Unusual rearrangements and cyclizations involving polycyclic indolic systems

Alamdar Ashnagar,Patrick D Bailey,Richard A Price,Timothy J Mills,Philip J Cochrane,Christopher A Ramsden

doi:10.3998/ark.5550190.0008.b14

Abstract

During the course of experiments to explore and develop cyclization reactions of indolic systems, a number of unusual rearrangement reactions were discovered, and are reported in this paper. We describe routes to 4-substituted (methylsufanylmethyl)indole derivatives, and a simple route to a cyclopropanone derivative of a tetrahydro-β-carboline. ©ARKAT-USA, Inc.

Highlights

There are an enormous number of important indolic natural products, containing a plethora of fused ring systems, as exemplified below (Figure 1)
We describe some of our cyclization studies, which have led to unusual and unexpected rearrangements. The first of these is a Sommelet-Hauser rearrangement, observed during the attempted ring-closure to the [6.5.5] fused system found in brevianamide E (2) and okaramine A (4); the second is a cyclopropanone forming reaction, observed whilst attempting the preparation of the spiro-system found in ajmaline (3)
Methylsulfanylmethylation via Sommelet-Hauser rearrangements A key reaction in the synthesis of brevianamide E (2) and okaramine A (4) would be a difficult oxidative cyclization, in which the indolic 2-position becomes bonded to nitrogen.[4]

Summary

Introduction

There are an enormous number of important indolic natural products, containing a plethora of fused ring systems, as exemplified below (Figure 1). Our interest has been in using tryptophan as the chiral starting material for the synthesis of such compounds,[2] and in developing synthetic methods for accessing the polycyclic structures.[3]. We describe some of our cyclization studies, which have led to unusual and unexpected rearrangements. The first of these is a Sommelet-Hauser rearrangement, observed during the attempted ring-closure to the [6.5.5] fused system found in brevianamide E (2) and okaramine A (4); the second is a cyclopropanone forming reaction, observed whilst attempting the preparation of the spiro-system found in ajmaline (3)

Results and Discussion

Section B. Cyclopropanone formation from a diazomethyl ketone

Section A

Section B