Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Scheme 3. Scaled-up synthesis of building blocks that are highly valuable for medicinal chemistry.Scheme 4. Mechanistic considerations. Yields were determined by 19 FNMR spectroscopy using trifluorotoluene as internalstandard. Yields of isolated products are shown in parentheses. dr = diastereomeric ratio, nd = not detected.
Single electron reduction
is more challenging for sulfamoyl chlorides
than sulfonyl chlorides. However, sulfamoyl and sulfonyl chlorides
can be easily activated by Cl-atom abstraction by a silyl radical
with similar rates. This latter mode of activation was therefore selected
to access aliphatic sulfonamides, applying a single-step hydrosulfamoylation
using inexpensive olefins, tris(trimethylsilyl)silane, and photocatalyst
Eosin Y. This late-stage functionalization protocol generates molecules
as complex as sulfonamide-containing cyclobutyl-spirooxindoles for
direct use in medicinal chemistry.
Sulfonyl chlorides are inexpensive reactants extensively explored for functionalization, but never considered for radical hydrosulfonylation of alkenes. Herein, we report that tris(trimethylsilyl)silane is an ideal hydrogen atom donor enabling highly effective photoredox‐catalyzed hydrosulfonylation of electron‐deficient alkenes with sulfonyl chlorides. To increase the generality of this transformation, polarity‐reversal catalysis (PRC) was successfully implemented for alkenes bearing alkyl substituents. This late‐stage functionalization method tolerates a remarkably wide range of functional groups, is operationally simple, scalable, and allows access to building blocks which are important for medicinal chemistry and drug discovery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.