Table 3 One pot hydrosilylation and fluoride-free cross coupling of
terminal acetylenes to form substituted (E)-stilbenesa
Acknowledgements
We would like to thank the EPSRC, BBSRC, Newman Foundation
and GlaxoSmithKline for their sponsorship and support.
Notes and references
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Entry
Acetylene
R2X (2)
Product
Yield, b%
1
8a
8a
8a
8d
4-(CH3CO)C6H4I
4-(CH3CO)C6H4Br
4-(NO2)C6H4I
3a
3a
3b
3k
89
82
86
98
2c
3
4c
4-(NO2)C6H4Br
a Reagents and conditions: 1,1,3,3-tetramethyldisiloxane (7) (1 equiv.),
acetylene (8) (2 equiv.), Pt(DVDS) (0.1 mol%), tBu3P (0.1 mol%), toluene,
rt, 16 h, followed by aryl halide (2) (1.5 equiv.), KOH (3 equiv.), Pd(dba)2
(2.5 mol%), MeOH, rt, 2–16 h. b Isolated yield. c Cross coupling reaction
heated to 50 ◦C.
coupling as good conversion to the (E)-stilbene products was
achieved for all the disiloxanes synthesised (Table 2, entries 13–17).
With the individual steps in hand, we then explored the
possibility of a ‘one-pot’ hydrosilylation followed by fluoride-free
cross coupling (Table 3). Pleasingly, excellent yields of the isolated
(E)-stilbenes were obtained for both aryl iodides (entries 1 & 3)
and bromides (entries 2 & 4). Significantly, the yields for the ‘one-
pot’ procedures were comparable to those for the individual steps.
In summary, we have demonstrated that disiloxanes cross couple
under fluoride-free conditions as a result of their equilibrium with
the active silanolates under basic conditions. An operationally
simple protocol for the synthesis of a range of substituted
(E)-stilbene derivatives in good to excellent yields with excellent
levels of geometrical purity from inexpensive starting materials
was developed. This method provides an attractive, cost-effective
alternative to the transition metal catalysed routes traditionally
used to generate molecules containing this privileged scaffold.
Though this study was limited in scope to the formation of
stilbene derivatives, it is hoped that the disiloxane-mediated cross
coupling methodology will find application in the synthesis of
other classes of compounds. For example, preliminary work on
the cross coupling of aryl halides with aryl, vinyl and alkyl substi-
tuted disiloxanes has yielded promising results. Another area for
further study is the use of disiloxanes as stable silanol/silanolate
equivalents in multi-step synthetic procedures which could offer
new disconnection strategies in the synthesis of complex molecular
architectures. Further exploration into the scope and diversity of
cross coupling with disiloxanes is under current investigation and
results will be reported in due course.
9 G. Chandra, P. Y. Lo, P. B. Hitchcock and M. F. Lappert,
Organometallics, 1987, 6, 191–192.
10 For example, Denmark has recently reported the fluoride-free cross
coupling of dimethylvinylsilanolate, generated in situ from divinylte-
tramethyldisiloxane (DVDS), with aromatic halides. This methodology
was exploited in the vinylation of a range of aryl iodides and bromides
(see ref. 8(a) and S. E. Denmark and C. R. Butler, J. Am. Chem. Soc.,
2008, 130, 3690–3704). See also ref. 14.
11 Triisopropylsilyl-protected alcohol was found to be stable under the
cross coupling reaction conditions.
12 The use of aryl bromide substrates required higher reaction tempera-
tures compared to the equivalent aryl iodide (see Table 2). Palladium
black formation was seen during the course of the reaction, indicating
decomposition of the palladium catalyst.
13 (a) L. Feimont, Life Sci., 2000, 66, 663–673; (b) H. Liu, A. Dong, C.
Gao, C. Tan, H. Liu, X. Zu and Y. Jiang, Bioorg. Med. Chem., 2008,
16, 10013–10021.
14 S. E. Denmark and Z. Wang, Org. Lett., 2001, 3, 1073–1076. In
this report, vinyldisiloxanes were used in Pd-catalysed cross coupling
reactions with aryl iodides; however, fluoride was required as the
activation source.
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