Hexafluoroisobutylation of enolates through a tandem elimination/allylic shift/hydrofluorination reaction
| dc.rights.license | open | en_US |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | DELAMARE, Aline | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | NAULET, Guillaume | |
| dc.contributor.author | KAUFFMANN, Brice | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | GUICHARD, Gilles
IDREF: 084339268 | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | COMPAIN, Guillaume | |
| dc.date.accessioned | 2023-04-26T13:08:12Z | |
| dc.date.available | 2023-04-26T13:08:12Z | |
| dc.date.issued | 2022-07-20 | |
| dc.identifier.issn | 2041-6539 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/173216 | |
| dc.description.abstractEn | The isobutyl side chain is a highly prevalent hydrophobic group in drugs, and it notably constitutes the side chain of leucine. Its replacement by a hexafluorinated version containing two CF3 groups may endow the target compound with new and advantageous properties, yet this modification remains overlooked due to the absence of a general and practical synthetic methodology. Herein, we report the first general method to introduce the hexafluoroisobutyl group into ketoesters, malonates, 1,3-diketones, Schiff base esters and malononitrile. We demonstrated that the reaction occurs through an elimination/allylic shift/hydrofluorination cascade process which efficiently overcomes the usual fluoride β-elimination observed with α-CF3-vinyl groups. We showed that with alkali metal bases, a pentafluorinated alkene is obtained predominantly, whereas the use of tetrabutylammonium fluoride (TBAF) allows hydrofluorination to occur. This tandem process represents a conceptually new pathway to synthesize bis-trifluoromethylated compounds. This methodology was applied to the multigram-scale synthesis of enantiopure (S)-5,5,5,5′,5′,5′-hexafluoroleucine. | |
| dc.description.sponsorship | Interactions supramoléculaires sélectives et directionnelles à base de synthons fluorés hautement polaires - ANR-20-CE06-0008 | en_US |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/us/ | * |
| dc.title.en | Hexafluoroisobutylation of enolates through a tandem elimination/allylic shift/hydrofluorination reaction | |
| dc.title.alternative | Chem. Sci. | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1039/D2SC02871A | en_US |
| dc.subject.hal | Chimie/Matériaux | en_US |
| bordeaux.journal | Chemical Science | en_US |
| bordeaux.page | 9507-9514 | en_US |
| bordeaux.volume | 13 | en_US |
| bordeaux.hal.laboratories | CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248 | en_US |
| bordeaux.issue | 33 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-04082573 | |
| hal.version | 1 | |
| hal.date.transferred | 2023-04-26T13:08:15Z | |
| hal.export | true | |
| dc.rights.cc | CC BY | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Chemical%20Science&rft.date=2022-07-20&rft.volume=13&rft.issue=33&rft.spage=9507-9514&rft.epage=9507-9514&rft.eissn=2041-6539&rft.issn=2041-6539&rft.au=DELAMARE,%20Aline&NAULET,%20Guillaume&KAUFFMANN,%20Brice&GUICHARD,%20Gilles&COMPAIN,%20Guillaume&rft.genre=article |
