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Microwave-assisted solid-phase organic synthesis (MASPOS) as a key step for an indole library construction
Wei-Min Dai1, Dian-Shun Guo, Li-Ping Sun
1Combinatorial Chemistry Laboratory, The Biotechnology Research Institute and Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China. chdai@ust.hk
Organic Letters
|August 2, 2003
Summary
Microwave-assisted solid-phase organic synthesis (MASPOS) accelerates copper or palladium-catalyzed indole synthesis. This method efficiently produces highly pure 1-acyl-2-alkyl-5-arenesulfamoylindoles in high yields.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Solid-phase organic synthesis (SPOS) offers advantages in purification and automation.
- Microwave irradiation can significantly accelerate reaction rates and improve yields in organic synthesis.
- Metal-catalyzed cyclization reactions are crucial for constructing heterocyclic compounds like indoles.
Purpose of the Study:
- To develop an efficient microwave-assisted solid-phase organic synthesis (MASPOS) method for indole derivatives.
- To investigate the utility of copper(II) and palladium(II) catalysts in this MASPOS approach.
- To synthesize 1-acyl-2-alkyl-5-arenesulfamoylindoles with high purity and yield.
Main Methods:
- Resin-bound 2-alkynylanilides were subjected to microwave irradiation.
- Copper(II) or Palladium(II) mediated cyclization was performed under microwave conditions.
- The final indole products were cleaved from the resin and purified.
Main Results:
- Microwave-assisted solid-phase organic synthesis (MASPOS) significantly facilitated the Cu(II)- or Pd(II)-mediated ring closure.
- 1-acyl-2-alkyl-5-arenesulfamoylindoles were obtained in 65-82% overall yields.
- Products exhibited high purities ranging from 95-99% after a 5-step sequence.
Conclusions:
- MASPOS provides a rapid and efficient route to substituted indole derivatives.
- The use of microwave irradiation enhances the performance of metal-catalyzed cyclizations in SPOS.
- This methodology is suitable for the synthesis of complex indole scaffolds.