Nickel-catalyzed enantioselective vinylation of aryl 2-azaallyl anions

Abstract

A unique enantioselective nickel-catalyzed vinylation of 2-azaallyl anions is advanced for the first time. This method affords diverse vinyl aryl methyl amines with high enantioselectivities, which are frequently occurring scaffolds...

α-Branched amines through radical coupling with 2-azaallyl anions, redox active esters and alkenes

“…Before initiating our investigation, reaction conditions used in 2-azaallyl coupling reactions, 19,42 alkene functionalization reactions 75,76 and reductive activation of RAEs 60,77–82 were studied. Based on these works, Ni(COD) 2 was selected as the metal source, 33 DIPEA as base, 31,59,69,83 THF/DMF as solvent (4 : 1, based on literature precedence 50,51,84 ). A series of ligands were screened in the cascade coupling between imine 1a , adamantyl RAE 2a and 1,1-diphenylethylene 3a .…”

“…[20][21][22][23][24][25][26][27] The 2-azaallyl anions can react with unhindered alkyl halides via S N 2, or with aryl halides in the presence of cross-coupling catalysts (Scheme 2a). [28][29][30][31][32] A similar approach was use with aryl bromides and alkyl substituted 2-azaallyl anions in the presence of an enantioenriched Pd catalyst 24 or with vinyl bromides and an enantioenriched nickel catalyst 33 for the synthesis of highly enantioenriched benzylic and homoallylic amine derivatives, respectively. Azadiene precursors have also been hydrometallated to generate 2-azaallyl anions for enantioselective transformations.…”

Transition-Metal-Catalyzed Asymmetric Couplings of α-Aminoalkyl Fragments to Access Chiral Alkylamines

“…40b Very recently, Li, Zhang, Yang, and Walsh introduced low-valent nickel catalysts for promoting vinylation reactions of 2-azaallyl anions (Scheme 13B). 41 Employing chiral bis(diphenylphosphino)butane (Chiraphos) as the stereocontrolling element, this approach was able to produce a variety of chiral allylic amines with moderate to high enantioselectivities, involving highly functionalized 1,3-diamine compounds. Moreover, hydrogenation of the allylic π-bond could be readily accomplished by Pd/C, thus providing the deprotected α-alkyl amine in 70% yield and 94% ee.…”

“…According to a theoretical study, the regio- and enantioselective determining step is the transmetalation step . Very recently, Li, Zhang, Yang, and Walsh introduced low-valent nickel catalysts for promoting vinylation reactions of 2-azaallyl anions (Scheme B) . Employing chiral bis­(diphenylphosphino)­butane (Chiraphos) as the stereocontrolling element, this approach was able to produce a variety of chiral allylic amines with moderate to high enantioselectivities, involving highly functionalized 1,3-diamine compounds.…”

Super-Electron-Donor 2-Azaallyl Anions Enable Construction of Isoquinolines

“…N -Benzyl groups with halogens, such as 4-F ( 1i ), 4-Cl ( 1j ), and 4-Br ( 1k ), gave products 3ia , 3ja , and 3ka in 47%, 42%, and 49% yields, respectively. In order to extend the range of imine substrates to those with N -alkyl groups, the N -benzyl ketimine was replaced by N -(9 H -fluoren-9-yl)­alkylanimine . Interestingly, ethyl ( 1l ), propyl ( 1m ), cyclopentylmethyl ( 1n ), and cyclohexylmethyl ( 1o ) containing compounds were also competent substituents, leading to the desired products 3la , 3ma , 3na , and 3oa in 54–72% yields.…”