Iodine-Catalyzed Oxidative Cross-Coupling of Indoles and Azoles: Regioselective Synthesis of N-Linked 2-(Azol-1-yl)indole Derivatives

Abstract

A highly efficient iodine-catalyzed regioselective oxidative cross-coupling of an indole C-H bond and azole N-H bond is described. This metal-free reaction can be easily carried out at room temperature under mild and environmentally friendly conditions and provides a series of N-linked 2-(azol-1-yl)indole derivatives in moderate to excellence yields.

Iodine/TBHP‐Promoted One‐Pot Deoxygenation and Direct 2‐Sulfonylation of Quinoline N‐Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2‐Sulfonylquinolines

“…Our group has been interested in developing a metal‐free approach to synthesizing biologically active nitrogen‐containing compounds and N‐heterocycles . We recently explored the compatibility of sulfinate salts as a readily available, bench‐stable, nonhygroscopic, easy‐to‐handle, and versatile sulfonyl source in the iodine‐catalyzed sulfonylation reaction.…”

“…We recently explored the compatibility of sulfinate salts as a readily available, bench‐stable, nonhygroscopic, easy‐to‐handle, and versatile sulfonyl source in the iodine‐catalyzed sulfonylation reaction. [15b], A combination of iodine and environmentally benign peroxides, such as tert ‐butyl hydroperoxide (TBHP) or hydrogen peroxide (H 2 O 2 ), under mild operating conditions may lead to broadening of the reaction scope, along with a better functional group tolerance. Following our continuous efforts towards the development of a metal‐free synthetic option, herein, we wish to report a facile regioselective synthesis of 2‐sulfonylquinolines and other related N‐heterocycles by a I 2 /TBHP‐mediated one‐pot deoxygenation and direct sulfonylation of quinoline N ‐oxide substrates by using sodium sulfinates as a stable, odorless, and easy‐to‐handle sulfonyl source (Scheme g).…”

Synthesis of 8-(1,2,3-triazol-1-yl)-7-deazapurine nucleosides by azide–alkyne click reactions and direct C H bond functionalization

“…and tert -butylhydroperoxide (TBHP; 5–6 M/decane, 2 equiv.) 47 in anhydrous DMF at 35 °C for 96 h showed ~30% conversion (TLC) to 8-(benzotriazol-1-yl)tubercidin 10 which was isolated in 18% yield after column chromatography and HPLC (Scheme 3). Increasing the amount of iodine from catalytic to stoichiometric (3 equiv.)…”

“…Because 7-deazapurine is structurally similar to indole, the coupling of 1b with benzotriazole might have occurred via initial iodination of the pyrrole ring of 7-deazapurine followed by trapping of the resulting iodonium, or 7-iodo iminium intermediates, with nucleophilic triazole. Subsequent elimination of HI, as proposed for the iodine-catalyzed direct activation of indoles with azoles mediated by TBHP, 47 should yield products 10–12 . Subjection of the sangivamycin 1c and toyocamycin 1b to direct C8-H functionalization with benzotriazole (r.t. to 80 °C/48 h) gave unchanged substrate or resulted in rather complex reaction mixture.…”

“…These results reiterate the literature report that the iodine catalyzed C-H activation of indoles with azoles works rather sluggishly with electron deficient indole substrates. 47 …”