Rapid construction of γ-lactam containing 3,3-disubstituted oxindoles via a silver-catalyzed cascade radical bicyclization reaction

Abstract

An efficient cascade bicyclization strategy for the construction of γ-lactam containing 3,3-disubstituted oxindole derivatives under silver catalysis is described. The method enables the sequential assembly of both unactivated and activated...

Silver-Catalyzed Cascade Radical Bicyclization Reaction: An Atom- and Step-Economical Strategy Accessing γ-Lactam Containing Isoquinolinediones

“…A nonterminal cyclic alkene 1 was also examined which is found to be also suitable for this reaction. 8 However, the product yield is less than 20% (the result was not shown in the scheme).…”

“…The intermediate A then intrigues the following intramolecular 5-exo-tig cyclization to form a carbon-centered radical B. 8 Next, formed intermediate B undergoes a radical addition to the double bond of 2a, generating a new radical C. This radical C underwent another intramolecular cyclization to form the intermediate D. 11 Finally, D is oxidized by Ag(II) via a single electron transfer (SET) process, accompanied by deprotonation, ultimately yielding desired product 3aa.…”

“…Recently, we have introduced a new radical cascade bicyclization platform that allows a γ-lactam carbon radical, generated from an amidyl radical-initiated cascade 5-exo-trig cyclization, to add to N- methyl- N -phenylacrylamides under silver catalysis to form two five-membered nitrogen heterocycles. Importantly, this new protocol represents a general approach toward formation of a series of hybrid molecules containing both γ-lactam and 3,3-disubstituted oxindole (Scheme b) . In an effort to demonstrate the wide-ranging applications of this new radical cascade bicyclization mode, we recently sought to explore the feasibility of this carbon radical on N -methyl- N -methacryloyl­benzamides to construct hybrid molecules containing both a five-membered N -heterocycle and a six-membered N -heterocycle ring (Scheme c).…”

“…Importantly, this new protocol represents a general approach toward formation of a series of hybrid molecules containing both γ-lactam and 3,3disubstituted oxindole (Scheme 1b). 8 In an effort to demonstrate the wide-ranging applications of this new radical cascade bicyclization mode, we recently sought to explore the feasibility of this carbon radical on N-methyl-N-methacryloylbenzamides to construct hybrid molecules containing both a five-membered N-heterocycle and a six-membered N-heterocycle ring (Scheme 1c). Herein, we report our latest findings.…”

Synthesis of cyano-substituted γ-lactams through a copper-catalyzed cascade cyclization/cyanation reaction

“…Our group has also been interested in the amidyl radicals and recently reported the functionalization of N -phenyl-4-pentenamides with quinone and N -methyl- N -phenylacrylamide. 11 Therefore, as an extension of our current research, we envision that combining a γ-lactam skeleton and a cyano group into a single molecule will be greatly useful. Herein, we wish to disclose a copper-catalyzed cascade radical cyclization/cyanation for the construction of cyano-substituted γ-lactam derivatives.…”