RuII-amidobis(phosphine) catalyzed alkylation of indole and epoxide opening followed by α-alkylation through alcohol oxidation

Abstract

Herein, we report a simple, microwave-assisted and open-air strategy for gram-scale C3-alkylation of indoles, along with an economically viable strategy for epoxide opening followed by α-alkylation, using the [Ru^IICl(bpy){o-Ph₂PC₆H₄CONC₆H₄PPh₂-o}-κ⁵-(P,N,P,N,N)] complex (hereafter referred to as [PNP-Ru]). This transformation proceeds via an alcohol dehydrogenation (oxidation) mechanism, with water being the sole byproduct in both reactions, underscoring the environmentally benign and sustainable nature of the methodology. The protocol efficiently delivers both mono- and bis(indolyl) derivatives in good to excellent yields. Notably, pharmaceutically relevant scaffolds such as arundine, vibrindole and orphan receptor molecules were successfully synthesized in good yields. A broad range of aliphatic and benzyl alcohols were compatible with this catalytic system, participating effectively in both the C3-alkylation of indoles and epoxide opening followed by α-alkylation.