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

In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a-e via alkylative dearomatization and intramolecularN-imination of indole-O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted in the presence of HBF4 center dot 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.

Automated summary

In this study, a method for synthesizing spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles was reported. The targets were obtained with high yields through alkylative dearomatization and intramolecular N-imination reactions.