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

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){<i>o</i>-Ph₂PC₆H₄CONC₆H₄PPh₂-<i>o</i>}-κ⁵-(<i>P</i>,<i>N</i>,<i>P</i>,<i>N</i>,<i>N</i>)] complex (hereafter referred to as [PNP-Ru]). This transformation proceeds <i>via</i> 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.