Electrophilic Sulfur Reagent Design Enables Directed syn-Carbosulfenylation of Unactivated Alkenes

Abstract

A multi-component approach to structurally complex organosulfur products is described via the nickel-catalyzed 1,2-carbosulfenylation of unactivated alkenes with organoboron nucleophiles and tailored organosulfur electrophiles. The key to the development of this transformation is the identification of a modular N-alkyl-N-(arylsulfenyl)­arenesulfonamide family of sulfur electrophiles. Tuning the electronic and steric properties of the leaving group in these reagents controls pathway selectivity, favoring three-component coupling and suppressing side reactions, as examined via computational studies. The unique syn-stereoselectivity differs from traditional electrophilic sulfenyl transfer processes involving a thiiranium ion intermediate and arises from the directed arylnickel­(I) migratory insertion mechanism, as elucidated through reaction kinetics and control experiments. Reactivity and regioselectivity are facilitated by a collection of monodentate, weakly coordinating native directing groups, including sulfonamides, alcohols, amines, amides, and azaheterocycles.

Directed Nickel-Catalyzed Selective Arylhydroxylation of Unactivated Alkenes under Air

“…On the basis of the results presented above and previous reports, ,− a plausible mechanism of this protocol was proposed (Scheme ). First, the coordination of a nitrogen atom of the amide and the double bond of alkene with a nickel complex forms intermediate A , which undergoes transmetalation with phenylboronic acid 2a followed by syn -1,2-migratory insertion to generate alkyl nickelacycle B .…”

Recent developments on 1,2-difunctionalization and hydrofunctionalization of unactivated alkenes and alkynes involving C–S bond formation

“…In 2022, Engle and co-workers 71 introduced a novel directing Ni-catalyzed syn -carbosulfenylation reaction of unactivated alkenes ( 240 ) with organoboron nucleophiles ( 241 ) (Scheme 41). The key to the process is the use of N -alkyl- N -(arylsulfinyl)arylsulfonamides ( 242 ) as electrophilic sulfur sources, which provide the opportunity to control the efficiency and selectivity through the tunable electronic and steric properties of the sulfonamide fragment.…”

Recent advances in thiolation via sulfur electrophiles

“…In 2021, Engle and co-workers described a multi-component approach to obtain structurally complex organosulfur products via the 1,2-carbothiolation of unactivated alkenes under nickel catalysis with organoboron nucleophiles and the designed sulfonamide-masked sulfur electrophiles 64 (Scheme 20a). 33 Different from the above traditional electrophilic sulfenyl transfer processes involving thiiranium ions, this carbothiolation arose from the directed arylnickel( i ) migratory insertion mechanism (Scheme 20b), and the thiolation was realized by N–S oxidative addition and subsequent C–S reductive elimination. Therefore, the desired carbothiolation products 66 had shown a unique syn -selectivity, and the thio group was installed into the internal carbon.…”