Bromo- or Methoxy-Group-Promoted Umpolung Electron Transfer Enabled, Visible-Light-Mediated Synthesis of 2-Substituted Indole-3-glyoxylates

Abstract

A visible-light-mediated radical tandem cyclization of ortho-isocyano-α-bromo cinnamates to 2-substituted indole-3-glyoxylates is achieved by formation of both C–C/C–S and C–O bonds. The reaction proceeds through a hitherto unprecedented bromine- or methoxy-group-promoted umpolung back electron transfer from an α-carbonyl radical to the photocatalyst. This method allows preparation of diverse 2-arylated or 2-thioarylated indole-3-glyoxylates. The glyoxylate group installed in the products can be utilized for several biologically relevant manipulations.

Recent Developments in Photo‐Catalyzed/Promoted Synthesis of Indoles and Their Functionalization: Reactions and Mechanisms

“…Reiser and co‐workers developed a photoredox‐mediated radical process for the synthesis of 2‐aryl or 2‐phenylthio‐indoleethyl‐3‐glyoxylates (Scheme 11). [24] These prepared compounds are important components in many natural products and pharmaceutical compounds. It is postulated that a bromine‐/methoxy group‐promoted electron transfer from α ‐carbonyl radical (oxidation) to photocatalyst or to radical precursor should be the main driving force for the transformation.…”

Photocatalytical and Photochemical Generation of Imidoyl Radicals: Synthetic Applications

“…Aryl halides [46] Aryl sulfonyl chlorides [46] Diaryliodonium salts [47] Aryl diazonium salts [48] E 1/2 red (V vs SCE) À 1.9 to À 1. Then in 2018, Reiser's group demonstrated Ir(III)catalysed radical tandem cyclization of ortho-isocyano-α-bromocinnamates 86 with diaryldiazonium salts 87 to access 2-aryl or 2-phenylthio-indole-ethyl-3glyoxylates 88 (Scheme 18).…”

“…Then in 2018, Reiser's group demonstrated Ir(III)catalysed radical tandem cyclization of ortho-isocyano-α-bromocinnamates 86 with diaryldiazonium salts 87 to access 2-aryl or 2-phenylthio-indole-ethyl-3glyoxylates 88 (Scheme 18). [48] Mechanistically, the Initially, during the early years of visible-lightinduced photocatalysis, the focus was mainly on the use of metal photocatalysts. Later on, due to their nontoxicity, inexpensive nature and easy availability, the focus started to shift to organo-photocatalysts.…”

Mn(III)‐Mediated Regioselective 6‐endo‐trig Radical Cyclization of o‐Vinylaryl Isocyanides to Access 2‐Functionalized Quinolines

“…For example, Ogawa and coworkers synthesized bisthiolated indoles via 5-exo-trig radical cyclization from o-ethenyl arylisocyanides with disulfide reagents. [16] In comparison of 5-exo cyclization, 6-endo ring closure seems inaccessible from the aspect of stereoelectronic and kinetic control. [14] Furthermore, the photoredox synthesis of 2-phosphinoylindoles though 5-exo-trig radical annulation/hydrogen atom transfer (HAT) process was disclosed by Yang's group.…”

“…[15] Very recently, Reiser's group utilized BrÀ /OMe-group promoted umpolung electron transfer to synthesize a series of 2substituted indole-3-glyoxylates. [16] In comparison of 5-exo cyclization, 6-endo ring closure seems inaccessible from the aspect of stereoelectronic and kinetic control. While, the indirect 6endo-trig radical cyclization was reported by Alabugin's group [17] and Shi's group, [18] respectively, through a domino sequence consisting of 5-exo-trig addition/3exo-trig cyclization/ring expansion (Scheme 1b).…”