Bykova, T, Al-Maharik, N, Slawin, AMZ et al. (3 more authors) (2018) Benzylic functionalisation of phenyl all cis-2, 3, 5, 6 -tetrafluoro -cyclohexane provides access to new organofluorine building blocks. Chemistry - A European Journal, 24 (50). pp. 13290-13296. ISSN 0947-6539
Abstract
Selectively fluorinated hydrocarbons continue to attract attention for tuning pharmacokinetic properties in agrochemical and pharmaceutical discovery programmes. This study identifies benzylic bromination of phenyl all‐cis‐2,3,5,6‐tetrafluorocyclohexane 2 as a key reaction for accessing building blocks containing the all‐cis‐2,3,5,6‐tetrafluorocyclohexane ring system. These cyclohexanes are of interest as the fluorines are only on one face of the cyclohexane, and this imparts an unusual polar aspect, very different to an otherwise hydrophobic cyclohexane. Ritter type reactions of benzyl bromide 4 with DMF and acetonitrile generated the corresponding benzyl alcohol 6 and benzylacetamide 7 respectively. Benzylacetamide 7 was hydrolysed to benzyl amine 8 and syn‐amino‐alcohol 9, and separately the phenyl ring was oxidatively cleaved to furnish carboxylic acid acetamide 10, which after hydrolysis gave the tetrafluorocyclohexyl amino acid 11. A trans‐halogenation of benzylbromide 4 with AgF2 gave benzyl fluoride 13. Oxidative cleavage of the aryl ring then gave pentafluorocyclohexyl carboxylic acid 14. This carboxylic acid was readily converted to amides 23–26 and the preferred conformations of these α‐fluoroamides were explored by DFT, X‐ray structure and 1H–19F HOESY NMR analysis.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Keywords: | conformational analysis; fluorinated building blocks; hydrocarbons; organofluorine; Ritter reaction |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Nov 2018 15:37 |
Last Modified: | 26 Nov 2018 15:37 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/chem.201802166 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138537 |