One-step construction of indolo[2,1-a]isoquinolines using solid calcium carbide as an alternative to gaseous acetylene

Abstract

An efficient method for the synthesis of indolo[2,1-a]isoquinolines using calcium carbide as an alkyne source, 2-(2-bromophenyl)-1H-indoles as starting materials, and copper as a catalyst is described. The target products are synthesized via Sonogashira cross-coupling/nucleophilic addition tandem reactions. The advantages of this protocol include the use of inexpensive and easy-to-handle solid alkyne source instead of flammable and explosive gaseous acetylene, cheap and readily available raw materials, wide range of substrates, and simple reaction procedure. The method can also be extended to gram scale. In addition, the desired product can also be obtained by one-pot three-component reaction of phenylhydrazine hydrochlorides, o-bromoacetophenones and calcium carbide.

Graphical abstract

Keywords:

• Alkyne source
• calcium carbide
• indolo[2,1-a]isoquinoline
• synthesis

Supporting information

Full experimental detail, analytical data, ¹H, ¹³C and ¹⁹F NMR spectra.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors thank the National Natural Science Foundation of China (21462038) and Gansu Province University Youth Doctoral Support Project (2023QB-022) for the financial support of this work.