Silazanes/catalytic bases: Mild, powerful and chemoselective agents for the preparation of enol silyl ethers from ketones and aldehydes

Article abstract of DOI:10.1039/b203783c

We have developed an efficient method for the preparation of enol silyl ethers using novel agents, silazanes together with NaH or DBU catalyst, wherein TMS and TBDMS groups were smoothly and chemoselectively introduced into ketones and aldehydes under mil

Full text of DOI:10.1039/b203783c

Silazanes/catalytic bases: mild, powerful and chemoselective agents for
the preparation of enol silyl ethers from ketones and aldehydes
Yoo Tanabe,* Tomonori Misaki, Minoru Kurihara, Akira Iida and Yoshinori Nishii
Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen,
Sanda, Hyogo 669-1337, Japan
Received (in Cambridge, UK) 18th April 2002, Accepted 5th June 2002
First published as an Advance Article on the web 28th June 2002
We have developed an efficient method for the preparation
of enol silyl ethers using novel agents, silazanes together with
NaH or DBU catalyst, wherein TMS and TBDMS groups
were smoothly and chemoselectively introduced into ketones
and aldehydes under mild conditions.
conventional TMSCl–Et3N under identical conditions (for 0.5
h; conversion yield; 100% and 0%, respectively).
A plausible reaction mechanism is proposed in Scheme 2 as
exemplified by the use of 1. First, catalytic NaH deprotonates a
ketone to form the enolate, which is trapped with 1 to furnish the
enol silyl ether while releasing the amidate anion. The anion, in
turn, deprotonates a ketone to reform the enolate, thus
completing the catalytic cycle.
Enol silyl ethers are widely employed as reactive precursors for
carbonyl compounds in a wide range of organic syntheses, for
various regio-, chemo- and stereoselective reactions.1 Conven-
tional preparations of enol silyl ethers use chlorosilanes with
amine (e.g. Et3N) and amide (e.g. LDA) agents.
We attempted to extend this work to aldehydes, because there
are few general methods that cover both ketones and aldehydes.
The NaH catalysis system, however, resulted in polymerization
of aldehydes. After screening milder amine–base catalysts, such
as Et3N, pyridine, TMEDA, etc., only DBU successfully
converted aldehydes into the desired enol silyl ethers (TMS and
TBDMS) (Table 2).§ Salient features are as follows. (a) Similar
to the case of ketones, among the same N-(TMS)amines
screened, N-methyl-N-(TMS)acetamide (1) gave the best re-
sults. (b) For preparation of enol TBDMS ethers, O-
(TBDMS)benzamide3c (3; Si-BEZA) was slightly better than
N,O-bis(TBDMS)acetamide (2). (c) DMF solvent was better
than cyclohexane. (d) Several aldehydes, including an a,b-
unsaturated aldehyde, 2-methylpentenal, were applicable.
A notable aspect of the present protocol is the highly
chemoselective conversion of aldehydes compared to ketones
(Scheme 3).
Despite these two well-established methods, there still
remains a need for an alternative method with improved
efficiency, that is, for an elaborate and practical scale synthesis
from a recent recognized standpoint of green chemistry.
All previously reported methods require more than equimolar
amounts of the bases to generate the enolate anion and/or to
capture HCl, except for the method using TMS–acetate/cat.
TBAF,2 which is not applicable to reactions with aldehydes due
to the predominant aldol addition of TMS–acetate with
aldehydes. In connection with the interest of mild, powerful
silylations of alcohols by specific catalytic promoters,3 we
present an efficient method for preparing enol silyl (TMS and
TBDMS) ethers applicable to both ketones and aldehydes using
a novel agent; available silazanes 1, 2, 3 with catalytic NaH for
ketones and with catalytic DBU for aldehydes (Scheme 1).
Table 1 lists the results for the ketones. Salient features are as
follows. (a) Among the commercially available N-(TMS)a-
mines screened, N-methyl-N-(TMS)acetamide (1) gave the best
result.† (b) Unreactive a,a-disubstituted and a-chloro ketones,
and labile a,b-unsaturated ketones could be converted under
mild and practical conditions. (c) Both polar DMF and
hydrophobic cyclohexane solvents were available. (d) Enol
TBDMS-ethers were obtained by the use of available N,O-
bis(TBDMS)acetamide (2). (e) On the regiochemistry, thermo-
dynamic controlled products were generally obtained.
In conclusion, we have developed a new type of mild,
practical, chemoselective method for preparing various enol
silyl ethers using neutral silazanes and catalytic bases.
Although the silyl halide method requires a slightly tedious
work-up procedure to remove HX and/or HX·amine because
enol silyl ethers are susceptible to such acids, the present nearly
neutral method has a practical advantage of easy isolation of
enol silyl ethers.‡ Regarding the reactivity, parallel experiments
of unreactive diisopropyl ketone demonstrated that the present
method is considered to surpass the two methods that use
Scheme 2
Scheme 1
Scheme 3
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Table 1 Preparation of enol silyl ethers from ketones using silazanes 1 and
2/cat. NaH
Table 2 Preparation of enol silyl ethers from aldehydes using silazanes 1, 2
and 3/cat. DBU
Product yield/%b
(Ratio)c
Product yield/%b
(Ratio)
Ketone
Silazane
Conditionsa
Aldehyde
Silazane
Conditionsa
1
1
2
3
A
B
C
C
86 (23+77)c
58 (43+57)c
65 (39+61)c
89 (38+62)c
1
1
2
A
B
C
84 (18+82)
94 (57+43)
77 (24+76
1
3
A
C
96d
94d
1
1
2
A
B
C
87 (98+2)
94 (98+2)
95 (95+5)
1
A
96
1
1
A
B
84 (16+60+24)
90 (15+64+21)
1
3
A
C
70d
92d
a A: In DMF at 15–20 °C. B: In cyclohexane at 15–20 °C. C: In DMF at 60
°C. b Isolated yields (100% GC conversions). c GLC analysis. d E/Z ratios
were not determined.
1
D
94
mide (3%), N-(TMS)morpholine (trace), N-(TMS)aniline (trace), N,O-
bis(TMS)hydroxylamine (trace).
‡ Typical procedure of the gram-scale experiment for ketones: N-methyl-N-
(TMS)acetamide (1; 8.72 g, 60.0 mmol) was added to a stirred suspension
of 2,6-dimethylcyclohexane (5.05 g, 40.0 mmol) and NaH (48 mg, 2.0
mmol) in cyclohexane (40 cm3) at 15–20 °C and the mixture was stirred for
1 h. Cool water (40 cm3) was added to the mixture, which was extracted
with hexane (20 cm3 3 2). The combined organic phase was washed with
water (40 cm3), brine, dried (Na2SO4), concentrated and distilled to give the
desired product (colorless oil; bp 49–50 °C, 1.8–2.2 mmHg; 7.54 g, 94%).
1H NMR (400 MHz; CDCl3): d 0.17 (9H, s), 1.04 (3H, d, J = 6.8 Hz),
1.32–1.39 (1H, m), 1.41–1.50 (1H, m), 1.54–1.55 (3H, m), 1.56–1.66 (1H,
m), 1.74–1.81 (1H, m), 1.92–1.96 (2H, m), 2.07–2.17 (1H, m). 13C NMR
(100 MHz; CDCl3): d 0.60, 16.81, 18.93, 20.46, 30.78, 32.24, 34.05,
112.01, 147.02.
1
1
2
A
B
96 (99+1)
trace
88 (99+1)
A (8 h)
1
A
84 (10+90)
§ Typical procedure of gram-scale experiment for aldehydes: N-methyl-N-
(TMS)acetamide (1; 8.72 g, 60.0 mmol) was added to a stirred solution of
octanal (5.13 g, 40.0 mmol) and DBU (305 mg, 2.0 mmol) in DMF (40 cm3)
at 20–25 °C and the mixture was stirred for 1 h. The mixture was extracted
with pentane and the separated pentane phase was washed with cool water,
and brine, dried (Na2SO4), concentrated and distilled to give the desired
product [colorless oil; bp 49–53 °C (oven temp. of Kügelrohr)/0.8 mmHg;
1
1
A
B
81
88
1
B
72
a A: In DMF at 15–20 °C for 0.5–1.0 h. B: In cyclohexane at 15–20 °C for
0.5–1.0 h. C: In DMF at 60 °C for 1.0–2.0 h. D: In cyclohexane at 60 °C for
0.5 h. b Isolated yields (100% GC conversions). c GLC and/or 1H NMR
analysis.
1
6.63 g, 83 %, E/Z = 20/80 determined by GLC and 1H NMR]. H NMR
(400 MHz; CDCl3): d 0.18 (9H, s), 0.88 (3H, t, J = 6.8 Hz), 1.22–1.36 (8H,
m), 1.84–1.91 (0.43H, m), 2.01–2.12 (1.57H, m), 4.46–4.51 (0.80H, m),
4.96–5.02 (0.20H, m), 6.12–6.15 (0.80H, m), 6.17–6.20 (0.20H, m).
1 E. W. Colvin, Silicon in Organic Synthesis, Butterworths, London, 1981,
pp. 198–287; M. B. Smith and J. March, MarchAs Advanced Organic
Chemistry, 5th ed., Wiley, New York, 2001, p. 793; J. K. Rasmussen,
Synthesis, 1977, 91; P. Brownbridge, Synthesis, 1983, 85; I. Fleming, A.
Barbero and D. Walter, Chem. Rev., 1997, 97, 2063; A. M. El-Khawaga
and H. M. R. Hoffmann, J. Pract. Chem., 1995, 337, 332.
This research was partially supported by a Grant-in-Aid for
Scientific Research on Priority Areas (A) BExploitation of
Multi-Element Cyclic MoleculesB and on Basic Areas (C) from
the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
2 E. Nakamura, T. Murofushi, M. Shimizu and I. Kuwajima, J. Am. Soc.
Chem., 1976, 98, 2346.
3 (a) Y. Tanabe, M. Murakami, K. Kitaichi and Y. Yoshida, Tetrahedron
Lett., 1994, 35, 8409; (b) Y. Tanabe, H. Okumura, A. Maeda and M.
Murakami, Tetrahedron Lett., 1994, 35, 8413; (c) T. Misaki, M. Kurihara
and Y. Tanabe, Chem. Commun., 2001, 2478.
Notes and references
† N-(TMS)imidazaole (under the identical conditions of Table 1, entry 1;
55%), N,O-bis(TMS)acetamide (78%), N-methyl-N-(TMS)trifluoroaceta-
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