Metal-Free Polychloromethylation/Cyclization ofN-Aryl Acrylamides

Abstract

A simple and metal-free radical addition/cyclization reaction of N-aryl acrylamides with CHCl 3 or CH 2 Cl 2 as radical source in the presence of benzoyl peroxide (BPO) as oxidant is developed, which affords polychloromethylated 2-oxindoles in moderate to good yields.

Recent Advances in Polychloromethylation Reactions

“…In 2016, Jia and co‐workers also developed a simple and metal‐free radical addition/cyclization of N ‐aryl acrylamides with CH 2 Cl 2 or CHCl 3 as radical source to afford polychloromethylated oxindoles [15] . In their procedure, benzoyl peroxide (BPO) was used as an oxidant and K 3 PO 4 used as a base (eq 6).…”

Recent Developments in the Polychloroalkylation by Use of Simple Alkyl Chlorides

“…Annulation of alkenes is an efficient and simple way to furnish cyclic compounds [18] . Recent research have showed that polychloro‐heterocycles, such as polychloro‐indoline and polychloro‐oxindoles, could be effectively obtained by using simple alkyl chloride [19–24] . Generally, the generation of alkyl radical from simple alkyl chlorides through C−H bond cleavage is more challenging than carbon‐halogen bond.…”

“…Subsequently, the similar metal‐free cyclization of N ‐Arylacrylamides is developed by Jia and coworkers, using benzoyl peroxide (BPO) as an oxidant in presence of K 3 PO 4 ⋅ 3H 2 O at 80 °C (Scheme 23). [22] …”

“…Recently, with the development of radical chemistry, simple alkyl chlorides (such as dichloromethane, chloroform etc.) have been used as effective precursors to introduce the polychlorinated groups through the coupling with alkanes, [4–7] addition of olefins [9–26] and cyclizations [27–36] . Among them, due to the high reactivity of polychlorinated radical intermediates, the radical‐mediated polychloroalkylation groups have been considered to be an indispensable tool for the synthesis of complex polychlorinated compounds.…”

Discovery of an Oxidative System for Radical Generation from Csp3–H Bonds: A Synthesis of Functionalized Oxindoles

“…Oxindoles represent an important class of heterocycles that occur frequently in natural products and pharmaceuticals . As a result, their efficient synthesis attracts much attention from the synthetic community and great advances have been made recently. , The radical cascade cyclization of alkenes with Csp 3 –H compounds involves the selective C–H bond cleavage and dual C–C bond formation in a single operation, showing high synthetic efficiency in creating functionalized oxindoles. − However, the reported reactions are carried out by employing expensive and/or toxic transition-metal catalysts, hazardous organic peroxides, and other unfriendly promoters (Scheme a). In 2017, Wang and co-workers reported a visible-light-induced radical cascade cyclization of alkenes with simple ethers (both the solvent and the Csp 3 –H donor) for the synthesis of oxindoles .…”