Oxygen Dependent Switchable Selectivity during Ruthenium Catalyzed Selective Synthesis of <i>C3</i>-Alkylated Indoles and Bis(indolyl)methanes

Abstract

Herein, we report a ligand-centered redox-controlled oxygen-dependent switchable selectivity during ruthenium-catalyzed selective synthesis of C3 -alkylated indoles and bis(indolyl)methanes (BIMs). A wide variety of C3 -alkylated indoles and BIMs were prepared selectively in moderate to good isolated yields by coupling a wide variety of indoles and alcohols, catalyzed by a well-defined, air-stable, and easy-to-prepare Ru(II)-catalyst ( 1a ) bearing a redox-active tridentate pincer ( L 1a ). Catalyst 1a efficiently catalyzed the C3 -alkylation of indoles under an argon atmosphere while, under an oxygen environment, exclusively producing the BIMs. A few drug molecules containing BIMs were also synthesized efficiently. 1a exhibited excellent chemoselectivity with alcohols containing internal carbon–carbon double bonds. Mechanistic investigation revealed that the coordinated azo-aromatic ligand actively participates during the catalysis. During the dehydrogenation of alcohols, the azo-moiety of the ligand stores the hydrogen removed from the alcohols and subsequently transfers the hydrogen to the alkylideneindolenine intermediate, forming the C3 -alkylated indoles. While under an oxygen environment, the transfer of hydrogen from the ligand scaffold to the molecular oxygen generates H 2 O 2, leaving no scope for hydrogenation of the alkylideneindolenine intermediate, rather than it undergoing 1,4-Michael-type addition forming the BIMs.

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