Two Novel Thermal Biradical Cyclizations in Theory and Experiment: New Synthetic Routes to 6H-Indolo[2,3-b]quinolines and 2-Aminoquinolines from Enyne-Carbodiimides

Schmittel, Michael; Steffen, Jens‐Peter; Engels, Bernd; Lennartz, Christian; Hanrath, Michael

doi:10.1002/(sici)1521-3773(19980918)37:17<2371::aid-anie2371>3.3.co;2-e

Cited by 21 publications

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“…Carbodiimide is considered to be an aza-equivalent of allene, and more importantly, canceled dipole moments of C-N bonds are expected to facilitate the homolytic cleavage of the C-N bond to form radical species. The Wang [24][25][26][27][28] and the Schmittel [29][30][31] groups have recently reported the thermal CA of AYCs, but their scopes are limited to conjugated systems, whose electronic and steric environments are far different from nonconjugated ones, and which would be unable to provide dibenzonaphthyridine derivatives. Herein, we report the synthesis and the CA reactions of AYCs 1 and 2.…”

Section: Notesmentioning

confidence: 99%

“…Moreover, the CA reaction of 2 proved to proceed even at 50°C, in a retained yield (77%). 37) Since conjugated AYCs tend to require higher temperature for their C 2 -C 6 thermal cyclizations, [24][25][26][27][28][29][30][31] this result implied a possibility that C 2 -C 7 cyclization of nonconjugated AYCs proceeds more facilely than that of conjugated ones.…”

Section: Notesmentioning

confidence: 99%

“…[29][30][31] Moreover, compounds comprised of a dibenzo-[b,g] [1,8]naphthyridine system are reported to exhibit intriguing biological activities. 21,22) Although a number of efficient synthetic methods for dibenzo [b,g] [1,8]naphthyridines have been reported, [38][39][40][41] the present method via the thermal isomerization of nonconjugated AYCs may alternatively be favored, because of the mildness of the conditions and the simple short-step procedure, which lead to a higher total yield of the product.…”

Section: Notesmentioning

confidence: 99%

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Thermal Cyclization of Nonconjugated Aryl-Yne-Carbodiimide Furnishing a Dibenzonaphthyridine Derivative

Kimura

Torikai

Ueda

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesConjugated enyne compounds have received considerable attention in the broad field of chemistry, because of their unique cyclization reactions affording aromatized products by way of radical intermediates capable of DNA cleavage. [2][3][4][5][6][7][8] To date, a number of polyenyne compounds, including both natural 2,4,7) and artificial products, 3,7,8) have been synthesized to evaluate their reactivity and to develop more potent and selective antitumor agents, however, modification of the conjugated enyne core structures has not been well investigated. We focused on nonconjugated polyenyne systems and found that nonconjugated aryl-ynes and aryl-yne-allenes undergo thermal cycloaromatization (CA) reactions [9][10][11][12][13][14] while cleaving DNA. [15][16][17] Thus, as a next goal, we set a reagent-free thermal isomerization of nonconjugated aryl-yne systems, which involves homolyses of carbon-nitrogen (C-N) unsaturated bonds to afford useful azaaromatic compounds via a domino radical reaction. 18)As target polycyclic aromatic compounds, we focused on dibenzonaphthyridine derivatives, which have never been synthesized via thermal isomerization of aryl-ynes, despite their fascinating and intriguing pharmacological properties. [19][20][21][22][23] In order to provide a novel synthetic methodology of dibenzonaphthyridines, we planned to examine the CA reactions of nonconjugated aryl-yne-carbodiimides (AYCs). Carbodiimide is considered to be an aza-equivalent of allene, and more importantly, canceled dipole moments of C-N bonds are expected to facilitate the homolytic cleavage of the C-N bond to form radical species. The Wang [24][25][26][27][28] and the Schmittel 29-31) groups have recently reported the thermal CA of AYCs, but their scopes are limited to conjugated systems, whose electronic and steric environments are far different from nonconjugated ones, and which would be unable to provide dibenzonaphthyridine derivatives. Herein, we report the synthesis and the CA reactions of AYCs 1 and 2.As AYC substrates, we selected two compounds (Fig. 1). One possesses a conjugated aryl-yne and a dependent carbodiimide moiety (1) and the other is equipped with a conjugated aryl-carbodiimide and a dependent alkyne moiety (2).Synthesis of AYC 1 commenced with 2-bromobenzylamine hydrochloride 3 (Chart 1). After tert-butoxycarbonyl (Boc) protection of 3 (98%), the resulting bromobenzene 4 was coupled with ethynylbenzene 5 under Sonogashira-Hagihara conditions 32,33) to give 6 in good yield (90%). 34) After removal of the Boc group with trifluoroacetic acid (TFA), amine 7 was converted to the corresponding thiourea 8 by the action of phenyl isothiocyanate in refluxing acetone (69%).35) Desulfurization of 8 by treatment with methanesulfonyl chloride (MsCl) in the presence of triethylamine and 4-dimethylaminopyridine (DMAP) 36) successfully furnished carbodiimide 1 (84%). As for AYC 2, the synthesis was initiated with 2-aminobenzylalcohol 9. Oxidation of alcohol 9 with MnO 2 into aldehyde, followed by addition of phenyleth...

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Section: Notesmentioning

confidence: 99%

Section: Notesmentioning

confidence: 99%

Section: Notesmentioning

confidence: 99%

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Thermal Cyclization of Nonconjugated Aryl-Yne-Carbodiimide Furnishing a Dibenzonaphthyridine Derivative

Kimura

Torikai

Ueda

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…We previously reported that reaction of 2-(triphenylphosphoimino)-1-azaazulene with aryl isocyanate proceeded via 2-aryl 1-azaazulen-2-yl carbodiimide intermediate. It is known that enyne-carbodiimides proceeded cyclization to give heteroaromatics such as carbolines and ellipticine analogues, [11][12][13][14][15][16][17] and underwent Pouson-Khand type reaction in the presence of Mo(CO) 6 . 26 Therefore, we next examined the reaction of 8 with aryl isocyanate.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…10 In the recent studies about heteroaromatics such as carbolines and ellipticine analogues, benzannulated enyne-carbodiimides and o-ethynylaryliminophosphoranes were used as key intermediates. [11][12][13][14][15][16][17] In the line of our studies about 1-azaazulenes, [18][19][20] we investigated the synthesis and reaction of 3-ethynyl-2-(triphenylphosphoimino)-1-azaazulenes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Reactions of 3-Ethynyl-2-(triphenylphosphoimino)-1-azaazulenes

Abe¹,

Nagamatsu²,

Ariyoshi³

et al. 2007

HETEROCYCLES

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-3-(Trimethylsilylethynyl)-and 3-(phenylethynyl)-2-(triphenylphosphoimino)-1-azaazulenes were synthesized by the Appel reaction of the corresponding 2-amino-3-ethynyl-1-azaazulenes. Reaction of 3-(phenylethynyl)-2-(triphenylphosphoimino)-1-azaazulene (8b) with Cu(OTf) 2 gave 3-(2-oxophenethyl)-2-(triphenylphosphoimino)-1-azaazulene (11), 3-(1,2-dioxophenethyl)-2-(triphenylphosphoimino)-1-azaazulene (12), and 2-amino-3-(1,2-dioxophenethyl)-1-azaazulene (13). The structure of 13 was decided by X-ray structure analysis, and the structure of 12 was discussed by molecular orbital calculation. Reaction of 8b with aryl isocyanate in the presence of benzoyl peroxide gave 1,10-diazabenz[a]azulene derivative. INTRODUCTIONIt is known that the iminophosphoranes, chemical species having the nitrogen-phosphorus double bond, reveal synthetic versatility for the construction of fused heterocycles.

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A Compilation of Synthetic Strategies to Access the Most Utilized Indoloquinoline Motifs

Thongsornkleeb

Tummatorn

Ruchirawat

2022

Chemistry An Asian Journal

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Indoloquinoline alkaloids constitute an important class of aromatic heterocycles consisting of quinoline and indole fused together in various orientations. These compounds, both natural and synthetic, often display various bioactivities which have established them to be one of the interesting medicinal targets. This class of compounds have stimulated much interest among synthetic and medicinal chemists as evidenced by growth in the number of synthetic methods to prepare and study this class of alkaloids. This review compiles the synthetic strategies and methods currently known in the literature for the construction of four important indoloquinoline skeletons.

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Two Novel Thermal Biradical Cyclizations in Theory and Experiment: New Synthetic Routes to 6H-Indolo[2,3-b]quinolines and 2-Aminoquinolines from Enyne-Carbodiimides

Cited by 21 publications

References 0 publications

Thermal Cyclization of Nonconjugated Aryl-Yne-Carbodiimide Furnishing a Dibenzonaphthyridine Derivative

Thermal Cyclization of Nonconjugated Aryl-Yne-Carbodiimide Furnishing a Dibenzonaphthyridine Derivative

Synthesis and Reactions of 3-Ethynyl-2-(triphenylphosphoimino)-1-azaazulenes

A Compilation of Synthetic Strategies to Access the Most Utilized Indoloquinoline Motifs

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