Trichloroisocyanuric Acid Induced Chlorine Radical Cascade Chlorination­/Carbocyclization of Acrylamides: Constructing Chlorinated Oxindoles by C–Cl and C–C Bond-Forming Reactions

Abstract

A metal- and additive-free strategy for the synthesis of oxindoles has been achieved through a chlorine radical-induced cascade chlorination/carbocyclization of N-aryl acrylamides. Trichloroiso­cyanuric acid (TCCA) is used as both radical initiator and chlorine source. A wide range of substrates can be applied in this process to directly afford chlorinated oxindoles via C–Cl and C–C bond formation.

Chemoselective Synthesis of 3-Bromomethyloxindoles via Visible-Light-Induced Radical Cascade Bromocyclization of Alkenes

“…In previous electrophilic halocyclization, overhalogenation at the benzene ring suffers more severely with electron-rich substrates. 6,12 To our delight, the side reaction is wellsuppressed in this reaction system, enabling the selective production of the desired products. Acrylamides with a N-pextended aryl group are also amenable to this selective reaction (2l and 2m).…”

“…Thus, high yields are obtained from acrylamides bearing electron-donating groups, such as alkoxyl, phenoxyl, methylthiol, and alkyl groups, at the benzene ring ( 2b – 2k ). In previous electrophilic halocyclization, overhalogenation at the benzene ring suffers more severely with electron-rich substrates. , To our delight, the side reaction is well-suppressed in this reaction system, enabling the selective production of the desired products. Acrylamides with a N-p-extended aryl group are also amenable to this selective reaction ( 2l and 2m ).…”

“…We find that the electrophilic bromination at the electron-rich benzene ring is well-suppressed in the reaction by adding a small amount of pyridine and carefully drying the solvent. It should be noted that Su and co-authors reported the synthesis of chlorinated oxindoles through chlorocyclization of acrylamides with trichloroisocyanuric acid (TCCA). , The authors claimed that this reaction proceeded via a radical process, because the reaction could be stopped by 6 equiv of (2,2,6,6-tetramethylpiperidin-1-yl)­oxyl (TEMPO) or butylated hydroxytoluene (BHT). We carefully analyzed the work and found that 3-chloromethyloxindoles without overhalogenation at the benzene ring could not be obtained.…”

Electrochemical oxidative Z-selective C(sp2)–H chlorination of acrylamides

“…When N,Ndiphenylacrylamide 24 was subjected to the optimized reaction conditions, oxindole 25 was accessed as the sole product (Scheme 2C), which can be formed via intramolecular trapping of a C-centered radical intermediate with a N-phenyl substituent. 20 Substituted methyl acrylate 26 produced a mixture of Z-b-chloroacrylate 27 and dichloro ester 28 in 44% and 32% NMR yields, respectively. The formation of 28 may indicate that it is an intermediate on route to the formation of 27, or that the operative reaction mechanism for methyl acrylate substrate 26 is distinct to the tertiary acrylamide substrates predominantly employed.…”