Defluoroalkylation of Trifluoromethane with Organolithium Reagents: Mechanism and Synthesis of Fluoroalkenes

We report a rare example of the transformation of HCF3 into a fluoroalkene functional group through defluoroalkylation. We rationalise product formation through DFT calculations, scale-up the synthes...

onlinelibrary.wiley.com

The stereochemistry of substitution at S(VI)

Since the re-birth of sulfur-fluoride exchange (SuFEx) chemistry, coined by Sharpless in 2014 as a ‘click’ reaction, the prevalence of sulfur(vi) moieties in medicinal, polymer and materials chemistry...

doi.org

Catalytic SuFEx Reactivity of Sulfonimidoyl Fluorides with Functionalized Amines with Automation Applicable Conditions

GA: Sulfonimidoyl fluorides react with a diverse set of amines in a HOBt-catalyzed sulfur(VI) fluorine exchange reaction to access sulfonimidamides, including directly NH-sulfonimidamides, and in an ....

chemistry-europe.onlinelibrary.wiley.com

Synthesis of gem-Difluorocyclobutanes: Organolanthanum Enabled Synthesis and Divergent Catalytic Functionalization of gem-Difluorocyclobutanols

Fluorinated cycloalkyl motifs continue to receive intense interest in medicinal chemistry due to their potential to modulate physicochemical properties. In recent years, this interest has extended to ...

pubs.acs.org

Catalytic SuFEx Reactivity of Sulfonimidoyl Fluorides with Functionalized Amines with Automation Applicable Conditions

Sulfonimidamides have emerged as attractive chemical motifs in drug discovery and as sulfonamide bioisosteres that can offer improved pharmacokinetic and physiochemical properties. Here we report a mi...

doi.org

Development of automated workflows for direct-to-biology drug discovery of kinase inhibitors at Imperial College London on FindAPhD.com

PhD Project - Development of automated workflows for direct-to-biology drug discovery of kinase inhibitors at Imperial College London, listed on FindAPhD.com

findaphd.com

Advanced Molecular Synthesis MRes | Study | Imperial College London

imperial.ac.uk

How to thrive at conferences

Five tips for making the most of meet-ups

chemistryworld.com

New dimensions for covalent enantioprobe chemoproteomics at Imperial College London on FindAPhD.com

PhD Project - New dimensions for covalent enantioprobe chemoproteomics at Imperial College London, listed on FindAPhD.com

findaphd.com

Studentships for October 2025 entry

2025 Studentship Opportunities

imperial.ac.uk

Description

Please note that job descriptions are not exhaustive, and you may be asked to take on additional duties that align with the key responsibilities ment...

shorturl.at

RSC Organic Chemistry Community South and East Regional Meeting 2025

rsc.org

Unconventional reactivity of sulfonyl fluorides

Sulfonyl fluorides are now established click reagents that find broad applications in synthesis, chemical biology, and drug discovery. Sulfonyl fluori…

sciencedirect.com

Harnessing Oxetane and Azetidine Sulfonyl Fluorides for Opportunities in Drug Discovery

Four-membered heterocycles such as oxetanes and azetidines represent attractive and emergent design options in medicinal chemistry due to their small and polar nature and potential to significantly impact the physiochemical properties of drug molecules. The challenging preparation of these derivatives, especially in a divergent manner, has severely limited their combination with other medicinally and biologically important groups. Consequently, there is a substantial demand for mild and effective synthetic strategies to access new oxetane and azetidine derivatives and molecular scaffolds. Here, we report the development and use of oxetane sulfonyl fluorides (OSFs) and azetidine sulfonyl fluorides (ASFs), which behave as precursors to carbocations in an unusual defluorosulfonylation reaction pathway (deFS). The small-ring sulfonyl fluorides are activated under mild thermal conditions (60 °C), and the generated reactive intermediates couple with a broad range of nucleophiles. Oxetane and azetidine heterocyclic, -sulfoximine, and -phosphonate derivatives are prepared, several of which do not have comparable carbonyl analogs, providing new chemical motifs and design elements for drug discovery. Alternatively, a SuFEx pathway under anionic conditions accesses oxetane-sulfur(VI) derivatives. We demonstrate the synthetic utility of novel OSF and ASF reagents through the synthesis of 11 drug analogs, showcasing their potential for subsequent diversification and facile inclusion into medicinal chemistry programs. Moreover, we propose the application of the OSF and ASF reagents as linker motifs and demonstrate the incorporation of pendant groups suitable for common conjugation reactions. Productive deFS reactions with E3 ligase recruiters such as pomalidomide and related derivatives provide new degrader motifs and potential PROTAC linkers.

doi.org