Stereodivergent Synthesis of (E)- And (Z)-2-Alken-4-yn-l-ols from 2-Propynoic Acid: A practical route via 2-alken-4-ynoates

Full text of DOI:10.1021/jo991350a

1558
J . Org. Chem. 2000, 65, 1558-1561
requires the stereodefined synthesis of (E)- and (Z)-3-
Ster eod iver gen t Syn th esis of (E)- a n d
iodo-2-propen-1-ol. Hydrostannation of 2-propyn-1-ol fol-
lowed by iodolysis has been reported to give (E)-3-iodo-
2-propen-1-ol.9 However, hydrostannation of 2-propyn-
1-ol with tributylstannane gave a mixture of (E)-3-tri-
butylstannyl-2-propen-1-ol, (Z)-3-tributylstannyl-2-pro-
pen-1-ol, and 2-tributylstannyl-2-propen-1-ol. Separation
of these isomers prior to iodolysis is necessary.
The hydroiodination of 2-propynoic acid and its deriva-
tives has been studied in detail.10 If the stereodivergent
synthesis of (E)- and (Z)-3-iodopropenoic acid and/or its
derivatives from 2-propynoic acid is possible, coupling of
(E)- and (Z)-3-iodo-2-propenoic acid or its derivatives with
1-alkynes followed by reduction should be a practical
route to (E)- and (Z)-2-alken-4-yn-1-ol from 2-propynoic
acid. This route has another advantage. 2-Alken-4-ynoic
acid and its derivatives, which are electron withdrawing
group substituted enynes, are obtained by this coupling.
The 1,6-addition of organocuprates to 2-alken-4-ynoates
is reported to be a convenient route to functionalized
allenes.11 The stereodefined synthesis of 2-alken-4-
ynoates provides a convenient route to functionalized
allenes.
(Z)-2-Alk en -4-yn -1-ols fr om 2-P r op yn oic
Acid : A P r a ctica l Rou te via
2-Alk en -4-yn oa tes
Ryo Takeuchi,* Keisuke Tanabe, and Shigeru Tanaka
Department of Environmental Science,
Faculty of Science and Graduate School of Integrated
Science, Yokohama City University, 22-2 Seto,
Kanazawa-ku, Yokohama 236-0027, J apan
Received August 25, 1999
Allylic alcohols and their derivatives play an important
role in organic synthesis. For example, they are used as
substrates for asymmetric epoxidation,1 transition metal
complex-catalyzed allylic substitution,2 and Claisen rear-
rangement.3 The stereodefined synthesis of allylic alco-
hols is necessary for such synthetic procedures. 2-Alken-
4-yn-1-ols are a versatile and potential synthetic inter-
mediate4 because of the presence of an enyne and an
allylic alcohol sharing the same carbon-carbon double
bond. 2-Penten-4-yn-1-ol is used as a starting material
for the preparation of 2-alken-4-yn-1-ols.5 The reaction
of epichlorohydrine with sodium acetylide in liquid
ammonia reportedly gives 2-penten-4-yn-1-ol, but in an
85:15 mixture of (E)- and (Z)-2-penten-4-yn-1-ol.6 Separa-
tion of these isomers is necessary for the stereochemical
integrity of the alkene. The regioselective reduction of
2,4-alkadiyn-1-ols to (Z)-2-alken-4-yn-1-ols mediated by
activated zinc has been reported.7 However, this reduc-
tion sometimes gives a mixture of (E)- and (Z)-2-alken-
4-yn-1-ols. The lack of a practical and stereodefined
synthesis of 2-alken-4-yn-1-ols from an easily accessible
starting material has impeded its utility as a synthetic
intermediate. In connection with our ongoing project
related to iridium complex-catalyzed allylic substitution,8
we became interested in developing a practical and
stereodefined route to 2-alken-4-yn-1-ols. In this paper,
we describe the stereodivergent synthesis of (E)- and (Z)-
2-alken-4-yne-1-ols from 2-propynoic acid.
We examined the reaction of 2-propynoic acid with
aqueous hydroiodic acid (eq 1). The selectivity of the
product strongly depended on the reaction conditions.
The results are summarized in Table 1. The reaction at
50 °C for 18 h gave a 93:7 mixture of (E)- and (Z)-3-iodo-
2-propenoic acid ((E)- and (Z)-1) in 90% yield (entry 1).
3,3-Diiodopropanoic acid (2) was also obtained in 8%
yield. Product 2 was formed by hydroiodination of (E)-
and (Z)-1. The reaction at room temperature gave a 41:
59 mixture of (E)- and (Z)-1 in 81% yield (entry 2). This
result suggested that (E)-1 was formed by isomerization
of the initially formed (Z)-1.12 Decreasing the amount of
HI and dilution with H2O increased the selectivity of (Z)-
1. The reaction at 50 °C for 17 h using 1.4 equiv of HI to
2-propynoic acid gave (Z)-1 exclusively in 90% yield (entry
3), and the formation of 2 was suppressed.
One efficient route to 2-alken-4-yn-1-ols is the coupling
of 3-iodo-2-propen-1-ol with 1-alkynes. This protocol
(1) (a) Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1. (b) J ohnson,
R. A.; Sharpless, K. B. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 389.
(2) (a) Harrington, P. J . In Comprehensive Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford,
1995; Vol. 12, p 797. (b) Tsuji, J . Palladium Reagents and Catalysts;
J ohn Wiley & Sons: New York, 1995; p 290. (c) Godleski, S. A. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 4, p 585. (d) Lipshutz, B. H.; Sengupta,
I. Org. React. 1992, 41, 135.
(9) (a) J ung, M. E.; Light, L. A. Tetrahedron Lett. 1982, 23, 3851.
(b) Lai, M.-T.; Li, D.; Oh, E.; Liu, H.-W. J . Am. Chem. Soc. 1993, 115,
1619.
(10) (a) Piers, E.; Wong, T.; Coishi, P. D.; Rogers, C. Can. J . Chem.
1994, 72, 1816. (b) Ma, S.; Lu, X.; Li, Z. J . Org. Chem. 1992, 57, 709.
(c) Ma, S.; Lu, X. J . Chem. Soc., Chem. Commun. 1990, 1643. (d)
Bowden, K.; Price, M. J . J . Chem. Soc. B 1970, 1466.
(3) Wipf, P. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, p 827.
(4) Base-catalyzed cyclization of 2-alken-4-yn-1-ols to furans is
reported, see: Schreurs, P. H. M.; Galesloot, W. G.; Brandsma, L. Recl.
Trav. Chim. Pays-Bas 1975, 94, 70.
(5) Poleschner, H.; Heydenreich, M. Magn. Reson. Chem. 1997, 35,
712.
(11) (a) Koop, U.; Handke, G.; Krause, N. Liebigs Ann. 1996, 1487.
(b) Gerold, A.; Krause, N. Chem. Ber. 1994, 127, 1547. (c) Arndt, S.;
Handke, G.; Krause, N. Chem. Ber. 1993, 126, 251. (d) Haubrich, A.;
Van Klavere, M.; Van Koten, G.; Handke, G. Krause, N. J . Org. Chem.
1993, 58, 5849. (e) Krause, N. Chem. Ber. 1991, 124, 2633. (f) Krause,
N.; Handke, G. Tetrahedron Lett. 1991, 32, 7229. (g) Krause, N. Chem.
Ber. 1990, 123, 2173.
(6) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier: Am-
sterdam, 1988; p 63.
(7) Aerssens, M. H. P. J .; Van der Heiden, R.; Heus, M.; Brandsma,
L. Synth. Commun. 1990, 20, 3421.
(8) (a) Takeuchi, R.; Shiga, N. Org. Lett. 1999, 1, 265. (b) Takeuchi,
R.; Kashio, M. J . Am. Chem. Soc. 1998, 120, 8647. (c) Takeuchi, R.;
Kashio, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 263.
(12) (a) I2-catalyzed isomerization of (Z)-1 to (E)-1 is reported, see:
J ung, M. E.; Kiankarimi, M. J . Org. Chem. 1998, 63, 2968. (b) The
isomerization of (Z)-1 to (E)-1 under refluxing xylene is reported, see:
Wojcik, J .; Stefaniak, L.; Witanowski, M.; Webb, G. A. Bull. Pol. Acad.
Sci. Chem. 1984, 32, 85. (c) Similar isomerization of 1-phenyl-3(Z)-
iodo-2-propenone to the E isomer in the presence of a catalytic amount
of NaI in acetic acid is reported, see: ref 10b.
10.1021/jo991350a CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/11/2000

Notes
entry
J . Org. Chem., Vol. 65, No. 5, 2000 1559
Ta ble 1. Hyd r oiod in a tion of 2-P r op yn oic Acid a
of 90% and 88%. Unlike the coupling of acid 1, both esters
4 coupled smoothly with 1-hexyne (eq 4); the results are
HI/2-propy-
noicacid
yield of
yield of
solvent conditions 1 (%)b E/Zc 2 (%)b
1
2.8
3.2
1.4
neat
neat
H2O
50 °C; 18 h
rt; 18 h
50 °C; 17 h
90
81
90
93/7
41/59
0/100
8
6
0
2
3d
a
A mixture of 2-propynoic acid (2 mmol) and aqueous hydroiodic
b
acid (55 wt %) was stirred under Ar atmosphere. Isolated yield.
c Determined by NMR. 2-Propynoic acid (100 mmol), H2O (30
d
mL).
Ta ble 2. Syn th esis of 2-Alk en -4-yn oa te 5a
time
(h)
yield
(%)b
entry ester
alkyne
(E)-4 1-hexyne
(Z)-4 1-hexyne
product
1c
2d
3e
4f
5g
6h
7i
17
15
3
3
17
5
(E)-5a
(Z)-5a
(E)-5b
(Z)-5b
(E)-5c
(Z)-5c
(E)-5d
(Z)-5d
83
90
93
93
80
81
98
87
(E)-4 phenylacetylene
(Z)-4 phenylacetylene
(E)-4 5-chloro-1-pentyne
(Z)-4 5-chloro-1-pentyne
(E)-4 1-ethynylcyclohexene
(Z)-4 1-ethynylcyclohexene
3
3
8j
a
A mixture of 4 (1 equiv), PdCl2(PPh3)2 (1 mol%), CuI (0.5
mol%), 1-alkyne (1.1 equiv), and Et3N (4 mL/4 mmol) was stirred
d
at 50 °C. b Isolated yield. c (E)-4 (43 mmol). (Z)-4 (30 mmol). e (E)-
summarized in Table 2. Under Sonogashira conditions,
(E)- and (Z)-4 coupled with 1-hexyne to give (E)- and (Z)-
5a in respective yields of 83% and 90% (entries 1 and 2).
The coupling was stereospecific, and both (E)- and (Z)-
5a were obtained in stereoisomeric pure form. Various
1-alkynes, including 3-alken-1-yne, could be used for the
coupling. The coupling with phenylacetylene and 5-chloro-
1-pentyne also gave the coupling products (5b and 5c)
in good yields (entries 3-6). The coupling with 1-ethy-
nylcyclohexene gave 2,6-diene-4-ynoate (E)- and (Z)-5d
in respective yields of 98% and 87% (entries 7 and 8).
Reduction of 5 gave 2-alken-4-yn-1-ol (6). Reduction of 5
with LiAlH4 resulted in the formation of a complex mix-
ture of products. Diisobutylaluminum hydride (DIBALH)
is a common reagent for the reduction of R,â-unsaturated
esters to allylic alcohols.15 The reduction of 5 with
DIBALH was examined. Ester 5 was smoothly reduced
to the corresponding allylic alcohol 6 by using 2 equiv of
DIBALH at -78 °C (eq 5); the results are summarized
h
4 (15 mmol). f (Z)-4 (18 mmol). g (E)-4 (14 mmol). (Z)-4 (15 mmol).
i
j
(E)-4 (13 mmol). (Z)-4 (15 mmol).
We examined the isomerization of (Z)-1 to (E)-1 (eq 2).
The reaction of (Z)-1 in the presence of a catalytic amount
of HI (14 mol %) under refluxing benzene for 5 h gave
(E)-1 in 89% yield. Acid (Z)-1 was converted to (E)-1. Both
(E)- and (Z)-1 could be obtained in excellent yields from
2-propynoic acid. When H2SO4 or HCl was used as a
catalyst, no isomerization occurred and the starting
material was recovered.
Acid (E)- and (Z)-1 showed different reactivities in the
coupling with 1-alkyne. The coupling of (Z)-1 with 1-hex-
yne under Sonogashira conditions13 did not give the
expected product despite the complete consumption of (Z)-
1, whereas (E)-1 coupled with 1-hexyne to give (E)-3 in
63% yield under the same reaction conditions (eq 3).14
To obtain both of the expected coupling products, we
prepared esters of 1 and subjected them to coupling with
1-alkyne. Esterification of (E)- and (Z)-1 with ethanol in
the presence of a catalytic amount of H2SO4 gave the
corresponding esters (E)- and (Z)-4 in respective yields
in Table 3. 1,4-, 1,6-, or 1,8-Reduction did not occur. Both
(E)- and (Z)-2-alken-4-yn-1-ols (6) were obtained in good
yields. The reduction of 5 was stereospecific except in the
case of (Z)-5b, where (E)-6b was obtained in 3% selectiv-
ity (entry 4).
In conclusion, we have developed a stereodivergent
route to (E)- and (Z)-2-alken-4-yn-1-ols from 2-propynoic
acid. In view of the ready availability of the starting
material and the simplicity of the procedure, 2-alken-4-
(13) (a) Campbell, B. In Organocopper Reagents: A Practical Ap-
proach; Taylor, R. J . K., Ed.; Oxford University Press: Oxford, 1994;
p 217. (b) Sonogashira, K. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, p 521. (c)
Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16,
4467.
(14) Pd complex-catalyzed coupling of (Z)-1 with an excess amount
of phenylacetylene gives γ-alkylidenebutenolides, see: Kotora, M.;
Negishi, E. Synthesis 1997, 121.
(15) Yoon, N. M.; Gyoung, Y. S. J . Org. Chem. 1985, 50, 2443.

1560 J . Org. Chem., Vol. 65, No. 5, 2000
Notes
Ta ble 3. Red u ction of 2-Alk en -4-yn oa te 5 to
2-Alk en -4-yn -1-ol 6a
organic layers were dried (MgSO4). The solvent was evaporated
in vacuo. Column chromatography (n-hexane/AcOEt 1/1) of the
residue gave (E)-3 as a pale yellow solid, yield 0.484 g (63%);
entry
ester
product
yield (%)b
1
mp 49-50 °C. H NMR (270 MHz, CDCl3) δ 0.93 (t, J ) 7.3 Hz,
1c
2d
3e
4f
5g
6h
7i
(E)-5a
(Z)-5a
(E)-5b
(Z)-5b
(E)-5c
(Z)-5c
(E)-5d
(Z)-5d
(E)-6a
(Z)-6a
(E)-6b
(Z)-6b
(E)-6c
(Z)-6c
(E)-6d
(Z)-6d
93
89
99
87k
96
79
98
84
3H), 1.43 (sixtet, J ) 7.3 Hz, 2H), 1.53 (quintet, J ) 6.9 Hz,
2H), 2.40 (td, J ) 6.9, 2.3 Hz, 2H), 6.14 (d, J ) 15.8 Hz, 1H),
6.85 (dt, J ) 15.8, 2.3 Hz, 1H), 10.79 (br, 1H). 13C NMR (67.8
MHz, CDCl3) δ 13.5, 19.5, 21.9, 30.3, 77.8, 102.8, 128.4, 128.8,
171.7. Anal. Calcd for C9H12O2: C, 71.03; H, 7.95; O, 21.03.
Found: C, 70.64; H, 7.94.
Eth yl (Z)-3-Iod o-2-p r op en oa te ((Z)-4).10b A mixture of (Z)-1
(3.959 g, 20 mmol), concentrated H2SO4 (0.4 mL), and EtOH (12
mL) was stirred under reflux for 4 h. After the mixture cooled
to room temperature, the solvent was evaporated in vacuo. Ether
and H2O were added to the residue, and the layers were
separated. The aqueous layer was extracted with ether, and the
combined organic layers were dried (MgSO4). The solvent was
evaporated in vacuo. Distillation of the residue under reduced
pressure gave (Z)-4 as a colorless oil, yield 3.953 g (88%); bp
8j
a
A mixture of 5 (1equiv) and 0.95 M DIBALH in n-hexane was
b
d
stirred at -78 °C for 2 h. Isolated yield. c (E)-5a (43 mmol). (Z)-
5a (30 mmol). e (E)-5b (16 mmol), DIBALH (2.6 equiv). f (Z)-5b (14
g
h
i
mmol). (E)-5c (11 mmol). (Z)-5c (10 mmol). (E)-5d (10 mmol).
j
k
(Z)-5d (11 mmol). (E)-6b was obtained in 3% yield.
yn-1-ols should be very important in organic synthesis.
In addition, this route also gives (E)- and (Z)-2-alken-4-
ynoates, which have wide synthetic applications.
1
78-79 °C/10 mmHg. H NMR (270 MHz, CDCl3) δ 1.32 (t, J )
7.3 Hz, 3H), 4.25 (q, J ) 7.3 Hz, 2H), 6.90 (d, J ) 8.9 Hz, 1H),
7.45 (d, J ) 8.9 Hz, 1H). 13C NMR (67.8 MHz, CDCl3) δ 14.1,
60.7, 94.6, 129.8, 164.5.
Eth yl (E)-3-Iod o-2-p r op en oa te ((E)-4).12a Bp 74-76 °C/9
mmHg. 1H NMR (400 MHz, CDCl3) δ 1.29 (t, J ) 7.1 Hz, 3H),
4.20 (q, J ) 7.1 Hz, 2H), 6.90 (d, J ) 14.8 Hz, 1H), 7.87 (d, J )
14.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 14.1, 60.9, 99.1,
136.6, 164.1.
Exp er im en ta l Section
Ma ter ia ls. All reagents and solvents were dried and purified
before use by the usual procedures. PdCl2(PPh3)2 was prepared
according to the published method.16 CuI, 2-propynoic acid, and
0.95 M DIBALH in n-hexane were purchased.
Eth yl (Z)-2-Non en -4-yn oa te ((Z)-5a ). Typ ica l P r oced u r e
for th e Cou p lin g of Eth yl 3-Iod o-2-p r op en oa te (4) w ith
1-Alk yn e. To a mixture of (Z)-4 (6.780 g, 30 mmol), PdCl2(PPh3)2
(210.6 mg, 0.3 mmol), CuI (28.6 mg, 0.15 mmol), and Et3N (120
mL) was added 1-hexyne (2.711 g, 33 mmol). The mixture was
stirred at 50 °C for 15 h. After the mixture cooled to room
temperature, ether and H2O were added, and the aqueous layer
was extracted with ether. The combined organic layers were
dried (MgSO4). The solvent was evaporated in vacuo. Column
chromatography (n-hexane/AcOEt 98/2) of the residue gave (Z)-
Gen er a l Meth od s. 1H and 13C NMR spectra were measured
on a 270 or 400 MHz spectrometer using Me4Si as an internal
standard. Samples were dissolved in CDCl3 solutions. GC
analyses were performed using 3 mm × 2 m glass columns
packed with either 5% PEG-HT on 60/80 mesh chromosorb w
AW-DMCS or 5% OV-17 on 60/80 mesh chromosorb w AW-
DMCS. Column chromatography was carried out on 70-230
mesh silica gel. Elemental analyses were performed at the
Microanalytical Center of Kyoto University.
(Z)-3-Iod o-2-p r op en oic Acid ((Z)-1).10b To a solution of 55%
aqueous HI (20 mL) and H2O (30 mL) was added propynoic acid
(7.005 g, 100 mmol). The mixture was heated at 50 °C for 17 h.
After the mixture cooled to room temperature, ether was added,
and the layers were separated. The aqueous layer was extracted
with ether, and the combined organic layers were washed with
aqueous Na2S2O3 and dried (MgSO4). The solvent was evapo-
rated in vacuo. Washing of the residue with n-hexane gave (Z)-1
as a pale yellow solid, yield 17.816 g (90%); mp 68-70 °C (lit.10b
mp 63-64 °C). 1H NMR (270 MHz, CDCl3) δ 6.99 (d, J ) 9.2
Hz, 1H), 7.69 (d, J ) 9.2 Hz, 1H), 9.94 (br, 1H). 13C NMR (67.8
MHz, CDCl3) δ 98.2, 129.4, 169.7.
1
5a as a pale yellow oil, yield 4.866 g (90%). H NMR (270 MHz,
CDCl3) δ 0.93 (t, J ) 7.3 Hz, 3H), 1.30 (t, J ) 7.3 Hz, 3H), 1.33-
1.64 (m, 4H), 2.45 (td, J ) 6.9, 2.3 Hz, 2H), 4.22 (q, J ) 7.3 Hz,
2H), 6.02 (d, J ) 11.5 Hz, 1H), 6.15 (dt, J ) 11.5, 2.3 Hz, 1H).
13C NMR (67.8 MHz, CDCl3) δ 13.4, 14.1, 19.6, 21.8, 30.2, 60.1,
77.2, 104.0, 123.8, 127.2, 164.7. Anal. Calcd for C11H16O2: C,
73.30; H, 8.95; O, 17.75. Found: C, 73.48; H, 9.18.
Eth yl (E)-2-Non en -4-yn oa te ((E)-5a ).11g 1H NMR (270 MHz,
CDCl3) δ 0.92 (t, J ) 7.3 Hz, 3H), 1.29 (t, J ) 7.3 Hz, 3H), 1.36-
1.60 (m, 4H), 2.38 (td, J ) 6.6, 2.3 Hz, 2H), 4.20 (q, J ) 7.3 Hz,
2H), 6.14 (d, J ) 15.8 Hz, 1H), 6.75 (dt, J ) 15.8, 2.3 Hz, 1H).
13C NMR (67.8 MHz, CDCl3) δ 13.5, 14.1, 19.4, 21.9, 30.3, 60.5,
77.9, 100.7, 126.0, 129.2, 166.1.
(E)-3-Iod o-2-p r op en oic Acid ((E)-1).12a To a solution of 55%
aqueous HI (0.6 mL) and benzene (8 mL) was added (Z)-1 (5.939
g, 30 mmol). The mixture was heated at 80 °C for 5 h. After the
mixture cooled to room temperature, ether was added, and the
layers were separated. The aqueous layer was extracted with
ether, and the combined organic layers were washed with
aqueous Na2S2O3 and dried (MgSO4). The solvent was evapo-
rated in vacuo. Washing of the residue with n-hexane gave (E)-1
Eth yl (E)-5-P h en yl-2-bu ten -4-yn oa te ((E)-5b).11g 1H NMR
(400 MHz, CDCl3) δ 1.31 (t, J ) 7.1 Hz, 3H), 4.24 (q, J ) 7.1
Hz, 2H),), 6.30 (d, J ) 15.8 Hz, 1H), 6.98 (d, J ) 15.8 Hz, 1H),
7.31-7.38 (m, 3H), 7.44-7.54 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ 14.2, 60.7, 86.3, 98.2, 122.2, 125.0, 128.4, 129.2, 130.0,
131.9, 165.9.
Eth yl (Z)-5-P h en yl-2-bu ten -4-yn oa te ((Z)-5b). 1H NMR
(400 MHz, CDCl3) δ 1.32 (t, J ) 7.1 Hz, 3H), 4.26 (q, J ) 7.1
Hz, 2H),), 6.12 (d, J ) 11.4 Hz, 1H), 6.35 (d, J ) 11.4 Hz, 1H),
7.31-7.36 (m, 3H), 7.51-7.55 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ 14.2, 60.3, 86.3, 101.1, 122.6, 122.7, 128.2, 128.3, 129.1,
132.0, 164.7. Anal. Calcd for C13H12O2: C, 77.98; H, 6.04; O,
15.98. Found: C, 77.80; H, 6.09.
1
as a pale yellow solid, yield 5.286 g (89%); mp 144-147 °C. H
NMR (270 MHz, CDCl3) δ 6.90 (d, J ) 14.8 Hz, 1H), 8.09 (d, J
) 14.8 Hz, 1H), 10.0 (br, 1H). 13C NMR (67.8 MHz, CDCl3) δ
103.2, 135.7, 169.4.
3,3-Diiod op r op a n oic Acid (2). Compound 2 could not be
isolated in pure form. Partial 1H NMR spectra was obtained from
the mixture of (E)- and (Z)-1. 1H NMR (270 MHz, CDCl3) δ 3.81
(d, J ) 7.3 Hz, 2H), 5.25 (t, J ) 7.3 Hz, 1H).
(E)-2-Non en -4-yn oic Acid ((E)-3). To a mixture of (E)-1
(0.990 g, 5 mmol), PdCl2(PPh3)2 (70.2 mg, 0.1 mmol), CuI (9.5
mg, 0.05 mmol), and MeCN (12 mL) were added Et3N (2.8 mL,
20 mmol) and 1-hexyne (0.509 g, 6.2 mmol). The mixture was
stirred at 50 °C for 3 h. After the mixture cooled to room
temperature, the solvent was evaporated in vacuo. Ether and
H2O were added to the residue, and the layers were separated.
The aqueous layer was extracted with ether, and the combined
Eth yl (E)-8-Ch lor o-2-octen -4-yn oa te ((E)-5c). 1H NMR
(400 MHz, CDCl3) δ 1.29 (t, J ) 7.1 Hz, 3H), 2.01 (quintet, J )
6.5 Hz, 2H), 2.58 (td, J ) 6.5, 2.3 Hz, 2H), 3.65 (t, J ) 6.5 Hz,
2H), 4.21 (q, J ) 7.1 Hz, 2H), 6.16 (d, J ) 15.8 Hz, 1H), 6.74 (dt,
J ) 15.8, 2.3 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 14.2, 17.1,
31.0, 43.4, 60.6, 78.7, 98.1, 125.5, 129.9, 165.9. Anal. Calcd for
C10H13ClO2: C, 59.86; H, 6.53; Cl, 17.67; O, 15.95. Found: C,
59.60; H, 6.59; Cl, 17.70.
Eth yl (Z)-8-Ch lor o-2-octen -4-yn oa te ((Z)-5c). 1H NMR
(400 MHz, CDCl3) δ 1.30 (t, J ) 7.1 Hz, 3H), 2.05 (quintet, J )
6.5 Hz, 2H), 2.64 (td, J ) 6.5, 2.3 Hz, 2H), 3.73 (t, J ) 6.5 Hz,
2H), 4.22 (q, J ) 7.1 Hz, 2H), 6.05 (d, J ) 11.4 Hz, 1H), 6.12 (dt,
J ) 11.4, 2.3 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 14.2, 17.4,
(16) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: New York, 1985; p 18.

Notes
J . Org. Chem., Vol. 65, No. 5, 2000 1561
31.0, 43.5, 60.2, 78.5, 101.3, 123.3, 128.1, 164.7. Anal. Calcd for
C10H13ClO2: C, 59.86; H, 6.53; Cl, 17.67; O, 15.95. Found: C,
59.57; H, 6.54; Cl, 17.76.
Eth yl (E)-5-(1-Cycloh exen -1-yl)-2-p en ten -4-yn oa te ((E)-
5d ).11g 1H NMR (400 MHz, CDCl3) δ 1.29 (t, J ) 7.1 Hz, 3H),
1.57-1.69 (m, 4H), 2.12-2.17 (m, 4H), 4.21 (q, J ) 7.1 Hz, 2H),
6.15 (d, J ) 15.8 Hz, 1H), 6.23 (quintet, J ) 2.0 Hz, 1H), 6.88
(d, J ) 15.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 14.2, 21.3,
22.1, 25.9, 28.7, 60.5, 84.1, 100.6, 120.4, 125.6, 128.9, 137.9,
166.0.
Eth yl (Z)-5-(1-Cycloh exen -1-yl)-2-p en ten -4-yn oa te ((Z)-
5d ). 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J ) 7.1 Hz, 3H), 1.57-
1.69 (m, 4H), 2.12-2.22 (m, 4H), 4.22 (q, J ) 7.1 Hz, 2H), 6.02
(d, J ) 11.4 Hz, 1H), 6.25 (d, J ) 11.4 Hz, 1H), 6.28-6.30 (m,
1H). 13C NMR (100 MHz, CDCl3) δ 14.2, 21.3, 22.1, 25.9, 28.7,
60.1, 84.2, 103.6, 120.8, 123.3, 126.9, 137.8, 164.8. Anal. Calcd
for C13H16O2: C, 76.44; H, 7.90; O, 15.67. Found: C, 76.67; H,
8.05.
(dt, J ) 15.9, 1.8 Hz, 1H), 6.32 (dt, J ) 15.9, 5.2 Hz, 1H), 7.26-
7.30 (m, 3H), 7.40-7.44 (m, 2H). 13C NMR (100 MHz, CDCl3) δ
62.7, 87.3, 90.0, 110.3, 123.1, 128.1, 128.2, 131.4, 141.8. Anal.
Calcd for C11H10O: C, 83.51; H, 6.37; O, 10.11. Found: C, 83.50;
H, 6.37.
(Z)-5-P h en yl-2-p en ten -4-yn -1-ol ((Z)-6b). 1H NMR (400
MHz, CDCl3) δ 2.31 (br, 1H), 4.48 (d, J ) 6.4 Hz, 2H), 5.78 (dt,
J ) 10.9, 1.4 Hz, 1H), 6.12 (dt, J ) 10.9, 6.4 Hz, 1H), 7.28-7.32
(m, 3H), 7.40-7.44 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 60.9,
85.0, 95.2, 110.5, 122.9, 128.3, 128.4, 131.4, 141.3. Anal. Calcd
for C11H10O: C, 83.51; H, 6.37; O, 10.11. Found: C, 83.27; H,
6.50.
(E)-8-Ch lor o-2-octen -4-yn -1-ol ((E)-6c). 1H NMR (400 MHz,
CDCl3) δ 1.98 (quintet, J ) 6.6 Hz, 2H), 2.33 (br, 1H), 2.50 (td,
J ) 6.6, 2.0 Hz, 2H), 3.65 (t, J ) 6.6 Hz, 2H), 4.16 (dd, J ) 5.6,
2.0 Hz, 2H), 5.70 (dquintet, J ) 15.9, 2.0 Hz, 1H), 6.16 (dt, J )
15.9, 5.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 16.7, 31.3, 43.6,
62.7, 79.2, 88.8, 110.6, 140.8. Anal. Calcd for C8H11ClO: C, 60.57;
H, 6.99; Cl, 22.35; O, 10.09. Found: C, 60.29; H, 7.08; Cl, 22.33.
(Z)-8-Ch lor o-2-octen -4-yn -1-ol ((Z)-6c). 1H NMR (400 MHz,
CDCl3) δ 1.69 (br 1H), 2.00 (quintet, J ) 6.8 Hz, 2H), 2.54 (td,
J ) 6.8, 2.2 Hz, 2H), 3.66 (t, J ) 6.8 Hz, 2H), 4.38 (dd, J ) 6.4,
1.3 Hz, 2H), 5.57 (dt, J ) 10.8, 1.3 Hz, 1H), 6.03 (dt, J )10.8,
6.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 16.9, 31.3, 43.6, 60.8,
76.7, 94.3, 110.9, 140.5. Anal. Calcd for C8H11ClO: C, 60.57; H,
6.99; Cl, 22.35; O, 10.09. Found: C, 60.14; H, 6.78; Cl, 22.22.
(E)-2-Non en -4-yn -1-ol ((E)-6a ).5 Typ ica l P r oced u r e for
Red u ction of Eth yl 2-Alk en -3-yn oa te (5). To 0.95 M diisobu-
tylaluminum hydride in n-hexane (91 mL) was added dropwise
(E)-5a (7.750 g, 43 mmol). The mixture was stirred at -78 °C
for 2 h. The cooling bath was removed, and the mixture was
allowed to warm to room temperature. The mixture was poured
into 6 M HCl, and the aqueous layer was extracted with ether.
The combined organic layers were dried (MgSO4). The solvent
was evaporated in vacuo. Column chromatography (n-hexane/
AcOEt 90/10) of the residue gave (E)-6a as a colorless oil, yield
(E)-5-(1-Cycloh exen -1-yl)-2-p en ten -4-yn -1-ol ((E)-6d ). 1H
NMR (400 MHz, CDCl3) δ 1.55-1.67 (m, 4H), 2.10-2.15 (m, 4H),
2.22 (br, 1H), 4.18 (dd, J ) 5.4, 1.7 Hz, 2H), 5.84 (d, J ) 15.9
Hz, 1H), 6.10 (quintet, J ) 2.0 Hz, 1H), 6.18 (dt, J ) 15.9, 5.4
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 21.4, 22.2, 25.6, 29.0,
62.8, 84.6, 92.0, 110.9, 120.6, 135.0, 140.5. Anal. Calcd for
1
5.527 g (93%). H NMR (400 MHz, CDCl3) δ 0.92 (t, J ) 7.2 Hz,
3H), 1.41 (sixtet, J ) 7.2 Hz, 2H), 1.51 (quintet, J ) 7.2 Hz,
2H), 1.97 (br, 1H), 2.30 (td, J ) 7.2, 1.8 Hz, 2H), 4.16 (d, J ) 5.5
Hz, 2H), 5.71 (dt, J ) 15.9, 1.8 Hz, 1H), 6.15 (dt, J ) 15.9, 5.5
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 13.9, 19.4, 22.3, 31.2,
63.3, 78.7, 91.7, 111.7, 140.5.
(Z)-2-Non en -4-yn -1-ol ((Z)-6a ). 1H NMR (400 MHz, CDCl3)
δ 0.92 (t, J ) 7.3 Hz, 3H), 1.42 (sixtet, J ) 7.3 Hz, 2H), 1.52
(quintet, J ) 7.3 Hz, 2H), 2.17 (br, 1H), 2.33 (td, J ) 7.3, 2.1
Hz, 2H), 4.37 (d, J ) 6.3 Hz, 2H), 5.56 (dt, J ) 10.8, 2.1 Hz,
1H), 5.99 (dt, J ) 10.8, 6.3 Hz, 1H). 13C NMR (100 MHz, CDCl3)
δ 13.5, 19.1, 21.9, 30.7, 60.8, 76.2, 96.6, 111.0, 139.9. Anal. Calcd
for C9H14O: C, 78.21; H, 10.21; O, 11.58. Found: C, 78.09; H,
10.41.
C
11H14O: C, 81.44; H, 8.70; O, 9.86. Found: C, 81.19; H, 8.72.
(Z)-5-(1-Cycloh exen -1-yl)-2-p en ten -4-yn -1-ol ((Z)-6d ). 1H
NMR (400 MHz, CDCl3) δ 1.56-1.68 (m, 4H), 2.11-2.16 (m, 5H),
4.39 (dd, J ) 6.4, 1.3 Hz, 2H), 5.69 (d, J ) 10.8 Hz, 1H), 6.02
(dt, J ) 10.8, 6.4 Hz, 1H), 6.12 (quintet, J ) 2.0 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ 21.7, 22.5, 26.0, 29.4, 61.2, 82.7, 97.6,
111.1, 120.9, 135.6, 140.4. Anal. Calcd for C11H14O: C, 81.44;
H, 8.70; O, 9.86. Found: C, 81.15; H, 8.63.
(E)-5-P h en yl-2-p en ten -4-yn -1-ol ((E)-6b). 1H NMR (400
MHz, CDCl3) δ 2.03 (br, 1H), 4.22 (dd, J ) 5.2, 1.8 Hz, 2H), 5.96
J O991350A