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Formation of N-Boc pyrrole 2,5-methyl diester, a key intermediate in the Donohoe synthesis of 1-epiaustraline and hyacinthacine A1.

External protocol Created on 03 May 2014

Authors

Timothy J. Donohoe and Rhian E. Thomas

Summary

Heterocyclic rings, such as pyrrolidines, tetrahydrofurans and piperidines, are found in the vast majority of natural product molecules including many of those exhibiting a wide variety of potent biological activities. These heterocyclic rings are often highly substituted and constitute part of complex structures and, therefore, represent a significant challenge to synthetic chemists. The use of aromatic compounds as precursors to these structural motifs is an attractive option because, by controlling the degree of reduction achieved, dihydro or tetrahydro compounds can be formed selectively. These can then be reacted further, increasing substitution and complexity, via use of a wide variety of standard synthetic chemistry found within the literature. The Birch (Li/NH3) and ammonia-free (Li/di- tert-butyl biphenyl [DBB])1 partial reductions, using the conditions developed by Donohoe, are applicable to a wide range of heteroaromatic compounds with a variety of substitution patterns, resulting in formation of the respective dihydro compounds in typically good to excellent yields.2-8 The reduction of the N-Boc pyrrole whose formation is described herein,9 (Figure 1) has recently been published by Donohoe et al. as a key step in the routes to the biologically active natural products 1-epiaustraline and hyacinthacine A1.10, 11

Further details

The protocol was published on Protocol Exchange in 2007. To see the entire protocol, click on the source link.

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