A one-pot synthesis of 2,2′-disubstituted diindolylmethanes (DIMs) via a sequential Sonogashira coupling and cycloisomerization/C3-functionalization of 2-iodoanilines

Abstract

A Pd(ii)-Ag(i) catalyzed highly efficient synthesis of diindolylmethane has been developed. This transformation consists of a one-pot sequential Sonogashira coupling (and desilylation) followed by cycloisomerization/C3-functionalization of 2-iodoanilines. Six new bonds (four C-C and two C-N) are formed in a one-pot fashion. A variety of diindolylmethanes were obtained in excellent yields (up to 94%) under mild reaction conditions and this strategy is amenable to gram scale synthesis also. The products were transformed into various synthetically useful compounds.

CF3SO2Na-Mediated, UV-Light-Induced Friedel–Crafts Alkylation of Indoles with Ketones/Aldehydes and Bioactivities of Products

“…It is especially so for the diindolylmethane derivatives (DIMs), which exhibit a wide range of bioactivities, such as antileishmanial, antistaphylococcal, and anticancer . For example (Scheme ), 3,3′-diindolylmethane ( A1 ) is a novel preventive for breast cancers and has been used in therapeutic treatment, and 3,3′-((4-methoxyphenyl)­methylene)­bis­(1 H -indole) ( 5b ) could serve as an orphan nuclear receptor . Furthermore, vibrindole A ( A2 ) is useful for the treatment of fibromyalgia, chronic fatigue, and irritable bowel syndrome .…”

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…Diindolylmethanes (DIMs), a subfamily of indoles, are beneficial antibacterial, antifungal, anti-androgenic, anticancer, growth-promoting, and anti-implantation drugs. In addition, synthetic DIMs are also known to act as dyes and colorimetric sensors . A large series of DIMs were prepared in 83–94% yields (Scheme ) taking advantage of this last mentioned methodology.…”

“…In the absence of silver salts, the reaction did not occur; the indole-free palladium intermediate must be quenched previously. Selected diindolylmethanes were converted into indolylmethyleneindoles and into diindolylmethylphenyl imines, ureas, and thioureas …”

“…In addition, synthetic DIMs are also known to act as dyes and colorimetric sensors. 85 A large series of DIMs were prepared in 83−94% yields (Scheme 55) taking advantage of this last mentioned methodology. In this example, once the indole ring was formed, a Friedel−Crafts reaction (at the 3-position of the heterocycle) with aldehydes and ketones in the presence of either AgSbF 6 or AgOTf in 1,2-dichloroethane took place (Scheme 55).…”

“…Selected diindolylmethanes were converted into indolylmethyleneindoles and into diindolylmethylphenyl imines, ureas, and thioureas. 85 Following this model reaction mechanism, preformed orthoalkynyl-anilines were employed for the synthesis of pentaleno-[2, 1-b]indoles in a range of 70−98% yields. In the elaborated tetracyclic indole framework, two neighboring stereocenters (one of them a quaternary carbon) were constructed in a single process with excellent diastereoselectivity.…”