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Synlett 2009(3): 333-353  
DOI: 10.1055/s-0028-1087546
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

The Art of the Soluble: Synthetic Problems from Industry as a Springboard for the Discovery of New Chemical Reactions

Samir Z. Zard
Laboratoire de Synthèse Organique, CNRS UMR 7652, École Polytechnique, 91128 Palaiseau, France
Fax: +33(1)69335972; e-Mail: zard@poly.polytechnique.fr;
Further Information

Publication History

Received 1 August 2008
Publication Date:
22 January 2009 (online)

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Abstract

This account relates the thought processes that went into solving synthetic problems, mostly related to steroids, submitted by industry and, in many cases, the evolution of the solutions into new reactions more generally useful in organic synthesis. A strong emphasis is placed on mechanistic considerations and serendipitous findings as the main basis for constructing working hypotheses from which novel reactions were derived.

1 Introduction

2 Early Steroid Problems

2.1 A Pleasant Encounter with Isocyanides

2.2 The Nitro Route to Corticosteroids

2.3 Explorations in Nitro Chemistry

3 The 16β-Methyl Problem

4 A Problem of Bile Acid Side-Chain Degradation

4.1 Planned and Unexpected Oxazoline Chemistry

4.2 New Reactions of Sulfines

4.3 An Unusual Route to Trifluoromethyl Ketones

5 From Enamides to Radical Chemistry

6 Solutions Waiting for Problems

Key words

steroids - rearrangements - pyrroles - radicals - deoxy­genation

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36

Quiclet-Sire, B.; Zard, S. Z. unpublished results.