-2,3-dihydro-3-pyrrolone. The crystal and molecular structure of the latter was studied by X-ray analysis.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1556–1558, August, 1995.     

A concise synthesis of functionalized 2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines

A strategy for the efficient and rapid one-pot synthesis of 2-aryl-2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines from readily available o-nitropicolines and aromatic aldehydes is described. The key transformation involves reaction of o-nitropicolines with aromatic aldehydes in the presence of TBAF and Hünig's base giving rise to functionalized products having molecular complexity suitable for further manipulation.     

Logical design and synthesis of indole-2,3-diones and 2-hydroxy-3(2H)-benzofuranones via one-pot intramolecular cyclization

A novel and attractive protocol to synthesis indole-2,3-diones and 2-hydroxy-3(2H)-benzofuranones and via copper(II) oxide catalyzed intramolecular cyclization is described. This method possesses functional-group compatibility, easy workup procedure, shorter reaction time and high yields.     

Asymmetric palladium-catalyzed annulation of benzene-1,2-diol and racemic secondary propargylic carbonates bearing two different substituents

The palladium-catalyzed cyclization of benzene-1,2-diol with various racemic secondary propargyl carbonates having no acetylenic hydrogen in the presence of (R)-Binap as the chiral ligand afforded the two regioisomers of the corresponding 2,3-dihydro-1,4-dioxin derivatives in quite good yields, and also in enantioselectivities going from 40 to 97%. The cyclization of benzene-1,2-diol with methyl (R)-1-methyl-3-phenylpro-2-yn-1-yl carbonate in the presence of dppb as the achiral ligand afforded 2-benzylidene-3-methyl-2,3-dihydro-1,4-benzodioxine as the major product with 15% ee. The use of (R)-Binap as the chiral ligand afforded the (+) cyclized compound in 45% ee, when the (−) enantiomer was obtained with 77% ee in the presence of (S)-Binap. All the results suggest that in this case the enantioselective step is the diastereoselective protonation of the palladium-carbene intermediates.     

The chemical behavior of 2-methylene-2,3-dihydro-3-furanones

Diphenylketene undergoes regioselective thermal [2+2]-cycloaddition to the heterocyclic C(3)=O carbonyl group of 5-aryl-2-methoxycarbonylmethylene-2,3-dihydrofuran-3-ones and 5-phenyl-2,3-dihydrofuran-2,3-dione to give the corresponding 3-diphenylmethylene derivatives of 2,3-dihydrofuran.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 331–334, February, 1995.     

2,3-Benzodiazepine-1-thione in the synthesis of substituted and hetero-annelated 2,3-benzodiazepines

A series of S-substituted and 1,2-annelated derivatives of 2,3-benzodiazepine has been obtained on the basis of 2,3-benzodiazepine-1-thione. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 594-601, April, 2009.     

Pd-Catalyzed annulation of benzene-1,2-diol and propargylic carbonates: a new example of asymmetric catalysis

The palladium-catalyzed cyclization of benzene-1,2-diol with various secondary propargylic carbonates in the presence of (R)-Binap as the chiral ligand afforded the corresponding 2,3-dihydrobenzo-1,4-dioxin derivatives in quite good yields, and also in enantioselectivities of up to 93%. The assumed enantioselective step is the protonation of a palladium-carbene intermediate.     

Synthesis and novel reactivities of several 1,9-dithiaalkane-bridged thianthrene 10-oxides

The irreversible photolytic axial to equatorial change (3ax-4ax→3eq-4eq) and the irreversible thermal equatorial to axial change (3eq-4eq→3ax-4ax) of the S-O configuration were first observed. Meanwhile, the shorter 1,9-bridged derivative (2ax) exhibited the interesting photolytic degradation, affording 1,9-dithiadibenzothiophene (5) by the elimination of SO and ethylene.     

Studies on the Synthesis of New 3-(3,5-Diamino-1-substituted-pyrazol-4-yl)azo-thieno[2,3-b]pyridines and 3-(2-Amino-5,7-disubstituted-pyrazolo[1,5-a]pyrimidine-3-yl)azothieno[2,3-b]pyridines

Coupling the diazonium salt of 3-amino-2-cyano-4,6-dimethylthieno[2,3-b]pyridine 1 with malononitrile 2 gave 2-cyano-3-(hydrazonomalononitrile)-4,6-dimethylthieno[2,3-b]pyridine 3 which then reacted with hydrazine compounds 4a-4h to yield corresponding 2-cyano-3-(3,5-diamino-1-substituted-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 5a-5h. The 2-cyano-3-(2-amino-5,7-disubstituted-pyrazolo-[1,5-a]pyrimidine-3-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 7a-7f were obtained in good yield by the cyclocondensation reaction of 2-cyano-3-(3,5-diamino-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridine 5a with the appropriate 1,3-diketones 6a-6f under acidic condition.     

Visible-light-induced synthesis of benzothiophenes and benzoselenophenes via the annulation of thiophenols or 1,2-diphenyldiselane with alkynes

An effective metal-free photoredox-mediated tandem addition/cyclization reaction of thiophenols or 1,2-diphenyldiselane with alkynes leads to 2,3-disubstituted benzothiophenes and benzoselenophenes. Blue light irradiation of the organic dye, Mes-Acr-Me⁺, initiates the photoredox catalysis. A series of functional groups could be tolerated under ambient conditions, and good to excellent yields were generated.     

Selective C-3 lithiation of 2,3-dibromo- and 2,3-diiodo-1-methylindoles

Reaction of 2,3-dibromo-1-methylindole with tert-butyllithium at −78 °C followed by treatment with tropylium ion gave 2-bromo-3-cycloheptatrienyl-1-methylindole in a moderate yield, indicating that 2-bromo-3-lithio-1-methylindole would be involved as an intermediate instead of 3-bromo-2-lithio-1-methylindole. The structure of 2-bromo-3-cycloheptatrienyl-1-methylindole was unequivocally determined by a single X-ray analysis. 2,3-Diiodo-1-methylindole also gave a 3-lithio derivative exclusively.     

Synthesis of Imidazo[1,2‐a]pyridines: C‐H Functionalization in the Direction of C‐S Bond Formation

Imidazo[1,2‐a]pyridines play an important role in medicinal chemistry. In spite of very drastic developments on syntheses and functionalization in this area, the use of inexpensive catalysts and mild reaction conditions constitutes an important role in pharmaceutical applications. This account describes our recent efforts on the development of new methods for the synthesis of imidazo[1,2‐a]pyridines using readily available starting substrates and catalysts under very mild reaction conditions. In the direction of enhancement of biological activity, we also described the synthesis of functionalized imidazo [1,2‐a]pyridine derivatives.     

A Facile Synthesis of 3H-Benzo[1,2]Dithiole-3-Thiones and Their Condensation with Active Methylene Compounds

Abstract

3H-Benzo[1,2]-dithiole-3-thiones were prepared from potassium sulfide and 2-halobenzaldehydes in moderate-to-good yields, and a plausible mechanism for this catalyst-free intramolecular heteroannulation reaction has been proposed. The Knoevenagel condensation reactions of 3H-benzo[1,2]dithiole-3-thiones with active methylene compounds such as ethyl 2-cyanoacetate and diethyl malonate, and the three-component one-pot reactions of potassium sulfide, 2-halobenzaldehydes, and ethyl 2-cyanoacetate, affording the corresponding products, have been developed.

GRAPHICAL ABSTRACT      

Stereoselective synthesis of 3-alkylidene/alkylazetidin-2-ones from azetidin-2,3-diones

Azetidin-2,3-diones have been used as synthons for the synthesis of C-3 alkylidene/alkylazetidin-2-ones. Some of the 3-alkylazetidin-2-ones are well known for their cholesterol absorption inhibitor activity. A regio and stereoselective Grignard reaction on a keto group followed by dehydration using PPh₃/CCl₄ reagent is a key step in this synthesis. Hydrogenation of the 3-alkylideneazetidin-2-ones provided stereoselectively cis-3-alkylazetidin-2-ones in very good yields.     

Stereoselective synthesis of morphine fragments trans- and cis-octahydro-1H-benzo[4,5]furo[3,2-e]isoquinolines

A stereoselective synthesis of the ACNO partial structures of morphine has been developed. Palladium-catalyzed cyclization of carbamate 2 provided the tetracyclic (ACNO) 3-ethoxycarbonyl-9-methoxy-2,3,5,6,7,7a-hexahydro-1H-benzofuro[3,2-e]isoquinoline (14); while treatment of 5-(2-bromo-6-methoxyphenoxy)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline (8) under the same reaction condition gave 8a-(2-hydroxy-3-methoxyphenyl)-1,2,3,4,6,7,8,8a-octahydroisoquinoline (11) via an unusual Claisen rearrangement. 9-Methoxy-3-methyl-2,3,5,6,7,7a-hexahydro-1H-benzofuro[3,2-e]isoquinoline (7) was successfully transformed to trans-octahydroisoquinoline 3 and cis-octahydroisoquinoline 4 via catalytical hydrogenation over PtO₂ and chemical reduction with acidic NaBH₄, respectively.