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