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New Synthetic Approaches for the Introduction of Pentafluorosulfanyl Group (SF5) Into Heterocycles Ewelina Falkowska

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New Synthetic Approaches for the Introduction of Pentafluorosulfanyl Group (SF5) Into Heterocycles Ewelina Falkowska New synthetic approaches for the introduction of pentafluorosulfanyl group (SF5) into heterocycles Ewelina Falkowska To cite this version: Ewelina Falkowska. New synthetic approaches for the introduction of pentafluorosulfanyl group (SF5) into heterocycles. Organic chemistry. INSA de Rouen, 2015. English. NNT : 2015ISAM0016. tel- 01309324 HAL Id: tel-01309324 https://tel.archives-ouvertes.fr/tel-01309324 Submitted on 29 Apr 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ÉCOLE DOCTORALE NORMANDE DE CHIMIE THÈSE Présentée à L’Institut National des Sciences Appliquées de Rouen Pour l’obtention du grade de DOCTEUR EN CHIMIE ORGANIQUE Par Ewelina FALKOWSKA New Synthetic Approaches for the Introduction of PentafluoroPentafluorosulfsulfanylanyl Group (SF5) into HeterocHeterocyclesycles le 16 décembre 2015 Devant le jury composé de: Dr. Julien PYTKOWICZ Université de Cergy-Pontoise Rapporteur Dr. Stéphane LEBRUN Université Lille 1 Rapporteur Dr. Petr BEIER Academy of Sciences of the Czech Republic Examinateur Pr. Jean-Philippe BOUILLON Université de Rouen Examinateur Pr. Philippe JUBAULT INSA de Rouen Examinateur Pr. Xavier PANNECOUCKE INSA de Rouen Examinateur Acknowledgement First of all, I would like to thank Dr. Petr Beier (Academy of Sciences of the Czech Republic), Dr. Stéphane Lebrun (Université Lille 1) and Dr. Julien Pytkowicz (Université de Cergy-Pontoise) for kindly accepting to examine my thesis. I am very thankfull to my supervisors Pr. Jean-Philippe Bouillon and Pr. Philippe Jubault for their guidance, patience and the support that I received from them trough last three years. I am also very grateful to Pr. Xavier Pannecoucke for giving me the opportunity to carry out my thesis in the team of “Synthesis of Fluorinated Biomolecules”. I would like to thank Dr. Morgane Sanselme for X-ray analyses; Dr. Albert Marcual and Dr. Dominique Harakat (Reims University) for HRMS analyses; Laetitia Bailly and Emilie Petit for their help with chromatography techniques; Dr. Vincent Tognetti and Pr. Laurent Joubert for the theoretical calculations. I would also like to thank Dr. Petr Beier, Dr. Mathieu Laurent (Université du Maine) and Dr. Pavel Mykhailiuk (Enamine Company) for the collaboration and the valuable advises. Many thanks to Elisabeth Roger (Babette) for her help and kindness. I also thank to all the former and current team members, and to all people from IRCOF. Finally, I would like to thank to my parents and to my future husband Szymek for their love and encouragement. They have been going trough the hardest moments together with me, especially during the final stages of this PhD, and I am deeply grateful for that. Dziękuję Wam kochani Rodzice i Szymku. Contents Abbreviations ..................................................................................................................................... - 9 - Abstract ............................................................................................................................................ - 13 - Résumé ............................................................................................................................................. - 14 - Chapter I ......................................................................................................................................... - 15 - 1. General introduction ............................................................................................................ - 16 - 2. Physicochemical properties of the pentafluorosulfanyl group ............................................. - 17 - 2.1. Structure and steric hindrance of the SF 5-group ...................................................... - 17 - 2.2. Electronic properties ................................................................................................ - 18 - 2.3. Lipophilicity ............................................................................................................. - 19 - 2.4. Chemical stability .................................................................................................... - 19 - 3. Synthesis of pentafluorosulfanylated compounds ................................................................ - 20 - 3.1. Introduction of the SF 5-group into aliphatic compounds ......................................... - 20 - 3.1.1. Direct fluorination of sulfur containing compounds ........................................... - 21 - 3.1.2. Radical addition of SF 5X to unsaturated compounds .......................................... - 22 - 3.2. Introduction of the SF 5-group into aromatic compounds ......................................... - 35 - 3.2.1. Fluorination of sulfur containing aromatic compounds ...................................... - 35 - 3.2.2. Approach based on the SF 5X addition to unsaturated compounds...................... - 38 - 3.2.3. Approach based on the reactions of novel Ar-SF 5 building-blocks .................... - 41 - 3.3. Preparation of SF 5-heterocycles ............................................................................... - 43 - 3.3.1. Derivatives bearing the SF 5-group on the aryl moiety ........................................ - 44 - 3.3.2. Derivatives bearing the SF 5-group directly on the heteroaryl moiety ................. - 45 - 4. Applications of SF 5-derivatives ........................................................................................... - 53 - 4.1. Active pentafluorosulfanylated aryl-containing derivatives .................................... - 53 - 4.1.1. Agrochemistry ..................................................................................................... - 53 - 4.1.2. Medicinal chemistry ............................................................................................ - 54 - 4.2. Active pentafluorosulfanylated heterocycle-containing derivatives ........................ - 57 - 4.2.1. Agrochemistry ..................................................................................................... - 57 - 4.2.2. Medicinal chemistry ............................................................................................ - 58 - 5. Presentation of the PhD project ........................................................................................... - 61 - Chapter II.........................................................................................................................................- 65 - 1. Synthesis of SF 5-substituted allylic and acrylic derivatives................................................. - 66 - 1.1. Synthetic sequence leading to SF 5-allyl alcohols 5a-c and acetate 6 ....................... - 66 - 1.2. Oxidation of SF 5-allyl alcohols 5a and 5b to aldehyde 7 and acids 8a and 8b ........ - 68 - 1.3. Synthesis of SF 5-acrylic esters 9,10 and amides 11,12 ............................................ - 70 - 1.3.1. State of the art ..................................................................................................... - 70 - 1.3.2. Optimization and scope of esterification reactions ............................................. - 71 - 1.3.3. Optimization and scope of amidification reactions ............................................. - 75 - 2. Attempts for the synthesis of new SF 5-substituted homoallylic alcohols ............................ - 77 - 2.1. Allylation reactions using new pentafluorosulfanylated allylsilanes ....................... - 78 - 2.1.1. Preparation of SF 5-allylsilanes ............................................................................ - 78 - 2.1.2. Attempts of allylation reactions using SF 5-allylsilanes ....................................... - 80 - 2.2. Indium-mediated allylation reactions ....................................................................... - 83 - 2.2.1. State of the art ..................................................................................................... - 83 - 2.2.2. Preparation of SF 5-allyl bromide 24 .................................................................... - 85 - 2.2.3. Optimisation of allylation conditions .................................................................. - 85 - 2.2.4. Scope of allylation reaction ................................................................................. - 88 - 3. Attempts for the synthesis of new SF 5-allylic and propargylic derivatives ......................... - 90 - 3.1. Attempts for the radical addition of SF 5Cl to functionalized allylic derivatives ..... - 90 - 3.2. Attempts for the synthesis of new SF 5-propargylic derivatives ............................... - 91 - 4. Conclusion ........................................................................................................................... - 93 - Chapter III ...................................................................................................................................... - 95 - 1. Attempts for the synthesis of SF 5-pyridines ......................................................................... - 96 - 1.1. Direct fluorination approach ...................................................................................
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