Electrophilic Sulfur Reagent Design Enables Catalytic 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. 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.

Regioselective 1,2-carbosulfenylation of unactivated alkenesviadirected nickel catalysis

“…[29][30][31][32][33][34][35][36][37][38][39] Carboheterofunctionalizations with concomitant formation of C-N, [40][41][42][43] C-O, [44][45] C-B, 46-48 and C-Si 48 have been explored, directed ole n carbosulfenylation remains untouched. 49 Recently, our group described a method for Ni(II)-catalyzed dicarbofunctionalization 37 and carboamination 43 of unactivated alkenes bearing picolinamide (PA) directing group via a Ni(I)/Ni(III) cycle rather than a Ni(0)/Ni(II) cycle, thus resulting in reversed regioselectivity that incorporate nucleophiles distal to the directing group. This method was initiated by transmetalation with arylboronic acids, yielding the Ni(I)-alkyl intermediate followed by ole n migratory insertion (Fig.…”

“…10 Carboheterofunctionalizations with concomitant formation of C–N, 11 C–O, 12 C–B, 13 and C-Si 13 c bonds have been explored; however, directed olefin carbosulfenylation remains to be explored. 14 During our continuous efforts in developing regioselective difunctionalization of alkenes, 10i,11d we have found that a Ni( i )-alkyl intermediate could be generated via transmetalation with arylboronic acids, followed by an olefin migratory insertion (Scheme 1C). As a consequence, we speculated that if the Ni( i )-alkyl species could be intercepted by an electrophilic thiolation reagent via an oxidative addition/reductive elimination sequence, 15 then a modular method for the intermolecular carbosulfenylation could be achieved.…”

Regioselective 1,2-Carbosulfenylation of Unactivated Alkenes via Directed Nickel Catalysis

“…[29][30][31][32][33][34][35][36][37][38][39] Carboheterofunctionalizations with concomitant formation of C-N, [40][41][42][43] C-O, [44][45] C-B, 46-48 and C-Si 48 have been explored, directed ole n carbosulfenylation remains untouched. 49 Recently, our group described a method for Ni(II)-catalyzed dicarbofunctionalization 37 and carboamination 43 of unactivated alkenes bearing picolinamide (PA) directing group via a Ni(I)/Ni(III) cycle rather than a Ni(0)/Ni(II) cycle, thus resulting in reversed regioselectivity that incorporate nucleophiles distal to the directing group. This method was initiated by transmetalation with arylboronic acids, yielding the Ni(I)-alkyl intermediate followed by ole n migratory insertion (Fig.…”