The direct use of phenyldimethylsilanes in silicon assisted palladium catalysed cross coupling

Article abstract of DOI:10.1039/b205765d

A vinyl-phenylsilane has been used as a masked vinyl organometallic for a cross coupling reaction with phenyl iodide to provide the cine substitution product in high yield.

Full text of DOI:10.1039/b205765d

The direct use of phenyldimethylsilanes in silicon assisted palladium
catalysed cross coupling†
James C. Anderson,* Stéphane Anguille and Rosalyn Bailey
School of Chemistry, University of Nottingham, Nottingham, UK NG7 2RD.
E-mail: j.anderson@nottingham.ac.uk; Fax: +44 (0) 115 951 3564; Tel: +44 (0) 115 951 4194
Received (in Cambridge, UK) 13th June 2002, Accepted 25th July 2002
First published as an Advance Article on the web 13th August 2002
A vinyl-phenylsilane has been used as a masked vinyl
organometallic for a cross coupling reaction with phenyl
iodide to provide the cine substitution product in high
yield.
mol %) with PhI (1 equiv.) in undried THF11 at room
temperature for 45 min and gave a 85% yield of 3. We believe
this is a significant advance as the phenyldimethylsilyl group is
resistant to most chemical reagents and so could be carried
through a multistep synthesis with more confidence than any of
the more reactive functionalised organosilanes presently used
for palladium catalysed cross coupling reactions. Our mild
conditions for the liberation of a silanol from the phenylsilane
precursor coupled with standard cross coupling conditions6h–j,8
provides an excellent benign organometallic nucleophile for
multi step syntheses.
Of course the striking observation with this particular
substrate is the high yield of cine substitution. The alkene 3 is
isolated as a ~ 90% pure trans stereoisomer contaminated with
a mixture of other alkene isomers.12 This product presumably
arises from a Heck type process or Pd(0)-carbene species
previously reported in organoborane2 and organostannane13
cross couplings, but not to the efficiency here. It is worth noting
that in the work developing the use of silanols in cross coupling
reactions only terminal silanols have been reported.6h–j,8
Preliminary investigations into the stereoselectivity and
generality of this cross coupling protocol has relied upon other
phenyldimethyl silanes we have generated from our aza-
[2,3]-Wittig sigmatropic rearrangement project. Treatment of
the more complex C-2 phenyldimethylsilyl terminal alkene 4
under identical reaction conditions gave a 42% yield of cine
Carbon–carbon bond formation by palladium catalysed cross
coupling reactions are now a general and powerful method in
organic synthesis.1 Arguably the most notable examples of
cross coupling between organometallic nucleophiles and or-
ganic halide (or triflate) are the Suzuki–Miyaura coupling of
organoboranes,2 Stille–Migita–Kosugi coupling of organos-
tannanes3 and Negishi coupling of organozincs.4 These meth-
ods have gained popularity amongst the synthetic community,
in part, as they employ isolatable or easily prepared organome-
tallics that are weak nucleophiles with good functional group
stability. However these methods have specific disadvantages
such as toxicity, ease of handling, functional group compatibil-
ity or air sensitivity. This has led to the development of
complimentary methods which have tried to address one or
more of these drawbacks.1a Over the past decade the palladium
catalysed cross coupling of organo silicon compounds to
organic halides has been developed as an alternative cross
coupling procedure.5 Pioneering studies by Hiyama have shown
that activation of organofuctional silicon compounds is possible
by addition of a fluoride source to promote the palladium-
catalysed, cross-coupling reactions to various organic halides.6
The activation of functionalised organo silicon compounds by a
fluoride source to form a reactive siliconate complex that
participates in transmetallation has been investigated by a
number of other research groups.7 More recent developments
have developed the use of silanols in cross coupling re-
actions.7h,i,8 A characteristic of all these methods is the use of
more reactive organo silicons such as haloorganosilanes,
orthosiliconates silyl ethers, silacyclobutanes and silyl hy-
drides. Functionality which could be tempremental in a multi
step synthesis. We wish to report here our preliminary
observations that the robust phenyldimethylsilyl group can be
used directly in a palladium catalysed cross coupling reaction.
We have recently reported a mild method for the proto-
desilylation of C-2 phenyldimethylsilyl terminal alkenes using
a mixture of t-BuOK-18-C-6-TBAF.9 In this work we found
that the intermediate in the protodesilylation reaction sequence
is a silanol. The formation of silanols from the treatment of
phenylsilanes with t-BuOK is not unprecedented, but it was
reported that the proposed mechanism required DMSO.10
Treatment of model compound 1 with t-BuOK (2 equiv.) and
18-C-6 (1.5 equiv.) in undried THF for 2 h at room temperature
gave a 76% yield of silanol 2 (Scheme 1). The extensive
optimisation of reaction conditions (Pd cat., fluoride source,
stoichiometry, solvent and temperature) already carried out by
Denmark et al.6h–j,8 provided ideal cross coupling conditions
with phenyl iodide to give cross coupled product 3 in 89% yield.
The key transformation by combining these two reactions was
carried out by treatment of 1 with a mixture of t-BuOK (2.5
equiv.), 18-C-6 (1.5 equiv.), TBAF (2 equiv) and Pd2dba3 (10
Scheme 1
† Electronic supplementary information (ESI) available: further experi-
mental details. See http://www.rsc.org/suppdata/cc/b2/b205765d/
Scheme 2
2018
CHEM. COMMUN., 2002, 2018–2019
This journal is © The Royal Society of Chemistry 2002

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substitution product 5 (Scheme 2). Treatment of phenyl-
dimethylsilyl alkene 6 under identical silanol forming/cross
coupling reaction conditions, but stirring overnight, led to
protodesilylation and gave 7 in 83% yield. Termination of the
reaction after 45 min gave the corresponding silanol (44%) and
7 (44%).
We are currently investigating the substrate tolerance and
stereoselectivity of this protocol which will form the basis of a
full publication in the near future. The preliminary results
presented here suggest that this mild procedure holds particular
promise for the use of phenyldimethylsilyl groups in direct
cross coupling reactions for complex molecule synthesis.
We would like to thank the EPSRC and the University of
Nottingham for financial support.
Notes and references
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10 T. Akiyama and S. Imazeki, Chem. Lett., 1997, 1077.
11 Related studies seem to suggest that 1.5% of H2O gives the best yields
in our protodesilylation experiments (ref. 9). J. C. Anderson and M.
Whiting, unpublished results.
12 These could be the corresponding cis- and 2-phenyl isomers, the identity
of which await further experiments.
13 See ref 3b, pp. 48–49.
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