Preparation of Oxindoles via Visible‐Light‐Induced Amination/Cyclization of Arylacrylamides with Alkyl Amines

Abstract

The cascade amination/cyclization of N‐arylacrylamides with alkyl amines under visible‐light photoredox catalysis is realized via intermediacy of aminium radicals. The aminium radicals are generated by a two‐step sequence which involves N‐chlorination of alkyl amines and subsequent reductive N−Cl cleavage. This method provides a convenient access to aminated oxindoles.magnified image

Visible Light Mediated Synthesis of Oxindoles

“…Recently, Liu and co‐workers developed a visible light mediated photocatalyzed strategy to construct 3‐aminated oxindoles 9 in moderate to good yields using Ru(bpy) 3 Cl 2 as a photocatalyst, N ‐phenylmethacrylamide 2 as a substrate, NCS ( N ‐chlorosuccinimide) as oxidant, TFA (CF 3 CO 2 H) as an acid, and HFIP (1,1,1,3,3,3‐hexaflouro‐2‐propanol) as a solvent (Scheme 3). [12] Both electron‐donating and electron‐withdrawing groups at various positions of aryl ring of N ‐phenylmethacrylamides were well tolerated, albeit lower yields from the ortho ‐substituents due to steric repulsions. Moreover, the strategy also afforded a tricyclic oxindole 9 e in excellent yields.…”

Photocatalytic Generation of Aminium Radical Cations for C–N Bond Formation

“…This pathway leads to aminated oxindoles after subsequent rearomatization of the arene. 173 In summary, two modes of reactivity have emerged through these works that enable arene C−H bond amination via either oxidative or reductive aminium radical cation generation. Challenges remain in the ability to control or alter innate regioselectivity preferences, which often leads to product mixtures in the case of monosubstituted arenes.…”

“…Yu and Liu have reported the anti-Markovnikov aminoarylation of tethered N -aryl acrylamides, where now the proposed transient aminium radical cation adds in a Giese-type fashion to the activated olefin, prior to a 5- exo -trig cyclization of the resultant carbon-centered radical onto the pendant anilide. This pathway leads to aminated oxindoles after subsequent rearomatization of the arene …”

Visible‐Light‐Catalyzed N‐Radical‐Enabled Cyclization of Alkenes for the Synthesis of Five‐Membered N‐Heterocycles

“…[46] Liu and co-workers reported a cascade amination/cyclization reaction of alkyl amines with N-arylacrylamides, leading to the formation of amine-containing oxindoles in moderate to high yields and high diastereoselectivities (Scheme 28). [47] Strong acid was necessary for the reaction to proceed, among which CF 3 COOH (TFA) was determined to be the optimal acid for enabling the conversion. In addition, steric hindrance on the aryl ring had significant impacts on the yield.…”