Highly enantioselective addition of linear alkyl alkynes to aromatic aldehydes

Article abstract of DOI:10.1016/j.tetasy.2011.06.020

An asymmetric linear alkyl alkyne addition to aromatic aldehydes catalyzed by the Ti-(R)-BINOL system is reported with high enantioselectivity and yield. Our study expands upon the synthetic scope of propargylic alcohols, which could serve as potentially useful intermediates for the synthesis of various natural products.

Full text of DOI:10.1016/j.tetasy.2011.06.020

Tetrahedron: Asymmetry 22 (2011) 1142–1146
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Highly enantioselective addition of linear alkyl alkynes to aromatic aldehydes
Xi Du a, Qin Wang a,b, , Xiao He a, Rui-Guang Peng a, Xiao Zhang a, Xiao-Qi Yu c,
⇑
⇑
a Department of Medicinal Chemistry, Luzhou Medical College, Luzhou, Sichuan 646000, PR China
b Center for Drug Research, Luzhou Medical College, Luzhou, Sichuan 646000, PR China
c College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An asymmetric linear alkyl alkyne addition to aromatic aldehydes catalyzed by the Ti-(R)-BINOL system
is reported with high enantioselectivity and yield. Our study expands upon the synthetic scope of prop-
argylic alcohols, which could serve as potentially useful intermediates for the synthesis of various natural
products.
Received 23 May 2011
Accepted 10 June 2011
Available online 19 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Ar
Ar
Chiral propargylic alcohols are key intermediates in the synthe-
sis of complex organic compounds including natural products,
pharmaceuticals, and materials.1 One efficient method to obtain
this class of compounds is a catalytic asymmetric alkyne addition
to aldehydes, which could simultaneously form a new C–C bond
and a chiral alcohol center in a single transformation. Over the last
few years, great progress has been made in developing this cata-
lytic enantioselective reaction.2–9 For example, Hoshino et al. dis-
covered that the pyridyl alcohol ligand 1 was effective for the
asymmetric alkynylzinc addition to aldehydes.2 However, the reac-
tion of 1-octyne with benzaldehyde gave much lower yield and
enantioselectivity, and the scope of the substrates was very lim-
ited. Recently, Pu et al. found that 1,10-bi-2-naphthol (BINOL) in
combination with Ti(OiPr)4 could catalyze the alkynylzinc addition
to both aromatic and aliphatic aldehydes with high enantioselec-
tivity.4b,4c More recently, this system was successfully applied to
highly enantioselective reactions of alkynoates with aldehydes4f
and of linear alkyl alkynes with linear aldehydes.4h However, the
number of studies on the enantioselective additions of linear alkyl
alkynes with aromatic aldehydes using a Ti-BINOL catalytic system
is small. We are currently interested in the development of propar-
gylic alcohols and their application in the synthesis of natural
products; and we attempted to evaluate the efficiency of this
catalytic system for the reaction of 1-octyne with benzaldehyde
in our preliminary study.4i Herein, we report in detail the
asymmetric addition of linear alkyl alkynes to aromatic aldehydes
catalyzed by a Ti-BINOL system to generate useful aliphatic prop-
argylic alcohols with high enantioselectivity and in high yields.
OH
OH
O
OH
N
H
1 Ar = α-Naphthyl
(S)-BINOL
2. Results and discussion
Hoshino et al. have reported the use of pyridyl alcohol ligand 1
to catalyze the asymmetric addition of 1-octyne to benzaldehyde
in low yield and moderate enantioselectivity (41% yield and 78%
ee).2 The reaction included two steps: 1) the treatment of 1-octyne
with fresh diethylzinc at reflux; and 2) the addition of benzalde-
hyde in the presence of the catalyst. The first step probably gener-
ated the ethyl 1-octynyl zinc intermediate 2, which then added to
benzaldehyde to form the chiral propargyl alcohol 3. According to
above procedure, we, therefore, tested the use of (R)-BINOL and
Ti(OiPr)4 as the catalyst for the asymmetric reaction of 1-octyne
with benzaldehyde (Scheme 1). We found that the use of (R)-BI-
NOL-Ti(OiPr)4 is favorable for the synthesis of chiral propargyl
alcohol 3 in 72% yield and 83% ee (Table 1, entry 1), which is better
than the results of the 1-catalyzed reaction.
Various conditions were explored for the reaction of 1-octyne
with benzaldehyde, and the results are summarized in Table 1.
We first tested the use of solvents for the two steps (entries 2-5).
Both good yield (81%) and high enantioselectivity (92%) were ob-
served when using toluene in step 1 and tetrahydrofuran (THF)
in step 2 (entry 2), respectively. The results revealed that toluene
in step 1 may be more favorable for the formation of alkynylzinc
2, while THF in step 2 may favor the chiral inducement of
⇑
Corresponding authors. Tel./fax: +86 830 3162292 (Q.W.).
E-mail addresses: wq_ring@hotmail.com (Q. Wang), xqyu@tfol.com (X.-Q. Yu).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.06.020

X. Du et al. / Tetrahedron: Asymmetry 22 (2011) 1142–1146
1143
significantly improved ees. Zinc precipitated from homogeneous
solution might decrease the enantioselectivity, and even the oppo-
site configuration of product was found in our preliminary study.4i
The optimized procedure was applied to the reaction of linear
alkyl alkynes with a variety of aromatic aldehydes. The results
summarized in Table 2 demonstrate that the reactions of 1-octyne
and 1-hexyne with ortho-, meta-, or para-substituted benzalde-
hydes took place with excellent enantioselectivities. For the
addition of 1-octyne, reactions with methylbenzaldehyde and
methoxybenzaldehyde gave 86%-92% ees and 87-93% ees, respec-
tively (entries 2-6). Reactions with meta- and para-substituted
benzaldehydes gave slightly higher enantioselectivities than those
involving ortho-substituted benzaldehydes. For example, the reac-
tion of m-methoxybenzaldehyde gave an excellent enantioselectiv-
ity of 93% ee (entry 5). Halogen-containing benzaldehydes with
fluoro-, chloro- and bromo-substituents on different positions also
gave their relative products with excellent stereoselectivities (82-
95% ee, entries 7-11). Likewise, meta- and para-halogenated benz-
aldehydes showed outstanding enantioselectivities. The reaction of
p-bromobenzaldehyde gave the product with 95% ee (entry 9),
while using ortho-chlorobenzaldehyde gave a slightly worse result
(entry 10). This addition was also suitable for 1-hexyne, which
could react smoothly with several of the above aromatic aldehydes
to give propargylic alcohols with good enantioselectivity (74-92%
ee, entries 12-15). For the two linear alkynes, 1-octyne with a
longer chain gave better results than the other.
Et2Zn
reflux
nC6H13
nC6H13
H
ZnEt
step 1
2
OH
(R)-BINOL/Ti (OiPr) 4
nC6H13
PhCHO
*
step 2
3
Scheme 1. Asymmetric alkynylzinc addition to benzaldehyde.
(R)-BINOL and Ti(OiPr)4. We then varied the temperature in step 2
for this reaction; a slightly increased ee value but a lower yield
were observed at 0°C (entry 6), thus indicating that room temper-
ature is suitable for the reaction. Increasing the amount of Et2Zn,
BINOL and Ti(OiPr)4 showed no great improvement in either the
enantioselectivity or the yield (entries 7-9). Meanwhile, decreasing
the amount of Ti(OiPr)4 gave distinctly decreased ees (entries 10
and 11). Thus, entry 2 was identified as the optimized condition
for this reaction because of the good yield and excellent enantiose-
lectivity. The configuration of the product was determined (S) by
the literature.4f In comparison with our previous results, fresh
diethylzinc. which could generate zinc intermediate 2, led to
Table 1
Attempted reactions of 1-octyne with benzaldehyde
Entry
1-octyne/Et2Zn (mmol)
BINOL (mmol)
(TiOiPr)4 (mmol)
Solvent Step 1
Solvent Step 2
Temp (°C)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
4/4
4/4
4/4
4/4
4/4
4/4
4/6
4/8
4/4
4/4
4/4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.6
0.4
0.4
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
0.7
0.4
THF
THF
THF
Toluene
CH2Cl2
Ether
THF
THF
THF
THF
THF
rt
rt
rt
rt
rt
0
rt
rt
rt
rt
rt
72
81
61
73
65
64
79
76
82
76
73
83
92
84
88
85
95
93
94
93
48
47
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
10
11
THF
Table 2
Results for the asymmetric addition of linear alkyl alkynes to aromatic aldehydes
OH
H
CHO
Et2Zn
R
R
H
+
R'
(R)-BINOL/Ti(OiPr)4
R'
Entry
R
R0
Isolated yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C4H9
n-C4H9
n-C4H9
n-C4H9
H
81
76
72
72
82
83
92
86
89
76
84
68
84
75
73
94
86
92
92
93
87
94
94
o-Me
m-Me
p-Me
m-MeO
p-MeO
m-F
m-Cl
m-Br
o-Cl
p-F
H
p-Me
m-MeO
m-F
95
82
92
74/(S)a
90
92
86
a
The absolute configuration was based on the measurement of the specific rotation in comparison with the literature values.8d,9

1144
X. Du et al. / Tetrahedron: Asymmetry 22 (2011) 1142–1146
chloride. The resulting mixture was extracted with methylene
3. Conclusion
chloride, dried over magnesium sulfate and concentrated under
vacuum. After the residue was passed through a short silica gel col-
umn and the solvent was removed by reduced pressure distillation,
the product was isolated.
We have successfully demonstrated that the effective (R)-BINOL
ligand in combination with Ti(OiPr)4 can catalyze the highly enan-
tioselective reaction of aliphatic terminal alkynes with aromatic
aldehydes including those with various substituents on different
positions. This method could expand the scope of terminal alkynes
in asymmetric alkynylzinc additions to aldehydes, and the result-
ing propargylic alcohols could serve as precursors for the synthesis
of natural products and pharmaceutical compounds.
4.3.1. 1-Phenyl-non-2-yn-1-ol
81% yield. 94% ee determined by HPLC analysis. Retention time:
tmajor = 5.3 min and tminor = 7.0 min. 1H NMR (CDCl3, 400 MHz) d:
7.53-7.29 (m, 5H), 5.41 (s, 1H), 2.55 (br, 1H), 2.27-2.22 (t, J = 8.2
Hz, 2H), 1.54-1.25 (m, 8H), 0.90-0.87 (t, J = 6.8 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) d: 141.4, 128.5, 128.5, 128.1, 126.7, 126.7, 87.6,
80.1, 64.8, 31.3, 29.5, 28.6, 22.6, 18.9, 14.1. GC-MS calcd. for
4. Experimental
[C15H20O]+: 216.32, found: 216. ½a 2D0
¼ ꢁ100:4 (c 0.91, CHCl3).
ꢀ
4.1. General methods
4.3.2. 1-(2-Methylphenyl)-non-2-yn-1-ol
All reactions were carried out in a round bottomed flask and un-
der nitrogen. All solvents were dried according to the standard
methods prior to use. 4-Fluorobenzaldehyde, diethylzinc were
purchased from Aldrich Chemical; 2-chlorobenzaldehyde, 3-chlo-
robenzaldehyde, 3-bromobenzaldehyde, titanium isopropoxide,
1-octyne, 1-hexyne, n-butyl lithium were purchased from ACROS
Co. and used directly. Isopropanol and n-hexane for HPLC were
purchased from Fisher Co. Other reagents were purchased from
China and purified according to standard procedures.
76% yield. 86% ee determined by HPLC analysis. Retention time:
tmajor = 5.3 min, and tminor = 5.7 min. 1H NMR (CDCl3, 400 MHz) d:
7.66-7.64 (d, J = 8.2 Hz, 1H), 7.24-7.19 (m, 2H), 7.17-7.15 (d, J = 8.8
Hz, 1H), 5.58 (s, 1H), 2.43 (s, 3H), 2.27-2.23 (t, J = 8.2 Hz, 2H), 2.12
(br, 1H), 1.54-1.25 (m, 8H), 0.90-0.86 (t, J = 7.0 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) d: 139.0, 135.9, 130.7, 128.2, 126.4, 126.2, 87.5,
79.7, 62.6, 31.3, 29.7, 28.6, 22.6, 18.9, 18.9, 14.1. GC-MS calcd. for
[C16H22O]+: 230.34, found: 230. ½a 2D0
¼ ꢁ29:4 (c 0.50, CHCl3).
ꢀ
The 1H NMR spectra and 13C NMR spectra were obtained using
the Bruker-400 MHz spectrometer and the Bruker-100 MHz spec-
trometer, respectively. Mass Spectra were obtained using the Agi-
lent 6890-5973N Mass Spectroscopy facility. HPLC analyses were
carried out with the Waters1525 by using the Diacel Chiralcel
OD column and eluting with 10% isopropanol in hexane at
1.0mL/min unless otherwise indicated, and were detected at 254
nm by the Waters 2487 (5% isopropanol in hexane at 1.0 mL/min
for 1-phenyl-non-2-yn-1-ol and 1-(3-fluorophenyl)-hept-2-yn-
1-ol. The specific rotation was determined with a Polarimeter
Autopol IV automatic polarimeter (Rudolph, America).
4.3.3. 1-(3-Methylphenyl)-non-2-yn-1-ol
72% yield. 92% ee determined by HPLC analysis. Retention time:
tmajor = 4.8 min, and tminor = 6.1 min. 1H NMR (CDCl3, 400 MHz) d:
7.35-7.33 (d, J = 11.2 Hz, 2H), 7.28-7.24 (s, 1H), 7.14-7.12 (d, J = 7.6
Hz, 1H), 5.41 (s, 1H), 2.37 (s, 3H), 2.17 (br, 1H), 2.29-2.25 (t, J = 8.0
Hz, 2H), 1.58-1.27 (m, 8H), 0.91-0.86 (t, J = 9.8 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) d: 141.3, 138.2, 129.0, 128.5, 127.3, 123.7, 87.6,
80.1, 64.9, 31.4, 29.7, 28.6, 22.6, 21.4, 18.7, 14.1. GC-MS calcd. for
[C16H22O]+: 230.34, found: 230. ½a 2D0
¼ ꢁ14:9 (c 0.50, CHCl3).
ꢀ
4.3.4. 1-(4-Methylphenyl)-non-2-yn-1-ol
72% yield. 92% ee determined by HPLC analysis. Retention time:
tmajor = 4.9 min, and tminor = 5.5 min. 1H NMR (CDCl3, 400 MHz) d:
7.44-7.42 (d, J = 8.0 Hz, 2H), 7.19-7.17 (d, J = 8.0 Hz, 2H), 5.42 (s,
1H), 2.36 (s, 3H), 2.29-2.25 (t, J = 8.2 Hz, 2H), 2.17 (br, 1H), 1.66-
1.22 (m, 8H), 0.91-0.88 (t, J = 7.0 Hz, 3H). 13C NMR (CDCl3, 100
MHz) d: 138.6, 137.9, 129.7, 129.2, 126.6, 126.6, 87.5, 80.2, 64.7,
31.3, 29.7, 28.6, 22.5, 21.1, 18.8, 14.0. GC-MS calcd. for
4.2. General procedure for the preparation of the racemic
propargylic alcohols
The racemic products of benzaldehyde and 3-methoxybenzal-
dehyde with 1-octyne were prepared for HPLC analysis in accor-
dance with the following procedure. Under nitrogen, distilled
THF (6 mL) and a 1-octyne (4.0 mmol, 600
lL) were added to a
[C16H22O]+: 230.34, found: 230. ½a 2D0
¼ ꢁ23:0 (c 0.50, CHCl3).
ꢀ
25 mL flask, which was cooled to –78°C with dry ice / acetone bath
after which 1.6 M nBuLi in hexanes (4.0 mmol) was added. After
stirring for 3 h, the aldehyde (2.0 mmol) was then added and the
reaction mixture was stirred for 10 h. The reaction was then
quenched with ice, extracted with methylene chloride, dried over
magnesium sulfate and concentrated under reduced pressure.
After the residue was passed through a short silica gel column
and the solvent was removed by rotoevaporation, the pure racemic
propargylic alcohol product was isolated. Other racemic products
were prepared by racemic BINOL according to the procedure for
the asymmetric addition.
4.3.5. 1-(3-Methoxyphenyl)-non-2-yn-1-ol
82% yield. 93% ee determined by HPLC analysis. Retention time:
tmajor = 6.1 min, and tminor = 8.2 min. 1H NMR (CDCl3, 400 MHz) d:
7.29-7.25 (t, J = 8.0 Hz, 1H), 7.12-7.11 (m, 2H), 6.86-6.83 (d, J = 12.0
Hz, 1H), 5.41 (s, 1H), 3.81 (s, 3H), 2.40 (br, 1H), 2.28-2.24 (t, J = 8.2
Hz, 2H), 1.55-1.26 (m, 8H), 0.90-0.87 (t, J = 6.8 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) d: 159.8, 142.9, 129.5, 118.9, 113.9, 112.0, 87.7,
79.9, 64.7, 55.2, 31.3, 28.6, 28.6, 22.5, 18.8, 14.0. GC-MS calcd. for
[C16H22O2]+: 246.34, found: 246. ½a 2D0
¼ ꢁ56:1 (c 0.50, CHCl3).
ꢀ
4.3. General procedure for the asymmetric addition
4.3.6. 1-(4-Methoxyphenyl)-non-2-yn-1-ol
83% yield. 87% ee determined by HPLC analysis. Retention time:
tmajor = 5.9 min, and tminor = 6.6 min. 1H NMR (CDCl3, 400 MHz) d:
7.44-7.40 (d, J = 14.4 Hz, 2H), 6.87-6.83 (d, J = 14.4 Hz, 2H), 5.35 (s,
1H), 3.75 (s, 3H), 2.84 (br, 1H), 2.27-2.21 (t, J = 8.2 Hz, 2H), 1.55-
1.29 (m, 8H), 0.90-0.87 (t, J = 6.8 Hz, 3H). 13C NMR (CDCl3, 100
MHz) d: 159.4, 133.8, 128.3, 127.7, 114.1, 113.5, 87.3, 80.3, 64.2,
55.2, 31.7, 29.6, 28.6, 22.6, 18.8, 14.1. GC-MS calcd. for
In a 25 mL flask, a toluene solution (2 mL) of 1-octyne or 1-hex-
yne (4.0 mmol, 600 lL) and diethylzinc (4.0mmol, 1.5M in toluene)
was heated at reflux under nitrogen for 2 h. After returning to room
temperature, (R)-BINOL (0.40 mmol, 120 mg), THF (16 mL),
Ti(OiPr)4 (1.0 mmol, 300
l
L) were added sequentially and stirred
for 1 h, after which aromatic aldehyde (1.0 mmol) was added. After
h, the reaction was quenched with saturated ammonium
5
[C16H22O2]+: 246.34, found: 246. ½a 2D0
¼ ꢁ59:7 (c 0.50, CHCl3).
ꢀ

X. Du et al. / Tetrahedron: Asymmetry 22 (2011) 1142–1146
1145
4.3.7. 1-(3-Fluorophenyl)-non-2-yn-1-ol
30.5, 21.8, 21.0, 18.3, 13.4. GC-MS calcd. for [C14H18O] +: 202.30,
92% yield. 94% ee determined by HPLC analysis. Retention time:
tmajor = 5.2 min, and tminor = 5.8 min. 1H NMR (CDCl3, 400 MHz) d:
7.30-7.25 (m, 3H), 7.01-6.97 (t, J = 8.0 Hz, 1H), 5.43 (s, 1H), 2.40 (br,
1H), 2.28-2.24 (t, J = 8.0 Hz, 2H), 1.57-1.23 (m, 8H), 0.89-0.86 (t, J =
6.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d: 163.6, 143.8, 129.8,
122.1, 114.8, 113.5, 87.8, 79.6, 63.8, 31.2, 28.5, 28.1, 22.4, 18.7,
13.9. GC-MS calcd. for [C15H19FO]+: 234.32, found: 234.
found: 202. ½a 2D0
¼ ꢁ67:4 (c 1.05, CHCl3).
ꢀ
4.3.14. 1-(3-Methoxyphenyl)-hept-2-yn-1-ol
75% yield. 92% ee determined by HPLC analysis. Retention time:
tmajor = 6.5 min, and tminor = 8.7 min. 1H NMR (CDCl3, 400 MHz) d:
7.31-7.26 (t, J = 9.8 Hz, 1H), 7.13-7.11 (m, 2H), 6.87-6.85 (d, J = 10.8
Hz, 1H), 5.42 (s, 1H), 3.82 (s, 3H), 2.29-2.25 (t, J = 8.0 Hz, 2H), 2.17
(br, 1H), 1.56-1.25 (m, 4H), 0.93-0.90 (t, J = 7.2 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) d: 159.5, 142.6, 129.4, 118.7, 113.8, 111.7, 87.5,
79.6, 64.6, 55.1, 30.4, 21.8, 18.3, 13.4. GC-MS calcd. for
½
a 2D0
ꢀ
¼ ꢁ54:4 (c 0.88, CHCl3).
4.3.8. 1-(3-Chlorophenyl)-non-2-yn-1-ol
86% yield. 94% ee determined by HPLC analysis. Retention time:
tmajor = 5.2 min, and tminor = 5.7 min. 1H NMR (CDCl3, 400 MHz) d:
7.54 (s, 1H), 7.39-7.38 (d, J = 4.0 Hz, 1H), 7.31-7.26 (m, 2H), 5.41 (s,
1H), 2.41 (br, 1H), 2.28-2.24 (t, J = 8.0 Hz, 2H), 1.48-1.22 (m, 8H),
0.93- 0.89 (t, J = 8.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d: 143.2,
134.4, 129.8, 128.2, 126.8, 124.8, 88.3, 79.4, 64.1, 31.3, 28.6, 28.5,
22.6, 18.8, 14.1. GC-MS calcd. for [C15H19OCl]+: 250.77, found:
[C14H18O2]+: 218.29, found: 218. ½a 2D0
¼ ꢁ63:2 (c 1.02, CHCl3).
ꢀ
4.3.15. 1-(3-Fluorophenyl)-hept-2-yn-1-ol
73% yield. 86% ee determined by HPLC analysis. Retention time:
tmajor = 7.8 min, and tminor = 8.3 min. 1H NMR (CDCl3, 400 MHz) d:
7.37-7.26 (m, 3H), 7.03-6.99 (m, 1H), 5.44 (s, 1H), 2.30-2.26 (t, J =
7.8 Hz, 2H), 2.01 (br, 1H), 1.57-1.25 (m, 4H), 0.94-0.90 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3, 100 MHz) d: 163.1, 149.5, 129.8, 122.0, 114.8,
113.4, 87.9, 79.2, 64.0, 30.4, 21.8, 18.3, 13.4. GC-MS calcd. for
250. ½a 2D0
¼ ꢁ73:6 (c 1.00, CHCl3).
ꢀ
4.3.9. 1-(3-Bromophenyl)-non-2-yn-1-ol
[C13H15FO]+: 206.25, found: 206. ½a 2D0
¼ ꢁ49:0 (c 0.97, CHCl3).
ꢀ
89% yield. 95% ee determined by HPLC analysis. Retention time:
tmajor = 5.4 min, and tminor = 5.8 min. 1H NMR (CDCl3, 400 MHz) d:
7.70 (s, 1H), 7.45-7.43 (m, 2H), 7.26-7.21 (m, 1H), 5.41 (s, 1H),
2.29-2.25 (t, J = 8.0 Hz, 2H), 2.19 (br, 1H), 1.50-1.25 (m, 8H),
0.91-0.87 (t, J = 8.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d: 143.4,
131.2, 130.1, 129.8, 125.3, 122.5, 88.4, 79.4, 64.1, 31.1, 28.6, 28.
6, 22.7, 18.8, 14.1. GC-MS calcd. for [C15H19OBr]+: 295.22, found:
Acknowledgments
This work was supported by the National Natural Science Foun-
dation of China (No. 21072088), Program for New Century Excel-
lent Talents in University (NCET-10-0945), the Key Project of
Chinese Ministry of Education (No. 211160), the Scientific Fund
of Sichuan Province for Outstanding Young scientist (No. 2009-
26-417), Science and Technology Department of Sichuan Province
(No. 2008SZ0052, 2008JY0090) and the Key grant Project of Luzhou
Medical College.
295. ½a 2D0
¼ ꢁ44:3 (c 0.45, CHCl3).
ꢀ
4.3.10. 1-(2-Chlorophenyl)-non-2-yn-1-ol
76% yield. 82% ee determined by HPLC analysis. Retention time:
tmajor = 6.1 min, and tminor = 6.8 min. 1H NMR (CDCl3, 400 MHz) d:
7.76-7.75 (d, J = 6.8 Hz, 1H), 7.36-7.22 (m, 3H), 5.80 (s, 1H), 2.53 (s,
1H), 2.27-2.23 (m, 2H), 1.42-1.26 (m, 8H), 0.90-0.83 (t, J = 6.8 Hz,
3H). 13C NMR (CDCl3, 100 MHz) d: 138.6, 132.7, 129.6, 129.1,
128.3, 127.1, 87.8, 78.9, 62.3, 31.6, 31.3, 28.5, 22.6, 18.8, 14.1.
References
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GC-MS calcd. for [C15H19OCl]+: 250.77, found: 250. ½a 2D0
¼ þ25:5
ꢀ
(c 0.95, CHCl3).
4.3.11. 1-(4-Fluorophenyl)-non-2-yn-1-ol
84% yield. 94% ee determined by HPLC analysis. Retention time:
tmajor = 5.3 min, and tminor = 5.8 min. 1H NMR (CDCl3, 400 MHz) d:
7.53-7.50 (d, J = 14.0 Hz, 2H), 7.26 (s, 1H), 7.05 (s, 1H), 5.43 (s, 1H),
2.29-2.26 (m, 2H), 2.20 (br, 1H), 1.56-1.28 (m, 8H), 0.91-0.87 (t, J =
7.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d: 163.8, 137.1, 128.5,
128.4, 115.4, 115.2, 88.0, 79.7, 64.1, 31.3, 28.5, 28.5, 22.5, 18.8,
14.0. GC-MS calcd. for [C15H19OF]+: 234.32, found: 234.
½
a 2D0
ꢀ
¼ ꢁ18:0 (c 0.52, CHCl3).
4.3.12. 1-Phenyl-hept-2-yn-1-ol
68% yield. 74% ee determined by HPLC analysis. Retention time:
tmajor = 5.6 min, and tminor = 7.4 min. 1H NMR (CDCl3, 400 MHz) d:
7.54-7.26 (m, 5H), 5.46 (s, 1H), 2.17 (br, 1H), 2.30-2.26 (t, J = 8.0 Hz,
2H), 1.55-1.25 (m, 4H), 0.94-0.90 (t, J = 7.4 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) d: 141.2, 131.3, 128.5, 128.2, 126.6, 126.6, 79.8,
77.0, 64.8, 30.6, 22.0, 18.5, 13.6. GC-MS calcd. for [C13H16O]+:
188.27, found: 188. ½a D20
ꢀ
¼ ꢁ54:1 (c 0.79, CHCl3).8d,9
4.3.13. 1-(4-Methylphenyl)-hept-2-yn-1-ol
84% yield. 90% ee determined by HPLC analysis. Retention time:
tmajor = 5.1 min, and tminor = 5.6 min. 1H NMR (CDCl3, 400 MHz) d:
7.44-7.42 (d, J = 8.0 Hz, 2H), 7.19-7.17 (d, J = 8.0 Hz, 2H), 5.41 (s,
1H), 2.35 (s, 3H), 2.29-2.25 (t, J = 8.0 Hz, 2H), 2.06 (br, 1H), 1.58-
1.38 (m, 4H), 0.93-0.90 (t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 100
MHz) d: 138.2, 137.8, 129.0, 129.0, 126.4, 126.4, 87.2, 79.8, 64.5,
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