A new synthesis of β,γ-unsaturated esters and allenic esters with construction of a carbon-carbon bond between α- and β-positions by the reaction of magnesium alkylidene carbenoids with lithium ester enolates

Article abstract of DOI:10.1016/j.tetlet.2009.08.102

Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide-magnesium exchange reaction, gave β,γ-unsaturated esters in moderate to good yield

Full text of DOI:10.1016/j.tetlet.2009.08.102

Tetrahedron Letters 50 (2009) 6280–6285
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Tetrahedron Letters
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A new synthesis of b,
c-unsaturated esters and allenic esters with construction
of a carbon–carbon bond between
a- and b-positions by the reaction
of magnesium alkylidene carbenoids with lithium ester enolates
*
Tsuyoshi Satoh , Hiroaki Kaneta, Ayako Matsushima, Masanobu Yajima
Graduate School of Chemical Sciences and Technology, Tokyo University of Science, Ichigaya-funagawara-machi 12, Shinjuku-ku, Tokyo 162-0826, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovi-
Received 4 August 2009
Revised 28 August 2009
Accepted 31 August 2009
Available online 2 September 2009
nyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide–magnesium exchange reac-
tion, gave b,
the lithium ester enolates of
provides an unprecedented way for the synthesis of b,
ketones with the construction of a carbon–carbon bond between
Ó 2009 Elsevier Ltd. All rights reserved.
c
-unsaturated esters in moderate to good yields. When this reaction was conducted with
-chlorocarboxylic acid esters, allenic esters were obtained. This procedure
-unsaturated esters and allenic esters from
- and b-positions.
a
c
a
Keywords:
Magnesium carbenoid
Magnesium alkylidene carbenoid
Sulfoxide–magnesium exchange reaction
b,c-Unsaturated ester
Allenic ester
1. Introduction
b,c-unsaturated carboxylic acids and their derivatives; however,
only three reports have appeared about the procedure. The first
one is a nickel-catalyzed coupling of vinyl halides with lithium es-
ter enolates.11 The second one is a carbon–carbon bond formation
of iodofluoroacetates with alkenyl iodides in the presence of cop-
Carboxylic acids, esters, amides, and their derivatives are
undoubtedly among the most important and fundamental com-
pounds in organic, synthetic organic, and bioorganic chemistry.1
Among the carboxylic acids and their derivatives, the unsaturated
ones are also quite important compounds in synthetic organic
per.12 The third one is a radical alkenylation of
amides with alkenylindiums.13
a-halo esters or
chemistry.
a,b-Unsaturated carboxylic acids and their derivatives
We have also been interested in the synthesis of b,c-unsatu-
are recognized to be easily synthesized from saturated carboxylic
rated carboxylic acids and their derivatives by our own method
using the rearrangement of lithium carbenoids4c or magnesium
carbenoids.14 In continuation of our investigation with regard to
acids2 or from carbonyl compounds by the Horner–Wadsworth–
Emmons reaction;3 however, general synthetic methods for b,
c-
unsaturated carboxylic acids or esters are quite limited and the
the development of new synthetic methods for b,
carboxylic acids and their derivatives, we recently found a new
procedure for the synthesis of b, -unsaturated carboxylic acid es-
c-unsaturated
synthesis of b, -unsaturated carboxylic acids and their derivatives
c
is still not so easy task.
c
The procedures so far reported for the synthesis of b,
c
-unsaturated
ters and allenic esters as follows (Scheme 1). Thus, 1-chlorovinyl
p-tolyl sulfoxides 2 were synthesized from ketones 1 and chloro-
methyl p-tolyl sulfoxide.15 Vinyl sulfoxides 2 were treated with
isopropylmagnesium chloride at À78 °C to afford magnesium
alkylidene carbenoids 3.16 Magnesium alkylidene carbenoids 3
were treated with lithium ester enolates, which were generated
carboxylic acids and their derivatives are as follows. One-carbon
elongation of
,b-unsaturated esters or aldehydes.4 Deconjugative pro-
tonation5 or photo deconjugation6 of
,b-unsaturated esters. Deconju-
gative alkylation of
,b-unsaturated esters.7 Reductive deconjugation
a
a
a
of a-bromo a
,b-unsaturated esters.8 Modified Knoevenagel condensa-
tion,9 and others.10
from esters with LDA at À78 °C, to give b,
acid esters 4 in moderate to good yields. When this reaction was
conducted with lithium enolates of -chlorocarboxylic esters,
c-unsaturated carboxylic
From the synthetic point of view, carbon–carbon coupling be-
tween a vinyl carbon and an
a-carbon of carboxylic acids or their
a
derivatives is the straightforward procedure for the synthesis of
allenic esters 5 were obtained. It is noteworthy that in both reac-
tions, a carbon–carbon bond between an alkenyl carbon and the
a
-carbon of the esters was constructed. Details and mechanism
* Corresponding author. Tel.: +81 3 5228 8272; fax: +81 3 5261 4631.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
of these reactions are reported hereinafter.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.102

T. Satoh et al. / Tetrahedron Letters 50 (2009) 6280–6285
6281
Li
O
R1
R2
H
R1
R2
R1
R2
R3R4CCOOBu-t R1
Cl
Cl
i-PrMgCl
-78 ºC
TolSCH2Cl
O
in three steps
MgCl -78 ~ -60 ºC
R2
STol
O
COOBu-t
R4
R3
3
1
4
Li
2
R3
R1
R2
R3(Cl)CCOOR
.
-78 ~ 0 ºC
COOR
5
Scheme 1.
When the reaction mixture was slowly allowed to warm to
2. Results and discussion
À60 °C, the yield remarkably improved to 57% (entry 2). The best
yield, 69%, was obtained when the temperature of the reaction
was À60 °C and the temperature was maintained for 2 h (entry
3).18 Higher temperature was not effective (entry 4). Toluene was
also found to be a useful solvent in this reaction (entries 5 and
6). We used the conditions given in entry 3 throughout this study.
The presumed mechanism of this reaction is shown in Scheme
2. Thus, the lithium ester enolate attacks the carbenoid carbon to
give alkenylmagnesium intermediate 10 with inversion of the con-
figuration of the carbenoid carbon.16 Quenching this intermediate
At first, to a solution of 1-chlorovinyl p-tolyl sulfoxide 617 in
THF at À78 °C was added t-BuMgCl (0.13 equiv) to remove a trace
of moisture in the reaction mixture. To this solution was added
i-PrMgCl (2.8 equiv) to afford magnesium alkylidene carbenoid 7.
A solution of lithium enolate of tert-butyl acetate (3 equiv), which
was generated from tert-butyl acetate with LDA at À78 °C, was
added to the solution of magnesium alkylidene carbenoid 7
through a cannula and the reaction mixture was stirred at À78 °C
for 30 min (Table 1, entry 1).
10 with water gave b,c-unsaturated ester 8. The evidence for the
Fortunately, the desired reaction took place to afford the desired
presence of alkenylmagnesium intermediate 10 was obtained
when the reaction was quenched with deuterated methanol (Table
in Scheme 2). Thus, as shown in entry 1, when this reaction was
b,c-unsaturated ester 8 in 42% yield. From this reaction, however,
about 20% of alkenyl chloride 9, which is the protonated product
of magnesium alkylidene carbenoid 7, was obtained as a by-prod-
uct. This result implied that the desired reaction had not been com-
pleted. In order to improve the yield of product 8, the optimal
conditions were investigated and the results are summarized in
Table 1.
quenched after 10 min at À78 °C with CH3OD, b,
ter 11 deuterated at the olefinic carbon (D content 61%) was ob-
tained. A trace of deuterium was incorporated at the -carbon
(4%). The anion was found to be rearranged slowly from the olefinic
carbon to the -carbon and after 2 h the -carbon was deuterated
c-unsaturated es-
a
a
a
about 20% (entry 3). Finally, after the reaction mixture was stirred
at À60 °C for 2 h, the anion was dispersed between the olefinic car-
bon and the a-carbon (entry 5).
Table 1
In order to know the scope and limitation of this reaction, the
reaction was carried out with 1-chlorovinyl p-tolyl sulfoxides
12a–c, prepared from cycloheptanone, cyclododecanone, and
cyclopentadecanone. The results are summarized in Scheme 3.
As shown in Scheme 3, the reaction of magnesium alkylidene
carbenoids generated from 12a–c with lithium enolates generated
from tert-butyl acetate gave the desired b,c-unsaturated esters
13a–c in up to 63% yield and the universality of this reaction
was verified.
Next, the reactions of magnesium alkylidene carbenoid 7, gen-
erated from 6, with the lithium ester enolates other than lithium
enolate of tert-butyl acetate were investigated and the results are
summarized in Table 2. Entries 1 and 2 show the reaction with
methyl acetate and phenyl acetate. The results were quite worse
compared with those of tert-butyl acetate. The results with tert-bu-
tyl propionate, tert-butyl phenylacetate, and tert-butyl 4-meth-
ylphenylacetate are summarized in entries 3–5. These reactions
Generation of magnesium alkylidene carbenoid 7 from 1-chlorovinyl p-tolyl sulfoxide
6 and reaction with lithium enolate of tert-butyl acetate to give b,
ester 8
c-unsaturated
O
Cl
1) -BuMgCl (0.13 eq)
t
O
O
O
O
TolSCH2Cl
O
in three steps
95 %
S(O)Tol
2) i-PrMgCl (2.8 eq)
THF, -78 ºC
6
1) LiCH2COOBu-t
(3.0 eq)
H
O
O
Cl
O
O
2) H2O
O
MgCl
OBu-t
8
7
Entry
Solvent
Conditions
Yield (%)
1
2
3
4
5
6
THF
THF
THF
THF
Toluene
Toluene
À78 °C, 30 min
42a
57
69
65
58
63
À78 ꢀ À60 °C, 30 min
gave the desired b,
the -position 14 in up to 57% yield. It is worthy to note that in
these reactions no double bond migration (giving ,b-unsaturated
esters) was observed. Lithium ester enolates generated from
c-unsaturated esters bearing a substituent at
À78 ꢀ À60 °C, 30 min, then À60 °C, 2 h
À78 ꢀ À40 °C, 1 h
a
À78 ꢀ À60 °C, 30 min
a
À78 ꢀ À60 °C, 30 min, then À60 °C, 2 h
a,a-
a
About 20% of vinyl chloride 9 was obtained.
disubstituted acetate also gave the desired product; however, the
yields were found to be low (entries 6 and 7). In these cases,
methyl esters gave better yields compared with the corresponding
tert-butyl esters.
In continuation of the aforementioned reaction, we used lith-
ium ester enolate of tert-butyl chloroacetate as the lithium enolate,
Cl
H
O
O
9

6282
T. Satoh et al. / Tetrahedron Letters 50 (2009) 6280–6285
LiCH2COOBu-t
Cl
Cl
(3.0 eq)
O
O
O
MgCl
O
O
O
O
MgCl
MgCl
OBu-t
7
10
CH2COOBu-t
D1
H2O or CH3OD
H
O
O
O
O
8
O
O
D2
OBu-t
OBu-t
11
Conditions
11, D-content / %
Entry
Temp. / ºC
D2
D1
Time / min.
1
2
3
-78
-78
-78
10
30
61
54
49
4
8
20
18
120
30
4
-78 ~ -60
-78 ~ -60
72
48
5a)
43
120
a) The reaction was conducted at -78 to -60 ºC for 30 min then
at -60 ºC for 2 h before quenching with CH3OD.
Scheme 2. The reaction of magnesium alkylidene carbenoid 7 with lithium enolate of tert-butyl acetate followed by deuterio methanol.
LiCH2COOBu-t
1) t-BuMgCl (0.13 eq)
2) i-PrMgCl (2.8 eq)
(3.0 eq)
H
Cl
Cl
O
THF
THF, -78 ºC
( )n
( )n
( )n
MgCl
S(O)Tol
OBu-t
-78 ~ -60 ºC, then
at -60 ºC for 2 h
12a n=2
b n=7
c n=10
13a n=2 (61%)
b n=7 (63%)
c n=10 (51%)
Scheme 3.
and quite interesting results were obtained (Scheme 4). Thus,
treatment of magnesium alkylidene carbenoid 7 with lithium eno-
late of tert-butyl chloroacetate under the above-mentioned condi-
tions gave allenic ester 16. After the investigation of optimized
conditions, LHMDS was used as the base and the reaction mixture
was allowed to warm from À78 to 0 °C, the yield was improved to
54%.19 This reaction is presumed to proceed as follows. The lithium
ester enolate attacks the carbenoid carbon of 7 to give alkenylmag-
nesium intermediate 15 with inversion of the configuration of the
carbenoid carbon.16 b-Elimination of both the magnesium chloride
and the chlorine atom of intermediate 15 took place simulta-
neously to afford allenic ester 16.
Finally, we studied the synthesis of fully substituted allenic es-
ters based on our method described above and the results are sum-
marized in Table 3. At first, 1-chlorovinyl p-tolyl sulfoxide 7 was
treated with lithium enolate of tert-butyl a-chloropropionate (en-
try 1). The reaction gave the desired fully substituted allenic ester
18 (R3 = CH3); however, the yield was miserable. Fortunately, the
yield was improved to 47% by using lithium enolate of methyl 2-
chloropropionate (entry 2). Entries 3–6 show the results for the
reaction of 7 with various esters of 2-chlorophenylacetic acid.
The tert-butyl, phenyl, and ethyl esters gave up to 40% yield of
the desired fully substituted allenic esters bearing a phenyl group.
Methyl ester, again, gave much better yield (entry 6).
Allenes are very interesting and important compounds in or-
ganic and synthetic organic chemistry.20 We investigated the gen-
erality of the synthesis of allenic esters using 1-chlorovinyl p-tolyl
sulfoxides 12a–d and the results are summarized in Scheme 5. As
shown in the scheme, the reaction starting from 12a–d gave the
desired allenic esters 17a–d; however, unfortunately, the yields
were not satisfactory (22–38%).
In conclusion, we found that the reaction of magnesium alkyl-
idene carbenoids with lithium ester enolates gave b,
esters and allenic esters with direct construction of a carbon–carbon
bond between - and b-positions. Althoughthe yields are not always
good at the present, the method mentioned above is an unprece-
dented way and contributes to the synthesis of various b, -unsatu-
rated esters and allenic esters, including fully substituted ones.
c-unsaturated
a
c

T. Satoh et al. / Tetrahedron Letters 50 (2009) 6280–6285
6283
Table 2
Reaction of magnesium alkylidene carbenoid 7 with various lithium ester enolates to give
a
,b-unsaturated esters 14
1) t-BuMgCl (0.13 eq)
2) i-PrMgCl (2.8 eq)
Lithium ester
H
Cl
O
O
Cl
O
O
enolate (3.0 eq)
O
THF
THF, -78 ºC
MgCl
S(O)Tol
R1
R2
OR
-78 ~ -60 ºC, then
at -60 ºC for 2 h
6
7
14
Entry
Lithium ester enolate
14
Yield (%)
36
H
O
O
1
Li
OCH3
OCH3
H
complex
mixture
O
O
2
3
4
5
6
7
Complex mixture
Li
OPh
OPh
H
O
O
Li
51
54
57
35
27
OBu-t
CH3
O
H3C
OBu-t
H
H
O
Li
OBu-t
Ph
OBu-t
Ph
O
O
Li
OBu-t
OBu-t
CH3
H
CH3
O
O
Li
OCH3
H3C
H3C CH3
OCH3
CH3
O
H
O
Li
OCH3
OCH3
Cl
Li
O
(3.0 eq)
MgCl
Cl
O
O
Cl
O
O
O
O
OBu-t
O
MgCl
MgCl
THF, -78 ~ 0 ºC
Cl
OBu-t
O
7
15
Cl
OBu-t
O
OBu-t
O
O
.
H
54%
16
Scheme 4.

6284
T. Satoh et al. / Tetrahedron Letters 50 (2009) 6280–6285
Cl
Li
O
O
1) t-BuMgCl (0.13 eq)
2) i-PrMgCl (2.8 eq)
(3.0 eq)
Cl
Cl
OBu-t
OBu-t
.
( )n
( )n MgCl
S(O)Tol
THF, -78 ºC
( )n
H
THF, -78 ~ 0 ºC
12a n=2
b n=7
c n=10
d n=1
17a n=2 (37%)
b n=7 (22%)
c n=10 (38%)
d n=1 (36%)
Scheme 5.
Promotion from Tokyo University of Science, which are gratefully
acknowledged.
Table 3
A synthesis of allenic esters 18 by the reaction of magnesium alkylidene carbenoid 7
with lithium ester enolates of
a
-chlorocarboxylic acid esters
References and notes
Cl
O
1. (a) Some monographs for the chemistry of carboxylic acids and their
derivatives: The Chemistry of Carboxylic Acids and Esters; Patai, S., Ed.; John
Wiley and Sons: London, 1969; (b) Zabicky, J. The Chemistry of Amides; John
Wiley and Sons: London, 1970; (c) The Chemistry of Acid Derivatives; Patai, S.,
Ed.; John Wiley and Sons: Chichester, 1979; (d) Comprehensive Organic
Chemistry; Sutherland, I. O., Ed.; Pergamon: Oxford, 1979; Vol. 2, p part 9; (e)
Chemistry and Biochemistry of the Amino Acids; Barrett, G. C., Ed.; Chapmann and
R3
O
(3.0 eq)
Cl
O
O
OR
O
Li
OR
.
R3
MgCl
O
THF, -78 ~ 0 °C
7
18
Hall: London, 1985; (f) Willisms, R. M. Synthesis of Optically Active
a-Amino
Entry
Lithium ester enolate
18
Acids; Pergamon: Oxford, 1989; (g) The Chemistry of Acid Derivatives; Patai, S.,
Ed.; John Wiley and Sons: Chichester, 1992. Part 1 and 2; (h) Enantioselective
Synthesis of b-Amino Acids; Juaristi, E., Ed.; Wiley: New York, 1997.
2. (a) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc. 1976, 98, 4887; (b)
Clive, D. L. Tetrahedron 1978, 34, 1049.
3. (a) Wadsworth, W. S., Jr. Org. React. 1977, 25, 73; (b) Maryanoff, B. E.; Reitz, A. B.
Chem. Rev. 1989, 89, 863; (c) Shen, Y. Acc. Chem. Res. 1998, 31, 584; (d) Ando, K.
J. Synth. Org. Chem. Jpn. 2000, 58, 869; (e) Li, J. J. Name Reactions; Springer:
Berlin, 2002.
4. (a) Kowalski, C. J.; Haque, M. S.; Fields, K. J. Am. Chem. Soc. 1985, 107, 1429; (b)
Kowalski, C. J.; Reddy, R. J. Org. Chem. 1992, 57, 7194; (c) Satoh, T.; Nakamura,
A.; Iriuchijima, A.; Hayashi, Y.; Kubota, K. Tetrahedron 2001, 57, 9689.
5. (a) Krebs, E.-P. Helv. Chim. Acta 1981, 64, 1023; (b) Ikeda, Y.; Ukai, J.; Ikeda, N.;
Yamamoto, H. Tetrahedron 1987, 43, 743.
6. Piva, O. Tetrahedron 1994, 50, 13687.
7. (a) Kende, A. S.; Todeer, B. H. J. Org. Chem. 1982, 47, 167; (b) Murphy, K. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 4690.
8. Hirao, T.; Fujihara, Y.; Kurokawa, K.; Ohsiro, Y.; Agawa, T. J. Org. Chem. 1986, 51,
2830.
9. Ragoussis, N. Tetrahedron Lett. 1987, 28, 93.
10. (a) Deng, M.-Z.; Li, N.-S.; Huang, Y.-Z. J. Org. Chem. 1992, 57, 4017; (b) Deng, M.-
Z.; Li, N.-S.; Huang, Y.-Z. J. Org. Chem. 1993, 58, 1949; (c) Ballini, R.; Bosica, G.;
Fiorini, D. Tetrahedron Lett. 2001, 42, 8471; (d) Shen, Y.; Ni, J. J. Fluorine Chem.
2003, 124, 65.
11. Millard, A. A.; Rathke, M. W. J. Am. Chem. Soc. 1977, 99, 4833.
12. Taguchi, T.; Kitagawa, O.; Morikawa, T.; Nishiwaki, T.; Uehara, H.; Endo, H.;
Kobayashi, Y. Tetrahedron Lett. 1986, 27, 6103.
13. Takami, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2004, 6, 4555.
14. (a) Satoh, T.; Yamashita, H.; Musashi, J. Tetrahedron Lett. 2007, 48, 7295; (b)
Yamashita, H.; Satoh, T. Tetrahedron 2009, 65, 613.
15. Satoh, T.; Kawashima, T.; Takahashi, S.; Sakai, K. Tetrahedron 2003, 59, 9599.
16. (a) Satoh, T.; Ogino, Y.; Ando, K. Tetrahedron 2005, 61, 10262; (b) Mori, N.;
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1998, 54, 5557.
Yield (%)
17
O
O
O
O
O
O
O
OBu-t
Li
1
OBu-t
Cl
.
.
.
.
.
.
CH3
CH3
O
OCH3
CH3
Li
2
3
4
5
6
47
39
31
40
51
OCH3
Cl
CH3
O
OBu-t
OPh
Li
OBu-t
Cl
Ph
Ph
Ph
Ph
Ph
O
Li
OPh
Cl
Ph
O
OC2H5
OCH3
Li
OC2H5
Cl
18. 3-(1,4-Dioxaspiro[4.5]dec-8-ylidene)propionic acid tert-butyl ester (8): t-BuMgCl
(0.025 mmol) was added dropwise to a solution of vinyl sulfoxide 6 (65 mg;
0.2 mmol) in 3 mL of dry THF in a flame-dried flask at À78 °C under argon
atmosphere to remove a trace of moisture in the reaction medium. After
10 min, i-PrMgCl (0.56 mmol) was added dropwise to the reaction mixture to
give magnesium alkylidene carbenoid 7. In another flame-dried flask at À78 °C
under argon atmosphere, THF solution of LDA (0.6 mmol) was prepared and
tert-butyl acetate (0.6 mmol) was added slowly to this solution. This solution
of the lithium ester enolate was transferred into the solution of the carbenoid 7
through a cannula. The reaction mixture was slowly allowed to warm up to
À60 °C, and then kept for 2 h at the same temperature. The reaction was
quenched by adding satd aq NH4Cl. The whole mixture was extracted three
times with CHCl3 and the organic layer was dried over MgSO4 and
concentrated. The residue was purified by flash column chromatography
(hexane/AcOEt) to give 8 (37 mg; 69%) as colorless oil. IR (neat); 2949, 1733
Ph
O
Li
OCH3
Cl
Ph
Acknowledgments
(CO), 1368, 1152, 1095, 1035, 905 cmÀ1 1H NMR d 1.44 (9H, s), 1.66–1.71 (4H,
;
m), 2.27 (4H, t, J = 6.4 Hz), 2.96 (2H, d, J = 7.2 Hz), 3.97 (4H, s), 5.32 (1H, t,
J = 7.2 Hz). MS m/z (%) 268 (M+, 13), 212 (81), 167 (19), 86 (57), 57 (100), Calcd
for C15H24O4: M, 268.1673. Found; m/z 268.1677.
This work was supported by a Grant-in-Aid for Scientific Re-
search No. 19590018 from the Ministry of Education, Culture,
Sports, Science, and Technology, Japan, and TUS Grant for Research

T. Satoh et al. / Tetrahedron Letters 50 (2009) 6280–6285
1288, 1230, 1143, 1068, 1027 cmÀ1
6285
19. 3-(1,4-Dioxaspiro[4,5]dec-8-ylidene)acrylic acid tert-butyl ester (16): To a solution
of 6 (65.4 mg, 0.2 mmol) in 2 mL of dry THF in a flame-dried flask at À78 °C under
argon atmosphere was added t-BuMgCl (0.025 mmol) dropwise with stirring.
After 10 min, i-PrMgCl (0.56 mmol) was added dropwise to the reaction mixture
at À78 °C to give magnesium alkylidene carbenoid 7. In another flame-dried
flask, tert-butyl chloroacetate (0.6 mmol) was added dropwise to a solution of
LHMDS (0.6 mmol) in 3 mL of dry THF at À78 °C under argon atmosphere to give
light yellow solution of the lithium enolate. This solution was added to the
solution of carbenoid 7 through a cannula. The reaction mixture was gradually
allowed to warm up to 0 °C for 2 h. The reaction was quenched with satd aq
NH4Cl and the whole was extracted with CHCl3 and the organic layer was dried
over MgSO4. After removal of the solvent, the product was purified by silica gel
column chromatography to give 16 (28.8 mg, 54%) as colorless crystals; mp 99–
99.5 °C (AcOEt–hexane). IR (KBr) 3004, 2972, 2932, 2874, 1963 (allene), 1714,
;
1H NMR d 1.47 (9H, s), 1.75–1.83 (4H, m),
2.33–2.46(4H, m), 3.97 (4H, s), 5.38–5.40 (1H, m). Calcd forC15H22O4:C, 67.65;H,
8.33. Found: C, 67.57; H, 8.25.
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Wiley and Sons: Chichester, 1980. Part 1 and 2; (b) Brandsma, L.; Verkruijsse,
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