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

Abstract

α-Branched amines are fundamental building blocks in a variety of natural products and pharmaceuticals. Herein is reported a unique cascade reaction that enables the preparation of α-branched amines bearing aryl...

Recent Advances in Radical Coupling Strategies Enabled by 2‐Azaallyl Anions as Super‐Electron‐Donors

“…They developed a Ni‐catalyzed cascade C( sp 3 )−C( sp 3 ) cross‐coupling reactions to form functionalized amines in an alkene difunctionalization process (Scheme 10). [32] After due screening of various ligands such as bipyridyl type ligands ( L1 − L3 ), phenanthroline type ligands ( L4 − L6 ), and phosphine ligands ( L7 − L9 ) in the cascade coupling between fluorenone imine, redox‐active adamantyl esters, and 1,1‐diphenylethylene, which conclusively led to the use of 1,3‐bis(diphenylphosphino)propane (DPPP , L9) as the most effective ligand, whereas Ni(cod) 2 was found to be the most effective metal catalyst. The optimum conditions involve the use of 10 mol% of Ni(cod) 2 , 20 mol% of L9 , and 3 equivalents of DIPEA ( N , N ‐diisopropylethylamine) in THF/DMF at room temperature with blue LED for 16 h. Compared to traditional benzophenone imine, fluorenone imine results in a significantly more acidic C−H bond, with a p K a of 14.5 in DMSO.…”

Efficient construction of functionalized pyrroloindolines through cascade radical cyclization/intermolecular coupling

“…We further employed 2-azaallyl anions to develop a series of radical C(sp 3 )-C(sp 2 ) and C(sp 3 )-C(sp 3 ) coupling strategies. [41][42][43][44][45][46][47] In view of the medicinal value of pyrroloindolines, we felt compelled to apply this radical coupling approach to the synthesis of C3a-substituted pyrroloindolines. Based on our prior generation of amidyl radicals, 48 we hypothesized that SET between the 2-azaallyl anions and indole N-aryloxy acetamides would generate 2-azaallyl radicals and amidyl radicals, the latter of which would trigger a radical cyclization to furnish C3apyrroloindoline radicals.…”

“…We further employed 2-azaallyl anions to develop a series of radical C(sp 3 )–C(sp 2 ) and C(sp 3 )–C(sp 3 ) coupling strategies. 41–47…”

Catalytic Chemo‐ and Regioselective Radical Carbocyanation of 2‐Azadienes for the Synthesis of α‐Amino Nitriles

“…Based on recent works from the groups of Hu, [29] Xiao, [30] Han [31] and ours [19f] on the use of redox active esters (RAEs) as the source of alkyl radicals for difunctionalization of olefins or 1,3‐dienes, and the impressive work by Malcolmson with 2‐azadienes, [32] we hypothesized that 2‐azadienes could serve as radical acceptors to capture alkyl radicals and generate 2‐azaallyl radical intermediates. In considering approaches to capture the resulting 2‐azaallyl radical, we were aware of radical trapping reactions promoted by L n Cu−CN complexes [33] .…”