Synthesis of conjugated enynes by assembly of three components, ketones, chloromethyl p-tolyl sulfoxide, and acetylenes, with the magnesium carbenoid 1,2-CC insertion as the key reaction

Article abstract of DOI:10.1016/j.tetlet.2009.11.082

The reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the adducts with Grignard reagents resulted in the formation of magnesium carbenoids by the sulfoxide-magnesium exchange reaction. 1,2-Carbon-carbon insertion (1,2-CC insertion) reaction of the generated magnesium carbenoids took place to afford conjugated enynes in good to high yields. This procedure provides a good method for the synthesis of multi-substituted conjugated enynes.

Full text of DOI:10.1016/j.tetlet.2009.11.082

Tetrahedron Letters 51 (2010) 633–637
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of conjugated enynes by assembly of three components, ketones,
chloromethyl p-tolyl sulfoxide, and acetylenes, with the magnesium
carbenoid 1,2-CC insertion as the key reaction
*
Hideki Saitoh, Naoyuki Ishida, Tsuyoshi Satoh
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:
The reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl
p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the
adducts with Grignard reagents resulted in the formation of magnesium carbenoids by the sulfoxide-
magnesium exchange reaction. 1,2-Carbon–carbon insertion (1,2-CC insertion) reaction of the generated
magnesium carbenoids took place to afford conjugated enynes in good to high yields. This procedure
provides a good method for the synthesis of multi-substituted conjugated enynes.
Received 9 October 2009
Revised 5 November 2009
Accepted 19 November 2009
Available online 22 November 2009
Keywords:
Ó 2009 Elsevier Ltd. All rights reserved.
Magnesium carbenoid
Sulfoxide–magnesium exchange reaction
Enyne
Conjugated enyne
1,2-CC Insertion
1. Introduction
sulfoxide, and acetylenes with the magnesium carbenoid 1,2-CC
insertion as the key reaction, as shown in Scheme 1.
Conjugated enynes have been receiving considerable attention
in organic, synthetic organic, and bio-organic chemistry. The fa-
mous enediyne antibiotics,1 such as calicheamicine2 and dynemi-
cin3, have conjugated enyne moiety as the essential structure for
their biological activities. Conjugated enynes are also very impor-
tant compounds in synthetic organic chemistry.4
The synthesis of conjugated enynes has received special atten-
tion in these days and some methods have already been published.
For example, the cross-coupling of vinyl halides with terminal
acetylenes in the presence of Pd(0) or Pd(II)/Cu is known to be
Sonogashira coupling.5 Rhodium- or palladium-catalyzed hydro-
alkynylation of alkynes with terminal and internal alkynes,6 and
dimerization of terminal alkynes with rare-earth metal alkyl com-
plexes7 are the methods for the synthesis of conjugated enynes
from two acetylenes. Some other methods for the synthesis of con-
jugated enynes have been reported.8
We are also interested in the synthesis of conjugated enynes
and have published their synthesis based on the reaction of mag-
nesium alkylidene carbenoids with lithium acetylides.9 In continu-
ation of our interest in the synthesis of conjugated enynes by our
original chemistry, the chemistry of magnesium carbenoids, here,
we report a new method for the synthesis of conjugated enynes
by assembly of three components, ketones, chloromethyl p-tolyl
Thus, 1-chlorovinyl p-tolyl sulfoxides 3 were synthesized from
ketones 1 and chloromethyl p-tolyl sulfoxide 2 in three steps in
high overall yields.10 Treatment of 3 with lithium acetylides re-
sulted in the formation of adducts 4. Finally, adducts 4 were trea-
ted with Grignard reagents to afford magnesium carbenoids 5,
from which 1,2-CC insertion reaction took place to give conjugated
enynes 6 in good to high yields.
2. Results and discussion
Representative example is reported in Scheme 2. 1-Chlorovinyl
p-tolyl sulfoxide 7, derived from cyclohexane-1,4-dione monoeth-
R2
TolS(O)CH2Cl
Li
R2
R1
R1
R1
R1
R1
R1
Cl
C
S(O)Tol
2
S(O)Tol
Cl
C
O
3 steps
4
1
3
R2
R2
RMgCl (in Et2O)
R1
R1
R1
R1
1,2-CC insertion
MgCl
Cl
C
C
Toluene, -78 ~ 0 °C
H
5
6
* Corresponding author. Tel.: +81 3 5228 8272; fax: +81 3 5261 4631.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.082

634
H. Saitoh et al. / Tetrahedron Letters 51 (2010) 633–637
Ph
Li
Ph
Cl
O
O
O
O
O
O
(5 eq)
2
O
THF, -78 °C to r.t.
73%
S(O)Tol
Lit. 10
S(O)Tol
Cl
8
7
(diastereomeric ratio 3:1)
Ph
Ph
O
O
1,2-CC insertion
i-PrMgCl (in Et2O)
Toluene, -78 ~ 0 °C
O
MgCl
from 8L 97%
from 8P 46%
O
H
Cl
9
10
11
Ph
1,3-CH insertion
O
O
not observed
Scheme 2.
ylene ketal and chloromethyl p-tolyl sulfoxide 2,10 was treated
with lithium acetylide (derived from phenylacetylene with n-BuLi)
to give adduct 8 in 73% yield as easily separable mixture of two
diastereomers (less polar adduct 8L and more polar adduct 8P on
silica gel TLC; with the ratio of 3:1, respectively). Treatment of a
toluene solution of the main diastereomer 8L with 5 equiv of i-
PrMgCl (in ether) at À78 °C resulted in the formation of magne-
sium carbenoid 9. The reaction mixture was slowly allowed to
warm to 0 °C to give a very clean reaction mixture in which we ob-
served a single product. At first, based on our experiences, we
anticipated that bicyclo[4.1.0]heptane 11 was the product by the
1,3-CH insertion reaction of magnesium carbenoid 9.11 However,
very interestingly, the product was confirmed to be conjugated
enyne 10 (97% yield) and no bicyclo[4.1.0]heptane 11 was ob-
tained. The same reaction of the minor diastereomer 8P gave the
same conjugated enyne 10; however, the yield was moderate
(46%). Significant difference about the yields of 10 from diastereo-
mers 8P and 8L was observed; however, the real reason is not clear
at present.
in Table 1. The conditions in entry 1 are the aforementioned ones.
The addition reaction can be started at À30 °C and a somewhat
better yield was obtained (entry 2). Starting the reaction at 0 °C
gave a diminished yield (entry 3). Using LDA instead of n-BuLi gave
a much better yield of 8 (entry 4).12 Toluene and diethyl ether were
proved to be unsuitable solvents in this reaction (entries 6 and 7).
We decided to use the conditions in entry 4 in this study.
By using the above-mentioned conditions, generality of this
procedure was investigated and the results are summarized in
Table 2. Thus, 1-chlorovinyl p-tolyl sulfoxides 3 derived from
cyclohexanone, cyclododecanone, cyclopentadecanone, and 4-hep-
tanone were used as the representative examples of the starting
material, and phenylacetylene was used as the representative
example of the acetylene. The addition reaction of 1-chlorovinyl
p-tolyl sulfoxides derived from large-membered cyclic ketones
and an acyclic ketone was not completed and about 30% yield of
adducts 12b–d were obtained (entries 3–8). In these cases, a signif-
icant amount of the staring materials was recovered and the yields
calculated based on the consumed starting material were not too
bad.
As we recognized that this reaction is unprecedented and would
become quite an interesting way for preparing conjugated enynes,
at first, increasing the yield of 10 from the minor diastereomer 8P
was investigated and the results are summarized in Scheme 3. As
shown in the table in Scheme 3, cyclopentylmagnesium chloride
(c-PentMgCl) was found to be the best Grignard reagent investi-
gated and 71% yield of 10 was obtained.
Treatment of adducts 12a–d with Grignard reagents was con-
ducted in the same way as described above. The reaction of 12a,
Table 1
Addition reaction of lithium acetylide derived from phenylacetylene to 1-chlorovinyl
p-tolyl sulfoxide 7 to afford adduct 8
Next, conditions for the addition reaction of 7 with lithium
phenylacetylide were investigated and the results are summarized
Ph
H
Ph
/ base
O
O
Cl
O
O
(5 eq)
Ph
S(O)Tol
Ph
Conditions
S(O)Tol
Grignard reagent
Cl
7
O
O
(5 eq)
O
O
8
(diastereomeric ratio 3:1)
S(O)Tol
Toluene, -78 ~ 0 °C
2 h
H
Cl
Entry
Conditions
8
10
8P
Grignard reagent
(in Et2O)
10 / Yield / %
Temp (°C)
Time (h)
Solvent
Base
Yield (%)
1
2
3
4
5
6
7
À78–rt
À30–rt
0–rt
À30–rt
À30–rt
À30–rt
À30–rt
3
2
1
2
2
2
2
THF
THF
THF
THF
THF
Toluene
Et2O
n-BuLi
n-BuLi
n-BuLi
LDA
LHMDS
LDA
73
75
60
46
i-PrMgCl
EtMgCl
80
40
51
71
48
20a
19b
PhMgCl
LDA
c-PentMgCl
a
Starting material 7 was recovered in 69% yield.
Starting material 7 was recovered in 64% yield.
b
Scheme 3. The yield for the reaction of 8P with Grignard reagents.

H. Saitoh et al. / Tetrahedron Letters 51 (2010) 633–637
635
Table 2
Addition reaction of 1-chlorovinyl p-tolyl sulfoxides 3 with lithium acetylide generated from phenylacetylene with LDA and the reaction of adducts 12 with Grignard reagents to
give conjugated enynes 13
Ph
Ph
Li
Ph
R1
R1
R1
R1
R1
R1
Cl
RMgCl
(5 eq)
S(O)Tol
Cl
H
S(O)Tol THF, -30 °C to r.t.,
then at r.t. for 30 min
Toluene, -78 ~ 0 °C
2 h
12
13
3
Entry
3
12
RMgCl
13
Yield (%)
Yield (%) (diastereomeric ratio)a
1
2
Cl
i-PrMgCl
c-PentMgCl
98 (from 12aL)
42 (from 12aP)
12a 73 (2:1)
S(O)Tol
Cl
3
4
i-PrMgCl
c-PentMgCl
93 (from 12bL)
96 (from 12bP)
12b 36 (3:2)b
S(O)Tol
5
6
i-PrMgCl
c-PentMgCl
91 (from 12cL)
99 (from 12cP)
Cl
12c 33 (3:2)c
S(O)Tol
7
8
n-Pr
n-Pr
i-PrMgCl
c-PentMgCl
98 (from 12dL)
99 (from 12dP)
Cl
12d 29 (9:2)d,e
S(O)Tol
a
b
c
The ratio for less polar product (L) and more polar product (P) on silica gel TLC.
Starting material was recovered in 27% yield.
Starting material was recovered in 42% yield.
Starting material was recovered in 59% yield.
The reaction mixture was slowly allowed to warm from À30 °C to room temperature for 2 h, then stirred at room temperature for 2 h.
d
e
which has medium-sized cyclic carbon chain, showed significant
difference with respect to the two diastereomers again (entries 1
and 2). Quite interestingly, in the reaction with adducts bearing a
large-membered cyclic carbon chain (12b, c) or acyclic carbon
chain (12d), both the diastereomers gave almost quantitative
yields of conjugated enynes 13 (entries 3–8). Generality of this pro-
cedure was verified from the results shown in Table 2.
Next, scope and limitation of the acetylenes were studied and
the results are summarized in Table 3. As shown in Table 3, addi-
tion reaction of lithium acetylides derived from arylacetylenes
and silylacetylenes with 1-chlorovinyl p-tolyl sulfoxide 7 pro-
ceeded smoothly to afford moderate to good yields of adducts
14a–d (entries 1–8). However, interestingly, the addition reaction
of lithium acetylide derived from an alkylacetylene, 4-phenyl-1-
Table 3
Addition reaction of 1-chlorovinyl p-tolyl sulfoxides 7 with lithium acetylide generated from arylacetylenes with LDA and reaction of the adducts with Grignard reagents to give
conjugated enynes 15
R
R
Acetylene
LDA
O
O
RMgCl
THF, -30 °C ~ r.t.
2 h
S(O)Tol
S(O)Tol
Toluene, -78 ~ 0 °C
2 h
H
Cl
7
15
14
Entry
Acetylene
14
RMgCl
15
Yield (%)
Yield (%) (diastereomeric ratio)a
1
2
i-PrMgCl
c-PentMgCl
15a 93 (from 14aL)
15a 54 (from 14aP)
H
H
CH3
14a 69b (2:1)
3
4
i-PrMgCl
c-PentMgCl
15b 93 (from 14bL)
15b 80 (from 14bP)
14b 55c (2:1)
OCH3
F
5
6
i-PrMgCl
c-PentMgCl
15c 95 (from 14cL)
15c 56 (from 14cP)
H
H
14c 66 (2:1)
14d 77 (5:2)
7
8
Si(CH3)3
i-PrMgCl
c-PentMgCl
15d 99 (from 14dL)
15d 52 (from 14dP)
H
d
9
—
a
b
c
The ratio for less polar product (L) and more polar product (P) on silica gel TLC.
The reaction mixture was slowly allowed to warm from À30 °C to room temperature for 2 h and then stirred for 30 min at the temperature.
Starting material was recovered in 15% yield.
d
No addition reaction was observed.

636
H. Saitoh et al. / Tetrahedron Letters 51 (2010) 633–637
LDA (1.2 eq), then
i-PrMgCl (for 16L) or
c-PentMgCl (for 16P)
good yields (entries 2 and 3).13 Benzoyl chloride and ethyl chloro-
TMS
H
formate gave the desired products 19d and 19e, respectively, in up
to 64% yield (entries 4 and 5). Benzaldehyde reacted with the lith-
ium acetylide to give adduct 19f in 65% yield (entry 6). Even iodine
reacted to give iodoacetylene 19g in good yield (entry 7).
In conclusion, we have found that the magnesium carbenoids
bearing an acetylenic group on the b-position gave conjugated eny-
nes via 1,2-CC insertion reaction in good to high yields. Both con-
jugated enynes bearing an aromatic group and an alkyl group on
the acetylenic carbon can be obtained by the presented procedure.
The chemistry presented here is unprecedented and should con-
tribute to the synthesis of conjugated enynes.
O
K2CO3
S(O)Tol
S(O)Tol
MeOH
95%
O
Toluene
-78 ~ 0 °C
Cl
Cl
16
14d
H
Li
1,2-CC insertion
O
O
MgCl
97% (from 16L)
77% (from 16P)
H
Cl
18
17
Acknowledgments
Scheme 4.
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
Promotion from Tokyo University of Science, which are gratefully
acknowledged.
butyne, did not proceed at all (entry 9). Generation of the magne-
sium carbenoids was conducted with i-PrMgCl or c-PentMgCl, and
similar results, less polar adducts gave almost quantitative yields
of conjugated enynes 15 and more polar adducts gave lower yields,
were observed (compare the results in Table 3 with those shown in
Scheme 2 and Table 2, entries 1 and 2).
The conjugated enyne without a substituent on the acetylenic
carbon was synthesized from 14d as shown in Scheme 4. Thus,
the trimethylsilyl group of 14d was cleaved with potassium car-
bonate to give terminal acetylene 16 in almost quantitative yield.
Acetylene 16 was treated with 1.2 equiv of LDA followed by a Grig-
nard reagent to afford conjugated enyne 18 through magnesium
carbenoid 17 in good to high overall yields.
As mentioned above, lithium acetylide derived from alkylacety-
lene did not give adduct 4 (see Table 3, entry 9). This result implies
that we could not synthesize conjugated enynes bearing an alkyl
group on the acetylenic carbon by the presented method. However,
they can be obtained by the alkylation of the aforementioned con-
jugated enyne 18. The results for the treatment of 18 with n-BuLi
followed by electrophiles including iodoalkanes are summarized
in Table 4.
Thus, as shown in Table 4, conjugated enyne 18 was treated
with 2 equiv of n-BuLi followed by iodomethane (5 equiv) in THF
at 0 °C and the reaction mixture was stirred at 0 °C for 30 min to
give conjugated enyne bearing a methyl group on the acetylenic
carbon 19a in 69% yield (entry 1). The alkylation with iodoethane
and 1-iodohexane required somewhat forcing conditions and an
additive (HMPA); however, the desired conjugated enynes having
ethyl (19b) or n-hexyl group (19c) were obtained in moderate to
References and notes
1. A review on the chemistry and biology of enediyne antibiotics: Nicolaou, K. C.;
Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991, 30, 1387.
2. Chemistry and synthesis of calicheamicin: Nicolaou, K. C.; Sorensen, E. J.
Classics in Total Synthesis; Wiley-VCH: Weinheim, 1996.
3. Chemistry and synthesis of dynemicin A: Nicolaou, K. C.; Snyder, S. A. Classics in
Total Synthesis II; Wiley-VCH: Weinheim, 2003.
4. (a) Saito, S.; Yamamoto, Y. Chem. Rev. 2000, 100, 2901; (b) Saito, S.; Yamamoto,
Y. J. Synth. Org. Chem. Jpn. 2001, 59, 346; (c) Tykwinski, R. R.; Zhao, Y. Synlett
2002, 1393; (d) Saito, S.; Yamamoto, Y.. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York,
2002; Vol. 1, pp 1635–1646.
5. (a) Mundy, B. P.; Ellerd, M. G.; Favaloro, F. G., Jr. Name Reactions and Reagents in
Organic Synthesis, 2nd ed.; John Wiley and Sons: Hoboken, 2005; (b) Li, J. J.
Name Reactions, 3rd ed.; Springer: Berlin, 2006.
6. (a) Tsukada, N.; Ninomiya, S.; Aoyama, Y.; Inoue, Y. Org. Lett. 2007, 9, 2919; (b)
Nishimura, T.; Guo, X.-X.; Ohnishi, K.; Hayashi, T. Adv. Synth. Catal. 2007, 349,
2669; (c) Nishimura, T. J. Synth. Org. Chem. Jpn. 2008, 66, 1160. and the
references cited therein.
7. (a) Nishiura, M.; Hou, Z.; Wakatsuki, Y.; Yamaki, T.; Miyamoto, T. J. Am. Chem.
Soc. 2003, 125, 1184; (b) Suzuki, T.; Zhang, W.-X.; Nishiura, M.; Hou, Z. J. Synth.
Org. Chem. Jpn. 2009, 67, 451. and the reference cited therein.
8. For example: (a) Harada, T.; Iwazaki, K.; Otani, T.; Oku, A. J. Org. Chem. 1998, 63,
9007; (b) Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zenti, G. J. Org. Chem. 2003, 68,
662; (c) Pal, M.; Parasuraman, P.; Subramanian, V.; Dakarapu, R.; Yeleswarapu,
K. R. Tetrahedron Lett. 2004, 45, 2305.
9. Watanabe, M.; Nakamura, M.; Satoh, T. Tetrahedron 2005, 61, 4409.
10. (a) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.; Koyama, M.
Tetrahedron 1998, 54, 5557; (b) Satoh, T.; Kawashima, T.; Takahashi, S.; Sakai,
K. Tetrahedron 2003, 59, 9599.
11. (a) Satoh, T.; Ogata, S.; Wakasugi, D. Tetrahedron Lett. 2006, 47, 7249; (b) Ogata,
S.; Masaoka, S.; Sakai, K.; Satoh, T. Tetrahedron Lett. 2007, 48, 5017; (c) Ogata,
S.; Saitoh, H.; Wakasugi, D.; Satoh, T. Tetrahedron 2008, 64, 5711.
12. Addition of lithium phenylacetylide to 7 and the synthesis of conjugated enyne 10:
Table 4
Treatment of conjugated enyne 18 with n-BuLi followed by electrophiles to afford
conjugated enynes 19
Phenylacetylene (0.055 mL; 0.5 mmol) was added to
a solution of LDA
H
E
(0.5 mmol) in 1 mL of dry THF in flame-dried flask under argon
a
1) n-BuLi (2 eq)
atmosphere dropwise at 0 °C with stirring. The reaction mixture was stirred
for 10 min at 0 °C and cooled to À30 °C. A solution of 7 (33 mg; 0.1 mmol) in
1 mL of THF was added to the solution and the reaction mixture was slowly
allowed to warm to room temperature for 2 h. The reaction was quenched with
satd aq NH4Cl and the whole mixture was extracted three times with CHCl3.
The organic layer was dried over MgSO4 and concentrated in vacuo. The
product was purified by flash column chromatography (hexane/AcOEt) to give
8L (25.7 mg; 60%) as colorless crystals and 8P (8.5 mg; 20%) as colorless oil. 8L:
mp 137.5–138 °C (hexane/AcOEt); IR (KBr) 2957, 2884, 1152, 1110, 1087 (SO),
O
O
O
O
2) Electrophile (5 eq)
THF
Conditions
H
H
19
18
Entry Electrophile
E
Additive
Conditions
19
Time
Temp
(°C)
Yield
(%)
1054 (SO), 809, 758, 693 cmÀ1 1H NMR d 1.75–1.93 (3H, m), 2.07–2.25 (5H, m),
;
2.41 (3H, s), 3.92–4.02 (4H, m), 4.40 (1H, s), 7.29–7.37 (5H, m), 7.46–7.55 (4H,
m). Anal. Calcd for C24H25ClO3S: C, 67.20; H, 5.87; Cl, 8.26; S, 7.48. Found: C,
67.06; H, 6.02; Cl, 8.14; S, 7.39. 8P: IR (neat) 2954, 2883, 2232, 1164, 1107,
1
2
CH3I
CH3CH2I
CH3
CH3CH2
non
HMPA
(6 equiv)
30 min
o.n.
0
rt
19a 69
19b 52
1083 (SO), 1052 (SO), 809, 757, 692 cmÀ1 1H NMR d 1.70–1.90 (3H, m), 1.94–
;
3
CH3(CH2)5I CH3(CH2)5 HMPA
(6 equiv)
non
ClCOOC2H5 COOC2H5 non
o.n.
rt
19c 82
2.25 (4H, m), 2.40 (3H, s), 2.72–2.80 (1H, m), 3.90–4.02 (4H, m), 4.40 (1H, s),
7.27–7.34 (5H, m), 7.44–7.48 (2H, m), 7.70–7.75 (2H, m). MS m/z (%) 428 (M+,
2), 289 (38), 253 (100), 167 (61), 139 (33), 99 (40). Calcd for C24H25ClO3S: M,
4
5
6
7
PhCOCl
PhCO
30 min
30 min
30 min
30 min
0
0
0
0
19d 64
19e 57
19f 65
19g 79
428.1213. Found: m/z 428.1219. To
a flame-dried flask under argon
atmosphere was added dry toluene (3 mL) followed by i-PrMgCl (2.0 M
solution in diethyl ether; 0.195 mL, 0.39 mmol) at À78 °C. A solution of 8L
(33.6 mg; 0.078 mmol) in toluene (1 mL) was added dropwise to the solution
PhCHO
I2
PhCH(OH) non
non
I

H. Saitoh et al. / Tetrahedron Letters 51 (2010) 633–637
637
of the Grignard reagent with stirring and the reaction mixture was slowly
allowed to warm to 0 °C for 2 h. The reaction was quenched with satd aq NH4Cl
and the whole mixture was extracted three times with CHCl3. The organic layer
was dried over MgSO4 and concentrated in vacuo. The product was purified by
flash column chromatography (hexane/AcOEt) to give 10 (19.2 mg; 97%) as
in 1.3 mL of dry THF in a flame-dried flask under argon atmosphere at 0 °C and
the reaction mixture was stirred for 10 min to generate lithium acetylide.
Iodohexane (0.09 mL; 0.6 mmol) was added to the reaction mixture dropwise
with stirring and the whole mixture was stirred at room temperature
overnight. The reaction was quenched with satd aq NH4Cl and the whole
mixture was extracted three times with CHCl3. The organic layer was dried
over MgSO4 and concentrated in vacuo. The product was purified by flash
column chromatography (hexane/AcOEt) to give 19c (25.7 mg; 82%) as light
colorless oil. IR (neat) 2951, 2882, 2197, 1120, 1087, 1034, 906, 756, 690 cmÀ1
;
1H NMR d 1.72–1.79 (4H, m), 2.36–2.42 (2H, m), 2.63–2.68 (2H, m), 3.97–4.00
(4H, m), 5.50 (1H, s), 7.27–7.32 (3H, m), 7.41–7.44 (2H, m). MS m/z (%) 254 (M+,
100), 209 (20), 192 (20), 167 (57), 153 (20), 115 (19). Calcd for C17H18O2: M,
254.1307. Found: m/z 254.1303.
yellow oil. IR (neat) 2931, 2858, 1120, 1083, 1035, 908, 684 cmÀ1 1H NMR d
;
0.89 (3H, t, J = 6.8 Hz), 1.24–1.59 (8H, m), 1.66–1.78 (4H, m), 2.27–2.36 (4H, m),
2.50–2.58 (2H, m), 3.97 (4H, s), 5.26 (1H, s). MS m/z (%) 262 (M+, 100), 233 (14),
191 (12), 147 (13), 119 (14), 105 (19), 91 (24), 80 (14). Calcd for C17H26O2: M,
262.1933. Found: m/z 262.1941.
13. Synthesis of conjugated enyne bearing hexyl group 19c from 18. A solution of 18
(20.6 mg; 0.12 mmol) in 1 mL of THF and HMPA (0.12 ml; 0.72 mmol) was
added to a solution of n-BuLi (1.57 M solution in hexane, 0.15 mL; 0.24 mmol)