In situ vinylindole synthesis: Diels–Alder reactions with N-phenylmaleimides, 1-tetralones and 4-chromanones to give annulated tetrahydrocarbazoles

Abstract

An acid-catalyzed condensation of indole 4 with 1-tetralones 5a–f formed a vinylindole which reacted in situ with N-phenylmaleimides 7a–g. This cascade of condensation and Diels–Alder reaction was performed in IPA (isopropyl alcohol) and in presence of p-TsOH (p-toluenesulfonic acid) at reflux to produce annulated tetrahydrocarbazoles 8a–g and 10a–e. Similarly, 9a–g were synthesized by substituting 4-chromanone 6 for 5a–f. The 1-tetralone derived products 8a–g and 10a–e were obtained in higher yields (19–79%) compared to 4-chromanone derived 9a–g (6–28%), likely due to additional side reactions in case of chromanones. To establish the structure and stereochemistry of products, the crystal structure of 10c was obtained, confirming endo-Diels–Alder addition.

GRAPHICAL ABSTRACT

Keywords:

• Diels–Alder
• N-phenylmaleimides
• one-pot synthesis
• tetrahydrocarbazoles
• vinylindole

Acknowledgments

The authors are grateful to Victor G. Young Jr., Ph.D. (X-Ray Crystallographic Laboratory, University of Minnesota) for assistance with the crystal structure; Andrew K. Schneerer for reviewing the manuscript; Alexei V. Novikov for giving experimental insights; and Taizong Shen for initial input of this project.

Additional information

Funding

The authors thank the Wayland E. Noland Research Fellowship Fund at the University of Minnesota Foundation for generous financial support of this project.