Highly selective 1,2- and 1,4-addition of silyl enol ethers to α,β- unsaturated carbonyl compounds in 5 M lithium perchlorate-nitromethane medium

Full text of DOI:10.1021/jo982363b

J . Org. Chem. 1999, 64, 2155-2157
2155
likely to be higher than that in ether. Also, the dielectric
constant and the dipole moment of nitromethane are
higher than ether, and hence, the formation of polar and
ionic intermediates is more favored in nitromethane than
in ether.11 Recently we have observed that the aldol
reaction of silyl enol ethers to aldehydes and ketones
proceeded in 5 M LPNM at room temperature whereas
the same reaction failed to proceed in 5 M LPDE.12
Herein we report the results of our study on the addition
of silyl enol ethers to R,â-unsaturated aldehydes and
ketones in which high regioselectivity has been observed.
High ly Selective 1,2- a n d 1,4-Ad d ition of
Silyl En ol Eth er s to r,â-Un sa tu r a ted
Ca r bon yl Com p ou n d s in 5 M Lith iu m
P er ch lor a te-Nitr om eth a n e Med iu m †
S. Sankararaman* and R. Sudha
Department of Chemistry, Indian Institute of Technology,
Madras, Chennai-600 036, India
Received December 1, 1998
Resu lts a n d Discu ssion
In tr od u ction
In a typical experiment to a solution of the R,â-
unsaturated carbonyl compound (2 mmol) in 2 mL of 5
M LPNM under nitrogen atmosphere was added the silyl
enol ether (6 mmol) and the mixture was stirred at room
temperature until the disappearance of the starting
materials, followed by TLC. Addition of silyl enol ethers
1 and 2 to unsaturated ketones 3a ,b led to the formation
of the corresponding Michael addition products 4a ,b and
5a ,b, respectively (Table 1). The products were purified
either by column chromatography or by preparative TLC
on silica gel. Analysis of the 1H NMR spectra of the crude
products revealed that the addition was highly regiose-
lective in that only the Michael adducts 4a ,b and 5a ,b
were formed as nearly a 1:1 mixture of diastereoisomers
and the 1,2-addition products 6a ,b and 7a ,b were not
formed in these reactions. In sharp contrast, when silyl
enol ethers 1 and 2 were reacted with unsaturated
aldehydes 3c,d it resulted in the predominant formation
of the 1,2-addition products 6c,d and 7c,d , respectively.
The Michael adducts 4c,d and 5c,d were formed in less
than 10% as indicated by the minor peaks corresponding
to these products in the 1H NMR spectra of the crude
products.
Addition of enol ethers 1 and 2 to cyclic R,â-unsatur-
ated ketones 8a ,b gave the corresponding Michael ad-
ducts 9a ,b and 10a ,b, respectively in good yields (Table
2). However, the more hindered â-substituted ketone 8c
failed to undergo Michael reaction in LPNM with silyl
enol ethers 1 and 2 as well as the more reactive ketene
silyl acetal 11. The lack of reactivity of 8c in LPNM
parallels its behavior in LPDE, reported by Grieco.6
Addition of ketene silyl acetal 11 to 3d resulted in the
formation of 13b18 exclusively, whereas with 3a it yielded
predominantly 12a .19
Highly concentrated solutions of lithium perchlorate
in various organic solvents have been used to effect
several synthetic transformations,1 and tremendous rate
acceleration as well as high selectivities have been
reported.2 We have reported high chemoselectivity in the
thioacetalization of carbonyl compounds,3 substitution of
acetals,4 and the Michael reaction5 in 5 M lithium
perchlorate in diethyl ether (5 M LPDE). Although
Michael addition of silyl enol ethers to nitro- and cyano-
olefins is facile in 5 M LPDE at room temperature, we
observed that the more commonly used Michael accep-
tors, namely, the R,â-unsaturated carbonyl compounds,
failed to undergo any reaction in this medium. The more
reactive ketene silyl acetals have been reported to
undergo Michael addition to R,â-unsaturated carbonyl
compounds in LPDE.6 Recently, Ayerbe and Cossio have
reported that lithium perchlorate in nitromethane (LPNM)
appears to be a much better medium than LPDE in
promoting certain Diels-Alder reactions.7 The lithium
ion in LPDE is a mild Lewis acid due to solvation.8 The
Lewis acidity of lithium ion is a major factor,9 although
probably not the only factor that governs the reactivity
of organic substrates in these media. The Lewis acidity
of lithium ion plays a major role in the activation of
organic substrates by coordination to the lone pairs on
the heteroatoms in these media and the consequent rate
acceleration of organic transformations.9 The donor num-
ber of nitromethane is lower than that of ether (2.7 vs
19.2 kcal mol-1),10 and hence, the Lewis acidity of lithium
ion in a less coordinating solvent like nitromethane is
† Dedicated to Prof. Dr. M. V. George, Photochemistry Division, RRL
(CSIR), Trivandrum, India, on the occasion of his 70th birthday.
(1) Grieco, P. A. Aldrichim. Acta 1991, 24, 59-66. (b) Waldmann,
H. Angew. Chem., Int. Ed. Engl. 1991, 30, 1306-1308. (c) Grieco, P.
A. In Organic Chemistry; Its Language and Its State of Art; ed. V.,
Kisaku¨rek, Ed.; VCH: Basel, 1993; pp 133-146. (d) Flohr A.; Wald-
mann, H. J . Prakt. Chem. 1995, 337, 609-611.
(2) Grieco, P. A.; Nunes, J . J .; Gaul, M. D. J . Am. Chem. Soc. 1990,
112, 4595-4596.
(3) Geetha Saraswathy, V.; Sankararaman, S. J . Org. Chem. 1994,
59, 4665-4670.
(4) Geetha Saraswathy, V.; Sankararaman, S. J . Chem. Soc., Perkin
Trans. 2 1996, 29-31.
(5) Geetha Saraswathy, V.; Sankararaman, S. J . Org. Chem. 1995,
60, 5024-5028.
In the IR spectroscopic studies, the CdO stretching
frequency of 3d is 1724 cm-1 in nitromethane and it is
(6) Grieco, P. A.; Cooke, R. J .; Henry, K. J .; Vander Roest, J . M.
Tetrahedron Lett. 1991, 32, 4665-4668.
(7) Ayerbe, M.; Cossio, F. P. Tetrahedron Lett. 1995, 36, 4447.
(8) Pagni, R. M.; Kabalka, G. W.; Bains, S.; Plesco, M.; Wilson, J .;
Bartmess, J . J . Org. Chem. 1993, 58, 3130-3133.
(9) Forman, M. A.; Dailey, W. P. J . Am. Chem. Soc. 1991, 113, 2761-
2762.
(10) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry,
2nd ed.; VCH: Weinheim, 1990; pp 20-22.
(11) Rajan Babu, T. V. J . Org. Chem. 1984, 49, 2083-2089.
(12) Sudha, R. Ph.D. Thesis, IIT, Madras, India, 1998.
(13) Wade, M.; Tokeichi, E.; Matsumoto, T. Bull. Chem. Soc. J pn.
1991, 64, 990-994.
(14) Roux, C. L.; Gaspard-Iloughmane, H.; Dubac, J .; J and, J .;
Vignaux, P. J . Org. Chem. 1993, 58, 1835-1839.
10.1021/jo982363b CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/03/1999

2156 J . Org. Chem., Vol. 64, No. 6, 1999
Notes
Ta ble 1. Ad d ition of Silyl En ol Eth er s to
r,â-Un sa tu r a ted Ca r bon yl Com p ou n d s in 5 M LP NM
depends on the basicity of the medium. We propose that
the 1,2-addition occurs by the reaction of the silyl enol
ether to the carbonyl group that is activated by the
coordination of the lithium ion.3 In the case of ketones,
for the 1,4-addition to proceed it is necessary to use at
least 2 equiv of the silyl enol ether which parallels the
behavior observed in the Michael addition reactions in
LPDE.5 Hence we conclude that the silyl transfer mech-
anism proposed earlier in the case of the Michael reac-
tions in LPDE medium5 might operate for the 1,4-
addition reactions in LPNM. The increased Lewis acidity
of the lithium ion is responsible for the enhanced reactiv-
ity of R,â-unsaturated carbonyl compounds toward silyl
enol ethers in LPNM in comparison to that in LPDE.
acceptor
R1 R2
yield (%)a
1,4-addition 1,2-addition
enol
ether
time
(h)
ref
1
2
1
2
1
1
2
3a Ph Me
Ph Me
3b Ph Ph
Ph Ph
8
16
10
20
17
16
24
4a
5a
4b
5b
4c
4d
5d
80
85
82
6a
7a
6b
7b
6c
6d
7d
0
0
0
13
14
15
15
78
0
3c Me
3d Ph
Ph
H
H
H
<10b
<10b
<10b
73
75
70
Exp er im en ta l Section
16
a
b
Isolated yield after purification. Based on 1H NMR spectral
Gen er a l Meth od s. Preparation of 5 M LPDE and the
instrumentation used are described earlier.3 Nitromethane (1
L) (analytical grade) was mixed with concentrated H2SO4 (150
mL) and allowed to stand for 24 h at room temperature. It was
separated and washed with water followed by aqueous NaHCO3
and then again with water. It was dried over anhydrous CaCl2,
filtered, and fractionally distilled using a vigreux column. The
distillate was stored over activated molecular sieve (4 Å) in an
amber colored bottle. Anhydrous lithium perchlorate (53 g) was
dissolved in dry nitromethane (100 mL) under N2 atmosphere
with ice bath cooling to yield a clear and free flowing solution.
The dissolution was not as exothermic as in the case of the
preparation of 5 M LPDE.3 (Caution: Solutions of lithium
perchlorate in organic solvents must be handled with care!20)
integration.
Ta ble 2. Mich a el Ad d ition of Silyl En ol Eth er s to Cyclic
Un sa tu r a ted Keton es in 5 M LP NM
acceptor
enol
ether
duration
(h)
yield (%)a
R1
R2
R3
ref
Gen er a l P r oced u r e. In a typical experiment the carbonyl
compound (2 mmol) was dissolved in 5 M LPNM (2 mL) under
N2 atmosphere. To this solution the enol silyl ether (6 mmol)
was added, and the mixture was stirred at room temperature
until the disappearance of the starting materials as shown by
TLC. The reaction mixture was cooled in an ice bath and diluted
with CH2Cl2 (15 mL) followed by addition of water (10 mL). The
organic layer was separated, and the aqueous layer was ex-
tracted with CH2Cl2 (3 × 15 mL). The combined extracts were
dried over anhydrous Na2SO4. Removal of solvent on the rotary
evaporator followed by column chromatographic purification on
silica gel yielded pure products. Except for compounds 6c,d , the
others are literature known compounds and were characterized
by IR, NMR (1H and 13C), and mass spectroscopy. Compounds
6c,d were characterized in the present study by IR, 1H (400
MHz) and 13C (100 MHz) NMR, and mass spectroscopic data by
comparison with that of 7d .
2-((E)-1-Hyd r oxy-3-p h en yl-2-p r op en yl)cyclop en ta n on e
(6c). Yield: 73%. IR (CCl4): 3484 (νOH), 1734 (νCdO) cm-1. Isomer
I: 1H NMR (400 MHz, CDCl3) δ 7.2 (m, 5H), 6.61 (d, 1H, J ) 16
Hz), 6.19 (dd, 1H, J ) 5.8 and 16 Hz), 4.75 (m, 1H), 3.3 (s, br,
OH), 2.8-1.5 (m, 7H) ppm; 13C NMR (100 MHz, CDCl3) δ 220.3
(s), 136.6 (s), 130.6 (d), 129.9 (d), 128.5 (d), 127.6 (d), 126.5 (d),
70.8 (d), 54.2 (d), 39.1 (t), 23.4 (t), 20.7 (t) ppm. Isomer II: 1H
NMR (400 MHz, CDCl3) δ 7.2 (m, 5H), 6.6 (d, 1H, J ) 16 Hz),
6.15 (dd, 1H, J ) 16 and 6.84 Hz), 4.4 (m, 1H), 3.3 (s, br, OH),
2.5-1.5 (m, 7H) ppm; 13C NMR (100 MHz, CDCl3) δ 221.5 (s),
136.5 (s), 131.5 (d), 128.8 (d), 128.5 (d), 127.7 (d), 126.5 (d), 73.4
(d), 53.9 (d), 38.6 (t), 26.4 (t), 20.5 (t) ppm; MS (70 eV, EI) m/z
216 (M+, 15), 198 (30), 133 (40), 84 (100), 77 (70), 55 (60).
1
2
1
2
1
2
8a
8b
8c
H
H
H
H
H
H
Me
Me
H
H
Me
Me
H
12
16
24
38
48
48
9a b
10a b
9bc
75
70
80
74
0
17
17
17
17
i-C3H5
i-C3H5
H
10bc
9c
H
H
10c
0
a
b
Isolated yield after purification. 1:1 mixture of diastereo-
isomers. c mixture of four diastereoisomers.
shifted to 1705 cm-1 in 5 M LPNM. In the case of 3a the
CdO stretching frequency is 1712 cm-1 in nitromethane,
which remained unaltered in 5 M LPNM. Similar results
were observed with benzaldehyde and acetophenone in
that the CdO stretching frequency of the former is
shifted from 1724 cm-1 in nitromethane to 1712 cm-1 in
LPNM whereas that of the latter remained unchanged
at 1692 cm-1. These results suggest that aldehydes are
selectively activated in LPNM, which is primarily due
to the steric factors that govern the coordination of the
solvated lithium ion to the carbonyl oxygen. These
changes to the lower wavenumbers in the stretching
frequency of the carbonyl functional group are consistent
with the coordination of the lithium ion to the carbonyl
oxygen lone pair. The carbonyl stretching frequency shifts
are lower in the case of LPDE in comparison with ether.3,5
For example the carbonyl stretching frequency of benz-
aldehyde is shifted from 1708 cm-1 in ether to 1699 cm-1
in 5 M LPDE. The extent of the shift is a qualitative
reflection of the Lewis acidity of the lithium ion which
2-((E)-1-Hyd r oxy-2-bu ten yl)cyclop en ta n on e (6d ). Yield:
75%. IR (CCl4): 3504 (νOH), 1737 (νCdO) cm-1. Isomer I: 1H NMR
(400 MHz, CDCl3) δ 5.6 (m, 1H), 4.5 (m, 1H), 4.0 (br, s, OH),
2.5-1.5 (m, 7H), 1.7 (d, 3H, J ) 7.0 Hz) ppm; 13C NMR (100
MHz, CDCl3) δ 221.3 (s). 131.5 (d), 130.8 (d), 70.9 (d), 54.1 (d),
39.2 (t), 23.4 (t), 20.7 (t), 17.7 (q) ppm. Isomer II: 1H NMR (400
MHz, CDCl3) δ 5.4 (m, 1H), 4.2 (m, 1H), 4.0 (br, s, OH), 2.5-1.5
(m, 7H), 1.72 (d, 3H, J ) 7.2 Hz) ppm; 13C NMR (100 MHz,
CDCl3) δ 223.0 (s), 128.3 (d), 127.2 (d), 73.5 (d), 53.8 (d), 38.8
(15) Narasaka, K.; Soai, K.; Aikawa, Y.; Mukaiyama, T. Bull. Chem.
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ma, K.; Noyori, R. J . Org. Chem. 1983, 48, 932-945.
(17) Boyer, J .; Corriu, R. J .; Perz, R.; Reye, C. Tetrahedron 1983,
39, 117-122.
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Tetrahedron Lett. 1992, 33, 6815-6818.
(20) See: (a) Silva, R. A. Chem. Eng. News 1992, Dec 21, 2. (b) Reetz,
M. T.; Gansa¨uer, A. Tetrahedron 1993, 49, 6025-6030.

Notes
J . Org. Chem., Vol. 64, No. 6, 1999 2157
(t), 26.5 (t), 20.6 (t), 17.5 (q) ppm; MS (70 eV, EI) m/z 154 (M+,
5), 120 (15), 84 (100), 71 (95), 55 (80).
Su p p or tin g In for m a tion Ava ila ble: IR, 1H NMR (400
MHz), 13C NMR (100 MHz), and mass spectroscopic data for
compounds 6a ,b, 7a ,b, 7d , 9a ,b, 10a ,b, 12a , and 13b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Ackn owledgm en t. Financial support from the CSIR,
New Delhi, in the form of a Senior Research Fellowship
(R.S) and a Sponsored Research Project (S.S) is grate-
fully acknowledged. We thank the RSIC, IIT, Madras,
India, for the NMR and mass spectral data.
J O982363B