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
Key words
unnatural steroids - Bistro - benzocyclobutenes - cyclization - Wacker process - kinetic
resolution
