Titanium tetrachloride promoted reaction of silyl ketene acetals with epoxides: A new method for the synthesis of γ-butanolides

Article abstract of DOI:10.1016/S0040-4039(02)01070-5

A new method for the synthesis of γ-butanolides is described. The titanium tetrachloride promoted reaction of silyl ketene acetals with epoxides, followed by acidic work-up, affords the corresponding butyrolactones in 44-83% yield.

Full text of DOI:10.1016/S0040-4039(02)01070-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5411–5413
Titanium tetrachloride promoted reaction of silyl ketene acetals
with epoxides: a new method for the synthesis of g-butanolides
a,b
a,b
a,b,
Veselin Maslak, Radomir Matovi c´ and Radomir N. Sai cˇ i c´
*
a
Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 158, 11000 Belgrade, Yugoslavia
b
I.C.T.M. Center for Chemistry, Njegoseva 12, 11001 Belgrade, Yugoslavia
Received 16 April 2002; revised 20 May 2002; accepted 7 June 2002
Abstract—A new method for the synthesis of g-butanolides is described. The titanium tetrachloride promoted reaction of silyl
ketene acetals with epoxides, followed by acidic work-up, affords the corresponding butyrolactones in 44–83% yield. © 2002
Elsevier Science Ltd. All rights reserved.
Contrary to nucleophilic epoxide ring opening with
organometallic reagents, which constitutes a well estab-
lished and synthetically highly useful method of car-
would probably be the most efficient approach to
homoaldols and butyrolactones (Fig. 1). Dianions of
simple carboxylic acids react with epoxides, however, a
3
1
bon–carbon bond formation, examples of epoxide
large excess of dianion and forcing conditions are often
required. Transmetallation of lithium ester enolates
with diethylaluminium chloride affords the more reac-
tive aluminium enolates, whose reactions with epoxides
2
reactions with enolates are scarce. Lithium enolates of
ketones and esters are unreactive towards epoxides,
which generally precludes the application of what
4
afford the g-hydroxy esters in moderate to good yields.
OH R2
In order to circumvent the aforementioned problems,
indirect methods have been devised, based on the appli-
5
R3
O
R3
R1
+
R2
(1)
(2)
4a
cation of diethylethoxyalkynylalane, or silylynamine,
R1
O
O
as the acetate enolate equivalents; these approaches are
limited to the synthesis of a-unsubstituted butanolides,
although the latter offers some possibilities to achieve
molecular diversity.
O
R2
OR3
O
R2
+
O
R1
O
1
R1
Recently, we have shown that enoxysilanes react with
epoxides in the presence of TiCl to give homoaldol
4
Figure 1.
products in moderate to good yields, thus enabling the
. Conditions,
-60 °C -20 °C
O
OH
OR
O
2.
Ph
Ph
+
O
Ph
CO Me
2
OTMS
2. p-TsOH, r.t., 2-4 h
1
2
i
Conditions:
R = Pr, solvent = CH Cl
19%
38%
2
2
R = Me, solvent = CH2Cl2
R = Me, solvent = n-hexane : CH2Cl2 = 2 : 1 62%
Scheme 1.
Keywords: epoxides; ketene acetals; lactones; titanium and compounds; alkylation.
*
Corresponding author. Tel.: +381-11-32-82-537; fax: +381-11-63-60-61; e-mail: rsaicic@chem.bg.ac.yu
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01070-5

5
412
V. Maslak et al. / Tetrahedron Letters 43 (2002) 5411–5413
a
Table 1. TiCl promoted reactions of silyl ketene acetals with epoxides
4
Yield b
Entry
Silyl ketene acetal
Epoxide
Product
O
OTMS
62% (97%) c
Ph
O
1
Ph
O
OMe
1
2
O
O
O
Ph
49%d
69%
2
3
4
Cl
Cl
O
Cl
O
OTMS
OMe
O
O
O
64%d
O
Cl
O
O
5
O
48%d
3
O
O
OTMS
OMe
O
O
6
7
8
9
64%
83%d
53%
44%
66%
69%
O
O
Cl
Cl
Cl
Cl
O
OTMS
O
O
O
OMe
4
O
O
Cl
O
O
OTMS
O
O
10
OMe
6
5
O
11
O
Cl
a) For the experimental procedure, see ref. 8; b) Yields of isolated, pure compounds; c) Calculated on
the basis of the converted starting compound; d) Obtained as a 1:1 mixture of diastereoisomers.
6
transform shown in Eq. (1) (Fig. 1). Herein, we
formation of two compounds which, upon treatment
with a catalytic amount of p-TsOH during work-up,
converged to a single product, identified as a-(2-
phenylethyl)-g-butanolide 2 (19%, Scheme 1). Other
report the extension of this new reaction to silyl
ketene acetals, whose reactions with epoxides under
modified Mukaiyama conditions afford g-butanolides
i
(
the overall transformation corresponding retrosyn-
Lewis acids (BF ·Et O, ZnCl , Ti(O Pr) , SnCl )
3
2
2
4
4
thetically to Eq. (2), Fig. 1).
proved inferior catalysts with respect to TiCl . Substi-
4
tuting the smaller methyl group for isopropyl in 1
resulted in a yield enhancement to 38%. After some
experimentation it was found that the reaction is best
When a dichloromethane solution of ethylene oxide
7
and silyl ketene acetal 1, derived from isopropyl 4-
phenylbutanoate, was treated with TiCl4 at −60“
carried out in
a
mixed solvent: n-hexane/
−20°C, TLC of the reaction mixture indicated the
dichloromethane=2/1; under these conditions lactone

V. Maslak et al. / Tetrahedron Letters 43 (2002) 5411–5413
5413
2
was isolated in 62% yield, along with some unreacted
3092–3093; Phenylthioacetic acid dianion reacts with epox-
ides under mild conditions: (d) Iwai, K.; Kosugi, H.; Uda,
H.; Kawai, M. Bull. Chem. Soc. Jpn. 1977, 50, 242–247; (e)
White, J. D.; Somers, T. C.; Reddy, G. N. J. Org. Chem.
methyl 4-phenylbutanoate (97% yield, based on the
recovered starting material).
1
992, 57, 4991.
The generality of the procedure was tested by reacting
several structurally different silyl ketene acetals with
ethylene oxide under the described conditions. In all
4
. (a) Danishefsky, S.; Kitahara, T.; Tsai, M.; Dynak, J. J.
Org. Chem. 1976, 41, 1669; (b) Sturm, T.-J.; Marolewski,
A. E.; Rezenka, D. S.; Taylor, S. K. J. Org. Chem. 1989,
8
cases the corresponding lactones were obtained in good
yields (Table 1, entries 1, 3, 6, 8 and 10). Formation of
a,a-disubstituted butanolides from a,a-disubstituted
silyl ketene acetals indicates the ease of formation of
quaternary centres (entries 8 and 10). The reaction with
cyclohexanecarboxylic ester derived silyl ketene acetal 5
produced a spirobicyclic lactone 6 (entry 10). In addi-
tion to ethylene oxide, reactions with epichlorohydrin
were also studied: in all cases 4-chloromethyl substi-
tuted butanolides were obtained in good yields, result-
ing from a nucleophilic attack at the less substituted
5
4, 2039–2040.
. Movassaghi, M.; Jacobsen, E. N. J. Am. Chem. Soc. 2002,
24, 2456–2457.
5
6
1
. Lalic, G.; Petrovski, Z.; Galonic, D.; Matovic, R.; Saicic,
R. N. Tetrahedron 2000, 57, 583–591; Under similar reac-
tion conditions bis(trimethylsilyloxy)butadienes, derived
from 1,3-dicarbonyl compounds, yield 2-alkylidenetetra-
hydrofurans: Langer, P.; Eckardt, T. Angew. Chem., Int.
Ed. Engl. 2000, 39, 4343–4346.
. Silyl ketene acetals were prepared according to:
Ainsworth, C.; Chen, F.; Kuo, Y.-N. J. Organomet. Chem.
1
. Typical experimental procedure: 2-(2-Phenylethyl)-4-
butanolide 2. To a cold (−60°C) solution of 1 (250 mg; 1
mmol) and ethylene oxide (88 mg; 100 mL; 2 mmol) in
n-hexane:CH Cl =2:1 (3 mL), a solution of TiCl in
7
8
9
epoxide carbon (entries 2, 4, 7, 9, and 11). Cyclohexene
972, 46, 59–71.
oxide, a 1,2-disubstituted epoxide, gave rise to a con-
densed bicyclic lactone 3 (entry 5). Reactions of 1, 4
and 5 with propene oxide afforded mixtures of regioiso-
meric lactones in modest yields (30–40%).
2
2
4
CH Cl (0.88 mL of 3.65 M; 3 mmol) was added dropwise,
2
2
To summarize, a new method for effecting ester/epox-
ide coupling under non-basic conditions is described,
which may prove a useful complement to existing
methodology for g-butanolide formation.
with stirring under an argon atmosphere. After the addi-
tion was complete, the reaction mixture was allowed to
reach −20°C, then cooled to −30°C and quenched with a
saturated aqueous solution of NH Cl (5 mL). The reaction
4
mixture was partitioned between water and CH Cl , a
2
2
catalytic amount of p-TsOH was added to the organic
solution and the mixture was stirred for 3 h at ambient
temperature. Usual work-up, followed by purification by
Acknowledgements
dry-flash chromatography (SiO ; eluent: 20% acetone in
2
petroleum-ether) afforded 117 mg (62%) of the title com-
pound 2 as a colourless oil. E0.3135–145°C (Kugelrohr);
Part of this work was performed at the Free University
of Berlin. One of us (V.M.) is grateful to Professor
Hans-Ulrich Reissig for helpful discussions and his
interest in this work. The authors gratefully acknowl-
edge the support of Professor Ernst-Walter Knapp and
the D.A.A.D. foundation.
IRfilm: 3063, 3029, 2922, 2861, 1769, 1495, 1454, 1376,
1
1
184, 1150, 1026; H NMR (200 MHz, CDCl ): 7.40–7.10
3
(
m, 5H); 4.34 (ddd, J =J =9.1 Hz, J =2.7 Hz, 1H); 4.16
1 2 3
(
2
ddd, J =J =9.1 Hz, J =6.6 Hz, 1H); 2.85–2.60 (m, 2H);
1 2 3
.60–2.10 (m, 3H); 2.10–1.60 (m, 2H); C NMR (50 MHz,
13
CDCl ): 179.3; 140.7; 128.4; 128.3; 126.1; 66.3; 38.2; 33.1;
3
+
3
(
1.8; 28.6; MS (EI) m/z: 190 (M ; 17%); 105 (15%); 91
25%); 85 (100%); HRMS (EI): M , found 190.09967,
References
+
C H O requires 190.09938.
12
14
2
1
. Reviews on the reactions of epoxides with carbon nucle-
ophiles: (a) with non-stabilized carbanions: Klunder, J.
M.; Posner, G. H. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds; Pergamon Press: Oxford,
9
. These products were obtained as 1:1 mixtures of
diastereoisomers which could not be separated by column
chromatography, but were separated by preparative gas
chromatography. Spectral data for 2-(3-butenyl)-4-
chloromethyl-4-butanolide (entry 7): E0.3100–105°C (Kugel-
rohr, for the mixture of isomers); Anal. Calcd for
C H O : C, 57.30; H, 6.95; Found: C, 56.98; H, 6.98;
1
991; Vol. 3, pp. 223–226; (b) with vinyl carbanions:
Knight, D. W. In Comprehensive Organic Synthesis; Trost,
B. M.; Fleming, I., Eds; Pergamon Press: Oxford, 1991;
Vol. 3, pp. 262–266; (c) with alkynyl carbanions: Garratt,
P. J. In Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I., Eds; Pergamon Press: Oxford, 1991; Vol. 3,
pp. 277–280.
9
13
2
Isomer A: IRfilm: 3074, 2919, 2862, 1774, 1641, 1347, 1170,
1
1
038; H NMR (200 MHz, CDCl ): 5.90–5.70 (m, 1H);
3
5.15–4.95 (m, 2H); 4.76 (app. hex., J=4.6, 1H); 3.71 (dd,
J =J =5.4, 2H); 2.85–2.65 (m, 1H); 2.60–2.30 (m, 2H);
1
2
1
3
2. For a review article on the reactions of epoxides with ester,
ketone and amide enolates, see: Taylor, S. K. Tetrahedron
2.30–1.90 (m, 2H); 1.70–1.50 (m, 2H); C NMR (50 MHz,
CDCl ): 178.6; 136.9; 115.9; 76.2; 46.0; 38.2; 31.2; 30.8;
3
2
000, 56, 1149–1163.
30.3. Isomer B: 3074, 2939, 2864, 1775, 1641, 1345, 1172,
1
3
. (a) Creger, P. L. J. Org. Chem. 1972, 37, 1907; For
examples of synthetic applications of this reaction, see: (b)
Danishefsky, S.; Kitahara, T.; Schuda, P. F.; Etheredge, S.
J. J. Am. Chem. Soc. 1976, 98, 3028–3030; (c) Grieco, P.
A.; Ohfune, Y.; Majetich, G. J. Org. Chem. 1979, 44,
1037; H NMR (200 MHz, CDCl ): 5.89–5.69 (m, 1H);
3
5.15–4.95 (m, 2H); 4.60 (m, 1H); 3.71 (dd, J =5.2, J =
1
2
1.1, 2H); 2.80–2.40 (m, 2H); 2.30–2.00 (m, 3H); 1.95–1.50
13
(m, 2H); C NMR (50 MHz, CDCl
76.3; 45.3; 39.6; 32.2; 31.2; 29.4.
): 177.8; 137.0; 115.9;
3