Synlett 2015; 26(06): 725-736
DOI: 10.1055/s-0034-1379991
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© Georg Thieme Verlag Stuttgart · New York

Synthesis of Unnatural Steroids Using the Bistro Strategy

Philippe Maurin
a  Ecole Normale Supérieure de Lyon, Université de Lyon, Laboratoire de Chimie, UMR CNRS UCBL 5182, Lyon, France
,
Delphine Moraleda
b  Aix-Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France
,
Hélène Pellissier
b  Aix-Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France
,
Raphaël Rodriguez
c  Institut Curie Research Center, Organic Synthesis and Cell Biology Group, 26 rue d’Ulm, 75248, Paris Cedex 05, France
,
Maurice Santelli*
d  Aix-Marseille Université, CNRS, ICR UMR 7273, 13397, Marseille, France   Email: m.santelli@univ-amu.fr
› Author Affiliations
Further Information

Publication History

Received: 07 October 2014

Accepted after Revision: 15 December 2014

Publication Date:
17 February 2015 (online)


Abstract

Lithium-mediated reductive dimerization of buta-1,3-diene in the presence of chloro(trimethyl)silane readily provides 1,8-bis(trimethylsilyl)octa-2,6-diene, commonly known as ‘Bistro’. This bisallylsilane can react with various electrophilic reagents to give 1,1-disubstituted 2,5-divinylcyclopentanes, which are precursors of the D rings of steroids. After slight alterations, these precursors can be coupled with benzocyclobutene derivatives. Heat induces ring opening of the benzocyclobutene to form an o-xylylene that subsequently undergoes intramolecular cycloaddition with a vinyl substituent to form the skeleton of a new unnatural steroid, according to the A + D → AD → ABCD strategy. In this way, more than 250 steroids have been prepared, including 3-, 11-, 12-heterosteroids bearing a 17-vinyl group that can be readily modified to form a 17-acetyl or 17-(2-oxoethyl) group, as well as some steroid building blocks. The steroids were obtained in few steps from buta-1,3-diene and benzocyclobutene derivatives in overall yields in excess of 25%. This powerful strategy, which has not yet been exhausted, paves the way towards various related synthetic pathways.

1 Introduction

2 Series A

3 Series B

4 Series C

5 Series D

6 Series E

7 X-Ray Crystallographic Data

8 Conclusion

 
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