Affiliation:
1. Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
2. Department of Applied Chemistry, National Chiayi University, Chiayi City 600, Taiwan
3. Development Center for Biotechnology, National Biotechnology Research Park, Taipei City 115, Taiwan
Abstract
In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a–e via alkylative dearomatization and intramolecular N-imination of indole–O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted in the presence of HBF4·OEt2, providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-b]indole (9) in a 63% yield. Compound 9 was reacted with hydroxylamine hydrochloride to afford oxime 10 (65% yield), which was subsequently bis-methanesulfonated to form 11 in a 85% yield. Heating 11 with various alcohols in the presence of N,N-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular N-imination, forming the spirocyclopropane and 4H-pyrazolo[1,5-a]indole structures in the targets 6a–e with 67–84% yields.
Funder
National Science and Technology Council (NSTC) of Taiwan
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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