Regioselective Oxyamination Cyclization of Alkynyl-Tethered Indoles to Prepare Functionalized δ-Carboline N-Oxides
Jin Zhao1,2, Yuan-Yuan Fan1,2, Zhong-Chen Huang1
1Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, College of Pharmacy, Guilin Medical University, 1 Zhi Yuan Road, Guilin 541199, China.
Abstract:
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.
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