Ni-Catalyzed Regio- and Stereoselective Alkylarylation of Unactivated Alkenes in γ,δ-Alkenylketimines

Abstract

We disclose a Ni-catalyzed vicinal alkylarylation of unactivated alkenes in γ,δ-alkenylketimines with aryl halides and alkylzinc reagents. The reaction produces γ-C­(sp3)-branched δ-arylketones with the construction of two C­(sp3)–C­(sp3) and C­(sp3)–C­(sp2) bonds. Electron-deficient alkenes play crucial dual roles as ligands to stabilize reaction intermediates and to increase catalytic rates for the formation of C­(sp3)–C­(sp3) bonds. This alkene alkylarylation reaction is also effective for secondary alkylzinc reagents and internal alkenes and proceeds with a complete regio- and stereocontrol, affording products with up to three contiguous all-carbon all-cis secondary stereocenters.

Salt-stabilized alkylzinc pivalates: versatile reagents for cobalt-catalyzed selective 1,2-dialkylation

“…Based on our findings and previous insights, 3 i ,23 a plausible catalytic cycle has been proposed as shown in Scheme 6E. The initial reduction of CoI 2 with alkylzinc pivalates formed the catalytically active L n Co n -species ( A ), which promotes the intermolecular halogen atom transfer of difluoroalkyl bromides by SET to generate the difluoroalkyl radical B , then followed by a facile radical insertion of B into dienoates ( 2 ) to form the allyl radical E. Transmetalation between the newly formed L n Co n +1 -species and Alk–ZnOPiv ( 3 ) gave the alkyl-Co n +1 ( D ).…”

Nickel‐Catalyzed Regioselective Intermolecular Dialkylation of Alkenylarenes: Generation of Two Vicinal C(sp3)−C(sp3) Bonds Across Alkenes**

“…Tertiary α‐bromocarboxylic esters, such as α‐bromoisobutyrate, α‐bromocyclobutyl carboxylate and α‐bromo‐α,α‐difluoroacetate, and secondary α‐bromocarboxylic esters, like α‐bromopropionate and α‐bromo‐α‐fluoroacetate, could be readily added to different alkenylarenes along with unfunctionalized and functionalized alkylzinc reagents. However, the reaction of α‐bromo‐α‐fluoroacetate with 2‐vinylnaphthalene and propylzinc iodide required to be conducted in toluene with the catalytic amounts of dimethyl fumarate (DMFU) and AgBF 4 [3v] . In alkene dicarbofunctionalization reactions, the majority of reactions are only compatible with secondary, tertiary, α‐monofluorinated and α,α‐difluororinated α‐bromocarboxylates owing to their ability to stabilize α‐carbon radicals and the developing positive charge during nucleophilic radical additions.…”

“…Reactions in which both alkylzinc reagents and alkenylarenes lacked functional groups required the addition of either 1.0 equiv. of ZnBr 2 ( 35 and 42 ) [3j] or 5 mol % DMFU and 30 mol % AgBF 4 ( 40 , 44 and 45 ) [3v] along with conducting the reactions in toluene or pentane. The structure of the dialkylation reaction with secondary alkylzinc reagents was confirmed by a single crystal X‐ray structure of compound 37 [12] .…”

Remote arylalkylation of unactivated alkenesvia6- or 7-membered nickelacycles with excellent diastereofidelity

“…Different from the well-developed alkene alkylarylation 8,10 via a radical process, arylalkylation that incorporates alkyl units at the internal olefinic position via coupling of C(sp 3 )–C(sp 3 ) 11 remains relatively rare. 7 a ,12 Recently, our group described a novel method for the dicarbofunctionalization of homoallylic amines with arylboronic acids and organohalides but with low diastereoselectivity for internal alkenes, which was initiated by a Ni( i ) species. 13 Accordingly, we hypothesized that the facile oxidative addition of alkyl halides to Ni( i ) species and the coordination of a suitable bidentate directing group may stabilize and intercept fluxional larger nickelacycles, thus providing an expedient avenue to achieve remote arylalkylation and suppress undesired side reactions (Scheme 1B).…”