Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes

Abstract Novel tetrahydroisoquinoline and piperidine derivatives were selectively synthesized from substituted indenes or cyclopentenes. The process starts with an oxidative cleavage of the ring olefin bond, which gives reactive diformyl intermediates. By a ring‐closing step using chiral (R) or (S)...

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Main Authors: Anas Semghouli, László Drahos, Jianlin Han, Loránd Kiss, Melinda Nonn
Format: Article
Language:English
Published: Wiley-VCH 2025-05-01
Series:ChemistryOpen
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Online Access:https://doi.org/10.1002/open.202400475
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author Anas Semghouli
László Drahos
Jianlin Han
Loránd Kiss
Melinda Nonn
author_facet Anas Semghouli
László Drahos
Jianlin Han
Loránd Kiss
Melinda Nonn
author_sort Anas Semghouli
collection DOAJ
description Abstract Novel tetrahydroisoquinoline and piperidine derivatives were selectively synthesized from substituted indenes or cyclopentenes. The process starts with an oxidative cleavage of the ring olefin bond, which gives reactive diformyl intermediates. By a ring‐closing step using chiral (R) or (S) α‐methylbenzylamine under a reductive amination protocol facilitated ring formation with ring expansion of the corresponding nitrogen‐containing heterocycles. The stereocontrolled methodology enabled accurate control of the stereochemistry of the final products. Additionally, the synthesized amino acid derivatives possessing an aryl moiety in their structure may be relevant building blocks for foldamer chemistry.
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institution Kabale University
issn 2191-1363
language English
publishDate 2025-05-01
publisher Wiley-VCH
record_format Article
series ChemistryOpen
spelling doaj-art-a529529fea4f40aab3e08edbfed66c232025-08-20T03:49:22ZengWiley-VCHChemistryOpen2191-13632025-05-01145n/an/a10.1002/open.202400475Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and CyclopentenesAnas Semghouli0László Drahos1Jianlin Han2Loránd Kiss3Melinda Nonn4Institute of Organic Chemistry Stereochemistry Research Group HUN-REN Research Center for Natural Sciences H-1117 Budapest Magyar tudósok krt. 2 HungaryInstitute of Organic Chemistry MS Proteomics Research Group HUN-REN Research Centre for Natural Sciences H-1117 Budapest Magyar tudósok krt. 2 HungaryJiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources College of Chemical Engineering Nanjing Forestry University Nanjing 210037 ChinaInstitute of Organic Chemistry Stereochemistry Research Group HUN-REN Research Center for Natural Sciences H-1117 Budapest Magyar tudósok krt. 2 HungaryMTA TTK Lendület Artificial Transporter Research Group Institute of Materials and Environmental Chemistry HUN-REN Research Center for Natural Sciences H-1117 Budapest Magyar tudósok krt. 2 HungaryAbstract Novel tetrahydroisoquinoline and piperidine derivatives were selectively synthesized from substituted indenes or cyclopentenes. The process starts with an oxidative cleavage of the ring olefin bond, which gives reactive diformyl intermediates. By a ring‐closing step using chiral (R) or (S) α‐methylbenzylamine under a reductive amination protocol facilitated ring formation with ring expansion of the corresponding nitrogen‐containing heterocycles. The stereocontrolled methodology enabled accurate control of the stereochemistry of the final products. Additionally, the synthesized amino acid derivatives possessing an aryl moiety in their structure may be relevant building blocks for foldamer chemistry.https://doi.org/10.1002/open.202400475CyclizationRing expansionRing openingRing closingPiperidineTetrahydroisoquinoline
spellingShingle Anas Semghouli
László Drahos
Jianlin Han
Loránd Kiss
Melinda Nonn
Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes
ChemistryOpen
Cyclization
Ring expansion
Ring opening
Ring closing
Piperidine
Tetrahydroisoquinoline
title Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes
title_full Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes
title_fullStr Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes
title_full_unstemmed Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes
title_short Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes
title_sort selective synthesis of tetrahydroisoquinoline and piperidine scaffolds by oxidative ring opening ring closing protocols of substituted indenes and cyclopentenes
topic Cyclization
Ring expansion
Ring opening
Ring closing
Piperidine
Tetrahydroisoquinoline
url https://doi.org/10.1002/open.202400475
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