Electron Transfer Photoredox Catalysis: Intramolecular Radical Addition to Indoles and Pyrroles

Abstract

The utilization of the photoredox catalyst, tris(2,2'-bipyridyl)ruthenium dichloride, and a household light bulb to effect radical cyclizations onto indoles and pyrroles at room temperature is reported. A reactive free radical intermediate is generated via the reduction of an activated C-Br bond by the single electron reductant, Ru(I), generated in a visible light induced photocatalytic cycle. This system represents an expansion of the application of photoredox catalysis in conventional free radical processes.

Photoredox‐Induced Radical 6‐exo‐trig Cyclizations onto the Indole Nucleus: Aromative versus Dearomative Pathways

“…[4] Complementary to these methods, our group reported a photoredoxinduced intermolecular tandem (4+2) cyclization of N-(2-iodoethyl)indoles 3 with acceptor-substituted alkenes 4. Although this protocol again operated under reductive conditions {the photocatalyst [Ir(dtbbpy)(ppy) 2 ] + (dtbbpy = 4,4′-di-tertbutyl-2,2′-bipyridine; ppy = 2-phenylpyridine} was used in combination with Hünig's base], it did not lead to aromatic products like 2 but furnished the saturated benzindolizidines 5 almost exclusively (Scheme 1b). Indole substrates 3 bearing C-3 acceptor substituents (R = CO 2 R, COR, CN) efficiently underwent dearomatization under our reaction conditions, and products 5 were obtained with excellent diastereoselectivity.…”

“…[2] However, both procedures have in common the generation of reactive carbon-centered radicals under reductive conditions, that is, in the presence of tertiary amines. Scheme 1.…”

“…[2,3] During the cyclizations of bromides 1, reactive malonyl radicals were generated under reductive conditions with tripletexcited [Ru(bpy) 3 ] 2+ (bpy = 2,2′-bipyridine) as the photocatalyst and tertiary amines as electron donors (Scheme 1a). More recently, Barriault and co-workers described similar intramolecular cyclizations of N-(bromoalkyl)indoles, which by contrast were initiated by an oxidative quench between the alkyl halide substrate and the dinuclear gold(I) photocatalyst [Au 2 (dppm) 2 ]…”

Photoredox catalysis by [Ru(bpy)3]2+ to trigger transformations of organic molecules. Organic synthesis using visible-light photocatalysis and its 20th century roots

“…Later on, a related photoredox manifold has been explored by Stephenson for the synthesis of valuable indoles and pyrroles (Scheme 47) 60 . Cyclizations of structurally diverse substrates via electron transfer photo- iPr 2 NEt 2 eq SCHEME 47 Electron-transfer photoredox catalysis for intramolecular radical addition to indoles and pyrroles (ref.…”

“…Cyclizations of structurally diverse substrates via electron transfer photo- iPr 2 NEt 2 eq SCHEME 47 Electron-transfer photoredox catalysis for intramolecular radical addition to indoles and pyrroles (ref. 60 ) reduced by-product 109 is formed when i-Pr 2 NEt is used. However, by replacing i-Pr 2 NEt with Et 3 N it is possible to suppress the simple reduction pathway and enhance the desired cyclization.…”