Di-tert-butylmagnesium as an atom-efficient, carbon-centred base reagent for the preparation of silyl enol ethers from ketones

Article abstract of DOI:10.1055/s-2008-1072739

Di-tert-butylmagnesium has been found to be a reactive, yet non-nucleophilic and non-reductive, carbon-centred base for the deprotonation of a series of ketones. This reagent demonstrates equally high reactivity when used as either the pre-formed reagent, or in a more accessible one-pot protocol from the parent Grignard reagent, and offers improved atom-efficiency over more traditionally employed bases. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072739

1386
LETTER
Di-tert-Butylmagnesium as an Atom-Efficient, Carbon-Centred Base Reagent
for the Preparation of Silyl Enol Ethers from Ketones
A
tom-Efficient, Carbon
i
ldBase
l
Reagen
i
t
for th
a
e
P
reparati
m
on of Silyl Enol Ethers J. Kerr,*a Allan J. B. Watson,a Douglas Hayesb
a
Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK
E-mail: w.kerr@strath.ac.uk
b
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
Received 3 March 2008
complementary to Mes2Mg but which also possesses in-
creased atom economy and potential synthetic applica-
tion.
Abstract: Di-tert-butylmagnesium has been found to be a reactive,
yet non-nucleophilic and non-reductive, carbon-centred base for the
deprotonation of a series of ketones. This reagent demonstrates
equally high reactivity when used as either the pre-formed reagent,
or in a more accessible one-pot protocol from the parent Grignard
reagent, and offers improved atom-efficiency over more traditional-
ly employed bases.
During the course of our studies towards the development
of a catalytic magnesium amide recycling system,6,7 we
considered the use of t-Bu2Mg8 as the stock organometal-
lic reagent from which the recycling magnesium amide
would be generated. However, our initial reactions were
fraught with problems relating to the alkylation (via nu-
cleophilic addition) and reduction (via b-hydride elimina-
tion) of the test substrate, cyclohexanone (2a, Scheme 1).
Key words: deprotonations, Grignard reagents, ketones, magne-
sium, organometallic reagents
The use of carbon-centred organometallic reagents to spe-
cifically mediate deprotonation reactions has recently re-
ceived renewed and growing attention.1,2 This is due to the
attractiveness of these protocols in terms of the lowered
number of required additives (and, in turn, reaction
byproducts), simplified reaction setup and, in some cases,
the selectivity exhibited by these processes over more tra-
ditionally used methods.3 Additionally, the potential ba-
sicity of the carbon-centred ligands bound to these
organometallic reagents is considerably greater than that
of more routinely employed metal amide reagents, such as
LDA, and therefore may, in due course, allow the estab-
lishment of synthetic interconversions which are present-
ly inaccessible using the more conventional classes of
reagent. However, the inherent properties of carbon-cen-
tred organometallic complexes can present some disad-
vantages in their use. For example, such highly reactive
reagents can lead to side-product formation and therefore
limit the potential substrate scope.4 Alternatively, low re-
activity can impose the requirement of increased complex
loading and more forcing reaction conditions.5
OH
O
OTMS
HO t-Bu
t-Bu2Mg (1, 1 mol)
+
+
i-Pr2NH (20 mol%), LiCl (2 mol),
TMSCl (4 mol), THF, 0 °C, 18 h
2a
3a
78%
3b
19%
3c
2%
Scheme 1 Initial t-Bu2Mg-based amide deprotonation processes
Interestingly, and despite these preliminary observations,
control reactions performed during the course of this work
revealed that, in the absence of the amine additive, the
conversion to product silyl enol ether was high and, per-
haps more importantly, no evidence of alkylation or re-
duction of the ketone starting material was observed. It
was therefore apparent that the parent t-Bu2Mg reagent
was capable of mediating deprotonation reactions prefer-
entially over addition and reduction processes. As such,
we sought to establish t-Bu2Mg as an efficient carbon-
centred base reagent. In this regard, our initial reactions in
this area were based on standard conditions developed
within our laboratory for chiral magnesium amide mediat-
ed asymmetric deprotonations,9 utilising DMPU and LiCl
as additives (Scheme 2). Here, excellent levels of conver-
sion were demonstrated at a range of temperatures without
the occurrence of side reactions, indicating the robust and
selective nature of this reagent system.
Recently, we described the development of conditions for
the application of bismesitylmagnesium, Mes2Mg, as a
carbon-centred base reagent.1b,c This magnesium-based
compound was shown to react in an efficient and non-nu-
cleophilic sense during the deprotonation and electro-
philic quenching of a series of ketone substrates under
mild reaction conditions (0 °C) while using only 0.5 mol
of the key Mes2Mg reagent. Accordingly, we now wish to
report an extension to these magnesium-based deprotona-
tion methods in the development of di-tert-butylmagne-
O
OTMS
t-Bu2Mg (1, 1 mol)
LiCl (2 mol), DMPU (0.5 mol),
THF, TMSCl (4 mol), Temp (°C), 18 h
sium (1), as
a
carbon-centred base, which is
Temp.: –40 °C, 92% conv.
–20 °C, 91% conv.
2a
3a
–10 °C, 92% conv.
SYNLETT 2008, No. 9, pp 1386–1390
x
x.
x
x.
2
0
0
8
Advanced online publication: 16.04.2008
DOI: 10.1055/s-2008-1072739; Art ID: D06708ST
Scheme 2 Initial reactions using t-Bu2Mg as a base reagent
© Georg Thieme Verlag Stuttgart · New York

LETTER
Atom-Efficient, Carbon-Centred Base Reagent for the Preparation of Silyl Enol Ethers
1387
Driven by these encouraging results, optimisation of this LiCl and TMSCl, the reaction efficiency could be im-
process was subsequently undertaken using –40 °C as the proved by increasing the reaction temperature to 0 °C
standard reaction temperature over 18 hours (Table 1). whereby a 96% conversion to product was recorded with-
Upon completion of the optimisation process, a system out any side products being detected (entry 6). Further it-
had been developed which could deliver 95% conversion erations delivered a procedure that, using only 0.5 mol of
to the desired silyl enol ether 3a at –40 °C using 1 mol of t-Bu2Mg over only one hour reaction time at 0 °C, deliv-
t-Bu2Mg (1), and only 1 equivalent of TMSCl, without the ers almost quantitative conversion to the desired silyl enol
requirement of the Lewis basic promoter DMPU (Table 1, ether 3a (entry 10). It is also worth noting entries 7 and 8,
entry 5).
which demonstrate the robust nature of this reagent and
subsequent deprotonation protocol at ambient and even
more elevated temperatures (40 °C), with no issues aris-
ing from addition or reduction.
Table 1 Optimisation of Additives and Electrophile
Entry
DMPU
(mol)
LiCl
(mol)
TMSCl
(mol)
Conversion
(%)a
Following this successful optimisation programme, the
generality of these conditions with 0.5 mol t-Bu2Mg were
subsequently assessed by application to a series of ketone
substrates (Table 3). Pleasingly, using this novel reagent,
1
2
3
4
5
0
1
0
0
0
2
2
0
1
1
4
4
4
4
1
88
93
29
92
95
Table 3 Application of t-Bu2Mg-Mediated Deprotonation Condi-
tionsa
O
OTMS
R
t-Bu2Mg (1, 0.5 mol), LiCl (1 mol)
R
R
THF, TMSCl (1 mol), 0 °C, 1 h
a Determined by GC analysis; see Typical Experimental Procedure.10
R
Entry
1
Ketone
Product
Yield (%)b
88
Despite the optimisation to this stage, we reasoned that
this process could be rendered more efficient by lowering
the quantity of the organometallic reagent. Di-tert-butyl-
magnesium (1) is dibasic and, therefore, the reaction
should only require 0.5 mol of this reagent for each mol of
substrate, if both alkyl ligands can be used in the deproto-
nation process. With this in mind, a further optimisation
process began using 0.5 mol of t-Bu2Mg as shown in
Table 2.
O
OTMS
2a
3a
OTMS
O
2
3
94
82
Reducing the quantity of t-Bu2Mg to 0.5 mol at –40 °C de-
livered only moderate levels of conversion in the presence
of LiCl and excess TMSCl (Table 2, entries 1 and 2),
while removal of the LiCl additive lowered the conversion
substantially (entry 3). However, with only 1 mol of both
3b
2b
OTMS
O
2c
3c
Table 2 Optimisation of Reaction Variables Using 0.5 mol t-Bu2Mg
OTMS
O
Entry
LiCl
(mol)
TMSCl Temp
Time
(h)
Conversion
(%)a
4
5
6
94
80
90
(mol)
(°C)
–40
–40
–40
–78
–40
0
1
2
2
1
0
1
1
1
1
1
1
1
4
4
4
1
1
1
1
1
1
1
18
18
18
18
18
18
18
18
8
70
72
40
3
t-Bu
3d
t-Bu
2d
O
OTMS
3
4
5
59
96
91
90
98
96
Me
Me
2e
3e
6
OTMS
O
7
r.t.
40
8
OTBS
OTBS
9
0
2f
3f
10
0
1
a See Typical Experimental Procedure.10
b Isolated yield after purification.
a Determined by GC analysis; see Typical Experimental Procedure.10
Synlett 2008, No. 9, 1386–1390 © Thieme Stuttgart · New York

1388
W. J. Kerr et al.
LETTER
excellent isolated yields of silyl enol ether products were Table 4 Application of the One-Pot Deprotonation Process with t-
BuMgCla
obtained, with no alkylated or reduced material being ob-
served in any case.
O
OTMS
t-BuMgCl (1 mol), 1,4-dioxane (1.05 mol)
LiCl (1 mol), TMSCl (1 mol), THF, 0 °C, 1 h
Following this successful first application of t-Bu2Mg as
a carbon-centred base, we next sought to develop a prac-
tically more accessible one-pot procedure which would
operate from the commercially available Grignard re-
agent, t-BuMgCl, and hence avoid the requirement to pre-
form, store, and separately handle the t-Bu2Mg species. In
this regard, treatment of t-BuMgCl with 1,4-dioxane was
used to generate t-Bu2Mg in situ,11 which was then ex-
pected to mediate the desired deprotonation reaction.
Pleasingly, the appreciable reactivity of t-Bu2Mg was
again reflected in this one-pot protocol and, once more,
without alkylation or reduction byproducts being ob-
served (Scheme 3).
R
R
R
R
Entry
1
Ketone
Product
Yield (%)b
OTMS
O
90
89
2a
3a
O
OTMS
2
3
2g
3g
O
OTMS
O
OTMS
t-BuMgCl (1 mol), 1,4-dioxane (1.05 mol)
LiCl (1 mol), TMSCl (1 mol), THF, 0 °C, 1 h
88
70
2a
3a
Ph
2h
Ph
3h
98% conv.
Scheme 3 A one-pot t-Bu2Mg-mediated deprotonation procedure
OTMS
O
As with the initial procedure, the generality of these one-
pot conditions was assessed by application to a series of
ketone substrates. As shown in Table 4, very good to ex-
cellent yields of the desired silyl enol ether products were
recorded following relatively short one-hour reactions at
0 °C to, in turn, establish a significantly more practically
accessible protocol from readily available and routinely
handled starting materials.
4
O
O
O
O
2i
3i
O
OTMS
5
6
85c
82
Ph
Ph
3j
2j
O
OTMS
In conclusion, the developed techniques, as described
here, now establish t-Bu2Mg as a readily applicable non-
nucleophilic carbon-centred base that delivers high yields
of silyl enol ethers from ketones. Notably only 0.5 mol of
the organometallic complex is required for excellent con-
versions to the desired products. Additionally, a consider-
ably more efficient one-pot procedure, utilising the parent
Grignard reagent, t-BuMgCl, has also been formulated.
2k
3k
a See Typical Experimental Procedure.12
b Isolated yield after purification.
c Z/E = 4.8:1.
These processes with t-Bu2Mg are clearly complementary
to our recently disclosed protocols with Mes2Mg,1b,c
whilst offering some potential preparative advantages. In
this regard, t-Bu2Mg exhibits superior reactivity at lower
reaction temperatures and provides greater overall atom-
economy when compared to the equivalent Mes2Mg re-
agent, as well as LDA. Additionally and in summary, the
establishment of these t-Bu2Mg-based protocols further
enhances the distinct set of emerging methods with such
carbon-centred magnesium reagents that are now becom-
ing available to the preparative chemistry community.
port, and the EPSRC Mass Spectrometry Service, University of
Wales, Swansea for analyses.
References and Notes
(1) (a) Nishimura, Y.; Miyake, Y.; Amemiya, R.; Yamaguchi,
M. Org. Lett. 2006, 8, 5077. (b) Kerr, W. J.; Watson, A. J.
B.; Hayes, D. Chem. Commun. 2007, 5049. (c) Kerr, W. J.;
Watson, A. J. B.; Hayes, D. Org. Biomol. Chem. 2008, 6,
1238.
(2) For applications of alternative carbon-centred organo-
metallic reagents in deprotonation reactions, see: (a)
Ph3CK: House, H. O.; Kramar, V. J. Org. Chem. 1963, 28,
3362. (b) Ph3CLi, Ph3CK: House, H. O.; Trost, B. M. J. Org.
Chem. 1965, 30, 1341. (c) AlMe3: Jeffery, E. A.; Meisters,
A. J. Organomet. Chem. 1974, 82, 307. (d) MesLi:
Woodward, R. B.; Logusch, E.; Nambiar, K. P.; Sakan, K.;
Ward, D. E.; Au-Yeung, B.-W.; Balaram, P.; Browne, L. J.;
Acknowledgment
We would like to thank the EPSRC and the Chemistry Innovation
Knowledge Transfer Network (formerly Crystal Faraday) for a stu-
dentship (A.J.B.W.), GlaxoSmithKline for further financial sup-
Synlett 2008, No. 9, 1386–1390 © Thieme Stuttgart · New York

LETTER
Atom-Efficient, Carbon-Centred Base Reagent for the Preparation of Silyl Enol Ethers
1389
Card, P. J.; Chen, C. H.; Chênevert, R. B.; Fliri, A.; Frobel,
mixture was allowed to warm to r.t. before being extracted
with Et2O (1 × 40 mL and 2 × 25 mL). The combined
organic extracts were dried (Na2SO4) and a representative
sample was analysed by GC to obtain the ketone to silyl enol
ether. The solution was then filtered and concentrated in
vacuo to afford a residue which was purified by column
chromatography eluting with 1% Et2O–PE to afford 1-
trimethylsiloxycyclohexene (3a, 150 mg, 88%).13 Gas
chromatography was carried out using a Hewlett Packard
5890 Series 2 Gas Chromatograph fitted with a Varian
WCOT Fused Silica Column containing a CP-SIL 19CB
coating and using H2 as carrier gas (80 kPa): (i) injector and
detector temperature, 200 °C; (ii) initial oven temperature,
45 °C; (iii) temperature gradient, 20 °C min–1; (iv) final oven
temperature, 190 °C; and (v) detection method, FID.
(11) For the preparation of dialkylmagnesium reagents using 1,4-
dioxane, see: Wakefield, B. J. Organomagnesium Methods
in Organic Synthesis; Academic Press: London, 1995.
(12) Typical Experimental Procedure for the Deprotonation
of Ketones Using in situ Generated t-Bu2Mg
K.; Gais, H.-J.; Garratt, D. G.; Hayakawa, K.; Heggie, W.;
Hesson, D. P.; Hoppe, D.; Hoppe, I.; Hyatt, J. A.; Ikeda, D.;
Jacobi, P. A.; Kim, K. S.; Kobuke, Y.; Kojima, K.;
Krowicki, K.; Lee, V. J.; Leutert, T.; Machenko, S.; Martens,
J.; Matthews, R. S.; Ong, B. S.; Press, J. B.; Rajan Babu, T.
V.; Rousseau, G.; Sauter, H. M.; Suzuki, M.; Tatsuta, K.;
Tolbert, L. M.; Truesdale, E. A.; Uchida, I.; Ueda, Y.;
Uyehara, T.; Vasella, A. T.; Vladuchick, W. C.; Wade, P. A.;
Williams, R. M.; Wong, H. N.-C. J. Am. Chem. Soc. 1981,
103, 3210. (e) n-BuLi, AlMe3: Seebach, D.; Ertaş, M.;
Locher, R.; Schweizer, W. B. Helv. Chim. Acta 1985, 68,
264. (f) n-BuLi, AlMe3: Ertaş, M.; Seebach, D. Helv. Chim.
Acta 1985, 68, 961.
(3) For both the efficacy and issues with reagents such as the
commonly used lithium-based amides, see: (a) Bakker, W.
I. I.; Wong, P. L.; Snieckus, V. In Encyclopedia of Reagents
for Organic Synthesis, Vol. 5; Paquette, L. A., Ed.; Wiley:
Chichester, 1995, 3096. (b) Heathcock, C. H. In Modern
Synthetic Methods, Vol. 3; Scheffold, R., Ed.; Wiley-VCH:
New York, 1992, 3. (c) Caine, D. In Comprehensive
Organic Synthesis, Vol. 3; Trost, B. M.; Fleming, I., Eds.;
Pergamon: Oxford, 1991, 1. (d) Kowalski, C.; Creary, X.;
Rollin, A. J.; Burke, M. C. J. Org. Chem. 1978, 43, 2601.
(4) For example, n-BuLi will deliver mostly addition products
when used in a general sense with ketones. Only in specific
cases will n-BuLi act solely as a base reagent. For general
information on the reactivity of n-BuLi, see: (a) Brandsma,
L.; Verkruijsse, H. D. Preparative Polar Organometallic
Chemistry; Springer: Berlin, 1987. (b) Brandsma, L.;
Verkruijsse, H. D. Synthesis of Acetylenes, Allenes and
Cumulenes, A Laboratory Manual; Elsevier: Amsterdam,
1981. (c) For the use of base reagent mixtures with n-BuLi,
see ref. 2e and 2f.
(5) For example, for GaEt3 to perform effectively in
deprotonation reactions, 1.5 mol of the complex (i.e., 4.5
equiv of base) was required at 125 °C; see ref. 1a.
(6) Kerr, W. J.; Watson, A. J. B. unpublished results.
(7) Dinsmore, A.; Billing, D. G.; Mandy, K.; Michael, J. P.;
Mogano, D.; Patil, S. Org. Lett. 2004, 6, 293.
(8) (a) Starowieyski, K. B.; Lewinski, J.; Wozniak, R.; Chrost,
A. Organometallics 2003, 22, 2458. (b) Kamienski, C. W.;
Eastham, J. F. J. Organomet. Chem. 1967, 8, 542.
(9) (a) Bassindale, M. J.; Crawford, J. J.; Henderson, K. W.;
Kerr, W. J. Tetrahedron Lett. 2004, 45, 4175. (b) Carswell,
E. L.; Hayes, D.; Henderson, K. W.; Kerr, W. J.; Russell, C.
J. Synlett 2003, 1017. (c) Henderson, K. W.; Kerr, W. J.;
Moir, J. H. Tetrahedron 2002, 58, 4573. (d) Anderson, J.
D.; García García, P.; Hayes, D.; Henderson, K. W.; Kerr,
W. J.; Moir, J. H.; Fondekar, K. P. Tetrahedron Lett. 2001,
42, 7111. (e) Henderson, K. W.; Kerr, W. J.; Moir, J. H.
Chem. Commun. 2001, 1722. (f) Henderson, K. W.; Kerr,
W. J.; Moir, J. H. Synlett 2001, 1253. (g) Henderson, K. W.;
Kerr, W. J.; Moir, J. H. Chem. Commun. 2000, 479.
(10) Typical Experimental Procedure for the Deprotonation
of Ketones Using (Isolated) t-Bu2Mg
A Schlenk tube was charged with LiCl (1 mmol, 85 mg) and
flame-dried under vacuum. The tube was purged three times
with N2 before being cooled to r.t. and charged with t-
BuMgCl (1 M solution in THF, 1 mmol, 1 mL), 1,4-dioxane
(1.05 mmol, 88 mg, 0.09 mL), and THF (9 mL). The mixture
was stirred for 15 min at r.t. before being cooled to 0 °C.
Then, TMSCl (1 mmol, 109 mg, 0.13 mL) was added and the
mixture was stirred for 5 min before addition of 1,4-
cyclohexanedione monoethylene ketal (2i, 1 mmol, 156 mg)
as a solution in THF (2 mL) over 1 h via syringe pump. The
reaction mixture was stirred at 0 °C under N2 for 1 h before
being quenched with sat. NaHCO3 aq soln (10 mL). The
mixture was allowed to warm to r.t. before being extracted
with Et2O (1 × 40 mL and 2 × 25 mL). The combined
organic extracts were dried (Na2SO4), and a representative
sample was analysed by GC (see ref. 10) to obtain the
conversion value of ketone to silyl enol ether. The solution
was then filtered and concentrated in vacuo to afford a
residue which was purified by column chromatography
eluting with 1% Et2O–PE to afford 8-trimethylsilyloxy-1,4-
dioxaspiro[4.5]dec-7-ene (3i, 160 mg, 70%).13
(13) Product Data
1-Trimethylsilyloxycyclohexene (3a):14,15,16a,17 IR (CH2Cl2):
n
max = 1668 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.18 [s,
9 H, Si(CH3)3], 1.48–1.54 (m, 2 H, CH2), 1.63–1.69 (m, 2 H,
CH2), 1.97–2.03 (m, 4 H, 2 × CH2), 4.86–4.88 (m, 1 H, CH).
1-Trimethylsiloxycyclopentene (3b):14,15,16b,18 IR (CH2Cl2):
n
max = 1645 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.20 [s,
9 H, Si(CH3)3], 1.82–1.90 (m, 2 H, CH2), 2.24–2.29 (m, 4 H,
2 × CH2), 4.62–4.63 (m, 1 H, CH).
6-Methyl-1-trimethylsilyloxy-1-cyclohexene (3c):14,15,17 IR
(CH2Cl2): nmax = 1660 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.19 [s, 9 H, Si(CH3)3], 1.04 (d, 3 H, CH3, J = 7.0 Hz),
1.36–1.41 (m, 1 H, CH), 1.45–1.49 (m, 1 H, CH), 1.57–1.59
(m, 1 H, CH), 1.78–1.82 (m, 1 H, CH), 1.98–2.02 (m, 2 H,
CH2), 2.14–2.15 (m, 1 H, CH), 4.81 (td, 1 H, CH, J = 3.95,
1.20 Hz).
A Schlenk tube was charged with LiCl (1 mmol, 42.5 mg)
and flame-dried under vacuum. The tube was purged three
times with N2 before being cooled to r.t. and charged with t-
Bu2Mg (0.5 M solution in THF, 0.5 mmol, 1 mL) and THF
(9 mL). The mixture was stirred for 15 min at r.t. before
being cooled to 0 °C. Then, TMSCl (1 mmol, 109 mg, 0.13
mL) was added and the mixture was stirred for 5 min before
addition of cyclohexanone (2a, 1 mmol, 98 mg) as a solution
in THF (2 mL) over 1 h via syringe pump. The reaction
mixture was stirred at 0 °C under N2 for 1 h before being
quenched with sat. aq NaHCO3 solution (10 mL). The
4-tert-Butyl-1-trimethylsilyloxy-1-cyclohexene (3d):9c,19,20
IR (CH2Cl2): nmax = 1672 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.19 [s, 9 H, Si(CH3)3], 0.90 (s, 9 H, 3 × CH3), 1.21–1.29
(m, 2 H, CH2), 1.78–1.85 (m, 2 H, CH2), 1.98–2.09 (m, 3 H,
CH and CH2), 4.84–4.86 (m, 1 H, CH).
4-Methyl-1-trimethylsilyloxy-1-cyclohexene (3e):9c,19,20 IR
(CH2Cl2): nmax = 1669 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.18 [s, 9 H, Si(CH3)3], 0.95 (d, 3 H, CH3, J = 6.3 Hz),
1.29–1.34 (m, 1 H, CH), 1.62–1.73 (m, 3 H, CH and CH2),
1.93–2.00 (m, 1 H, CH), 2.05–2.09 (m, 2 H, CH2), 4.82–4.83
Synlett 2008, No. 9, 1386–1390 © Thieme Stuttgart · New York

1390
W. J. Kerr et al.
(m, 1 H, CH).
LETTER
(CH2Cl2): nmax = 1638 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.38 [s, 9 H, Si(CH3)3], 2.42–2.47 (m, 2 H, CH2), 2.89 (t,
2 H, CH2, J = 7.8 Hz), 5.32 (t, 1 H, CH, J = 4.6 Hz), 7.21–
7.36 (m, 3 H, 3 × ArCH), 7.54 (d, 1 H, ArCH, J = 7.4 Hz).
(14) Bonafoux, D.; Bordeau, M.; Biran, C.; Cazeau, P.;
Dunogues, J. J. Org. Chem. 1996, 61, 5532.
4-(tert-Butyldimethylsiloxy)-1-trimethylsilyloxy-1-cyclo-
hexene (3f):20 IR (CH2Cl2): nmax = 1668 cm–1. 1H NMR (400
MHz, CDCl3): d = 0.06 {s, 3 H, Si[C(CH3)3]CH3}, 0.07 {s,
3 H, Si[(C(CH3)3]CH3}, 0.18 [s, 9 H, Si(CH3)3], 0.89 [s, 9 H,
Si(C(CH3)3], 1.60–1.83 (m, 2 H, CH2), 1.97–2.16 (m, 3 H,
CH and CH2), 2.17–2.27 (m, 1 H, CH), 3.84–3.93 (m, 1 H,
CH), 4.66–4.73 (m, 1 H, C=CH).
(15) House, H. O.; Czuba, L. J.; Gall, M.; Olmstead, H. D. J. Org.
Chem. 1969, 34, 2324.
1-Trimethylsilyloxycycloheptene (3g):21 IR (CH2Cl2): nmax
=
(16) (a) Commercially available from Aldrich Chemical Co.,
CAS# [6651-36-1], cat. no. 144819; (b) Commercially
available from Aldrich Chemical Co., CAS# [19980-43-9],
cat. no. 283126; (c) Commercially available from Aldrich
Chemical Co., CAS# [38858-72-9], cat. no. 540390.
(17) Kopka, I.; Rathke, M. W. J. Org. Chem. 1981, 46, 3771.
(18) Heathcock, C. H.; Davidsen, S. K.; Hug, K. T.; Flippin, L.
A. J. Org. Chem. 1986, 51, 3027.
(19) Graf, C.-D.; Malan, C.; Knochel, P. Angew. Chem. Int. Ed.
1998, 37, 3014.
(20) Graf, C.-D.; Malan, C.; Harms, K.; Knochel, P. J. Org.
Chem. 1999, 64, 5581.
(21) Rathore, R.; Kochi, J. K. J. Org. Chem. 1996, 61, 627.
(22) (a) Crawford, J. J.; Kerr, W. J.; McLaughlin, M.; Morrison,
A. J.; Pauson, P. L.; Thurston, G. J. Tetrahedron 2006, 62,
11360. (b) Kerr, W. J.; McLaughlin, M.; Morrison, A. J.;
Pauson, P. L. Org. Lett. 2001, 3, 2945. (c) Loon, H.-Y.;
Lee, S.; Kim, D.; Kim, B. K.; Bahn, J. S.; Kim, S.
Tetrahedron Lett. 1998, 39, 7713.
(23) Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Pirrung, M.
C.; Sohn, J. E.; Lampe, J. J. Org. Chem. 1980, 45, 1066.
(24) Davis, F. A.; Sheppard, A. C.; Chen, B.-C.; Haque, M. S.
J. Am. Chem. Soc. 1990, 112, 6679.
1660 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.18 [s, 9 H,
Si(CH3)3], 1.50–1.59 (m, 4 H, 2 × CH2), 1.66–1.70 (m, 2 H,
CH2), 1.97–2.01 (m, 2 H, CH2), 2.22–2.24 (m, 2 H, CH2),
4.86–4.88 (m, 1 H, CH).
4-Phenyl-1-trimethylsilyloxy-1-cyclohexene (3h):19,20 IR
(CH2Cl2): nmax = 1669 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.24 [s, 9 H, Si(CH3)3], 1.86–1.93 (m, 1 H, CH), 1.96–
1.99 (m, 1 H, CH), 2.06–2.11 (m, 1 H, CH), 2.19–2.34 (m, 3
H, CH and CH2), 2.76–2.78 (m, 1 H, CH), 4.97–4.98 (m, 1
H, CH), 7.19–7.34 (m, 5 H, C6H5).
8-Trimethylsilyloxy-1,4-dioxaspiro[4.5]dec-7-ene (3i):22 IR
(CH2Cl2): nmax = 1671 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.15 [s, 9 H, Si(CH3)3], 1.81 (t, 2 H, CH2, J = 6.6 Hz),
2.20–2.23 (m, 2 H, CH2), 2.25–2.28 (m, 2 H, CH2), 3.95–
4.01 (m, 4 H, CH), 4.73 (m, 1 H).
1-Phenyl-1-trimethylsilyloxyprop-1-ene (3j):14,18,23,24 IR
(CH2Cl2): nmax = 1686, 1652 cm–1. 1H NMR (400 MHz,
CDCl3): d (Z-isomer) = 0.17 [s, 9 H, Si(CH3)3], 1.76 (d, 3 H,
CH3, J = 6.9 Hz), 5.35 (q, 1 H, CH, J = 6.9 Hz), 7.23–7.49
(m, 5 H, 5 × ArCH); d (E-isomer) = 0.15 [s, 9 H, Si(CH3)3],
1.73 (d, 3 H, CH3, J = 7.3 Hz), 5.13 (q, 1 H, CH, J = 7.3 Hz),
7.23–7.49 (m, 5 H, C6H5).
(3,4-Dihydro-1-naphthyloxy)trimethylsilane (3k):16c,21 IR
Synlett 2008, No. 9, 1386–1390 © Thieme Stuttgart · New York

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