Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime

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.

Keywords

• 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indole
• pyrazoloindole
• spirocyclopropane
• alkylative dearomatization
• <i>N</i>-imination
• indole