Using a temporary silicon connection in a highly stereoselective synthesis of a new class of cyclic allenylsilanes

Article abstract of DOI:10.1055/s-2005-918465

Aldehyde 4 reacts in the presence of TMSOTf and an acid scavenger to provide the corresponding oxasilacycle 5 in very good yield and as a single diastereoisomer. The sense of 1,3-stereoinduction serves to introduce a 1,3-syn-diol relationship into the cyc

Full text of DOI:10.1055/s-2005-918465

PAPER
3389
Using a Temporary Silicon Connection in a Highly Stereoselective Synthesis of
a New Class of Cyclic Allenylsilanes
Synthesis of
a
N
e
u
w Class of
C
i
yclic Allenyl
R
silane
s
amalho,a Julien Beignet,a,1 Alexander C. Humphries,b Liam R. Cox*a
a
School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
Fax +44(121)4144403; E-mail: l.r.cox@bham.ac.uk
b
The Neuroscience Research Centre, Merck, Sharp & Dohme, Terlings Park, Harlow, Essex, CM20 2QR, UK
Received 9 September 2005
Dedicated to Professor Steven Ley on the occasion of his 60th birthday, with particular thanks from two members of the group, ACH
(1995–1998) and LRC (1994–1997)
that more subtle steric effects likely govern the 1,4-induc-
Abstract: Aldehyde 4 reacts in the presence of TMSOTf and an
tion.6
acid scavenger to provide the corresponding oxasilacycle 5 in very
good yield and as a single diastereoisomer. The sense of 1,3-ste-
reoinduction serves to introduce a 1,3-syn-diol relationship into the
cyclic product. This is in accord with a previous study involving an
analogous intramolecular allylation.
Acyclic dienes, 3, were also obtained as side-products in
these allylations. We believe that these products arise
through a cascade process initiated by premature cleavage
of the silyl ether tether in the collapse of the initially
formed carbocationic intermediate.7 This transformation
Key words: cyclisations, intramolecular allenylation, Lewis acids,
stereoselective synthesis, Temporary Silicon Connection
provides an acyclic allylsilane which then undergoes a vi-
nylogous silicon-mediated olefination8 to provide the ob-
served diene product.9
Forming a tether between two reacting partners allows a
Replacing the allylsilane nucleophile in our cyclisation
subsequent reaction to proceed in an intramolecular fash-
precursor with a propargylsilane would provide aldehyde
ion and benefit from the advantages associated with uni-
4. In analogy with the reaction of aldehyde 1, exposure of
molecular processes. However, if the tether is then
4 to a Lewis acid should effect an intramolecular allenyla-
cleaved, the product obtained is the result of a net inter-
tion to provide a novel oxasilacycle, 5, containing one
molecular reaction.2 We recently employed such a strate-
new stereogenic centre and an allenylsilane moiety, which
gy in the stereoselective allylation of a series of aldehydes
is ripe for further elaboration (Scheme 2).10 We reasoned
1, in which the carbinol centre provided the site for ap-
that such a reaction should be highly selective for a single
pending an allylsilane through its g-terminus (Scheme 1).3
stereoisomer since the formation of the allene moiety in 5
Aldehyde 1 reacted in the presence of TMSOTf and an
removes the issue of 1,4-stereoinduction, which had prov-
acid scavenger,4 providing the corresponding intramolec-
en to be only modest in our previous allylation study (see
ular allylation product, oxasilacycle 2, in good yield.
Scheme 1).3 This leaves just the issue of 1,3-induction to
While levels of 1,4-stereoinduction were modest and rath-
be considered. Since the factors governing the formation
er substrate-dependent, 1,3-induction was consistently ex-
of this new carbinol stereocentre should be the same as
cellent; thus of the four possible diastereoisomeric
those in our allylation study, a similar level and sense of
products, only two were ever observed. We postulate that
1,3-induction ought to be observed. Furthermore, since
the adoption of reactive conformations in which the di-
the silyl tether should be less efficient in stabilising the
poles across the polar C–O and C=O bonds are opposed,
positive charge in the oxasilacyclic intermediate 6,11 the
are responsible for the high levels of 1,3-induction,5 and
likelihood of premature tether collapse, resulting in the
3:1 to 9:1
Et Et
Et Et
Si
Et Et
Si
γ
Si
SiMe3
SiMe3
TMSOTf,
acid scavenger
O
O
O
O
α
CHO
R
R
OTMS
R
CH2Cl2, –78 °C
1
3
2
single
side-product
configuration
Scheme 1 Reaction of an allylsilane tethered through a silyl ether to a b-hydroxy aldehyde provides a stereoselective route to a novel series
of oxasilacycles.
SYNTHESIS 2005, No. 19, pp 3389–3397
x
x.
x
x
.
2
0
0
5
Advanced online publication: 14.11.2005
DOI: 10.1055/s-2005-918465; Art ID: C06605SS
© Georg Thieme Verlag Stuttgart · New York

3390
R. Ramalho et al.
PAPER
Et Et
Si
Et Et
predicted
stereochemistry
Si
O
·
O
intramolecular
allenylation
R
R
OTMS
SiMe3
4
5
?
CHO
TMSOTf
Nu
SiMe3
Nu
SiMe3
OSi OTMS
O
cyclisation
Si
O
O
Si
R
R
x
R
6
7
O
TMS
TMS
SiMe3
Scheme 2 A tethered propargylsilane should cyclise to provide a stereodefined allenylsilane product with high selectivity.
formation of an acyclic propargylsilane product 7, should We were then ready to investigate the intramolecular alle-
also be reduced (Scheme 2). Propargylsilanes have re- nylation. Previous work employing allylsilanes had re-
ceived far less attention than their allylsilane conge- vealed the extreme sensitivity of this type of reaction to
ners.12,13 We now report an extension of their synthetic the Lewis acid employed.3 TMSOTf had provided the best
utility to the synthesis of the chiral, cyclic allenylsilanes 5. results when used in conjunction with an acid scavenger4
to remove adventitious triflic acid. Thus we were delight-
ed to find that treating a solution of aldehyde 4 in CH2Cl2
We first required a synthesis of a g-silyl-substituted pro-
pargylsilane possessing suitable functionality at the g-ter-
at –78 °C, with an equimolar quantity of TMSOTf and a
minus to allow the formation of the Temporary Silicon
slight excess (1.2 equiv) of either 2,6-di-tert-butyl-4-
Connection in our cyclisation precursor. Encouraged by
our previous success using aminosilanes as silyl etherifi-
methylpyridine (2,6-DTBMP) or tri-tert-butylpyrimidine
(TTBP)18 [both were equally effective acid scavengers al-
cation reagents in our allylsilane work,3,7 we chose to in-
though the latter was preferred (see below)], provided the
vestigate a similar strategy with this new class of
desired cyclisation product 5 in good to very good isolated
nucleophile. Our first target was therefore g-aminosilyl-
substituted propargylsilane 9, which was readily prepared
in two steps (Scheme 3): reaction of propargyl magnesium
yield (Table 1). The reaction also proved to be highly ste-
reoselective: analysis of the crude reaction mixture by
NMR spectroscopy revealed the presence of only one dia-
bromide, readily prepared from propargyl bromide and
stereoisomer in every case. We therefore conservatively
Mg in the presence of HgCl2, with TMSCl, provided pro-
estimate the diastereoselectivity of this allenylation to be
pargyltrimethylsilane 8 along with a small amount (~5%)
>95%. Products resulting from premature cleavage of the
Temporary Silicon Connection were also not observed,
even with aldehyde 4i, which had been particularly prone
of allenyltrimethylsilane;14,15 subsequent generation of
the lithium acetylide of 8 with n-BuLi and trapping in situ
with diethyl(diethylamino)chlorosilane7,16 afforded 9 in
to following this reaction pathway in the analogous in-
very good yield. As expected, reaction of this silylating
tramolecular allylation.3
agent with a range of b-hydroxy esters17 proceeded un-
eventfully to provide the corresponding silyl ethers 10, Since we had employed TMSOTf as the Lewis acid in the
and thence the aldehyde cyclisation precursors 4 after re- presence of an acid scavenger, products in which the gen-
duction of the ester functionality in 10 with DIBAL-H erated alcohol is protected as its TMS ether were obtained.
(Scheme 3).
The high level of substitution around the ring clearly pro-
OH
O
R
OEt
b
a
Br
Me3Si
Me3Si
c
8
9
SiEt2(NEt2)
Et Et
Et Et
Si
Si
O
O
d
SiMe3
SiMe3
R
R
4
10
CO2Et
CHO
Scheme 3 Reagents and conditions: a) Mg, HgCl2 (2 mol%), Et2O, r.t., 1 h then Me3SiCl, 0 °C to r.t., 2 h (48%); b) n-BuLi, THF, –78 °C to
–50 °C, 1 h, then Et2Si(NEt2)Cl, –78 °C to r.t., 1 d (88%); c) imidazole, DMAP, CH2Cl2, r.t., 18 h (57–91%); d) DIBAL-H, –78 °C, CH2Cl2,
1 h (40–95%).
Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York

PAPER
Synthesis of a New Class of Cyclic Allenylsilanes
3391
Table 1 TMSOTf-Mediated Allenylation of Aldehyde 4 Provided a
Single Diastereoisomeric Oxasilacyclic Product 5a
lanes had shown that Brønsted acids rapidly cleaved the
silyl ether tether or led exclusively to diene products.21
Since elimination pathways were not a problem in the
present study, we replaced the Lewis acid activator with a
Brønsted acid and did away with the base altogether. Re-
action of aldehyde 4f with methanesulfonic acid resulted
in the rapid (5 min) consumption of starting material at
–78 °C and concomitant formation of the oxasilacycle 11
in an encouraging 65% yield (Scheme 4).
Et Et
Si
Et Et
Si
·
O
O
a
SiMe3
R
R
OTMS
4a–i
5a–i
CHO
Aldehyde 4
R
Yield of 5 (%)b
a
b
c
d
e
f
Ph
80
72
73
85
68
83
66
70
67
Et Et
Si
Et Et
Si
2-furyl
·
O
O
SiMe3
MeSO3H
(E)-cinnamyl
TIPS-C≡C
cyclohexyl
s-Bu
OH
CH2Cl2, –78 °C
5 min, 65%
4f CHO
11
Scheme 4 Brønsted acid mediated cyclisation provides an alcohol
product.
g
h
i
n-Bu
We provisionally assigned the sense of 1,3-induction in 5
by analogy with that observed in our allylation study.3
However, we were keen to confirm the result indepen-
dently. Since NMR studies, including NOE experiments,
on the cyclisation products proved inconclusive, we chose
to remove the tether and investigate the ring-opened pro-
todesilylated product. Reaction of 5a with KF in a
MeOH–THF solvent mix at 60 °C effected clean
protodesilylation22 and the formation of two diol products
12 and 13, with the allene 13 resulting from ipso protode-
silylation accounting for the major product (Scheme 5).
Exposure of this diol mixture to acetone in the presence of
PTSA and Na2SO4 provided the corresponding acetonides
14 and 15. In accordance with Rychnovsky’s observa-
tions,23 analysis of the 13C NMR spectra of 14 and 15 al-
lowed the assignment of a 1,3-syn diol relationship in both
products, thus confirming the stereochemical outcome
that we had predicted based on our previous results. Fur-
ther corroboration was achieved by NOE experiments
(Scheme 5).
BnOCH2CH2
Me
a Reagents and conditions: TMSOTf, 2,6-DTBMP or TTBP, CH2Cl2,
–78 °C, 18 h.
b Isolated yield of 5 following purification by column chromatogra-
phy.
tects this potentially labile silyl protecting group, which
survived a standard aqueous work-up and product purifi-
cation by flash column chromatography on silica gel.
However, the very low polarity of the oxasilacycles called
for care in separating the desired product from the non-po-
lar acid scavengers, especially 2,6-DTBMP (relative po-
larity: TTBP > 2,6-DTBMP ~ 5). Since all attempts to
deprotect the TMS ether selectively led to product decom-
position, we investigated a number of modifications to our
method that might improve matters:
1) A polymer-supported acid scavenger would allow its
facile separation from the allene product by filtration, as
well as permit its potential reuse after regeneration of the
free base.19 Polymer-supported 2,6-DTBMP20 is commer-
cially available, albeit expensive. However in our hands,
its use led to inferior results compared with its organic-
soluble analogue.
In summary, we have shown that forming a ‘Temporary
Silicon Connection’ between a propargylsilane and a b-
hydroxyaldehyde allows a highly stereoselective intramo-
lecular allenylation to take place in the presence of TM-
SOTf and an acid scavenger. The reaction is general for a
wide range of aldehydes and provides a single stereoiso-
meric product in good to excellent yield. Preliminary re-
sults suggest that Brønsted acids might also be able to
effect this cyclisation. Optimisation of this process, to-
gether with the development of novel ways in which to
elaborate the allene products, are the focus of ongoing and
future studies.
2) Theoretically, it should be possible to employ the
Lewis acid in sub-stoichiometric quantities as the ‘TMS+’
activator should be regenerated after each cyclisation.
This in turn would allow the use of reduced quantities of
the acid scavenger, and again facilitate the purification
step. However when aldehyde 4a was treated with 20
mol% TMSOTf in the presence of 50 mol% 2,6-DTBMP,
the reaction failed to go to completion; indeed complete
conversion could only be achieved with stoichiometric
quantities of Lewis acid.
Elemental analyses were recorded on a Carlo Erba EA1110 simul-
taneous CHNS analyser. IR spectra were recorded neat as thin films
on a Perkin-Elmer FT-IR PARAGON 1000 or a Spectrum 1000
spectrometer. 1H NMR spectra were recorded at ambient tempera-
ture unless stated otherwise on a Bruker AC-300 (300 MHz), AMX
400 (400 MHz), DRX-500 (500 MHz) or DPX-500 (500 MHz)
spectrometer. The term ‘stack’ is used to describe a region where
3) The reason for using an acid scavenger in the first place
had been to remove adventitious triflic acid from the reac-
tion mixture, as our work with the corresponding allylsi-
Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York

3392
R. Ramalho et al.
PAPER
Et Et
Si
·
a
OH OH
1 : 3
O
OH OH
·
Ph
Ph
OTMS
Ph
5a
12
13
b
NOE
NOE
δ
C 19.5
C 30.3
C 99.5
δ
C 19.7
H
H
H
H
Ph
Ph
O
O
δ
δC 30.3
O
O
δ
δC 99.7
·
14
15
Scheme 5 Reagents and conditions: a) KF, KHCO3, THF–MeOH, 70 °C, 1.5 h, 76%; b) acetone, PTSA, Na2SO4, quant.
resonances arising from non-equivalent nuclei are coincident. ‘Mul-
tiplet’, m, is used to describe a region where a resonance arises from
a single nucleus (or equivalent nuclei) but where coupling constants
cannot be assigned. Residual protic solvent CHCl3 (dH = 7.26) was
used as an internal reference. 13C NMR spectra were recorded at
ambient temperature unless stated otherwise on a Bruker AC-300
(75 MHz), AV-300 (75 MHz), DPX-360 (90 MHz), AMX-400 (100
MHz) or DRX-500 (125 MHz) spectrometer. The central resonance
of CDCl3 (dC = 77.0) was used as an internal reference. Unit mass
resolution mass spectra were recorded on a Micromass LCT spec-
trometer (TOF-ES+), or a Micromass ZMD spectrometer. HRMS
were recorded on a Micromass LCT spectrometer or a Micromass
Micro QToF spectrometer, using a lock mass incorporated into the
mobile phase. All reagents were obtained from commercial sources
and used without further purification unless stated otherwise. Pro-
pargyltrimethylsilane was prepared according to a literature
procedure14 and purified by reduced pressure distillation (106
mbar). The distillate comprised a 55:37:5:3 mixture of propargyl-
trimethylsilane:toluene:Et2O:allenyltrimethylsilane (as determined
by 1H NMR) which was used without further purification (note: pro-
pargyl bromide was purchased as a solution in toluene). THF and
Et2O were distilled from sodium benzophenone ketyl. All solutions
are aqueous and saturated, unless otherwise stated. All reactions
were conducted in flame-dried glassware under N2, and at ambient
temperature (19 to 25 °C) unless otherwise stated, with magnetic
stirring. Volumes of 1 mL or less were measured and dispensed with
Hamilton gastight syringes. Flash column chromatography was car-
ried out using Fluka 60 (40–60 mm mesh) or BDH (33–70 mm mesh)
silica gel. Analytical TLC was performed on Whatman or Fluka 60
Å 0.25 mm pre-coated glass-backed plates and visualised by UV
(254 nm), KMnO4 solution and (NH4)2MoO4/Ce(SO4)2 solution.
Evaporation and concentration under reduced pressure were per-
formed at 50–500 mbar. Residual solvent was removed under high
vacuum (1 mbar).
fitted with an oven-dry Whatman filter paper 1. Concentration of
the solution under reduced pressure (400 mbar) afforded a red-or-
ange liquid, which was rapidly transferred to a 50-mL round-bot-
tomed flask. Purification by reduced pressure distillation afforded
propargyl silane 9 as a colourless liquid (12.5 g, 88%); bp 128 °C/
49 mbar. The moisture sensitivity of this compound precluded full
characterisation.
IR (film): 2958s, 2874s, 2154s (C≡C), 1461m, 1413m, 1374s,
1342m, 1292m, 1250s, 1233m, 1204s, 1174s, 1148m, 1029s, 1007s,
923m, 852s, 761s, 726s cm–1.
1H NMR (300 MHz, C6D6): d = 0.09 [s, 9 H, Si(CH3)3], 0.76 [q,
J = 7.7, 4 H, Si(CH2CH3)2], 1.09 [t, J = 7.0, 6 H, N(CH2CH3)2], 1.20
[t, J = 7.7, 6 H, Si(CH2CH3)2], 1.46 (s, 2 H, C≡CCH2), 2.96 [q,
J = 7.0, 4 H, N(CH2CH3)2].
13C NMR (75 MHz, C6D6): d = –2.2 [Si(CH3)3], 7.4 [Si(CH2CH3)2],
7.7 [Si(CH2CH3)2], 8.8 (C≡CCH2), 15.9 [N(CH2CH3)2], 40.4
[N(CH2CH3)2], 81.0 (C≡C), 105.4 (C≡C).
Silyletherification of b-Hydroxy Esters to Silyl Ethers 10;
General Procedure
A solution of the b-hydroxy ester (2.5 mmol) in CH2Cl2 (25 mL)
was added to a flask charged with aminosilane 9 (2.5 mmol), imida-
zole (5.1 mmol) and DMAP (5 mol%). The reaction was stirred
overnight at r.t., and after approximately 18 h, quenched by the ad-
dition of NaHCO3 solution (20 mL). The mixture was extracted
with CH2Cl2 (2 × 20 mL). The combined organic extracts were
washed with brine (20 mL) and dried (MgSO4). Removal of the sol-
vent under reduced pressure and purification by flash column chro-
matography (eluent: hexane–Et2O) afforded silyl ether 10 as a
colourless oil (Table 2).
Reduction of Esters 10 to Aldehydes 4; General Procedure
DIBAL-H (1.5 mmoL, 1.5 M in toluene) was added dropwise over
5 min to a solution of ester 10 (1.2 mmol) in CH2Cl2 (12 mL) at
–78 °C. The progress of the reaction was monitored by TLC. Upon
consumption of starting material (generally 1 h), the reaction was
quenched by the dropwise addition of MeOH (1.2 mmol) and then
dropwise addition of H2O (6.0 mmol). The resulting slurry was
warmed to r.t. and then filtered through a pad of MgSO4 and Celite,
and washed with CH2Cl2 (4 × 25 mL). Concentration of the filtrate
under reduced pressure and purification of the residue by flash col-
umn chromatography (eluent: hexane–Et2O) afforded aldehyde 4 as
a colourless oil (Table 3).
3-[Diethyl(diethylamino)silyl]propargyltrimethylsilane (9)
n-BuLi (24 mL, 58 mmol, 2.4 M in hexane) was added dropwise
over 30 min to a solution of propargyltrimethylsilane (53 mmol,
prepared as a solution in Et2O and toluene) in THF (106 mL) at
–78 °C. The mixture was stirred at this temperature for 1 h and then
at –50 °C for 30 min, before re-cooling to –78 °C. Diethyl(diethyl-
amino)chlorosilane (10.2 mL, 53 mmol) was then added dropwise
over 15 min. The mixture was allowed to warm to r.t. over 12 h and
then stirred for a further 12 h. The solution was transferred to a dry
flask and separated from the precipitated LiCl salts using a cannula
Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York

PAPER
Synthesis of a New Class of Cyclic Allenylsilanes
3393
Table 2 Characterisation Data for Esters 10
10a,b
1H NMR (CDCl3)
d, J (Hz)
13C NMR (CDCl3)
d
TOF-MSm/z Yield (%)
(%)
a
0.09 [s, 9 H, Si(CH3)3], 0.42 (q, J = 7.7, 2 H, SiCH2CH3), 0.58 (q, J = 7.7, 2 H, –2.1, 6.6 (2 ×), 6.8, 413.1 (100)
SiCH2CH3), 0.80 (t, J = 7.7, 3 H, SiCH2CH3), 0.95 (t, J = 7.7, 3 H, SiCH2CH3), 7.1, 8.7, 14.1, 45.8,
1.21 (t, J = 7.5, 3 H, OCH2CH3), 1.54 (s, 2 H, CH2TMS), 2.61 (dd, J = 14.6, 5.3, 60.3, 72.4, 78.8,
91
1 H, CHaHbCO), 2.80 (dd, J = 14.6, 8.4, 1 H, CHaHbCO), 4.02–4.28 (m, 2 H,
OCH2CH3), 5.32 (dd, J = 8.4, 5.3, 1 H, CHOSi), 7.19–7.40 (stack, 5 H, C6H5)
107.4, 126.0, 127.4,
128.1, 143.6, 170.8
b
c
0.11 [s, 9 H, Si(CH3)3], 0.42–0.72 [stack, 4 H, Si(CH2CH3)2], 0.83 (t, J = 7.9, 3 –2.2, 6.3, 6.5, 6.6,
H, CH2CH3), 0.95 (t, J = 8.0, 3 H, CH2CH3), 1.22 (t, J = 7.3, 3 H, OCH2CH3), 7.0, 8.7, 14.1, 41.8,
403.1 (100)
86
1.58 (s, 2 H, CH2TMS), 2.79 (dd, J = 15.1, 6.2, 1 H, CHaHbCO), 2.91 (dd,
60.3, 65.7, 78.4,
J = 15.1, 7.8, 1 H, CHaHbCO), 4.02–4.18 (m, 2 H, OCH2CH3), 5.36 (dd, J = 7.8, 106.4, 107.6, 110.0,
6.2, 1 H, CHOSi), 6.24 (d, J = 2.9, 1 Hfuryl), 6.28 (dd, J = 2.9, 1.8, 1 Hfuryl), 7.31– 141.7, 155.7, 170.3
7.35 (m, 1 Hfuryl
)
0.10 [s, 9 H, Si(CH3)3], 0.58–0.69 [stack, 4 H, Si(CH2CH3)2], 0.98 [t, J = 7.7, 6 –2.2, 6.60, 6.64, 6.8, 439.3 (100)
H, Si(CH2CH3)2], 1.24 (t, J = 7.0, 3 H, OCH2CH3), 1.56 (s, 2 H, CH2TMS), 2.50 7.3, 8.7, 14.2, 43.6,
70
(dd, J = 14.4, 6.4, 1 H, CHaHbCO), 2.71 (dd, J = 14.4, 7.4, 1 H, CHaHbCO),
4.07–4.19 (m, 2 H, OCH2CH3), 4.93 (app q, J = 6.3, 1 H, CHOSi), 6.23 (dd,
60.3, 71.0, 79.0,
107.4, 126.5, 127.4,
J = 15.9, 6.6, 1 H, =CHCHO), 6.60 (d, J = 15.9, 1 H, PhCH=), 7.19–7.39 (stack, 128.4, 130.1, 131.1,
5 H, C6H5) 136.8, 170.7
d
e
0.01 [s, 9 H, Si(CH3)3], 0.56–0.74 [stack, 4 H, Si(CH2CH3)2], 0.93–0.99 [stack, –2.1, 6.5, 6.6, 6.8,
517.3 (100), 57
6 H, Si(CH2CH3)2], 1.04 {s, 21 H, Si[CH(CH3)2]3}, 1.25 (t, J = 7.4, 3 H,
OCH2CH3), 1.55 (s, 2 H, CH2TMS), 2.68 (dd, J = 14.9, 6.2, 1 H, CHaHbCO),
2.78 (dd, J = 14.9, 7.7, 1 H, CHaHbCO), 4.08–4.17 (m, 2 H, OCH2CH3), 5.03
(dd, J = 7.7, 6.2, 1 H, CHOSi)
7.2, 8.7, 11.1, 14.1, 383.3 (10)
18.4, 44.2, 60.4,
60.7, 78.2, 85.1,
107.5, 107.9, 169.8
0.12 [s, 9 H, Si(CH3)3], 0.55–0.66 [stack, 4 H, Si(CH2CH3)2], 0.88–1.30 [stack, –2.1, 6.7, 6.8, 7.0,
14 H, Si(CH2CH3)2, 5 × CyH, OCH2CH3], 1.42–1.80 (stack, 8 H, 6 × CyH, 7.2, 8.8, 14.2, 26.3,
CH2TMS), 2.39–2.54 (stack, 2 H, CH2CO2Et), 3.97–4.15 (stack, 3 H, CHOSi, 26.4, 26.6, 28.1,
439.3 (100)
67
89
OCH2CH3)
28.5, 39.6, 43.6,
60.2, 74.2, 79.5,
106.9, 172.3
f
0.11 [s, 9 H, Si(CH3)3], 0.62 [q, J = 7.7, 4 H, Si(CH2CH3)2], 0.90 [d, J = 6.6, 3 –2.1, 6.7 (2 ×), 7.12, 393.1 (100)
H, 1 × CH(CH3)2], 0.92 [d, J = 6.2, 3 H, 1 × CH(CH3)2], 0.97 [t, J = 7.7, 6 H,
Si(CH2CH3)2], 1.25 (t, J = 7.2, 3 H, OCH2CH3), 1.44–1.60 (stack, 4 H,
7.14, 8.8, 14.2, 22.3,
23.3, 24.4, 43.1,
CH2TMS, i-PrCH2), 1.65–1.79 [m, 1 H, CH(CH3)2], 2.42 (dd, J = 14.7, 6.6, 1 H, 46.6, 60.1, 68.6,
CHaHbCO), 2.57 (dd, J = 14.7, 6.3, 1 H, CHaHbCO), 4.06–4.19 (m, 2 H,
CH2CH3), 4.28–4.38 (m, 1 H, CHOSi)
79.3, 107.2, 171.5
g
0.11 [s, 9 H, Si(CH3)3], 0.59 [q, J = 7.7, 4 H, Si(CH2CH3)2], 0.82–1.01 [stack, 9 –1.2, 6.6 (2 ×), 6.9, 393.2 (100)
H, Si(CH2CH3)2, CH3], 1.18–1.38 (stack, 7 H, OCH2CH3, 2 × CH2), 1.47–1.60 7.1, 8.6, 14.1, 14.2,
(stack, 4 H, CH2TMS, CH2), 2.42 (dd, J = 14.7, 6.3, 1 H, CHaHbCO), 2.57 (dd, 22.6, 27.3, 36.8,
J = 14.7, 7.0, 1 H, CHaHbCO), 4.11 (q, J = 7.0, 2 H, OCH2CH3), 4.25 (app quin- 42.5, 60.4, 70.1,
91
66
tet, J = 6.2, 1 H, CHOSi)
79.2, 107.0, 171.5
h
0.08 [s, 9 H, Si(CH3)3], 0.52–0.62 [stack, 4 H, Si(CH2CH3)2], 0.91–0.96 [stack, –2.2, 6.53, 6.56, 6.8, 471.1 (100)
6 H, Si(CH2CH3)2], 1.25 (t, J = 7.0, 3 H, OCH2CH3), 1.53 (s, 2 H, CH2TMS), 6.9, 8.6, 14.1, 36.9,
1.81–1.89 (stack, 2 H, BnOCH2CH2), 2.48 (dd, J = 14.7, 6.2, 1 H, CHaHbCO), 42.6, 60.0, 66.7,
2.58 (dd, J = 14.7, 6.6, 1 H, CHaHbCO), 3.56 (t, J = 6.6, 2 H, BnOCH2), 4.05– 67.6, 72.7, 79.1,
4.12 (stack, 2 H, OCH2CH3), 4.37–4.51 (stack, 3 H, CHOSi, PhCH2), 7.23–7.31 107.1, 127.2, 127.4,
(stack, 5 H, C6H5)
128.1, 138.5, 171.1
i
0.11 [s, 9 H, Si(CH3)3], 0.59 [q, J = 7.5, 4 H, Si(CH2CH3)2], 0.96 [t, J = 7.5, 6
H, Si(CH2CH3)2], 1.23–1.28 (stack, 6 H, CH3, OCH2CH3), 1.58 (s, 2 H,
–2.7, 6.1 (2 ×), 6.4, 351.2 (100)
6.7, 8.2, 13.7, 23.1,
78
CH2TMS), 2.38 (dd, J = 14.4, 6.3, 1 H, CHaHbCO), 2.58 (dd, J = 14.4, 7.0, 1 H, 44.3, 59.9, 66.3,
CHaHbCO), 4.06–4.15 (m, 2 H, OCH2CH3), 4.36–4.47 (m, 1 H, CHOSi) 79.1, 107.1, 171.8
a Satisfactory microanalyses obtained for 10a–g: C 0.42, H 0.41.
10h: HRMS: m/z [(M + Na)+] calcd for C24H40O4Si2 + Na: 471.2363; found: 471.2367.
10i: HRMS: m/z [(M + Na)+] calcd for C16H32O3Si2 + Na: 351.1788; found: 351.1784.
b All compounds showed the characteristic peaks for acetylenic and carbonyl bonds. IR (film): 2154s (C≡C), 1740s cm–1 (C=O).
Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York

3394
R. Ramalho et al.
PAPER
Table 3 Characterisation Data for Aldehydes 4
4a
a
1H NMR (CDCl3, 300 MHz)
d, J (Hz)
13C NMR (CDCl3, 75 TOF-MS m/z
HRMS
Yield
(%)
MHz), d
(%)
0.10 [s, 9 H, Si(CH3)3], 0.42 (q, J = 8.1, 2 H, CH2CH3),
0.57–0.66 (m, 2 H, CH2CH3), 0.78 (t, J = 8.1, 3 H,
CH2CH3), 0.97 (t, J = 7.7, 3 H, CH2CH3), 1.56 (s, 2 H,
–2.1, 6.3, 6.4, 6.7,
7.1, 8.7, 53.4, 71.0,
78.5, 108.1, 125.7,
401.2 [100,
(M + Na +
MeOH)+],
m/z [(M + Na +
MeOH)+] calcd
for C19H30O2Si2 +
95
CH2TMS), 2.68 (ddd, J = 15.8, 4.4, 2.2, 1 H, CHaHb), 2.83 127.5, 128.3, 143.3, 369.2 (15, M+) Na + MeOH:
(ddd, J = 15.8, 8.1, 2.9, 1 H, CHaHb), 5.42 (dd, J = 8.1, 4.4, 201.6
1 H, CHOSi), 7.25–7.34 (stack, 5 H, C6H5), 9.81 (app t,
J = 2.5, 1 H, CHO)
401.1944; found:
401.1953
b
c
0.12 [s, 9 H, Si(CH3)3], 0.47–0.67 [stack, 4 H,
Si(CH2CH3)2], 0.86 (t, J = 7.9, 3 H, CH2CH3), 0.97 (t,
J = 7.9, 3 H, CH2CH3), 1.60 (s, 2 H, CH2TMS), 2.82 (ddd, 78.3, 106.7, 108.3,
J = 16.2, 5.3, 2.4, 1 H, CHaHb), 2.96 (ddd, J = 16.2, 7.3,
2.6, 1 H, CHaHb), 5.43 (dd, J = 7.3, 5.3, 1 H, CHOSi),
6.24–6.26 (m, 1 Hfuryl), 6.30–6.32 (m, 1 Hfuryl), 7.35–7.36
(m, 1 Hfuryl), 9.83 (app t, J = 2.4, 1 H, CHO)
–2.2, 6.3, 6.4, 6.6,
7.0, 8.7, 49.5, 64.4,
359.0 (100)
m/z [(M + Na)+]
calcd for
C17H28O3Si2 + Na:
359.1475; found:
359.1481
40
67
110.1, 141.9, 154.9,
200.8
0.10 [s, 9 H, Si(CH3)3], 0.59–0.71 [stack, 4 H,
Si(CH2CH3)2], 0.93–1.02 [stack, 6 H, Si(CH2CH3)2], 1.58 7.3, 8.7, 51.3, 69.6,
(s, 2 H, CH2TMS), 2.60–2.77 (stack, 2 H, CH2CHO), 5.03 78.7, 108.1, 126.5,
(app q, J = 6.1, 1 H, CHOSi), 6.24 (dd, J = 15.8, 6.2, 1
H, =CHCHOSi), 6.62 (d, J = 15.8, 1 H, PhCH=), 7.21–
7.38 (stack, 5 H, C6H5), 9.84 (app. t, J = 2.2, 1 H, CHO)
–2.1, 6.61, 6.64, 6.8, 427.3 [100,
m/z [(M + Na)+]
calcd for
C21H32O2Si2 + Na:
395.1839; found:
395.1837
(M + Na +
MeOH)+],
127.7, 128.5, 130.2, 395.3 (18)
131.0, 136.5, 201.6
d
e
0.11 [s, 9 H, Si(CH3)3], 0.57–0.75 [stack, 4 H,
Si(CH2CH3)2], 0.83–0.99 {stack, 27 H, Si(CH2CH3)2,
Si[CH(CH3)2]3}, 1.58 (s, 2 H, CH2TMS), 2.63–2.80 (stack, 51.3, 59.2, 78.1,
2 H, CH2CHO), 5.07 (app t, J = 5.9, 1 H, CHOSi), 9.86
(app t, J = 2.2, 1 H, CHO)
–2.1, 6.5, 6.66, 6.74, 473.4 (100)
7.2, 8.8, 11.1, 18.5,
m/z [(M + Na)+]
calcd for
C24H46O2Si3 + Na:
473.2703; found:
473.2704
90
56
86.6, 107.0, 108.4,
200.8
0.11 [s, 9 H, Si(CH3)3], 0.56–0.66 [stack, 4 H,
–2.2, 6.55, 6.59, 7.0, 407.3 [85,
m/z [(M + Na)+]
calcd for
C19H36O2Si2 + Na:
375.2152; found:
375.2166
Si(CH2CH3)2], 0.93–1.00 [stack, 8 H, Si(CH2CH3)2 + 2 × 7.1, 8.6, 26.1 (2 ×),
CyH], 1.07-1.23 (stack, 3 H, 3 × CyH), 1.43–1.76 (stack, 8 26.4, 28.1, 28.6,
H, 6 × CyH, CH2TMS), 2.52–2.55 (stack, 2 H, CH2CHO), 43.8, 47.7, 72.9,
4.16 (app q, J = 5.8, 1 H, CHOSi), 9.83 (app t, J = 2.6, 1 H, 79.0, 107.6, 202.4
CHO)
(M + Na +
MeOH)+],
375.3 (100)
f
0.11 [s, 9 H, Si(CH3)3], 0.57–0.66 [stack, 4 H,
–2.1, 6.6 (2 ×), 7.1,
7.2, 8.7, 22.5, 23.0,
24.4, 46.8, 51.1,
67.4, 79.0, 107.9,
202.4
381.0 [100,
(M + Na +
MeOH)+],
349.0 (75)
m/z [(M + Na)+]
calcd for
C17H34O2Si2 + Na:
349.1995; found:
349.2000
92
47
90
94
Si(CH2CH3)2], 0.89–1.00 [stack, 12 H, Si(CH2CH3)2,
CH(CH3)2], 1.25–1.34 (m, 1 H, i-PrCHaHb), 1.54–1.58
(stack, 3 H, i-PrCHaHb, CH2TMS), 1.65–1.73 [m, 1 H,
CH(CH3)2], 2.48–2.62 (stack, 2 H, CH2CHO), 4.39–4.50
(m, 1 H, CHOSi), 9.84 (app t, J = 2.2, 1 H, CHO)
g
h
i
0.11 [s, 9 H, Si(CH3)3], 0.56–0.65 [stack, 4 H,
–2.2, 6.51, 6.53, 6.9, 381.3 [65,
m/z [(M + Na)+]
calcd for
C17H34O2Si2 + Na:
349.1995; found:
349.1996
Si(CH2CH3)2], 0.86–0.91 (m, 3 H, CH3), 0.91–1.00 [stack, 7.1, 8.5, 13.9, 22.5,
6 H, Si(CH2CH3)2], 1.25–1.34 (stack, 4 H, 2 × CH2), 1.54– 27.3, 37.2, 50.6,
1.60 (stack, 4 H, CH2, CH2TMS), 2.52–2.57 (stack, 2 H,
CH2CHO), 4.35 (app quintet, J = 6.1, 1 H, CHOSi), 9.84 202.1
(app t, J = 2.2, 1 H, CHO)
(M + Na +
MeOH)+],
349.3 (100)
69.0, 78.9, 107.6,
0.10 [s, 9 H, Si(CH3)3], 0.42 [q, J = 7.6, 4 H,
Si(CH2CH3)2], 0.96 [t, J = 7.7, 6 H, Si(CH2CH3)2], 1.56 (s, 7.0, 8.6, 37.3, 50.8,
2 H, CH2TMS), 1.81–1.95 (stack, 2 H, BnOCH2CH2),
2.52–2.70 (stack, 2 H, CH2CHO), 3.56 (t, J = 6.0, 2 H,
BnOCH2), 4.43–4.59 (stack, 3 H, CHOSi + PhCH2), 7.25– 127.5, 128.2, 138.3,
–2.1, 6.56, 6.60, 6.9, 459.4 [100,
m/z [(M + Na)+]
calcd for
C22H36O3Si2 + Na
427.2101; found:
427.2112
(M + Na +
MeOH)+],
427.3 (90)
66.42, 66.45, 72.9,
78.9, 107.9, 127.4,
7.36 (stack, 5 H, C6H5), 9.81 (app t, J = 2.2, 1 H, CHO)
202.0
0.11 [s, 9 H, Si(CH3)3], 0.55–0.74 [stack, 4 H,
Si(CH2CH3)2], 0.96 (t, J = 8.1, 3 H, CH2CH3), 0.97 (t,
–2.1, 6.6 (2 ×), 6.8,
7.3, 8.7, 23.8, 52.7,
339.3 [45, (M + m/z [(M + Na)+]
Na+MeOH)+], calcd for
J = 7.7, 3 H, CH2CH3), 1.26 (d, J = 6.2, 3 H, CH3), 1.58 (s, 65.2, 78.9, 107.6,
307.3 (100)
C14H28O2Si2 + Na:
307.1526; found:
307.1535
2 H, CH2TMS), 2.43–2.61 (stack, 2 H, CH2CHO), 4.46–
4.54 (m, 1 H, CHOSi), 9.80 (app t, J = 2.2, 1 H, CHO)
202.3
a All compounds showed the characteristic peaks for acetylenic and carbonyl bonds. IR (film): 2152s (C≡C), 1728s cm–1 (C=O).
Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York

PAPER
Synthesis of a New Class of Cyclic Allenylsilanes
3395
Intramolecular Allenylation of Aldehydes 4; General Proce-
dure
extracts were washed with brine (25 mL) and dried (MgSO4). Re-
moval of the solvent under reduced pressure and purification of the
residue by flash column chromatography (eluent: hexane–Et2O) af-
forded the allene 5 as a colourless oil (Table 4).
TMSOTf (2.0 mmol) was added dropwise over 5 min to a solution
of aldehyde 4 (2.0 mmol) and 2,6-DTBMP or TTBP (2.4 mmol) in
CH2Cl2 (24 mL) at –78 °C. The mixture was stirred at –78 °C and
monitored by TLC. After approximately 18 h, NaHCO3 solution (15
mL) was added and the solution allowed to warm to r.t. The mixture
was extracted with CH2Cl2 (2 × 30 mL) and the combined organic
Table 4 Characterisation Data for Allenes 5
5a
1H NMR (CDCl3, 300 MHz)
d, J (Hz)
13C NMR (CDCl3, TOF-MS
HRMS
Yield
(%)
75 MHz), d
m/z (%)
a
0.13 [s, 9 H, Si(CH3)3], 0.71–0.86 [stack, 4 H,
Si(CH2CH3)2], 0.96–1.08 [stack, 6 H, Si(CH2CH3)2], 1.73– 7.7, 46.5, 68.8,
1.82 (m, 1 H, CHaHb), 1.87–1.94 (m, 1 H, CHaHb), 4.37–
4.39 (stack, 2 H, =CH2), 4.64–4.65 (m, 1 H, CHOTMS),
5.35 (dd, J = 11.0, 1.8, 1 H, PhCHO), 7.21–7.36 (stack, 5 H, 128.2, 145.3,
0.2, 5.4, 6.4, 6.5,
369.2 (100)
m/z [(M + Na)+]
calcd for
C19H30O2Si2 +
Na: 369.1682;
found: 369.1689
80
72
73
69.9, 71.5, 91.6,
125.4, 126.9,
C6H5)
207.7
b
c
0.11 [s, 9 H, Si(CH3)3], 0.64–0.75 (stack, 2 H, CH2CH3),
0.75–0.80 (stack, 2 H, CH2CH3), 0.95–1.04 [stack, 6 H,
Si(CH2CH3)2], 1.96–2.04 (stack, 2 H, CH2), 4.42 (s, 2
0.1, 5.5, 6.32,
6.45, 7.6, 41.8,
64.2, 69.1, 70.8,
359 (100),
301 (13)
m/z [(M + Na)+]
calcd for
C17H28O3Si2 +
Na: 359.1475;
found: 359.1484
H, =CH2), 4.67–4.69 (m, 1 H, CHOTMS), 5.36 (dd, J = 9.2, 91.8, 105.3, 110.0,
3.7, 1 H, CHOSiEt2), 6.21 (d, J = 2.9, 1 Hfuryl), 6.30–6.32
(m, 1 Hfuryl), 7.34 (br s, 1 Hfuryl
141.6, 157.3,
207.7
)
0.12 [s, 9 H, Si(CH3)3], 0.66–0.89 [stack, 4 H,
Si(CH2CH3)2], 0.93–1.03 [stack, 6 H, Si(CH2CH3)2], 1.64– 7.6, 43.8, 68.5,
0.2, 5.4, 6.4, 6.5,
411 [100, (M +
Na + MeOH)+],
m/z [(M + Na)+]
calcd for
1.73 (m, 1 H, CHaHb), 1.87 (ddd, J = 13.6, 4.4, 1.8, 1 H,
CHaHb), 4.40 (s, 2 H, =CH2), 4.64–4.65 (m, 1 H, CHOT-
68.9, 71.1, 91.8,
126.4, 127.2,
395 (45), 339 (15) C21H32O2Si2 +
Na: 395.1839;
MS), 4.93–4.98 (m, 1 H, CHOSiEt2), 6.19 (dd, J = 15.8, 5.5, 128.4, 128.7,
1 H, =CHCHO), 6.62 (d, J = 15.8, 1 H, PhCH=), 7.19–7.38 132.8, 137.1,
found: 395.1845
(stack, 5 H, C6H5)
207.6
d
e
0.01 [s, 9 H, Si(CH3)3], 0.64–0.79 [stack, 4 H,
Si(CH2CH3)2], 0.90–0.98 [stack, 6 H, Si(CH2CH3)2], 1.04
{s, 21 H, Si[CH(CH3)2]3}, 1.90–1.98 (stack, 2 H, CH2),
4.45–4.58 (ABX, JA,B = 11.0, 2 H, =CH2), 4.76–4.80 (m, 1 71.0, 85.1, 94.1,
H, CHOTMS), 4.98 (dd, J = 4.8, 4.5, 1 H, CHOSiEt2)
–0.1, 6.3, 6.4, 6.5, 473 (100)
7.0, 11.2, 18.6,
44.0, 61.6, 68.0,
m/z [(M + Na)+]
calcd for
C24H46O2Si3 +
Na: 473.2703;
found: 473.2699
85
68
108.2, 206.8
0.08 [s, 9 H, Si(CH3)3], 0.59–0.77 [stack, 4 H,
Si(CH2CH3)2], 0.95 [t, J = 8.7, 6 H, Si(CH2CH3)2], 1.00–
0.2, 5.4, 6.4, 6.5,
7.4, 26.37, 26.43,
375 (100)
m/z [(M + Na)+]
calcd for
1.32 (stack, 6 H), 1.50–1.80 (stack, 7 H), 3.98–4.03 (m, 1 H, 26.7, 28.1, 28.8,
C19H36O2Si2 +
Na: 375.2152;
found: 375.2166
CHO), 4.35 (s, 2 H, =CH2), 4.60–4.61 (m, 1 H, CHO)
39.9, 44.3, 68.4,
71.46, 71.49, 92.5,
207.5
f
0.09 [s, 9 H, Si(CH3)3], 0.60–0.70 (stack, 2 H, CH2CH3),
0.71–0.80 (stack, 2 H, CH2CH3), 0.87–0.90 [stack, 6 H,
0.2, 5.4, 6.4, 6.5,
7.1, 22.2, 23.2,
349.2 (100)
m/z [(M + Na)+]
calcd for
83
CH(CH3)2], 0.92–0.99 [stack, 6 H, Si(CH2CH3)2], 1.08–1.17 24.4, 43.8, 47.3,
(m, 1 H), 1.39–1.50 (stack, 2 H), 1.65–1.73 (m, 1 H), 1.73– 65.8, 68.5, 71.3,
C17H34O2Si2 +
Na: 349.1995;
found: 349.2002
1.86 (m, 1 H), 4.26–4.33 (m, 1 H, CHOSiEt2), 4.36 (s, 2
H, =CH2), 4.57–4.58 (m, 1 H, CHOTMS)
92.3, 207.6
g
0.09 [s, 9 H, Si(CH3)3], 0.58–0.80 [stack, 4 H,
0.2, 5.4, 6.4, 6.5,
7.2, 14.2, 22.8,
27.6, 38.0, 43.2,
67.7, 68.5, 71.3,
92.3, 207.6
349.2 (100),
304.3 (7)
m/z [(M + Na)+]
calcd for
C17H34O2Si2 +
Na: 349.1995;
found: 349.1992
66
70
Si(CH2CH3)2], 0.86–0.98 [stack, 9 H, Si(CH2CH3)2, CH3],
1.24–1.44 (stack, 6 H), 1.46–1.53 (m, 1 H), 1.70 (ddd,
J = 13.6, 4.4, 1.8, 1 H), 4.18–4.23 (m, 1 H, BuCHO), 4.36
(s, 2 H, =CH2), 4.57–4.59 (m, 1 H, CHOTMS)
h
0.09 [s, 9 H, Si(CH3)3], 0.57–0.69 (stack, 2 H, CH2CH3),
0.70–0.79 (stack, 2 H, CH2CH3), 0.91–0.99 [stack, 6 H,
0.1, 5.3, 6.3, 6.4,
7.2, 38.3, 43.5,
427.2 (100)
m/z [(M + Na)+]
calcd for
Si(CH2CH3)2], 1.55–1.61 (m, 1 H), 1.70–1.77 (stack, 3 H), 65.0, 67.1, 68.6,
3.59–3.63 (stack, 2 H, CH2OBn), 4.36 (s, 2 H, =CH2), 4.41– 71.2, 73.1, 92.1,
4.46 (m, 1 H, CHO), 4.50 (s, 2 H, PhCH2), 4.58–4.59 (m, 1 127.4, 127.5,
C22H36O3Si2 +
Na: 427.2101;
found: 427.2105
H, CHO), 7.24–7.35 (stack, 5 H, C6H5)
128.3, 138.7,
207.5
Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York

3396
R. Ramalho et al.
PAPER
Table 4 Characterisation Data for Allenes 5 (continued)
5a
i
1H NMR (CDCl3, 300 MHz)
d, J (Hz)
13C NMR (CDCl3, TOF-MS
HRMS
Yield
(%)
75 MHz), d
m/z (%)
0.09 [s, 9 H, Si(CH3)3], 0.63–0.79 [stack, 4 H,
Si(CH2CH3)2], 0.93–0.99 [stack, 6 H, Si(CH2CH3)2], 1.18
(d, J = 6.2, 3 H, CH3), 1.48–1.56 (m, 1 H, CHaHb), 1.70
(ddd, J = 15.5, 4.6, 1.9, 1 H, CHaHb), 4.37 (s, 2 H, =CH2),
4.40–4.46 (m, 1 H, CH3CHO), 4.57 (dd, J = 4.4, 1.9, 1 H,
CHOTMS)
0.1, 5.4, 6.3, 6.4,
7.4, 24.4, 45.1,
64.0, 68.6, 71.3,
91.8, 207.7
307.2 (100),
213.1 (45)
m/z [(M + Na)+]
calcd for
C14H28O2Si2 +
Na: 307.1526;
found: 307.1534
67
a All compounds showed the characteristic peak for allenyl group. IR (film): 1936s cm–1 (C=C=C).
Formation of Acetonides 14 and 15
(3) Beignet, J.; Cox, L. R. Org. Lett. 2003, 5, 4231.
A mixture of the allene 5a (100 mg, 0.27 mmol), KF (40 mg, 0.81
mmol) and KHCO3 (80 mg, 0.81 mmol) in THF–MeOH (1:1, 1 mL)
was heated at 70 °C for 1.5 h. After cooling, the mixture was diluted
with H2O (4 mL) and extracted with EtOAc (5 × 2 mL). The com-
bined organic phases were washed with brine (4 mL) and then dried
(MgSO4). Concentration under reduced pressure followed by puri-
fication of the residue by flash column chromatography (eluent:
40% EtOAc in hexane) afforded a mixture of the diols 12 and 13 as
a colourless oil (36 mg, 76%, 12:13, ~1:3), which was used directly
in the next step: Na2SO4 (48 mg, 0.34 mmol) and p-TsOH·H2O (3
mg, 0.01 mmol) were added to a solution of diols 12 and 13 (36 mg,
0.19 mmol) in acetone (3 mL). The resulting mixture was stirred
overnight and then poured into NaHCO3 solution (3 mL). The phas-
es were separated and the aqueous layer extracted with EtOAc (3 ×
5 mL). The combined organic layers were washed with brine (5 mL)
and then dried (MgSO4). Filtration and evaporation of the volatiles
under reduced pressure provided a mixture of the acetonides 14 and
15 (44 mg, quant) as a colourless oil.
(4) Tri-tert-butylpyrimidine (TTBP) and 2,6-di-tert-butyl-4-
methylpyridine (2,6-DTBMP) were equally effective in this
role.
(5) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M. G. J. Am.
Chem. Soc. 1996, 118, 4322.
(6) Beignet, J. Ph.D. Thesis; University of Birmingham:
Birmingham, 2004.
(7) Beignet, J.; Tiernan, J.; Woo, C. H.; Kariuki, B. M.; Cox, L.
R. J. Org. Chem. 2004, 69, 6341.
(8) (a) Stragies, R.; Blechert, S. Tetrahedron 1999, 55, 8179.
(b) Bradley, G. W.; Thomas, E. J. Synlett 1997, 629.
(c) Angoh, A. G.; Clive, D. L. J. J. Chem. Soc., Chem.
Commun. 1984, 534.
(9) The E-stereochemical outcome of this side-reaction is in
accord with mechanistic studies on this type of E¢
elimination: (a) Matassa, V. G.; Jenkins, P. R.; Kümin, A.;
Damm, L.; Schreiber, J.; Felix, D.; Zass, E.; Eschenmoser,
A. Isr. J. Chem. 1989, 29, 321. (b) Fleming, I.; Morgan, I.
T.; Sarkar, A. K. J. Chem. Soc., Perkin Trans. 1 1998, 2749.
(10) For some recent examples of allenylsilanes in synthesis:
(a) Pacheco, M. C.; Gouverneur, V. Org. Lett. 2005, 7,
1267. (b) Daidouji, K.; Fuchibe, K.; Akiyama, T. Org. Lett.
2005, 7, 1051. (c) Archibald, S. C.; Barden, D. J.; Bazin, J.
F. Y.; Fleming, I.; Foster, C. F.; Mandal, A. K.; Mandal, A.
K.; Parker, D.; Takaki, K.; Ware, A. C.; Williams, A. R. B.;
Zwicky, A. B. Org. Biomol. Chem. 2004, 2, 1051.
(d) Buckle, M. J. C.; Fleming, I.; Gil, S.; Pang, K. L. C. Org.
Biomol. Chem. 2004, 2, 749. (e) Denmark, S. E.; Gomez, L.
Heterocycles 2002, 58, 129. (f) See also: Pornet, J. In
Science of Synthesis; Fleming, I., Ed.; Georg Thieme Verlag:
Stuttgart, 2002, Chap. 4.4.32, 669–683; and references cited
therein.
Selected Data for Alkyne 14
13C NMR (125 MHz, C6D6): d = 3.7 (C≡CCH3), 19.5 (CH3ax), 30.3
(CH3eq), 39.8 (CH2), 60.8 (CHC≡C), 71.2 (PhCH), 77.8 (C≡CCH3),
81.3 (C≡CCH3), 99.7 [C(CH3)2], 126.0 (o-Ph), 127.8 (p-Ph), 128.5
(m-Ph), 141.6 (ipso-Ph).
Selected Data for Allene 15
13C NMR (125 MHz, C6D6): d = 19.7 (CH3ax), 30.3 (CH3eq), 38.9
(CH2), 67.8 (=CHCH), 71.4 (PhCH), 77.2 (CH2=C=CH), 92.4
(CH2=C=CH), 99.5 [C(CH3)2], 125.9 (o-Ph), 127.6 (p-Ph), 128.4
(m-Ph), 142.1 (ipso-Ph), 208.3 (CH2=C=CH).
Acknowledgment
(11) The silyl tether is part of a vinylsilane in this intermediate
and will be less effective in stabilising the b-vinyl
carbocation on geometric grounds.
We thank Merck, Sharp & Dohme and the University of Birming-
ham for a studentship to R.R., and the Engineering and Physical
Sciences Research Council (Grant No. GR/N32556) for a stu-
dentship to J.B.
(12) For some recent examples of propargylsilanes in synthesis:
(a) Patel, P. P.; Zhu, Y.; Zhang, L.; Herndon, J. W. J.
Organomet. Chem. 2004, 689, 3379. (b) Nishikawa, T.;
Mishima, Y.; Ohyabu, N.; Isobe, M. Tetrahedron Lett. 2004,
45, 175. (c) Niimi, L.; Shiino, K.; Hiraoka, S.; Yokozawa, T.
Macromolecules 2002, 35, 3490. (d) Billet, M.;
Schoenfelder, A.; Klotz, P.; Mann, A. Tetrahedron Lett.
2002, 43, 1453.
(13) For recent examples where propargylsilanes have been
employed in intramolecular reactions: (a) Shin, C.; Chavre,
S. N.; Pae, A. N.; Cha, J. H.; Koh, H. Y.; Chang, M. H.;
Choi, J. H.; Cho, Y. S. Org. Lett. 2005, 7, 3283.
(b) Dziedzic, M.; Lipner, G.; Furman, B. Tetrahedron Lett.
2005, 46, 6861. (c) Dziedzic, M.; Lipner, G.; Illangua, J. M.;
Furman, B. Tetrahedron 2005, 61, 8641; and references
cited therein.
References
(1) Current address: Metcalf Center for Science and
Engineering, Boston University, 590, Commonwealth
Avenue, Boston, MA 02215-2521, USA.
(2) For general reviews on the use of the ‘Temporary Connection’
in synthesis: (a) Cox, L. R.; Ley, S. V. In Templated Organic
Synthesis; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 2000, Chap. 10, 275–375. (b) Bols, M.;
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(b) Pornet, J.; Kolani, N.; Mesnard, D.; Miginiac, L.;
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(15) Propargyltrimethylsilane iscommerciallyavailable although
expensive and invariably contaminated with varying
amounts of allenyltrimethylsilane. We find it more
convenient to prepare the reagent ourselves.
(16) Tamao, K.; Nakajo, E.; Ito, Y. Tetrahedron 1988, 44, 3997.
(17) The b-hydroxy esters were prepared uneventfully by a
Reformatski reaction between ethyl bromoacetate and the
corresponding aldehyde: Picotin, G.; Miginiac, P. J. Org.
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(19) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.;
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(20) 2,6-Di-tert-butylpyridine bound through the 4-position to a
polystyrene support (1% divinylbenzene) is available from
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(21) Allylsilanes are particularly susceptible to decomposition in
the presence of Brønsted acids: Chan, T. H.; Fleming, I.
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(22) Oda, H.; Sato, M.; Morizawa, Y.; Oshima, K.; Nozaki, H.
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Synthesis 2005, No. 19, 3389–3397 © Thieme Stuttgart · New York