P-Stereogenic ligands: synthesis and application to asymmetric hydrogenation
[eng] P-Stereogenic ligands have demonstrated to be highly efficient for asymmetric catalysis, especially in metal-catalyzed asymmetric hydrogenation reactions. Among them, those bearing bulky substituents at phosphorus have emerged as one of the best class of ligands. Nevertheless, the preparation...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/191368 |
| Acceso en línea: | https://hdl.handle.net/2445/191368 http://hdl.handle.net/10803/687210 |
| Access Level: | acceso abierto |
| Palabra clave: | Química orgànica Hidrogenació Catàlisi asimètrica Iridi Fosfina Organic chemistry Hydrogenation Enantioselective catalysis Iridium Phosphine |
| Sumario: | [eng] P-Stereogenic ligands have demonstrated to be highly efficient for asymmetric catalysis, especially in metal-catalyzed asymmetric hydrogenation reactions. Among them, those bearing bulky substituents at phosphorus have emerged as one of the best class of ligands. Nevertheless, the preparation of P-stereogenic ligands with certain bulky substituents such as tert-butyl is still challenging, and the field requires the development of new methodologies for their preparation or for the synthesis of key intermediates. In this thesis, we have developed an efficient strategy to prepare P-stereogenic tertiary phosphine intermediates with the useful tert-butyl methyl pair. The methodology consists in the O-functionalization of tert-butyl methyl phosphinous acid-borane with a proper leaving group, followed by a SN2@P with organolithium reagents. The method tolerates the addition of alkyl, alkynyl and diverse aryl organolithiums, providing the tertiary phosphines in moderate to excellent yield and very high enantioselectivities. The usefulness of these synthons has been proven with the synthesis of a P-stereogenic diphosphine ligand with an unexplored pair of groups at phosphorus. The performance of this ligand in Rh-catalyzed asymmetric catalysis has also been studied. Regarding Ir-catalyzed asymmetric hydrogenation, phosphinooxazoline ligands are among the most successful for the hydrogenation of unfunctionalized or minimally functionalized substrates. However, very few P-stereogenic phosphinooxazoline ligands have been reported. In this way, we devised a synthetic methodology for the preparation of a family of P-stereogenic ThrePHOX analogues, from tert-butyl methyl phosphinous acid-borane and commercially available L-threonine methyl ester. Certain of the obtained catalysts presented a spontaneous C-H activation that delivered octahedral isomers unactive for hydrogenation. Their structure, stability, and use as precatalysts has also been examined. The performance of the stable catalysts was studied in the asymmetric hydrogenation of different minimally functionalized substrates such as homoallylic alcohols, allylic alcohols and different allylic amines. In the case of 2,3- and 3,3-diarylallylamines, the new family of catalysts provided very high enantioselectivities (up to 99% ee) for an important range of substrates. Regarding 2,3-diarylallyl amines, the utility of the resulting 2,3-diarylpropyl amines was demonstrated with the preparation of enantioenriched 3- aryl-tetrahydroquinolines and 4-benzyl-tetrahydroisoquinolines. |
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