Xinlan Cook received her MChem degree from the University of York in 2017, completing her master's thesis during ayear-long placementa tF.Hoffmann-La Roche (Basel, Switzerland),synthesising novel molecules for the treatment of Alzheimer's disease. She is now completing her doctoral research in the group of Prof. M. C. Willis at the University of Oxford, investigating novel reagents for C(sp 2 )ÀC(sp 2 )d esulfinative cross-coupling reactions. Antoine de Gombert graduated from Chimie ParisTech and UniversitØ Pierre et Marie Curie with aDiplôme d'IngØnieur and MSci. After working on visible light catalysis at CSIRO (Australia), he completed a6 -month internship at F. Hoffmann-La Roche in Switzerland. He is currently aPhD student with Prof. M. C. Willis at the University of Oxford, where his research focuses on the mechanistica spects of palladium-catalysed desulfinative cross-coupling reactions. Janette McKnight obtained her MChem degree from the University of Bath in 2017. During this time, she undertook an industrial placementy ear in process chemistry at GSK Stevenage, before returning to complete afinal year project in the field of CÀH activation with Prof. C. Frost. She moved to the University of Oxford for postgraduate study,where she is currently working on C(sp 2 )ÀC(sp 3 )desulfinativec ross-coupling reactions under the supervision of Prof. M. C. Willis.

Heteroaromatic sulfinates are effective nucleophilic reagents in Pd0‐catalyzed cross‐coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi‐step transformations. Here we introduce base‐activated, latent sulfinate reagents: β‐nitrile and β‐ester sulfones. We show that under the cross‐coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium‐catalyzed desulfinative cross‐coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi‐step substrate elaboration, and amenable to scale‐up.

We propose the use of a bridged piperidine moiety as a phenyl bioisostere, leading to strongly improved drug like properties. This concept was applied to the discovery of γ-secretase modulators for the potential treatment of Alzheimer's disease.

Xinlan Cook received her MChem degree from the University of York in 2017, completing her master's thesis during ayear-long placementa tF.Hoffmann-La Roche (Basel, Switzerland),synthesising novel molecules for the treatment of Alzheimer's disease. She is now completing her doctoral research in the group of Prof. M. C. Willis at the University of Oxford, investigating novel reagents for C(sp 2 )ÀC(sp 2 )d esulfinative cross-coupling reactions. Antoine de Gombert graduated from Chimie ParisTech and UniversitØ Pierre et Marie Curie with aDiplôme d'IngØnieur and MSci. After working on visible light catalysis at CSIRO (Australia), he completed a6 -month internship at F. Hoffmann-La Roche in Switzerland. He is currently aPhD student with Prof. M. C. Willis at the University of Oxford, where his research focuses on the mechanistica spects of palladium-catalysed desulfinative cross-coupling reactions. Janette McKnight obtained her MChem degree from the University of Bath in 2017.During this time, she undertook an industrial placementy ear in process chemistry at GSK Stevenage, before returning to complete afinal year project in the field of CÀH activation with Prof. C. Frost. She moved to the University of Oxford for postgraduate study,where she is currently working on C(sp 2 )ÀC(sp 3 )desulfinativec ross-coupling reactions under the supervision of Prof.