Regioselective Oxyamination Cyclization of Alkynyl-Tethered Indoles to Prepare Functionalized δ-Carboline N-Oxides.

We report a transition-metal free approach to prepare a variety of functionalized δ-carboline N-oxides in good yields with high regioselectivity through tert-butyl nitrite (TBN)-mediated intramolecular oxyamination cyclization of alkynyl-tethered indoles. Mechanistic studies show that the cascade reaction involves TBN-mediated nitrosation of indole moiety to oxime, followed by a regioselective 6-exo-dig cyclization of alkyne moiety, nucleophilic addition of H2O to the electrophilic alkene moiety, and oxidation of alcohol to ketone over four steps in a one-pot reaction. The obtained functionalized δ-carboline N-oxides could be easily converted into functionalized δ-carbolines and an estrone derived δ-carboline N-oxide is obtained in total 24% yield from estrone in four steps.