Electrochemical 5-exo-dig aza-cyclization of 2-alkynylbenzamides toward 3-hydroxyisoindolinone derivatives

Abstract

Preparation of the biologically relevant 3-hydroxyisoindolinones from the readily available 2-alkynylbenzamides is an appealing synthetic approach. However, such kind of compounds preferably undergoes O-attacked 5-exo-dig/6-endo-dig cyclizations. Herein, we report the...

Electrochemical reductive cascade cyclization of o-alkynylated derivatives for saturated amides/amines

“…From the above observations and earlier literature reports, 14 we propose the plausible mechanism as shown in Scheme 3. Initially, substrate 1 undergoes the proton coupled electron transfer (PCET) process to generate the amidyl radical B in the presence of a base via single electron transfer (SET) at the anode.…”

Electrochemical cascade migratory versus ortho-cyclization of 2-alkynylbenzenesulfonamides

“…The attachment of an o -alkyne 14 shifts the reactivity from the above migratory cyclization to a straightforward aza-cyclization. 15 Indeed, we found that linking the aryl acetylene to the ortho -position of the benzenesulfonamide results in the anticipated cascade ortho -cyclization ( Scheme 1C ). 16 More interestingly, the extra incorporation of the 2-methyl substitution favors migratory cyclization.…”

Current-Controlled Electrochemical Approach Toward Mono- and Trifluorinated Isoindolin-1-one Derivatives

“…13 In our previous research, we found that the electrochemically generated amidyl radical of 2-alkynylbenzamide underwent 5-exo-dig radical aza-cyclization to afford diverse 3-hydroxyisoindolinone. 14 We envisaged that the use of Et 3 N•3HF as the supporting electrolyte should also facilitate the generation of the same amidyl radical. While Et 3 N•3HF also serves as the nucleophilic fluorinating agent, 15 the corresponding fluorinated isoindolin-1-one derivatives should be readily obtained.…”

“…Specifically, the electrochemical synthesis of heterocyclic compounds via the electrochemically generated N-centered radicals has been widely reported . In our previous research, we found that the electrochemically generated amidyl radical of 2-alkynylbenzamide underwent 5 -exo-dig radical aza-cyclization to afford diverse 3-hydroxyisoindolinone . We envisaged that the use of Et 3 N·3HF as the supporting electrolyte should also facilitate the generation of the same amidyl radical.…”