Photocatalytic Sulfinyl-Smiles Rearrangements: Enabling Asymmetric Difunctionalization of Alkenes

The Smiles rearrangement represents a fundamental intramolecular aryl migration process proceeding through a nucleophilic substitution pathway. In recent years, sulfinyl-Smiles rearrangement has emerged as an appealing platform for assembling enantioenriched arylated architectures where the chiral sulfinyl auxiliary dictates the excellent stereochemical outcomes under mild photoredox conditions. In this thesis, chiral sulfinylamides and sulfoxides bearing olefinic moieties are designed and explored to enable the asymmetric functionalization of alkenes, including 1,2-difunctionalization as well as remote difunctionalization at distalpositions. The first chapter of the thesis describes a visible-light-mediated asymmetric remote arylation of alkenes via sequential 1,n-HAT (hydrogen atom transfer) and sulfinyl-Smiles rearrangement. The reaction features the radical addition to a double bond followed by a site-selective radical translocation (1,n-HAT) as well as a stereocontrolled aryl migration via sulfinyl-Smiles, thereby furnishing a wide range of chiral α-arylated amides with up to >99:1 er. Mechanistic studies including deuterium labeling experiments and DFT calculations indicate that the sulfinamido group governs the stereochemistry of the product with the aryl migration being the rate determining step preceded by a kinetically favored 1,n-HAT process. The second chapter presents an efficient and stereocontrolled 1,5-carbosulfonylation and dicarbofunctionalization of vinylcyclopropanes through the sulfinyl-Smiles rearrangement. This cascade reaction involves a sequence of radical addition, C–C bond cleavage, aryl migration and desulfinylation, enabling efficient access to a diverse range of chiral α-allylic amides under mild photoredox conditions. This protocol demonstrates broad functional group tolerance and exhibits excellent enantioselectivity. Further product derivatizations also show the high synthetic value of this transformation. In the last chapter, a more atom-economical variant of the sulfinyl-Smiles rearrangement is described where chiral sulfoxides featuring remote double bonds serve as viable acceptors for various in-situ generated radicals under mild photoredox conditions. Following a stereocontrolled aryl migration via a six-membered spirocyclic intermediate, a highly reactive sulfinyl radical is formed which can be subsequently intercepted by the reactive carboncentered radical present in the reaction media, thus closing the photocatalytic cycle. By matching the redox-potentials of the reaction components and the photocatalyst, electrondeficient radical precursors and electron-rich alkylating reagents can be successfully combined to construct three new different bonds (1 C–S and 2 C–C) in a single operation while retaining the ‘SO’ moiety. This protocol delivers a wide range of high-value sulfoxides and sulfones with excellent stereocontrol (up to 96:4 er). Successful derivatizations of products further highlight the utility of this methodology. Together, these three chapters established the combination of sulfinyl Smiles rearrangement with alkene difunctionalization as a novel and robust approach for accessing complex enantioenriched molecules with high stereocontrol that are otherwise challenging to obtain.