Chemoselective activation of trimethylsilyl enol ether functionalities in the presence of silyl-protected alcohols by trimethylsilyl-nonaflyl exchange

Article abstract of DOI:10.1055/s-0030-1260207

Trimethylsilyl enol ethers bearing trialkylsilyl-protected hydroxy groups were converted into synthetically valuable bifunctional alkenyl nonaflates under the action of nonafluorobutane-1-sulfonyl fluoride combined with potassium fluoride in the presence

Full text of DOI:10.1055/s-0030-1260207

PAPER
3507
Chemoselective Activation of Trimethylsilyl Enol Ether Functionalities in the
Presence of Silyl-Protected Alcohols by Trimethylsilyl–Nonaflyl Exchange
C
hemoselective
k
Trimethylsi
a
lyl–Nonafly
t
l
Exch
e
ange rina V. Boltukhina, Andrey E. Sheshenev,*1 Ilya M. Lyapkalo
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6,
Czech Republic
Fax +44(20)75945804; E-mail: a.sheshenev@imperial.ac.uk
Received 1 July 2011; revised 2 August 2011
This article is dedicated to the memory of our colleague and friend Dr. Ilya Lyapkalo who passed away September 10, 2010
The major challenge consists of the extension of the tri-
Abstract: Trimethylsilyl enol ethers bearing trialkylsilyl-protected
methylsilyl–nonaflyl-exchange methodology to the syn-
thesis of complex products. This requires studying the
chemo- and regioselectivity of the reaction. It is therefore
hydroxy groups were converted into synthetically valuable bifunc-
tional alkenyl nonaflates under the action of nonafluorobutane-1-
sulfonyl fluoride combined with potassium fluoride in the presence
of catalytic amounts of dibenzo-18-crown-6. The methodology has especially important to develop a soluble anhydrous fluo-
been demonstrated for structurally diverse substrates possessing
ride catalyst able to efficiently activate trimethylsilyl enol
ether functionalities,11d while not affecting alkylsilyl ether
various trialkylsilyl-protected hydroxy groups which remained in-
tact during the reaction course.
groups, with a high degree of chemo- and regiocontrol.
The activator must be robust and not too basic16 to avoid
Key words: biphasic catalysis, crown ether, sulfonylating reagent,
trialkylsilyl ethers, alkenyl nonaflates
E2 elimination of NfOH from acyclic alkenyl nonaflates.
Ideally, it should be easy to generate in an anhydrous
form, preferably shortly prior to the reaction, to ensure re-
producibility of results.
Sulfonic acid enol esters (alkenyl sulfonates) constitute a
synthetically important link that enables the extension of
transition-metal-catalyzed cross-coupling methodology to
enolizable carbonyl compounds, one of the most abundant
and ubiquitous classes of organic substrates. The applica-
tions of alkenyl triflates in palladium(0)-catalyzed cross-
coupling reactions have been systematically studied and
reviewed.2 Alkenyl nonaflates (nonafluorobutane-
sulfonates) represent a useful alternative3–10 to the tri-
flates, not least owing to the advantageous properties of
nonafluorobutane-1-sulfonyl fluoride11,12 (hereinafter re-
ferred to as NfF), a mild and easy-to-handle sulfonylating
reagent routinely used for the preparation of nonaflates
from carbonyl compounds.
In a previous study by Reissig, Lyapkalo and co-work-
ers,3e a single example of a selective activation of a tri-
methylsilyl enol ether functionality in the presence of
silyl-protected hydroxy using potassium fluoride with a
catalytic amount of dibenzo-18-crown-6 was shown. The
study, however, was not devoted to this transformation;
therefore, neither scope and limitations nor the possibility
to perform such reactions using other catalytic systems
was explored. The aim of the present work was to study
the scope of this transformation as well as to gain mecha-
nistic insight. As far as we can ascertain, there is no fo-
cused study prior to this work.17,18
In this paper, we present a selective method for the ex-
change of easy-to-generate silyl enol ether functionalities
to versatile alkenyl nonaflates in the presence of silyl-
protected alcohol groups. This method opens the way to
synthetically valuable polyfunctional building blocks
bearing nonaflyl enol ether groups along with silyl-pro-
tected hydroxy units which can be subsequently used in
metal-catalyzed cross-coupling reactions.3–10
Most generally, alkenyl nonaflates are accessed either by
direct O-sulfonylation of aldehydes or cyclic ketones with
NfF combined with phosphazene bases,7c,13 or by fluo-
ride-catalyzed SiMe3 for SO2(CF2)3CF3 group exchange
in trimethylsilyl enol ethers.3a,c,11d While the former pro-
cedure is more straightforward, the latter is milder and ex-
hibits greater scope as it allows alkenyl nonaflates14 to be
derived from acyclic ketones, which are unstable in the
presence of phosphazene bases.7c,13 Tetrabutylammonium
fluoride (TBAF) is routinely employed as a soluble source
of catalytic fluoride for such exchanges, which can be
problematic in the case of polyfunctional substrates bear-
ing silyl-protected alcohol groups as TBAF is known to be
one of the most general and efficient deprotecting re-
agents for silyl ethers (protected alcohol groups) ranging
widely in steric and electronic demands.15
A first attempt to prepare alkenyl nonaflate 2a from the
model compound (R)-2-methyl-3-(trimethylsilyloxy)-5-
[2-(trimethylsilyloxy)propan-2-yl]cyclohexa-1,3-diene
(1a)3e using TBAF11d resulted in a mixture containing
only a minor quantity of desired 2a, along with enone 3a,
parent hydroxy enone 4 and several unidentified
products19 (Table 1, entry 1).
Gratifyingly, a combination of thoroughly ground and
dried potassium fluoride with a catalytic amount of diben-
zo-18-crown-6 (db-18-c-6) turned out to be a much more
selective catalyst (Table 1, entry 2). Although the rate of
conversion of the starting bis-trimethylsilyl ether 1a
SYNTHESIS 2011, No. 21, pp 3507–3515
x
x.
x
x
.
2
0
1
1
Advanced online publication: 05.09.2011
DOI: 10.1055/s-0030-1260207; Art ID: T66111SS
© Georg Thieme Verlag Stuttgart · New York

3508
E. V. Boltukhina et al.
PAPER
slowed down considerably, the reaction proceeded much lated in 76% yield compared to 42% yield in DMSO–hex-
more cleanly; the formation of the protiodesilylated prod- ane.
uct 3a was insignificant, while the tertiary trimethylsilyl
Experiments using substrates 1b and 1e were run in dupli-
ether function was not affected. Switching from THF to
cate, and the results demonstrated that the methodology is
the dipolar aprotic solvent DMF resulted in an appreciable
fully reproducible. On the other hand, a 10-fold increase
of the substrate concentration in the case of substrate 1d
(Table 2, entry 4) led to a very similar result (72% vs 69%
acceleration of the reaction rate, although the selectivity
was slightly lower (Table 1, entry 3). Finally, the biphasic
solvent mixture DMSO–hexane (1:1.5) gave the optimal
yield).
result in terms of selectivity and reaction rate, furnishing
The reactivity of 1j exemplifies a limitation of the proto-
the desired alkenyl nonaflate 2a in 84% isolated yield
col for substrates possessing a trimethylsilyl ether derived
(Table 1, entry 4). Dibenzo-18-crown-6 was found to be
from a secondary alcohol (Table 3). No alkenyl nonaflate
vital for the reaction to occur. In its absence, the nonafla-
2j was formed in the biphasic DMSO–hexane system (ac-
tion did not proceed at all (Table 1, entry 5).
cording to the 1H NMR data of the crude reaction mixture,
Encouraged by this finding, the generality of this optimal
protocol was tested using a number of bis-trialkylsilyl
substrates 1b–j (Tables 2 and 3). The secondary trimeth-
conversion of starting 1j was 96% and only protiodesily-
lated product 3j was formed) (Table 3, entry 1), while the
reaction was sluggish in THF at room temperature (<20%
ylsilyl ether moiety in compound 1b was not affected un-
conversion of 1j after 20 h, according to the 1H NMR data
der the reaction conditions and the desired product 2b was
of the crude reaction mixture) (Table 3, entry 2). Thus,
obtained in high yield (Table 2, entry 1). However, there
heating had to be applied to achieve reasonable conver-
remained a legitimate suspicion that erosion of selectivity
sion (94% after 24 h at 50 °C, according to the 1H NMR
may occur due to silyl scrambling by means of a putative
data of the crude reaction mixture) (Table 3, entry 3). The
intramolecular O,O-silyl migration,13 especially via the
desired alkenyl nonaflate 2j was nonetheless isolated in
entropically favorable five- or six-membered (n = 0 or 1,
only 39% yield and ca. 80% purity. The use of THF mix-
respectively) cyclic pentacoordinated silicate intermedi-
tures with polar NMP or DMF as reaction medium at
room temperature (Table 3, entries 4 and 5, respectively)
ate A (see Scheme 1, path I).
To address this, a range of bis-silyl derivatives 1c,i (n = 1) improved the reaction rate and selectivity compared to
and 1d–h,j (n = 0) was tested under the optimized non- those observed in the DMSO–hexane mixture and pure
aflation conditions (Table 2). The reactions proceeded THF. Unfortunately, it proved impossible to isolate the
cleanly in the biphasic DMSO–hexane medium, furnish- desired product 2j from the reaction mixtures due to de-
ing the anticipated silylated alkenyl nonaflates 2 in good composition during the unavoidable aqueous workup. In
to high yields for all substrates examined (Table 2, entries contrast, the transformation of the TBS-protected ana-
2–8), except 1i and 1j. The reaction outcome achieved in logue (1g → 2g) in DMSO–hexane proceeded smoothly
the case of substrate 1i in DMSO–hexane (Table 2, entry with good yield and selectivity (Table 2, entry 7).
9) was significantly improved by switching to THF
(Table 2, entry 10) as the reaction medium. Although it
took much longer for the reaction to complete (120 h in
THF vs 18 h in DMSO–hexane), pure product 2i was iso-
To investigate a possible pathway of the trimethylsilyl–
nonaflyl exchange, aliquots (30–40 mL) were collected
from the hexane phase or the THF solution and diluted
with the deuterated solvent. The reaction progress could
Table 1 Model Reaction for Optimization of the Fluoride Source
O
OTMS
O
ONf
NfF (130 mol%), cat. F–
solvent, r.t., 24 h
+
+
OTMS
2a
OTMS
OH
OTMS
1a
4
3a
Entry
Fluoride catalyst
Solvent
THF
Conv. of 1aa (%)
Ratio 2a/3a/4a
1:1.7b
1
2
3
4
5
TBAF (10 mol%), KF (100 mol%)
~85
db-18-c-6 (15 mol%), KF (100 mol%)
db-18-c-6 (15 mol%), KF (100 mol%)
db-18-c-6 (15 mol%), KF (100 mol%)
KF (100 mol%)
THF
25
12:1:0
9:1:0
DMF
95
DMSO–hexane
>99c
10:1:0
–
DMSO–hexane
0 (no change)
a Estimated based on the 1H NMR data of the crude reaction mixtures.
b Combined amount of 3a and 4.
c Isolated yield 84%.
Synthesis 2011, No. 21, 3507–3515 © Thieme Stuttgart · New York

PAPER
Chemoselective Trimethylsilyl–Nonaflyl Exchange
3509
be easily monitored by the appearance and steady increase anistically, these observations can be rationalized as
of the Me3SiF signal in the 1H NMR spectrum (d, depicted in path II of Scheme 1. Soluble fluoride in the
3
d = 0.235 ppm, J1H,19F = 7.4 Hz in CDCl3 or d = 0.022 form [(db-18-c-6)·K]+F– adds reversibly to the silicon
ppm, 3J1H,19F = 7.3 Hz in C6D6).
center of the silyl enol ether group to produce pentacoor-
dinated anionic silicate intermediate B. The formation of
B is apparently preferred over that of the alternative silyl
ether derived silicate. The silicate enolate unit should ad-
ditionally be a better nucleophile compared to a simple al-
coholate-derived silicate. The exact further pathway to
products 2 cannot be derived with certainty from the ex-
perimental data. The attack of NfF may proceed subse-
quently by direct O-sulfonylation of B. The very low
Besides the fact that the fluoride source had to be soluble
(cf. Table 1), control experiments showed that prolonged
exposure (20–24 h) of 1a or 1b to 15–20 mol% of [(db-18-
c-6)·K]+F– in the absence of NfF did not produce any de-
tectable amount of Me3SiF. This excludes A or a free eno-
late C (Scheme 1) as intermediates within the detection
limits of the NMR method. However, shortly after the ad-
dition of NfF, the signal of Me3SiF became visible. Mech-
Table 2 Selective Conversion of TMS Enol Ethers Possessing Trialkylsilyl-Protected Hydroxy Groups into the Corresponding Alkenyl Non-
aflates
NfF (130 mol%)
Me3Si
SiR2
R3
Nf
SiR2
R3
3
3
db-18-c-6 (20 mol%), KF (100 mol%)
O
O
O
O
(R1)n
(R1)n
solvent, r.t.
1
2
Entry
1b
Substrate
Solvent
Time (h)
Product
Yielda (%)
83
OTMS
ONf
1b
DMSO–hexane
22
2b
TMSO
TMSO
TMSO
TMSO
OTMS
ONf
2c
1c
DMSO–hexane
19
2c
90
OTMS
OTMS
3
DMSO–hexane
DMSO–hexane
48
48
69
72
1d
2d
4d
OTMS
OTBS
ONf
OTBS
5b
1e
1f
DMSO–hexane
DMSO–hexane
23
48
2e
2f
72
OTMS
OTMS
ONf
ONf
74e
TMSO
TMSO
6
OTBS
OTBS
7
8
1g
1h
1i
DMSO–hexane
DMSO–hexane
36
24
2g
2h
2i
73
51
OTMS
ONf
OTBS
OTBS
ONf
OTMS
9c,f
DMSO–hexane
THF
18
120
42
76
OTMS
OTMS
ONf
10c,f
OTMS
a Isolated yield.
b Duplicate experiments for substrates 1b,e were carried out. The yields of products 2b,e were identical in each pair of experiments.
c Reaction was carried out with 15 mol% db-18-c-6.
d Repetitive experiment using a 10-fold increase of the starting 1d amount and conditions similar to entry 3.
e Purity of the isolated product was 88% based on the 1H NMR data.
f Room temperature was 28 °C.
Synthesis 2011, No. 21, 3507–3515 © Thieme Stuttgart · New York

3510
E. V. Boltukhina et al.
PAPER
TMS protection of primary hydroxy groups largely re-
mains intact during the reaction. Both components of the
fluoride catalytic system can be conveniently dried by
heating under high vacuum, thus ensuring the reproduc-
ibility of the results. The highest reaction rate was ob-
served in a DMSO–hexane biphasic system, from which
the nonaflate products 2 can be conveniently isolated by
nonaqueous extraction with hexane. The reaction rate in
THF medium was lower; however, the selectivity was
higher, thus THF should be the solvent of choice for those
substrates which give unsatisfactory results in DMSO–
hexane.
Table 3 Optimization of the Reaction Conditions for 1j
NfF (130 mol%)
db-18-c-6 (20 mol%)
KF (100 mol%)
OTMS
OTMS
OTMS
+
O
OTMS
1j
ONf
2j
3j
Entry
Conditions
Ratio 1j/2j/3ja
1:0:18
1
DMSO–hexane, r.t., 20 h
THF, r.t., 20 h
2
9:1:1
3b
4
THF, 50 °C, 24 h
0.2:2.1:1
0:1.9:1
THF–NMP (2:1), r.t., 20 h
THF–DMF (2:1), r.t., 20 h
All reactions were carried out in oven-dried glassware (140 °C)
equipped with PTFE-coated magnetic stirrer bars in anhydrous sol-
vents under an atmosphere of dry argon. Air- and moisture-sensitive
reagents were transferred using a syringe. 1H NMR spectra of the re-
action mixtures were routinely recorded to ensure complete conver-
sion of the starting materials. Solvents were dried by standard
procedures: THF was distilled over Na/K alloy with addition of
benzophenone; MeCN was distilled over CaH2 and stored over 4 Å
molecular sieves; hexane and CH2Cl2 were distilled over P2O5. An-
hyd DMSO was prepared as described previously.20 Commercially
available, dry KF (ca. 20 g) (Fluka) was placed in a mortar and
maintained in an oven at 200 °C for 12 h. Then, whilst still hot, it
was thoroughly ground to a fine powder using a hot pestle. This pre-
dried KF was dried further under vacuum (0.01 mbar) using a heat
gun (heating program 350 °C) before each reaction. Commercially
available NaI (Penta) was dried under vacuum (10–2 mbar) at
120 °C (oil bath) for 2 h before each reaction. 2.4 M n-BuLi solution
in hexanes was purchased from Aldrich. Unless otherwise stated,
materials obtained from commercial suppliers were used without
further purification. Recondensation was carried out as bulb-to-bulb
distillation at r.t. under high vacuum with the trapping bulb cooled
by a liquid N2–EtOH bath (for picture, see Supporting Information).
All the products obtained were of >95% purity according to the 1H
NMR data, unless otherwise noted. NMR spectra were recorded in
5
0:2.3:1
a Estimated based on the 1H NMR data of the crude reaction mixtures.
b Isolated yield 39%, purity ca. 80% based on the 1H NMR data.
inclination for the aforementioned migration (Scheme 1,
path I) points to a very transient, if at all, existence of a
free enolate intermediate C; however, although the equi-
librium between B and C is shifted to the left to such an
extent that the concentration of free Me3SiF remains be-
yond the detection limit of the NMR method in the ab-
sence of the electrophile, the nonaflation reaction might
be then driven by reaction of transient C with the large ex-
cess of NfF compared to it. Alternatively, the reaction
with NfF can also proceed via a contact ion pair laying in
between the two limiting equilibrium structures B and C
+ Me3SiF, accounting for the preparative and mechanistic
results (Scheme 1, path II).
In summary, we have developed a general, efficient and
highly selective protocol for the anhydrous fluoride-cata-
lyzed conversion of trimethylsilyl enol ethers into the cor-
responding nonaflates. Catalytic dibenzo-18-crown-6
combined with potassium fluoride offers a remarkable se-
1
C6D6 or CDCl3 on a Bruker Avance I 400 (400 MHz for H, 100
MHz for 13C) or WH 270 (270 MHz for 1H, 67.5 MHz for 13C) spec-
trometer (Bruker BioSpin GmbH). Chemical shifts are reported as
the d scale in ppm relative to TMS (d = 0) as an internal standard for
lectivity as it activates trimethylsilyl enol ether functions 1H NMR and to CDCl3 (d = 77.16) or C6D6 (d = 128.06) for 13C
NMR. The 13C NMR signals of the (CF2)3CF3 fragment of the non-
readily while not affecting trialkylsilyl alcohol protection
aflates are not given, as no unambiguous assignments were possible
regardless of its nature (primary to tertiary), bulkiness
due to strong coupling with the 19F nuclei. High-resolution mass
(TMS or TBS) or position in the molecule. Even fragile
spectra were measured on an LTQ Orbitrap XL spectrometer
Me3SiF
R2
Si 3
F
+
–
–
SiR2
R3
Me3Si
SiR2
R3
Me3Si
SiR2
R3
3
3
3
–
–
O
O
O
O
O
O
O
O
F
F
R3
(R1)n
(R1)n
(R1)n
(R1)n
Me3SiF
path I
A
path II
1 (n = 0, 1)
NfF
O
–
B
C
F
NfF
R23Si
Nf
Nf
SiR2
3
O
O
O
R3
R3
(R1)n
(R1)n
not observed
2
Scheme 1 Proposed mechanism of the [(db-18-c-6)·K]+F– induced transformation of TMS enol ethers to alkenyl nonaflates
Synthesis 2011, No. 21, 3507–3515 © Thieme Stuttgart · New York

PAPER
Chemoselective Trimethylsilyl–Nonaflyl Exchange
3511
(Thermo Fisher Scientific) using APCI and ESI methods with
MeOH or MeCN, or on a GTC Premier spectrometer (Waters) using
EI. IR spectra were recorded as films or in CDCl3 on a Bruker Equi-
nox 55 IR spectrometer (Bruker BioSpin GmbH). Preparative sepa-
rations were performed using silica gel gravity column
chromatography (silica gel 60, Fluka, 12479). Column chromatog-
raphy was monitored by TLC (silica gel 60, glass plates, Merck,
105631) and visualized using 5% phosphomolybdic acid solution in
EtOH. Elemental analysis was performed using a PE 2400 Series II
CHN analyzer.
tion; yield: 4.28 g (82%); colorless liquid; bp 79–80 °C/2 mbar. The
spectroscopic data were in accordance with the literature values.25
3-(tert-Butyldimethylsilyloxy)-3-methyl-2-(trimethylsilyl-
oxy)but-1-ene (1e)
Starting 3-(tert-butyldimethylsilyloxy)-3-methylbutan-2-one was
obtained according to a literature procedure,26 and its spectroscopic
data were in accordance with the literature values. Product 1e was
prepared according to GP2 using 0.70 g (3.20 mmol) of 3-(tert-bu-
tyldimethylsilyloxy)-3-methylbutan-2-one and purified by distilla-
tion.
tert-Butyldimethylsilyloxy Ketones (Starting Materials for 1g
and 1h); General Procedure 1 (GP1)
Yield: 0.849 g (91%); colorless liquid; bp 92–94 °C/3 mbar.
IR (CDCl3): 3010–2880, 1623, 1453, 1253 cm–1.
1H NMR (400 MHz, C6D6): d = 0.17 (s, 6 H, 2 Me-TBS), 0.17 (s, 9
H, TMS), 1.04 (s, 9 H, t-Bu-TBS), 1.41 (s, 6 H, CMe2), 4.12 (d,
J = 1.0 Hz, 1 H, H-1), 4.72 (d, J = 1.0 Hz, 1 H, H-1).
13C NMR (100 MHz, C6D6): d = –1.94, 0.13, 18.54, 26.24, 29.10,
75.23, 86.68, 164.62.
HRMS (EI+): m/z [M]+ calcd for C14H32O2Si2: 288.1941; found:
288.1938.
The corresponding starting hydroxy ketone (1 equiv) was dissolved
in anhyd CH2Cl2 (15–20 mL per 1.00 mmol of substrate), and the
obtained solution was cooled to 0 °C whereupon imidazole (1.3
equiv) and TBSCl (1.1 equiv) were added. The reaction mixture
was allowed to warm to r.t. and stirred overnight. The resulting in-
homogeneous mixture was filtered through a pad of silica gel
(CH2Cl2, 65–130 mL per 1.00 mmol of substrate) and concentrated.
The obtained tert-butyldimethylsilyloxy ketones were of >95% pu-
1
rity according to the H NMR data and were used without further
purification.
3-(tert-Butyldimethylsilyloxy)-2-(trimethylsilyloxy)but-1-ene
(1g)
Product 1g was prepared according to GP2 using 4.50 g (22.23
mmol) of 3-(tert-butyldimethylsilyloxy)butan-2-one and purified
by distillation; yield: 5.83 g (96%); colorless liquid; bp 110 °C/3.5
mbar (Lit.27 140 °C/18 mbar). The spectroscopic data were in accor-
dance with the literature values.
3-(tert-Butyldimethylsilyloxy)butan-2-one (Starting Material
for 1g)
This compound was obtained according to GP1 using 2.00 g (22.7
mmol) of 3-hydroxybutan-2-one; yield: 4.50 g (quantitative); color-
less oil. The spectroscopic data were in accordance with the litera-
ture values.21
3-Methyl-2,4-bis(trimethylsilyloxy)but-1-ene (1i)
Product 1i was prepared according to GP2 using 2.04 g (19.97
mmol) of 4-hydroxy-3-methylbutan-2-one and purified by distilla-
tion; yield: 3.84 g (78%); colorless liquid; bp 71.5–72.5 °C/2 mbar.
The spectroscopic data were in accordance with the literature val-
ues.25
2-(tert-Butyldimethylsilyloxy)cyclohexanone (Starting Material
for 1h)
This compound was obtained according to GP1 using 0.50 g (2.2
mmol) of 2-hydroxycyclohexanone dimer; yield: 0.97 g (97%); col-
orless oil. The spectroscopic data were in accordance with the liter-
ature values.22
2,3-Bis(trimethylsilyloxy)but-1-ene (1j)
Bis(trialkylsilyloxy) Derivatives 1b,c,e,g,i,j; General Procedure
2 (GP2)
Product 1j was prepared according to GP2 using 2.00 g (22.70
mmol) of 3-hydroxybutan-2-one and purified by distillation; yield:
3.06 g (58%); pale yellow oil; bp 52 °C/6 mbar. The analytical data
were in accordance with the literature values.28
Predried NaI (2.3 equiv) [or 1.15 equiv] was suspended in anhyd
MeCN (3–10 mL per 1.00 mmol of substrate) under argon. The cor-
responding starting hydroxy ketone (1 equiv) or tert-butyldimethyl-
silyloxy ketone [1 equiv] and Et3N (2.7 equiv) [or 1.35 equiv] were
added and the obtained suspension was cooled to –30 °C. TMSCl
(2.5 equiv) [or 1.25 equiv] was added dropwise and the reaction
mixture was allowed to warm to r.t. After being stirred overnight,
the reaction mixture was quenched with an ice–hexane mixture. The
layers were separated and the aqueous phase was extracted with
hexane (2 ×). The combined extracts were washed with H2O and
brine, dried over Na2SO4 and concentrated. Products 1b,c,e,g,i,j
were isolated by recondensation or distillation under reduced pres-
sure.
(R)-2-Methyl-3-(trimethylsilyloxy)-5-[2-(trimethylsilyloxy)pro-
pan-2-yl]cyclohexa-1,3-diene (1a)
Compound 1a was obtained as described previously.3e The spectro-
scopic data were in accordance with the literature values.
3-Methyl-2,3-bis(trimethylsilyloxy)but-1-ene (1d)
Compound 1d was obtained according to a literature procedure.29
The spectroscopic data were in accordance with the literature val-
ues.
(1R,4R,5R)-4,6,6-Trimethyl-3,4-bis(trimethylsilyloxy)bicyc-
lo[3.1.1]hept-2-ene (1f)
1,4-Bis(trimethylsilyloxy)cyclohex-1-ene (1b)
Starting 4-hydroxycyclohexanone was prepared according to a lit-
erature procedure from cyclohexane-1,4-diol,23 and its spectroscop-
ic data were in accordance with the literature values. Product 1b was
prepared according to GP2 using 0.50 g (4.37 mmol) of 4-hydroxy-
cyclohexanone and purified by recondensation at 0.01 mbar; yield:
1.04 g (92%); colorless oil. The spectroscopic data were in accor-
dance with the literature values.24
(1R,2R,5R)-2-Hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-one
(1.00 g, 5.94 mmol) dissolved in anhyd THF (5 mL) was added to
LDA soln [prepared from BuLi (8.60 mL, 21.40 mmol) and i-Pr2NH
(2.17 g, 21.40 mmol) in anhyd THF (20 mL)] at –15 °C and the re-
action mixture was allowed to warm to r.t. After 2 h at r.t., TMSCl
(2.91 g, 26.70 mmol) was added and the reaction mixture was
stirred for 1 h. It was then poured into an ice–sat. NaHCO3–hexane
mixture (100 mL, 20:20:60). The organic layer was separated; the
aqueous layer was extracted with hexane (3 × 20 mL). The com-
bined organic layers were washed with H2O (25 mL) and brine (25
4-Methyl-2,4-bis(trimethylsilyloxy)pent-1-ene (1c)
Product 1c was prepared according to GP2 using 2.33 g (20.04
mmol) of 4-hydroxy-4-methylpentan-2-one and purified by distilla-
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E. V. Boltukhina et al.
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(R)-6-Methyl-3-[2-(trimethylsilyloxy)propan-2-yl]cyclohexa-
mL), dried over Na2SO4 and concentrated. Product 1f was purified
by distillation.
1,5-dien-1-yl Nonaflate (2a; Table 1, Entry 4)
Compound 2a was prepared according to GP3 from 1a (0.625 g,
2.00 mmol) and NfF (0.785 g, 2.60 mmol), employing KF (0.116 g,
2.00 mmol) and dibenzo-18-crown-6 (0.108 g, 0.30 mmol) in
DMSO–hexane (2 mL:3 mL). Product 2a was isolated by column
chromatography on silica gel (hexane).
Yield: 1.633 g (88%); colorless oil; bp 104–105 °C/0.4 mbar.
IR (neat): 2953, 1635, 1420, 1247 cm–1.
1H NMR (400 MHz, C6D6): d = 0.23 (s, 9 H, TMS), 0.28 (s, 9 H,
TMS), 0.98 (s, 3 H), 1.25 (s, 3 H), 1.45 (s, 3 H), 1.96–2.01 (m, 2 H,
H-1 and H-5), 2.12–2.15 (m, 1 H, H-7), 2.31–2.36 (m, 1 H, H-7),
5.20 (d, J = 6.9 Hz, 1 H, H-2).
13C NMR (100 MHz, C6D6): d = 0.45, 2.80, 24.23, 24.91, 27.75,
33.96, 41.03, 46.70, 55.39, 79.03, 110.84, 151.70.
HRMS (EI+): m/z [M]+ calcd for C16H32O2Si2: 312.1941; found:
312.1935.
Yield: 0.874 g (84%); pale yellow oil; Rf = 0.62 (hexane–EtOAc,
10:1).
IR (neat): 2989–2893, 1637, 1421, 1239, 1147 cm–1.
1H NMR (270 MHz, CDCl3): d = 0.11 (s, 9 H, TMS), 1.18 and 1.22
(both s, 3 H, CMe2), 1.81 (m, 3 H, Me-6), 2.11–2.30 (m, 2 H, H-4),
2.53–2.64 (m, 1 H, H-3), 5.67 (m, 1 H, H-5), 5.80 (d, J = 3.4 Hz, 1
H, H-2).
13C NMR (100 MHz, CDCl3): d = 2.33, 16.64, 24.08, 26.80, 27.58,
46.83, 75.60, 117.41, 126.26, 127.20, 148.13.
6-(tert-Butyldimethylsilyloxy)-1-(trimethylsilyloxy)cyclohex-1-
ene (1h)
LDA [prepared from BuLi (2.03 mL, 5.07 mmol) and i-Pr2NH (0.56
g, 5.49 mmol) in anhyd THF (5 mL)] was added dropwise to a soln
of 2-(tert-butyldimethylsilyloxy)cyclohexanone (0.965 g, 4.22
mmol) in anhyd THF (20 mL) at –100 °C and the reaction mixture
was stirred at this temperature for 40 min. Then, the temperature
was allowed to reach –78 °C and, after 30 min with stirring at this
temperature, TMSCl (0.688 g, 6.33 mmol) was added dropwise.
The reaction mixture was allowed to warm to r.t., stirred for 30 min
and quenched with an ice–hexane mixture (50 mL, 1:1). The organ-
ic layer was separated; the aqueous was extracted with hexane
(3 × 20 mL). The combined organic extracts were washed with H2O
(20 mL) and brine (20 mL), dried over Na2SO4 and concentrated.
Product 1h was purified by flash chromatography on silica gel (hex-
ane).
HRMS (ESI): m/z [M – CH3]+ calcd for C16H20F9O4SSi: 507.0702;
found: 507.0703.
Anal. Calcd for C17H23F9O4SSi: C, 39.08; H, 4.44. Found: C, 38.91;
H, 4.32.
4-(Trimethylsilyloxy)cyclohex-1-en-1-yl Nonaflate (2b; Table 2,
Entry 1)
Compound 2b was prepared according to GP3 from 1b (0.258 g,
1.00 mmol) and NfF (0.393 g, 1.30 mmol), employing KF (0.058 g,
1.00 mmol) and dibenzo-18-crown-6 (0.072 g, 0.20 mmol) in
DMSO–hexane (1 mL:1.5 mL). Product 2b was purified by recon-
densation at 0.01 mbar.
Yield: 0.386 g (83%); colorless liquid.
IR (CDCl3): 3000–2900, 1623, 1418, 1239, 1144 cm–1.
1H NMR (400 MHz, C6D6): d = 0.01 (s, 9 H, TMS), 1.33–1.45 (m,
2 H), 1.78–1.84 (m, 2 H), 1.94–2.02 (m, 1 H), 2.12–2.19 (m, 1 H),
3.49–3.55 (m, 1 H, H-4), 5.24–5.26 (m, 1 H, H-2).
13C NMR (100 MHz, C6D6): d = 0.10, 25.36, 31.10, 33.22, 65.13,
115.98, 148.60.
HRMS (APCI–): m/z [M – H]– calcd for C13H16F9O4SSi: 467.0400;
found: 467.0397.
Yield (purity 87% by NMR): 1.00 g (71%); colorless oil.
IR (neat): 2933–2857, 1662, 1467, 1251 cm–1.
1H NMR (400 MHz, C6D6): d = 0.24 (s, 3 H, Me-TBS), 0.31 (s, 3 H,
Me-TBS), 0.32 (s, 9 H, TMS), 1.14 (s, 9 H, t-Bu-TBS), 1.45–1.50
(m, 1 H), 1.60–1.70 (m, 1 H), 1.82–1.93 (m, 2 H), 1.94–2.01 (m, 1
H), 2.02–2.09 (m, 1 H), 4.13 (t, J = 3.93 Hz, 1 H, H-6), 4.96 (dd,
J = 3.0, 4.9 Hz, 1 H, H-2).
13C NMR (100 MHz, C6D6): d = –4.62, –3.98, 0.51, 18.10, 18.50,
24.55, 26.21, 33.46, 68.54, 104.81, 151.94.
HRMS (ESI): m/z [M + H]+ calcd for C15H33O2Si2: 301.2014;
found: 301.2011.
4-Methyl-4-(trimethylsilyloxy)pent-1-en-2-yl Nonaflate (2c;
Table 2, Entry 2)
Compound 2c was prepared according to GP3 from 1c (0.521 g,
2.00 mmol) and NfF (0.785 g, 2.6 mmol), employing KF (0.116 g,
2.00 mmol) and dibenzo-18-crown-6 (0.108 g, 0.30 mmol) in
DMSO–hexane (2 mL:3 mL). Product 2c was isolated by column
chromatography on silica gel (hexane).
Alkenyl Nonaflates 2; General Procedure 3 (GP3)
Exact quantities of the reaction components and solvents are speci-
fied in the individual entries. Finely ground, predried KF (0.058 g,
1.00 mmol) was placed in a reaction flask equipped with a three-
way tap and heated with a heat gun (heating program 350 °C) under
vacuum for 5 min, then cooled under a stream of argon. Dibenzo-
18-crown-6 (0.072 g, 0.20 mmol) was added and the contents were
heated with a heat gun (heating program 150–160 °C) for 2–3 min
and then cooled to r.t. An appropriate reaction medium [DMSO–
hexane (1:1.5) or THF], the corresponding starting bis-silyl ether 1
(1 mmol) and NfF (0.393 g, 1.30 mmol) were successively added,
and the reaction mixture was vigorously stirred under the conditions
(time and temperature) given in Table 2. The reaction progress was
Yield: 0.845 g (90%); colorless oil; Rf = 0.58 (hexane).
IR (neat): 2965–2930, 1665, 1420, 1237, 1145 cm–1.
1H NMR (270 MHz, CDCl3): d = 0.12 (s, 9 H, TMS), 1.32 (s, 6 H,
CMe2), 2.46 (s, 2 H, CH2), 5.03 (d, J = 3.2 Hz, 1 H, H-1), 5.21 (d,
J = 3.2 Hz, 1 H, H-1).
13C NMR (67.5 MHz, CDCl3): d = 2.30, 29.61, 49.00, 72.82,
107.56, 154.34.
HRMS (ESI): m/z [M]+ calcd for C13H19F9O4SSi: 470.0624; found:
1
monitored by H NMR spectroscopy. Unless described otherwise,
upon completion of the reaction, the mixture was diluted with hex-
ane and cooled with a dry ice–MeOH bath. The hexane layer was
decanted; the DMSO layer was allowed to warm to r.t. and the pro-
cedure was repeated four times. The combined hexane extracts were
concentrated and the products were isolated by column chromatog-
raphy on silica gel (hexane or hexane–EtOAc), distillation or recon-
densation under reduced pressure.
470.0625.
3-Methyl-3-(trimethylsilyloxy)but-1-en-2-yl Nonaflate (2d)
Table 2, Entry 3
Compound 2d was prepared according to GP3 from 1d (0.493 g,
2.00 mmol) and NfF (0.785 g, 2.60 mmol), employing KF (0.116 g,
2.00 mmol) and dibenzo-18-crown-6 (0.144 g, 0.40 mmol) in
Synthesis 2011, No. 21, 3507–3515 © Thieme Stuttgart · New York

PAPER
Chemoselective Trimethylsilyl–Nonaflyl Exchange
IR (neat): 2933–2860, 1668, 1420, 1238, 1143 cm–1.
3513
DMSO–hexane (2 mL:3 mL). Product 2d was purified by distilla-
tion.
1H NMR (400 MHz, CDCl3): d = 0.09 (s, 3 H, Me-TBS), 0.10 (s, 3
H, Me-TBS), 0.91 (s, 9 H, t-Bu-TBS), 1.34 (d, J = 6.4 Hz, 3 H, Me-
3), 4.33 (q, J = 6.4 Hz, 1 H, H-3), 5.17 (d, J = 3.42 Hz, 1 H, H-1),
5.26 (dd, J = 3.42, 0.93 Hz, 1 H, H-1).
13C NMR (100 MHz, CDCl3): d = –5.02, –4.96, 18.23, 22.13, 25.80,
67.99, 102.72, 158.93.
Yield: 0.630 g (69%); pale yellow liquid; bp 85–86 °C/0.5 mbar.
IR (neat): 2962–2890, 1663, 1420, 1235, 1142 cm–1.
1H NMR (400 MHz, C6D6): d = 0.12 (s, 9 H, TMS), 1.19 (s, 6 H,
CMe2), 4.74 (d, J = 3.9 Hz, 1 H, H-1), 4.89 (d, J = 3.9 Hz, 1 H, H-1).
13C NMR (100 MHz, C6D6): d = 2.16, 28.12, 73.63, 101.24, 161.26.
HRMS (APCI–): m/z [M – H]– calcd for C12H16F9O4SSi: 455.0400;
HRMS (APCI–): m/z [M – H]– calcd for C14H20F9O4SSi: 483.0713;
found: 483.0705.
found: 455.0388.
6-(tert-Butyldimethylsilyloxy)cyclohex-1-en-1-yl Nonaflate (2h;
Table 2, Entry 8)
Compound 2h was prepared according to GP3 from 1h (0.270 g,
0.90 mmol) and NfF (0.353 g, 1.17 mmol), employing KF (0.052 g,
0.90 mmol) and dibenzo-18-crown-6 (0.065 g, 0.18 mmol) in
DMSO–hexane (1 mL:1.5 mL). Product 2h was purified by column
chromatography on silica gel (hexane–EtOAc, 40:1 to 30:1).
Table 2, Entry 4
Compound 2d was prepared according to GP3 from 1d (4.920 g,
20.00 mmol) and NfF (7.854 g, 26.00 mmol), employing KF (1.16
g, 20.00 mmol) and dibenzo-18-crown-6 (1.44 g, 4.00 mmol) in
DMSO–hexane (20 mL:30 mL). Product 2d was purified as in entry
3; yield: 6.57 g (72%).
Yield: 0.231 g (51%); colorless liquid; Rf = 0.49 (hexane–EtOAc,
20:1).
IR (neat): 2954–2860, 1637, 1419, 1236, 1142 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.10 (s, 3 H, Me-TBS), 0.12 (s, 3
H, Me-TBS), 0.90 (s, 9 H, t-Bu-TBS), 1.56–1.63 (m, 1 H), 1.71–
1.87 (m, 3 H), 2.09–2.18 (m, 1 H), 2.22–2.30 (m, 1 H), 4.29–4.31
(m, 1 H, H-6), 5.86 (dd, J = 3.6, 4.6 Hz, 1 H, H-2).
3-(tert-Butyldimethylsilyloxy)-3-methylbut-1-en-2-yl Nonaflate
(2e; Table 2, Entry 5)
Compound 2e was prepared according to GP3 from 1e (0.240 g,
0.83 mmol) and NfF (0.326 g, 1.08 mmol), employing KF (0.048 g,
0.83 mmol) and dibenzo-18-crown-6 (0.060 g, 0.166 mmol) in
DMSO–hexane (1 mL:1.5 mL). Product 2e was purified by column
chromatography on silica gel (hexane–EtOAc, 40:1).
Yield: 0.298 g (72%); colorless liquid; Rf = 0.51 (hexane–EtOAc,
20:1).
IR (CDCl3): 2933–2859, 1664, 1467, 1238, 1144 cm–1.
1H NMR (400 MHz, C6D6): d = 0.02 (s, 6 H, 2 Me-TBS), 0.93 (s, 9
H, t-Bu-TBS), 1.18 (s, 6 H, CMe2), 4.91 (d, J = 4.0 Hz, 1 H, H-1),
4.96 (d, J = 4.0 Hz, 1 H, H-1).
13C NMR (100 MHz, C6D6): d = –2.26, 18.28, 25.91, 28.08, 73.83,
100.88, 161.15.
13C NMR (100 MHz, CDCl3): d = –4.76, –4.57, 16.98, 18.13, 24.58,
25.86, 33.10, 66.54, 121.03, 150.41.
HRMS (APCI–): m/z [M – H]– calcd for C16H22F9O4SSi: 509.0870;
found: 509.0869.
3-Methyl-4-(trimethylsilyloxy)but-1-en-2-yl Nonaflate (2i)
Table 2, Entry 9
Compound 2i was prepared according to GP3 from 1i (0.247 g, 1.00
mmol) and NfF (0.393 g, 1.30 mmol), employing KF (0.058 g, 1.00
mmol) and dibenzo-18-crown-6 (0.054 g, 0.15 mmol) in DMSO–
hexane (1 mL:1.5 mL). Typical workup followed by purification us-
ing Kugelrohr distillation at 90–95 °C/0.5 mbar afforded product 2i
as a colorless liquid.
HRMS (APCI–): m/z [M – H]– calcd for C15H22F9O4SSi: 497.0870;
found: 497.0866.
(1R,4R,5R)-4,6,6-Trimethyl-4-(trimethylsilyloxy)bicy-
clo[3.1.1]hept-2-en-3-yl Nonaflate (2f; Table 2, Entry 6)
Compound 2f was prepared according to GP3 from 1f (0.313 g, 1.00
mmol) and NfF (0.393 g, 1.30 mmol), employing KF (0.058 g, 1
mmol) and dibenzo-18-crown-6 (0.072 g, 0.20 mmol) in DMSO–
hexane (1 mL:1.5 mL).
Yield: 0.191 g (42%).
IR (neat): 2997–2903, 1659, 1423, 1241, 1145 cm–1.
1H NMR (270 MHz, CDCl3): d = 0.10 (s, 9 H, TMS), 1.15 (d,
J = 6.9 Hz, 3 H, Me-3), 2.54–2.62 (m, 1 H, H-3), 3.54 (dd, J = 10.1,
5.8 Hz, 1 H, H-4), 3.65 (dd, J = 10.1, 5.8 Hz, 1 H, H-4), 4.99 (dd,
J = 3.9, 0.7 Hz, 1 H, H-1), 5.17 (d, J = 3.9 Hz, 1 H, H-1).
13C NMR (67.5 MHz, CDCl3): d = 2.44, 29.79, 49.19, 72.93,
107.71, 154.49.
HRMS (ESI): m/z [M]+ calcd for C12H17F9O4SSi: 456.0468; found:
456.0468.
Yield (purity 88% by NMR): 0.409 g (74%); pale yellow oil.
IR (neat): 2956, 1655, 1419, 1225, 1126 cm–1.
1H NMR (400 MHz, C6D6): d = 0.17 (s, 9 H, TMS), 0.80 (s, 3 H,
Me), 1.04 (s, 3 H, Me), 1.37 (s, 3 H, Me), 1.74–1.79 (m, 1 H, H-1),
1.85 (d, J = 9.4 Hz, 1 H, H-5), 1.95–1.99 (m, 1 H, H-7), 2.06–2.14
(m, 1 H, H-7), 5.96 (d, J = 7.3 Hz, 1 H, H-2).
13C NMR (100 MHz, C6D6): d = 2.41, 23.66, 23.95, 27.32, 32.96,
41.24, 47.17, 55.37, 77.81, 126.72, 149.96.
Table 2, Entry 10
Compound 2i was prepared according to GP3 from 1i (0.247 g, 1.00
mmol) and NfF (0.393 g, 1.30 mmol), employing KF (0.058 g, 1.00
mmol) and dibenzo-18-crown-6 (0.054 g, 0.15 mmol) in anhyd
THF (2 mL). Aqueous workup with ice water–hexane (30 mL, 1:1),
quick extraction with hexane (2 × 15 mL) while the aqueous phase
still contained some ice, and drying of the combined hexane layers
over Na2SO4 followed by Kugelrohr distillation at 90–95 °C/0.5
mbar afforded product 2i; yield: 0.346 g (76%); colorless liquid.
HRMS (APCI–): m/z [M – H]– calcd for C17H22F9O4SSi: 521.0870;
found: 521.0870.
3-(tert-Butyldimethylsilyloxy)but-1-en-2-yl Nonaflate (2g;
Table 2, Entry 7)
Compound 2g was prepared according to GP3 from 1g (1.000 g,
3.64 mmol) and NfF (1.429 g, 4.73 mmol), employing KF (0.211 g,
3.64 mmol) and dibenzo-18-crown-6 (0.262 g, 0.728 mmol) in
DMSO–hexane (3 mL:4.5 mL). Product 2g was purified by column
chromatography on silica gel (hexane–EtOAc, 30:1 to 10:1).
3-(Trimethylsilyloxy)but-1-en-2-yl Nonaflate (2j; Table 3,
Entry 3)
Compound 2j was prepared according to GP3 from 1j (0.968 g, 4.16
mmol) and NfF (1.634 g, 5.41 mmol), employing KF (0.241 g, 4.16
Yield: 1.28 g (73%); pale yellow liquid; Rf = 0.26 (hexane–EtOAc,
10:1).
Synthesis 2011, No. 21, 3507–3515 © Thieme Stuttgart · New York

3514
E. V. Boltukhina et al.
PAPER
mmol) and dibenzo-18-crown-6 (0.300 g, 0.83 mmol) in THF (8
mL). Aqueous workup with ice water–hexane (30 mL, 1:1), quick
extraction with hexane (2 × 15 mL) while the aqueous phase con-
tained still some ice, and drying of the combined hexane layers over
Na2SO4 followed by distillation afforded product 2j.
(7) For the Sonogashira reaction, see refs. 5a, 5b and:
(a) Suffert, J.; Eggers, A.; Scheuplein, S. W.; Brückner, R.
Tetrahedron Lett. 1993, 34, 4177. (b) Okauchi, T.; Yano,
T.; Fukamachi, T.; Ichikawa, J.; Minami, T. Tetrahedron
Lett. 1999, 40, 5337. (c) Lyapkalo, I. M.; Vogel, M. A. K.
Angew. Chem. Int. Ed. 2006, 45, 4019; Angew. Chem. 2006,
118, 4124. (d) Högermeier, J.; Reissig, H.-U. Tetrahedron
2007, 63, 8485. (e) Uemura, M.; Yorimitsu, H.; Oshima, K.
Tetrahedron 2008, 64, 1829.
Yield (purity 80% by NMR): 0.720 g (39%); colorless liquid; bp
73–77 °C/0.5 mbar.
IR (CDCl3): 2960–2924, 1658, 1453, 1234, 1142 cm–1.
1H NMR (400 MHz, C6D6): d = 0.04 (s, 9 H, TMS), 1.11 (d, J = 6.4
Hz, 3 H, Me-3), 4.11 (q, J = 6.4 Hz, 1 H, H-3), 4.79 (dd, J = 3.6, 0.9
Hz, 1 H, H-1), 4.87 (d, J = 3.6 Hz, 1 H, H-1).
13C NMR (100 MHz, C6D6): d = 0.29, 21.88, 67.73, 102.96, 158.90.
HRMS (APCI–): m/z [M – H]– calcd for C11H14F9O4SSi: 441.0238;
found: 441.0234.
(8) Sudo, Y.; Shirasaki, D.; Harada, S.; Nishida, A. J. Am.
Chem. Soc. 2008, 130, 12588.
(9) For iron-catalyzed coupling with arylcopper reagents, see:
Dunet, G.; Knochel, P. Synlett 2006, 407.
(10) For the Wulff–Stille synthesis of vinylstannanes, see: Shipe,
W. D.; Sorensen, E. J. J. Am. Chem. Soc. 2006, 128, 7025.
(11) (a) Hirsch, E.; Hünig, S.; Reissig, H.-U. Chem. Ber. 1982,
115, 3687. (b) Hertenstein, U.; Hünig, S.; Reichelt, H.;
Schaller, R. Chem. Ber. 1986, 119, 699. (c) Zimmer, R.;
Webel, M.; Reissig, H.-U. J. Prakt. Chem./Chem.-Ztg. 1998,
340, 274; and references cited therein. (d) Lyapkalo, I. M.;
Webel, M.; Reissig, H.-U. Eur. J. Org. Chem. 2002, 1015.
(e) Aulenta, F.; Reissig, H.-U. Synlett 2006, 2993.
(12) Högermeier, J.; Reissig, H.-U. Adv. Synth. Catal. 2009, 351,
2747.
Supporting Information for this article is available online at
1
http://www.thieme-connect.com/ejournals/toc/synthesis. H and 13C
NMR spectra for all new compounds are included.
Acknowledgment
(13) Vogel, M. A. K.; Stark, C. B. W.; Lyapkalo, I. M. Synlett
2007, 2907.
(14) Note: The procedure has been extended to the enol
derivatives which are not accessible directly from the
carbonyl precursors; see ref. 3c.
(15) (a) Nelson, T. D.; Crouch, R. D. Synthesis 1996, 1031.
(b) Crouch, R. D. Tetrahedron 2004, 60, 5833.
(16) Schwesinger, R.; Link, R.; Wenzl, P.; Kossek, S. Chem. Eur.
J. 2006, 12, 438.
Financial support by IOCB in the form of grant Z4 055 0506 and a
postdoctoral grant for E.V.B. is gratefully acknowledged. We thank
Lanxess Deutschland GmbH for the generous donation of nonafluo-
robutane-1-sulfonyl fluoride. The authors are grateful to Dr. Mimi
Hii (Imperial College London) and Dr. Ullrich Jahn (IOCB Prague)
for their kind help in the preparation of the manuscript.
References
(17) For examples of TMS for alkali metal or acetyl exchange in
the presence of TMS-protected hydroxy, see: (a) Gooding,
O. W. J. Org. Chem. 1990, 55, 4209. (b) Limat, D.;
Schlosser, M. Tetrahedron 1995, 51, 5799. (c) Yu, W.; Jin,
Z. J. Am. Chem. Soc. 2002, 124, 6576. (d) For the sole
example of enol TMS–Nf exchange in the presence of TMS
ether, see ref. 3e.
(18) For Hg(OAc)2 or Pd(OAc)2 catalyzed TMS for SiCl3
exchange in TMS enol ethers in the presence of TBS- or
TIPS-protected hydroxy, see: (a) Denmark, S. E.;
Stavenger, R. A.; Winter, S. B. D.; Wong, K.-T.; Barsanti, P.
A. J. Org. Chem. 1998, 63, 9517. (b) Denmark, S. E.;
Fujimori, S. Synlett 2001, 1024. (c) Denmark, S. E.; Pham,
S. M. Org. Lett. 2001, 3, 2201. (d) Denmark, S. E.;
Fujimori, S. Org. Lett. 2002, 4, 3477. (e) Denmark, S. E.;
Fujimori, S.; Pham, S. M. J. Org. Chem. 2005, 70, 10823.
(19) Sulfonylation of the deprotected hydroxy group with NfF
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