Controlled Photochemical Synthesis of Substituted Isoquinoline-1,3,4(2H)-triones, 3-Hydroxyisoindolin-1-ones, and Phthalimides via Amidyl Radical Cyclization Cascade

Abstract

We report a controlled radical cyclization cascade of isoquinoline-1,3,4­(2H)-triones, 3-hydroxyisoindolin-1-ones, and phthalimides from o-alkynylated benzamides by metal-free photoredox catalyzed amidyl N-centered radical addition to the C–C triple bond using the proton-coupled electron transfer (PCET) process under mild reaction conditions. A time tunable synthesis of 3-hydroxyisoindolin-1-ones and phthalimides via β-carbonyl-C­(sp3) bond cleavage was also achieved under visible light irradiation. A mechanistic rationale for the radical cyclization cascade is supported by various control and quenching experiments as well as EPR studies.

Radical-Induced Cascade Annulation/Hydrocarbonylation for Construction of 2-Aryl-4H-chromen-4-ones

“…Based on the literature reports [ 65 , 66 , 67 ] and the results of the above control experiments, a plausible mechanism is proposed ( Scheme 6 ). Initially, AIBME releases nitrogen under thermal conditions to form the free radical A , which attacks (PhSe) 2 to generate the phenylselenyl radical (PhSe∙) and compound B (detected by CC-Ms) via radical transfer.…”

Photocatalysis as a green alternative toolkit for the construction of nitrogen-enriched heterocycles via the direct and indirect activation of alkynes/alkenes

“…The Anandhan group created a controlled radical cyclization cascade process in 2022 (Table 6A) 39 for the synthesis of isoquinoline-1,3,4(2 H )-triones ( 157 ), 3-hydroxyisoindolin-1-ones ( 155 ), and phthalimides ( 156 ) from o -alkynylated benzamides ( 154 ). This study produced three distinct compounds with a high reaction yield upon exposure to oxygen and blue LED light using organic photocatalyst PC5A based on acridinium.…”

Multiple-cycle photochemical cascade reactions

“…In 2022, by employing Mes-Acr-MeBF 4 as a photocatalyst in the presence of oxygen, the Anandhan group also disclosed a photocatalytic N-radicalmediated intramolecular radical addition, oxidation, rearrangement and carbon-carbon bond cleavage cascade reaction of o-alkynylated benzamides 20 to deliver a variety of functionalized phthalimides 21 (Scheme 7b). 40 In 2013, Pandey and co-workers reported a visible lightinduced sequential photoredox alkylation of dihydroacridine derivative 23 with dienone 24 (Scheme 8a). 41 Specifically, this methodology exploited the excited state Ru-catalyst induced SET oxidation to facilitate the double activation of the sp 3 C-H bond, leading to the spirocyclic product 25 in 42% yield through intermediate 23-A.…”