A new access to various functionalised trimethylsilyl substituted carbo- and heterocycles

Article abstract of DOI:10.1016/S0040-4039(02)00591-9

Trimethylsilyl substituted carbo- and heterocycles could be efficiently prepared using a ring closing metathesis reaction of the corresponding silylated dienes.

Full text of DOI:10.1016/S0040-4039(02)00591-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3513–3516
A new access to various functionalised trimethylsilyl substituted
carbo- and heterocycles
Marc Schuman and Ve´ronique Gouverneur*
University of Oxford, The Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, UK
Received 14 February 2002; revised 12 March 2002; accepted 21 March 2002
Abstract—Trimethylsilyl substituted carbo- and heterocycles could be efficiently prepared using a ring closing metathesis reaction
of the corresponding silylated dienes. © 2002 Elsevier Science Ltd. All rights reserved.
Silyl olefins are widely utilised as versatile synthetic
intermediates.1 The SiꢀC bonds in alkenylsilylanes are
Mes N N Mes
Mes N N Mes
Cl
Cy3P
Cl
Ru
Cl
amenable to cleavage in the presence of fluoride, gener-
ating carbon nucleophiles that can react further with a
variety of electrophiles or alternatively, undergo cross-
coupling reactions with vinyl or aryl halides in the
presence of palladium catalysts.2 Silylated olefins can
also undergo electrophile-induced substitution reactions
in a similar fashion to arylsilanes.3 In addition, they are
direct precursors of epoxysilanes which are also valu-
able intermediates in organic synthesis since they can
undergo regioselective and stereospecific ring opening
with a range of nucleophiles to give b-hydroxysilanes or
can be hydrolysed to give carbonyl compounds.4
Ru
Ru
Cl
Cl
Ph
PCy3
Ph
Cl
Ph
PCy3
PCy3
Mes = 2,4,6-trimethylphenyl
3
4
2
The dienes were prepared according to standard proce-
dures (Schemes 1 and 2). C-Alkylation of the commer-
cially available diethylallylmalonate afforded diene 1a
in 44% yield.11 The azadiene 1b was obtained by reduc-
tive amination of ketone 6 with allylamine followed by
N-protection with an overall yield of 81%.12 The b,g-
unsaturated ketone 6 was prepared by oxidation of the
corresponding secondary alcohol 5, a product resulting
from the ring opening of propylene oxide with 1-lithio-
1-trimethylsilylethylene.13 Dienes 1c–i were all prepared
Further to our studies on the use of vinylsilanes for
electrophilic fluorodesilylation processes,5 we embarked
on the development of a general strategy towards the
synthesis of various functionalised trimethysilyl substi-
tuted cycloalkenes. Ring closing metathesis catalysed by
ruthenium or molybdenum complexes has revolu-
tionised the way in which carbocycles and heterocycles
are constructed and therefore, we anticipated that the
ring closing metathesis might emerge as a powerful tool
for the preparation of diverse functionalised
trimethylsilyl olefins.6 Several groups have recently
reported on the metathesis reactions of vinylalkoxy-
silane derivatives as well as on the cross coupling of
cycloalkenylsiloxanes.2,7 We now report on the prepara-
tion and ring closing metathesis of vinyltrimethylsilyl
substituted dienes 1a–i. The reactivity of these dienes
towards the ruthenium-based ring closing metathesis
catalysts 2,8 39 and 410 was examined.
a
Ph
Br
SiMe3
SiMe3
OH
b
7
Me
Me
d
RO
SiMe3
O
SiMe3
6
5 R = H
R = Ts
c
Scheme 1. Synthesis of compounds 5–7. (a) tBuLi, ether,
−78°C then PhCH2CH2CHO, ether, −78°C to rt, 74%; (b)
tBuLi, ether, −78°C then propylene oxide, ether, −78°C to rt,
73%; (c) TsCl, pyridine, 0°C to rt, 5 h, 84%; (d) (COCl)2,
DMSO, Et3N, DCM, −60°C to rt, 1 h, 86%.
* Corresponding author. Fax: +44 1865 275 644; e-mail:
veronique.gouverneur@chem.ox.ac.uk
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00591-9

3514
M. Schuman, V. Gou6erneur / Tetrahedron Letters 43 (2002) 3513–3516
using 2 mol% of catalyst 3. Gratifyingly, diene 1c did
undergo the RCM process using the ruthenium com-
plex 4 as the catalyst (entry 3, Table 1). After optimisa-
tion, a near quantitative yield of compound 8c was
isolated after 3 hours of reaction in the presence of 3
mol% of 4 in refluxing dichloromethane. No dimerisa-
tion product could be detected in the crude mixture.
Similarly, the carbocycle 8a was obtained in almost
quantitative yield after 8 hours reaction in the presence
of 3 mol% catalyst 4 (entry 1, Table 1). Ring closure of
the N-Boc protected diene 1b leading to the corre-
sponding 4-trimethylsilyl-3,6-dehydro-2H-pyridine 8b
proved feasible but required an increase in the catalyst
load to 5 mol% and extended reaction time in order to
achieve high yield (entry 2, Table 1). To further illus-
trate the potential of this technology, the RCM of some
ethers and esters was investigated. Diene 1d was the
most reactive substrate as it underwent cyclisation to
afford the five-membered ring 8d in 90% yield after just
1 h in the presence of 2 mol% catalyst 4 (entry 4, Table
1). Interestingly, catalyst 4 also cyclised substrate 1e
despite the significant increase in steric demand. How-
ever, for this reaction, 12 mol% catalyst was used to
afford product 8e in 83% yield after 29 h (entry 5,
Table 1). Finally, the methodology allowed the prepa-
ration of the five- and six-membered a,b-unsaturated
lactones 8f and 8g in good yields albeit at the expense
of extended reaction times (entries 6 and 7, Table 1).
This might be explained by the formation of an unpro-
ductive metal chelate as hypothesised previously by
Fu¨rstner and Ghosh.14 Attempts to cyclise dienes 1h–i
were unsuccessful, resulting in the formation of the
non-cyclic dimers 8h and 8i (entry 8, Table 1). For both
dimers, the E stereoisomer was the major product.15 In
light of the longevity of the catalyst, the Z:E ratios
could result from subsequent isomerisation of the initial
products.
by a Williamson ether synthesis or by acylation starting
with alcohols 5 or 7 in chemical yields ranging from
86% to 97%. Alcohol 7 was obtained in 74% yield by
addition of 1-lithio-1-trimethylsilylethylene to hydro-
cinnamaldehyde.12
Initially, it was necessary to determine if the ruthenium
alkylidenes 2, 3 and 4 were active for the RCM of
dienes containing a trimethylsilyl substituted olefin. Ini-
tial attempts to cyclise diene 1c using the Grubbs’
catalyst 2 failed. Analysis of the crude mixture revealed
the presence of starting material only and none of the
desired product. Even the more reactive catalyst 3
failed to promote the RCM reaction of diene 1c
efficiently. Indeed, only 12% conversion could be
obtained after 15 hours in refluxing dichloromethane
Me3Si
Me
EtOOC
COOEt
a
H
EtOOC COOEt
1a
a: NaH, THF, 0oC, 1 h then
CH2=C(TMS)CH2CHMeOTs, THF, rt, 44%
Me3Si Me
Me
a,b
N
O
SiMe3
1b
Boc
a: allylamine, AcOH, NaBH(OAc)3, 1,2-dichloroethane,
rt, 86%; b: (tBOC)2O, Et3N, DCM, rt, 94%
Me
Me
a
O
SiMe3
HO
SiMe3
1c
a: NaH, THF, 0oC, 1 h then CH2=CH-CH2Br, THF, rt, 97%
a
Ph
Ph
SiMe3
SiMe3
OH
OR
7
1d R = CH2CH=CH2
Herein, we have presented a brief survey of the
behaviour of ruthenium catalysts 2, 3 and 4 with the
silicon-containing substrates 1a–i. In addition to previ-
ous reports on metathesis reactions of silicon contain-
ing substrates where the silicon functionality served as a
temporary tethering group, our work has demonstrated
that the ring closing metathesis could be applied to the
preparation of a series of functionalised trimethylsilyl
substituted carbo- or heterocycles.16 These findings fur-
ther illustrate the high activity and functional group
compatibility of the catalyst 4 and significantly expand
the number of substrates that can participate in this
powerful reaction.
1e R = CH2C(Me)=CH2
a: NaH, THF, 0oC, 1 h then RBr or RI , THF, rt, 86-96%
Ph
a
Ph
SiMe3
SiMe3
1f
OH
O
O
a: CH2=CHCOCl, Et3N, DMAP cat, DCM, -15oC, 1 h, 61%
Me
Me
O
a
HO
SiMe3
O
SiMe3
1g
a: CH2=CHCOCl, Et3N, DMAP cat, DCM, -15oC, 1 h, 61%
a
Ph
Ph
SiMe3
Acknowledgements
SiMe3
O
1h n = 1
1i n = 2
OH
n
O
a: for 1h: CH2=CHCH2COCl, Et3N, DMAP cat, DCM,
-15oC, 1.5 h, 30 %; for 1i: CH2=CH(CH2)2COOH, DCC,
DCM, DMAP cat, 90%.
This work was supported by the European Community
Training and Mobility Research Programme (COS-
SAC, ERBFMRXCT 980193 to M.S.) and the ‘Minis-
te`re de la Culture, de l’Enseignement Supe´rieur et de la
Recherche’ of Luxembourg (BFR 01/018 to M.S.).
Scheme 2.

M. Schuman, V. Gou6erneur / Tetrahedron Letters 43 (2002) 3513–3516
Table 1. Results of the RCM of trimethylsilyl substituted dienes 1a–i
3515
yielda
mol % of 4
reaction time
Entry
1
Substrates
Products
Me
Me3Si
Me
98%
3 mol %
8 h
EtOOC
EtOOC
EtOOC COOEt
1a
SiMe3
8a
Me
93%
5 mol %
18 h
Me3Si
Me
Boc
2
3
N
N
Boc
SiMe3
Me
8b
1b
O
93%
3 mol %
3 h
O
SiMe3
Me
8c
8d
1c
SiMe3
O
Ph
Ph
Ph
90%
2 mol %
1 h
4
5
SiMe3
SiMe3
O
O
1d
SiMe3
O
O
Ph
Ph
83%
12 mol %
29 h
8e
SiMe3
1e
1f
6
7
Ph
O
86%
10 mol %
36 h
SiMe3
O
SiMe3
O
O
8f
O
O
79%
8 mol %
72 h
O
SiMe3
SiMe3
8g
1g
8h n = 1
87% E:Z = 73:27
4 mol %, 17 h
Ph
Me3Si
SiMe3
n
Ph
O
SiMe3
8
O
O
8i n = 2
84% E:Z = 66:34
6 mol %, 25 h
1h n =1
1i n = 2
O
O
O
n
n
Ph
a: isolated yields
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