Synthesis of Benzoazocines from Substituted Tetrahydroisoquinolines and Activated Alkynes in a Tetrahydropyridine Ring Expansion

Voskressensky, Leonid G.; Listratova, Anna V.; Борисова, Т. Н.; Alexandrov, Grigoriy G.; Varlamov, A. V.

doi:10.1002/ejoc.200700602

Cited by 30 publications

(5 citation statements)

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“…The preceding trends were further confirmed by experimental measurements of the p K a of two additional pairs of enamino ester-containing annulated medium-sized cyclic derivatives (Chart ), namely, β-CO 2 Me and α,β-(CO 2 Me) 2 derivatives of 4-ethyl-1,4,5,6,7,8-hexahydroazonino[5,6- b ]indole ( IIIa-b ) , and 3-ethyl-1,2,3,6-tetrahydro-8,9-dimethoxybenzo[ d ]azocine ( IVa-b ) . The hexahydroazonino[5,6- b ]indole scaffold III is a ring-expanded (azocine → azonine) analogue of I , whereas the dimethoxybenzo moiety in IV replaces the indole ring in II .…”

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confidence: 55%

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

et al. 2019

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Depending on the chemical scaffold, the bioactive species could reflect the interplay between ionization and tautomerism, often complicated by the possibility to populate different conformational states in the case of flexible ligands. In this context, theoretical methods can be valuable to discern the role of these factors, as shown here for βenamino esters of 1,2,3,6-tetrahydroazocino fused ring systems, some of which had proven to be suitable scaffolds for designing novel acetylcholinesterase inhibitors. The compounds investigated herein form two clusters with distinctive experimental pK a values (i.e., α,β-diesters and β-esters ranging within 6.1-7.3 and 8.2-9.0 pK a intervals, respectively), which implies a drastic difference in the most populated species at physiological conditions. While chemoinformatic tools did not provide a consistent description of the actual pK a values, the theoretical analysis performed for the protonated and neutral species of these compounds revealed a marked change in the tautomeric preference of the tetrahydroazocine moiety upon (de)protonation. Excellent agreement between calculated and experimental pK a values was found when the tautomeric preference of protonated and neutral species was considered. Overall, this study highlights the potential use of high-level computational methods to disclose the mutual influence between ionization, tautomerism and conformational preferences in multifunctional (bio)organic compounds.

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Section: Resultssupporting

confidence: 55%

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

et al. 2019

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“…It was shown that tetrahydroisoquinolines with 1-phenyl substituents reacted with methyl propiolate and acetylacetylene to give the expected benzazocines in good yields. [17][18][19] As it turned out, 1,1-disubstituted tetrahydroisoquinolines, 1-methyland 1-benzyl-1-phenylethynyl-1,2,3,4-tetrahydroisoquinolines 1a-c reacted differently with activated terminal alkynes 2a,b in trifluoroethanol (Scheme 1). The reaction occurred rather quickly in this solvent at +7 1C.…”

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confidence: 99%

First synthesis of heterocyclic allenes – benzazecine derivatives

et al. 2017

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“…A different type of ring expansion was reported by Vokressensky et al, starting from α-aryltetrahydroisoquinolines 429 and 11 . The formation of the corresponding zwitterion and aryl-assisted dissociation of the C−N bond was followed by an intramolecular S N 1 substitution, leading to two-carbon ring-expanded products 430 (Scheme ).…”

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confidence: 84%

Cycloadditions and Cyclizations of Acetylenic, Allenic, and Conjugated Dienyl Sulfones

2010

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Introduction 4499 2. Diels-Alder Cycloadditions 4499 2.1. Unsaturated Sulfones as Dienophiles 4499 2.1.1. Early Studies 4499 2.1.2. Aromatization of Cycloaddition Products of Acetylenic Sulfones 4501 2.1.3. Iterative Diels-Alder and Ramberg-Backlund Reactions of Chloroalkylsulfonyl Allenes 4502 2.1.4. Diels-Alder Cycloadditions of Bis(sulfonyl)acetylenes and Their Equivalents 4502 2.1.5. Diels-Alder Cycloadditions of Acetylenic Sulfones Containing Heteroatom Substituents 4503 2.1.6. Diels-Alder Reactions of Dienyl Sulfones as Dienophiles 4504 2.1.7. Diels-Alder Reactions of Unsaturated Sulfones with Pyrroles 4505 2.1.8. Diels-Alder Reactions of Unsaturated Sulfones with Furans and Isobenzofurans 4507 2.1.9. Miscellaneous Cycloadditions 4508 2.2. Dienyl Sulfones As the Diene Components in Diels-Alder Reactions 4509 2.2.1. 1-Sulfonyl Derivatives † Dedicated to Professor David N. Harpp, for his inspiring contributions as a teacher, mentor and scholar.

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Synthesis of Benzoazocines from Substituted Tetrahydroisoquinolines and Activated Alkynes in a Tetrahydropyridine Ring Expansion

Abstract: Tetrahydroisoquinolines underwent tandem piperidine ring enlargement in the presence of activated alkynes in acetonitrile or methanol, producing tetrahydrobenzo[d]azocines in high yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Cited by 30 publications

References 23 publications

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

First synthesis of heterocyclic allenes – benzazecine derivatives

Cycloadditions and Cyclizations of Acetylenic, Allenic, and Conjugated Dienyl Sulfones

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