Indole Functionalization via Photoredox Gold Catalysis

Abstract

The use of photoredox catalyst [Au2(dppm)2]Cl2 to initiate free-radical cyclizations onto indoles is reported. Excitation of the dimeric Au(I) photocatalyst for the reduction of unactivated bromoalkanes and bromoarenes is used for the generation of carbon-centered radicals. Previous to this work, reduction processes leading to indole functionalization utilizing photoredox catalysts were limited to activated benzylic or α-carbonyl-positioned bromoalkanes. This method offers a mild and safe alternative to organostannanes and pyrophoric initiators for access to high energy radicals that were previously inaccessible through catalytic or stoichiometric means.

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

“…The cyclization of substrate 1a gave product 2a, for which the analytical data were reported previously. [2] Cyclization of 10 to 5c: By the general procedure, iodide 10 (39.8 mg, 0.11 mmol), DIPEA (97 μL, 0.55 mmol), and [Ir(dtbbpy)(ppy) 2 ](PF 6 ) (B; 1.0 mg, 1.1 μmol) in MeCN (2.20 mL) were irradiated for 24 h. The 1 H NMR spectrum of the crude product showed 68 % conversion of substrate 10 and a 93:7 ratio for the reduced cyclization products 5c/10-epi-5c [diastereomeric ratio (dr) 70:30] as well as the (known) [4] aromatic cyclization product. Column chromatography (EtOAc/petroleum ether, 1:6) gave 10-epi-5c α-Bromo Ester 9.…”

“…[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).…”

Development of New Gold (I)‐Catalyzed Carbocyclizations and their Applications in the Synthesis of Natural Products

“…Taking advantage of this distinctive mechanism, we hypothesized that β‐enone radicals such as 37 could be formed though photoredox catalyst (Scheme ). Using the inherent reactivity of these radical species, we developed an intramolecular radical arylation using butenolides and cyclic enones for the formation of polycyclic compounds …”

Design for carbon–carbon bond forming reactions under ambient conditions

“…Kaldas et al 460 have developed a light-mediated process for the generation of organic free radicals with unactivated bromoalkanes/arenes (237) using dimeric Au(I) photocatalyst under basic conditions at room temperature for functioanlization of substituted indoles (238) (Scheme 92). This method may be a mild and relatively safe alternative to organostannanes and pyrophoric initiators used for accessing high energy radicals that were previously inaccessible through catalytic or stoichiometric means.…”