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Synthesis of Highly Enantioenriched Sulfonimidoyl Fluorides and Sulfonimidamides by Stereospecific SuFEx Reaction

preprint
submitted on 04.05.2020 and posted on 06.05.2020 by Stephanie Greed, Edward L. Briggs, Fahima Idiris, Andrew J. P. White, Ulrich Lücking, James Bull
Sulfonimidamides present exciting opportunities as chiral isosteres of sulfonamides, with potential for additional directional interactions. Here we present the first modular enantioselective synthesis of sulfonimidamides, including the first stereoselective synthesis of enantioenriched sulfonimidoyl fluorides, and studies on their reactivity. A new route to sulfonimidoyl fluorides is presented from solid bench-stable, NBoc-sulfinamide salt building blocks. Enantioenriched arylsulfonimidoyl fluorides are shown to be readily racemized by fluoride ions. Conditions are developed which trap fluoride, and enable the stereospecific reaction of sulfonimidoyl fluorides with primary and secondary amines (100% es) generating sulfonimidamides with up to 99% ee. Aryl and alkyl sulfonimidoyl fluoride reagents are suitable for mild late stage functionalization reactions, exemplified by coupling with a selection of complex amines in marketed drugs.

Funding

The Royal Society, UF140161

The Royal Society, RG150444

The Royal Society, RGF\EA\180031

EP/J001538/1, EPSRC

History

Email Address of Submitting Author

j.bull@imperial.ac.uk

Institution

Imperial College London

Country

UK

ORCID For Submitting Author

0000-0003-3993-5818

Declaration of Conflict of Interest

No conflict of interest

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