Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles.

Ming-Xi Bi,Yangen Huang,Feng-Ling Qing,Shuai Liu,Xiu-Hua Xu

doi:10.3762/bjoc.16.62

Abstract

A cascade oxidative trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles with AgSCF3 is described. This protocol allows for the synthesis of novel bis(trifluoromethylthiolated) or trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones in moderate to good yields. Mechanistic investigations indicated that radical processes were probably involved in these transformations.

Highlights

The trifluoromethylthio (SCF3) group could significantly improve the lipophilicity of organic molecules as shown by its high Hansch constant (π = 1.44 for SCF3, 0.88 for CF3, and 0.61 for SMe) [1] that helps permeation across biological membranes
Song [21] and Liang [22] reported the one-pot synthesis of novel phosphorylated and sulfonylated pyrrolo[1,2-a]indol-3-ones from N-[(3-phenyl)propioloyl]indole and N-propargylindoles, respectively. Inspired by these elegant results, we became interested in the preparation of SCF3-substituted pyrrolo[1,2-a]indol-3-ones, which might be potentially useful in medicinal chemistry
When the N-[(3-aryl)propioloyl]indole substrates (3a–d) with different substituents at the 3-position of the indole ring were subjected to the standard conditions, the cascade trifluoromethylthiolation and cyclization occurred to yield trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones (4a–d) in moderate yields (Scheme 3)

Summary

Introduction

Pyrrolo[1,2-a]indol-3-ones are prevalent scaffolds that widely exist in many bioactive compounds and natural products [1720]. Inspired by these elegant results, we became interested in the preparation of SCF3-substituted pyrrolo[1,2-a]indol-3-ones, which might be potentially useful in medicinal chemistry. As part of our continuing research interest in radical trifluoromethylthiolation reactions [33,34,35,36,37,38], we disclose a cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles to access SCF3substituted pyrrolo[1,2-a]indol-3-ones (Scheme 1e). Radical cascade reactions constitute highly efficient strategies for the construction of compounds with structural diversity and complexity.

Results

Conclusion