Highly enantioselective alkynylation of aldehydes catalyzed by a new oxazolidine-titanium complex

Article abstract of DOI:10.1039/b719624e

The readily available and inexpensive new chiral oxazolidine 2a in combination with Ti(OⁱPr)₄ was found to catalyze the reaction of an alkynylzinc reagent with various types of aldehydes to generate chiral propargylic alcohols with high enantioselectivities (up to 95%) and excellent yields (up to 98%). The Royal Society of Chemistry.

Full text of DOI:10.1039/b719624e

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Highly enantioselective alkynylation of aldehydes catalyzed by a new
oxazolidine–titanium complex†
Zhou Xu, Jincheng Mao* and Yawen Zhang*
Received 20th December 2007, Accepted 30th January 2008
First published as an Advance Article on the web 22nd February 2008
DOI: 10.1039/b719624e
The readily available and inexpensive new chiral oxazolidine 2a in combination with Ti(OiPr)4 was
found to catalyze the reaction of an alkynylzinc reagent with various types of aldehydes to generate
chiral propargylic alcohols with high enantioselectivities (up to 95%) and excellent yields (up to 98%).
the ligand A afforded higher chemical selectivity and enantios-
electivity than the corresponding C2- or C1-symmetric ligands.
Wang and co-workers also reported that the C2-symmetric bis-
sulfonamide ligand B catalyzed the asymmetric alkynylation of
Introduction
The asymmetric alkynylzinc addition to aldehydes can simul-
taneously form a new C–C bond and a stereogenic centre in
aldehydes and ketones to give chiral products with high ee values.6
In addition, C2-symmetric bisoxazolidine ligand C has been used
for highly enantioselective addition of alkynes to aldehydes, while
oxazolidine ligand D afforded the corresponding product with
only 17% ee.7
However, it is a dilemma that C2 or C3-symmetric ligands
definitely have higher synthetic cost and are more difficult to
synthesize than C1-symmetric ligands. Therefore, the development
of easily accessible and operationally simple ligands is still a
challenge. In the long run, we are interested in ligands which
are easily prepared by a short pathway from readily available
starting materials, and their applications in asymmetric transition
processes.8
one step, which has become the preferred way of synthesizing
useful chiral propargylic alcohols.1 In recent years, the catalytic
enantioselective addition of terminal alkynes to aldehydes has
generated great amount of interest, and some impressive results
have been obtained since the leading example reported by Corey.2
Among the catalysts developed, those based on ephedrine
or 1,1ꢀ-bi-2-naphthol are the outstanding representatives.3 Since
axially chiral symmetric ligands have proved to be exceptionally
versatile and effective in many asymmetrically catalytic processes,4
development of such catalysts for asymmetric alkynylation addi-
tions is meaningful.
Recently, Du has developed the complex of a C3-symmetric
tris(b-hydroxyamide) ligand (A, Fig. 1) and Ti(OiPr)4 for asym-
metric alkynylation, and moderate to excellent enantioselectivities
(up to 92% ee) have been obtained.5 Under the same conditions,
With the current interest in oxazolidine catalysts, we have
designed and synthesized chiral ligands derived from (1R,2S)-
cis-1-amino-2-indanol (1).9 However, poor results were obtained
during their application to asymmetric alkynylzinc additions to
benzaldehyde.
In contrast to the traditional oxazolidine or bisoxazolidine
catalysts, which did not require Ti(OiPr)4, addition of Ti(OiPr)4
to the reaction unexpectedly provided a highly effective catalytic
system. In this paper, we report an example of highly enantios-
elective addition of terminal alkynes to aldehydes using a very
simple oxazolidine–titanium complex catalyst with high yields and
excellent enantioselectivities.
Results and discussion
Initially, ligand 2a was synthesized from 1, a readily available
chiral source (see the Experimental section). When 2a was used as
the ligand to catalyze the asymmetric addition of phenylacetylene
to benzaldehyde, only (S)-product with 21% ee was obtained.10
To our surprise, the addition of an equivalent of Ti(OiPr)4 not
only resulted in reversal of the configuration of the product, but
also enhanced ee values greatly. Thus this ligand, traditionally
believed to be rather poor, became an excellent catalyst (Fig. 2).
The reaction used THF as the solvent, with a reagent ratio of
phenylacetylene–Et2Zn–benzaldehyde–ligand–Ti(OiPr)4 = 1 : 1 :
0.5 : 0.1 : 0.2, and was conducted under argon at room temperature.
We also synthesized three similar ligands (2b–2d), all of which
Fig. 1 Previously reported chiral axial symmetric ligands.5–7
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chem-
istry and Chemical Engineering, Suzhou (Soochow) University, Suzhou,
215123, China. E-mail: jcmao@suda.edu.cn
† Electronic supplementary information (ESI) available: 1H NMR, 13C
NMR and IR spectra of ligands and products; HPLC data; expanded
version of Table 1; crystal structure data in CIF format (CCDC reference
number 667689. See DOI: 10.1039/b719624e
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to its inexpensiveness. The effects of the reaction conditions such
as the choice of solvent and the Ti(OiPr)4–2a ratio were also
investigated. As can be seen from Fig. 3, the Ti(OiPr)4–2a ratio was
important in determining the enantioselectivities of the products;
in addition, the optimal Ti(OiPr)4–ligand ratios varied between
solvents. The best result (85% ee) was obtained when the Ti(OiPr)4–
ligand ratio was 2 : 1 with THF as solvent.
Other reaction conditions employing ligand 2a were then
explored, and are summarized in Table 1. Enhancement of the
amounts of Et2Zn and phenylacetylene had no effect on the
enantioselectivity (entries 1–4). Increasing the amount of 2a gave
enhanced ee (entries 5–9), but further increasing the ligand amount
from 20 to 30 mol% did not lead to a dramatic increase in ee. Thus,
20 mol% was chosen as the optimal loading of ligand. Reducing the
reaction temperature gave enhanced enantioselectivity (entries 10
and 11). Replacement of Et2Zn with Me2Zn at room temperature
boosted the enantioselectivity to 90% ee (entries 12 and 13). At this
time, reducing the reaction temperature from room temperature
to 0 ◦C gave the best enantioselectivity (at the expense of chemical
yield) of the product (entry 14).
Fig. 2 The chiral ligands evaluated in this paper, and the results of using
them in the asymmetric addition of phenylacetylene to benzaldehyde.
afforded good enantioselectivities in the presence of Ti(OiPr)4, as
can be seen from Fig. 3.
Under the optimized conditions of entry 12 in Table 1, the
reactions of phenylacetylene with a variety of aldehydes catalyzed
by 2a–Ti(OiPr)4 were investigated. As shown by the results
summarized in Table 2, high enantioselectivities (ranging from
90–95% ee) were achieved for the addition of phenylacetylene to
aromatic aldehydes. Substituents of aromatic aldehydes containing
electron-donating or electron-withdrawing groups at the ortho,
meta, or para positions have little effect on the enantioselectivity.
Good enantioselectivity (77%) was also obtained with an aliphatic
aldehyde (entry 11).
Good results can also be obtained for this asymmetric addition
reaction with other acetylenes. For example, 83% ee was obtained
for the addition of 4-phenyl-1-butyne to 2-naphthaldehyde, while
88% ee was obtained when trimethylsilylacetylene was used as the
substrate (Fig. 4).
Fig. 3 The relationship between ee values and the Ti(OiPr)4–ligand
ratio when different solvents were used in the asymmetric addition of
phenylacetylene to benzaldehyde.
Since similar results were obtained for all ligands (2a–2d), ligand
2a was chosen as the model ligand for further investigations due
Table 1 Asymmetric addition of phenylacetylene to benzaldehyde with 2a as liganda
Entry
Cat. (%)
T/◦C
PhC≡CH (equiv.)
R2Zn (equiv.)
ee (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14c
20
20
20
20
5
10
15
25
30
20
20
20
30
20
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
−25
rt
rt
0
1.4
2.0
3.0
4.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Et2Zn (1.4)
Et2Zn (2.0)
Et2Zn (3.0)
Et2Zn (4.0)
Et2Zn (2.0)
Et2Zn (2.0)
Et2Zn (2.0)
Et2Zn (2.0)
Et2Zn (2.0)
Et2Zn (2.0)
Et2Zn (2.0)
Me2Zn (2.0)
Me2Zn (2.0)
Me2Zn (2.0)
85
86
86
87
66
81
83
85
87
89
90
90
90
93
a All the reactions were processed in THF under argon at room temperature. Ti(OiPr)4 was freshly distilled. Ligand 2a–Ti(OiPr)4–benzaldehyde = 1 :
2 : 5. GC indicated the complete conversion of benzaldehyde after the reaction time of 20 h. b The enantiomeric excess was determined by chiral HPLC
analysis of the corresponding products on a Chiralcel OD-H column. c The yield of the product was 46%.
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Table 2 Enantioselective alkynylation of various aldehydes with pheny-
lacetylene using ligand 2aa
General procedure for the synthesis of chiral ligands 2a–2d (Fig. 5)
A solution of (1R,2S)-cis-1-amino-2-indanol (1) (10 mmol) and
the corresponding aldehyde (10 mmol) in DCM (20 mL) was
stirred at room temperature for 24 h. After evaporation of
the solvent, the residue was purified by recrystallization from
isopropanol–petroleum ether (1 : 6).
Entry
Aldehyde
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
Benzaldehyde
2-Anisaldehyde
4-Anisaldehyde
4-Tolualdehyde
2-Chloroaldehyde
3-Chloroaldehyde
a-Naphthaldehyde
b-Naphthaldehyde
2,3-Dimethoxybenzaldehyde
2-Furaldehyde
98
91
91
87
96
97
96
97
91
91
81
90
92
95
90
93
91
90
93
90
90
77
10
11
Hydrocinnamaldehyde
Fig. 5 Synthesis of chiral ligand 2a.
a All the reactions were carried out under argon at room temperature for
20 h. Phenylacetylene–Et2Zn–aldehyde–2a–Ti(OiPr)4= 2 : 2 : 0.5 : 0.1 : 0.2.
b Isolated yield. c The enantiomeric excess was determined by chiral HPLC
analysis of the corresponding products on a Chiralcel OD-H column.
◦
Ligand 2a. Mp 69–70 C; [a]2D5 = +82.8 (c 1.02, abs. EtOH);
dr = 1 : 5 (determined by 1H NMR); 1H NMR (400 MHz, CDCl3)
d 8.58–7.07 (m, 9H), 5.12–5.07 (m, 2H), 4.81 (d, J = 4.4 Hz, 1H),
3.24–3.17 (m, 2H), 2.53 (s, 1H); 13C NMR (100 MHz, CDCl3) d
142.8, 141.3, 136.6, 133.7, 130.3, 130.0, 129.2, 129.0, 128.0, 127.8,
127.6, 127.4, 126.3, 126.1, 125.9, 125.3, 90.7, 89.8, 81.2, 80.6, 69.5,
39.8, 38.7; IR (cm−1): 3280, 1026, 895, 756; HRMS (EI+) calc. for
[C16H15NO]+ requires m/z 237.1154, found 237.1165.
Single-crystal X-ray structure (Fig. 6). Careful evaporation of
a solution of 2a in isopropanol–petroleum ether (1 : 6) gave a
single crystal of 2a suitable for crystallographic analysis.† Selected
crystal structure data: C16H15NO, monoclinic, space group C2,◦a
Fig. 4 Products of the reactions of 4-phenyl-1-butyne and trimethylsily-
lacetylene with 2-naphthaldehyde.
˚
˚
˚
= 19.246(6) A, b = 5.8447(16) A, c = 14.509(5) A, a = 90.00 ,
◦
◦
3
˚
b = 129.844(4) , c = 90.00 , V = 1253.1(7) A , Z = 4, qcalcd
=
Conclusions
1.258 g cm−3, T = 223(2) K.
In conclusion, we have developed a very simple catalyst system
for the highly enantioselective synthesis of propargylic alcohols
by alkynylzinc addition to various aldehydes. The study has
shown that a combination of 2a with Ti(OiPr)4 generated a highly
enantioselective and chemically active catalyst that could afford
products with up to 95% ee and 98% yield. The application of
this catalyst system to other asymmetric catalytic reactions is in
progress.
Experimental
Fig. 6 X-Ray crystal structure of ligand 2a.†
General methods
◦
Ligand 2b. Mp 87–88 C; [a]2D5 = +52.0 (c 1.00, abs. EtOH);
dr = 1 : 3 (determined by1H NMR); 1H NMR (400 MHz, CDCl3)
d 7.78–7.06 (m, 8H), 5.10–5.06 (m, 2H), 4.94 (m, 1H), 3.86–3.77
(m, 3H), 3.31–3.16 (m, 2H), 2.58 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 162.3, 159.9, 142.6, 141.5, 141.5, 141.2, 130.8, 128.8,
128.7, 128.5, 128.2, 127.7, 127.5, 127.5, 127.4, 127.3, 126.7, 126.0,
125.7, 125.7, 125.3, 124.9, 124.5, 114.2, 113.8, 93.4, 91.5, 80.8, 79.9,
75.6, 74.6, 68.9, 55.4, 40.0, 39.5, 38.5; IR (cm−1): 3272, 2917, 1613,
1513, 1428, 1243, 1034, 756; HRMS (EI+) calc. for [C17H17NO2]+
requires m/z 267.1259, found 267.1248.
All manipulations were carried out under an argon atmosphere in
dried and degassed solvents. All solvents were dried and degassed
by the standard methods; all aldehydes, as well as dimethylzinc
and diethylzinc, were commercially available. Melting points
were determined using a standard melting point apparatus and
are uncorrected. The reactions were monitored by thin layer
chromatography (TLC). NMR spectra were measured in CDCl3
on a Varian-Inova-400 NMR spectrometer (400 MHz) with TMS
as an internal reference. Optical rotations were measured with a
HORIBA SEPA-200 high sensitivity polarimeter. Enantiomeric
excess (ee) determination was carried out using a chiral OD-H
column: solvent, hexane–isopropanol; flow rate, 1 cm3 min−1; UV
detection, 254 nm. High resolution mass spectra (HRMS) were
performed using EI.
◦
Ligand 2c. Mp 91–92 C; [a]2D5 = +70.0 (c 1.00, abs. EtOH);
dr = 1 : 5 (determined by 1H NMR); 1H NMR (400 MHz, CDCl3)
d 7.63–7.09 (m, 8H), 5.45 (s, 1H), 5.38–5.12 (m, 1H), 4.95–4.94
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(m, 1H), 3.53–3.19 (m, 2H), 2.66 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 142.7, 141.7, 141.3, 136.5, 133.6, 130.2, 129.9, 129.2,
128.9, 128.0, 127.8, 127.6, 127.4, 126.2, 126.0, 125.8, 125.3, 90.7,
89.8, 81.2, 80.6, 69.5, 39.8, 38.7; IR (cm−1): 3319, 2948, 1436, 1027,
749; HRMS (EI+) calc. for [C16H14NOCl]+ requires m/z 267.1259,
found 267.1248.
1-(4-Methylphenyl)-3-phenylprop-2-yn-1-ol. 87% yield. 90%
ee determined by HPLC analysis (Chiralcel OD-H column,
isopropanol–hexane = 10 : 90). Retention time: tmajor = 8.38, tminor
=
1
16.31. H NMR (400 MHz, CDCl3) d 7.50 (d, J = 8.0 Hz, 2H),
7.47 (t, J = 7.2 Hz, 2H), 7.32–7.21 (m, 5H), 5.65 (d, J = 6.4 Hz,
1H), 2.37 (s, 3H), 2.24 (d, J = 6.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 138.7, 138.2, 132.2, 130.0, 129.0, 128.7, 127.2, 122.9,
89.4, 86.9, 65.4.
Ligand 2d. Mp 129–130◦C; [a]2D5 = +46.7 (c 0.42, abs. EtOH);
dr = 1 : 4 (determined by 1H NMR); 1H NMR (400 MHz, CDCl3)
d 8.74–7.10 (m, 11H), 5.29 (s, 1H), 5.13 (d, J = 5.2 Hz, 1H), 4.98
(s, 1H), 3.37–3.20 (m, 2H), 2.70 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 142.6, 141.2, 136.2, 133.5, 133.2, 131.1, 129.0, 128.9,
128.9, 128.8, 128.8, 128.7, 128.6, 128.4, 128.3, 128.3, 128.1, 127.8,
127.7, 127.4, 126.8, 126.4, 126.3, 126.1, 125.8, 125.5, 125.0, 124.5,
123.8, 93.7, 91.9, 81.6, 80.2, 74.8, 69.0, 39.6, 38.6; IR (cm−1): 3442,
1651, 1250, 1189, 756; HRMS (EI+) calc. for [C20H17NO]+ requires
m/z 287.1310, found 287.1304.
1-(2-Chlorophenyl)-3-phenylprop-2-yn-1-ol. 96% yield. 93%
ee determined by HPLC analysis (Chiralcel OD-H column,
isopropanol–hexane = 10 : 90). Retention time: tmajor = 8.25, tminor
=
9.51. 1H NMR (400 MHz, CDCl3) d 7.84 (d, J = 7.6 Hz, 1H), 7.47
(t, J = 7.6 Hz, 2H), 7.42–7.28 (m, 6H), 6.05 (d, J = 4.8 Hz, 1H),
2.36 (d, J = 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 138.4,
133.3, 132.2, 130.2, 129.1, 128.9, 128.8, 127.7, 122.7, 88.1, 87.1,
62.8.
1-(3-Chlorophenyl)-3-phenylprop-2-yn-1-ol. 97% yield. 91%
ee determined by HPLC analysis (Chiralcel OD-H column,
General procedure for the addition of phenylacetylene to aldehydes
All manipulations were carried out under an argon atmosphere
using dried and degassed solvent. The ligand 2a (23.8 mg, 0.1
mmol) and Ti(OiPr)4 (60 ll, 0.2 mmol) were mixed in dry THF
(2.0 ml) at room temperature. Then, a solution of Me2Zn (1.2 M
in toluene, 0.84 ml) was added. After the mixture was stirred at
room temperature for 1.5 h, phenylacetylene (109 ll, 1.0 mmol)
was added and the stirring continued for another 1.5 h. The yellow
solution was cooled to 0 ◦C and treated with benzaldehyde (50 ll,
0.5 mmol), and then the resultant mixture was allowed to warm
up to room temperature naturally and stirred for 20 h. After the
reaction was complete, it was cooled to 0 ◦C again and quenched
by 5% aqueous HCl (2 ml). The mixture was extracted with ethyl
acetate (2 × 10 ml). The organic layer was dried over Na2SO4 and
concentrated under vacuum. The residue was purified by flash
column chromatography (silica gel, EtOAc–petroleum ether = 1 :
6) to give the pure product.
isopropanol–hexane = 15 : 85). Retention time: tmajor = 6.61, tminor
=
1
16.90. H NMR (400 MHz, CDCl3) d 7.62 (s, 1H), 7.48 (t, J =
7.6 Hz, 3H), 7.34–7.27 (m, 5H), 5.67 (d, J = 5.6 Hz, 1H), 2.36
(d, J = 5.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 143.0, 135.0,
132.3, 130.4, 129.3, 129.0, 128.8, 127.4, 125.3, 122.5, 88.5, 87.5,
64.9.
1-(2-Naphthyl)-3-phenylprop-2-yn-1-ol. 97% yield. 93% ee
determined by HPLC analysis (Chiralcel OD-H column,
isopropanol–hexane = 20 : 80). Retention time: tmajor = 7.72, tminor
=
18.35. 1H NMR (400 MHz, CDCl3) d 8.06 (s, 1H), 7.91–
7.85 (m, 3H), 7.73 (d, J = 8.4 Hz, 1H), 7.51–7.33 (m, 7H),
5.87 (d, J = 6.0 Hz, 1H), 2.40 (d, J = 6.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 138.4, 133.7, 132.3, 129.1, 128.8, 128.7, 128.2,
126.8, 126.0, 125.1, 122.8, 89.2, 87.4, 65.7.
1-(1-Naphthyl)-3-phenylprop-2-yn-1-ol. 96% yield. 91% ee de-
termined by HPLC analysis (Chiralcel OD-H column, iso-
1,3-Diphenylprop-2-yn-1-ol. 98% yield. 90% ee determined by
HPLC analysis (Chiralcel OD-H column, isopropanol–hexane =
propanol–hexane = 15 : 85). Retention time: tmajor = 9.87, tminor
=
1
1
17.45. H NMR (400 MHz, CDCl3) d 8.38 (d, J = 8.4 Hz, 1H),
7.94–7.86 (m, 3H), 7.61–7.48 (m, 5H), 7.47–7.32 (m, 3H), 6.36 (d,
J = 4.4 Hz, 1H), 2.43 (d, J = 5.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 136.1, 134.5, 132.3, 131.1, 129.9, 129.2, 129.1, 128.8,
127.0, 126.4, 125.7, 125.2, 124.4, 122.9, 89.0, 87.8, 63.9.
20 : 80). Retention time: tmajor = 7.63, tminor = 11.69. H NMR
(400 MHz, CDCl3) d 7.62 (d, J = 7.2 Hz, 2H), 7.48–7.25 (m, 8H),
5.69 (s, 1H), 2.36 (s, 1H); 13C NMR (100 MHz, CDCl3) d 141.1,
132.2, 129.2, 129.1, 128.9, 128.8, 127.2, 122.9, 89.1, 87.2, 65.6.
1-(2-Methoxyphenyl)-3-phenylprop-2-yn-1-ol. 91% yield. 92%
1-(2,3-Dimethoxyphenyl)-3-phenylprop-2-yn-1-ol. 91% yield.
90% ee determined by HPLC analysis (Chiralcel OD-H column,
isopropanol–hexane = 20 : 80). Retention time: tmajor = 8.30,
ee determined by HPLC analysis (Chiralcel OD-H column,
isopropanol–hexane = 20 : 80). Retention time: tmajor = 8.05, tminor
=
9.11. 1H NMR (400 MHz, CDCl3) d 7.64 (d, J = 8.0 Hz, 1H), 7.46
(t, J = 7.2 Hz, 2H), 7.36–7.28 (m, 4H), 6.98 (t, J = 7.6 Hz, 1H),
6.88 (d, J = 8.4 Hz, 1H), 5.93 (s, 1H), 3.85 (s, 3H), 3.27 (s, 1H);
13C NMR (100 MHz, CDCl3) d 157.2, 132.1, 130.0, 129.1, 128.7,
128.6, 128.3, 123.1, 121.2, 111.3, 88.8, 86.3, 61.8, 55.9.
1
tminor = 9.92. H NMR (400 MHz, CDCl3) d 7.46–7.44 (m, 2H),
7.31–7.29 (m, 3H), 7.17 (d, J = 8.0 Hz, 1H), 7.09 (t, J = 8.0 Hz,
1H), 6.92 (d, J = 8.4 Hz, 1H), 5.80 (s, 1H), 3.91 (s, 3H), 3.89 (s,
3H), 3.26 (s, 1H); 13C NMR (100 MHz, CDCl3) d 153.2, 147.1,
135.2, 132.1, 128.9, 128.7, 124.8, 123.1, 120.1, 113.3, 89.8, 86.2,
62.5, 61.6, 56.3.
1-(4-Methoxyphenyl)-3-phenylprop-2-yn-1-ol. 91% yield. 95%
ee determined by HPLC analysis (Chiralcel OD-H column,
isopropanol–hexane = 20 : 80). Retention time: tmajor = 7.20, tminor
=
1-(Furan-2-yl)-3-phenylprop-2-yn-1-ol. 91% yield. 90% ee de-
termined by HPLC analysis (Chiralcel OD-H column, iso-
11.83. 1H NMR (400 MHz, CDCl3) (d, ppm): 7.55 (d, J = 8.4 Hz,
2H), 7.49–7.48 (m, 2H), 7.33–7.27 (m, 3H), 6.93 (d, J = 8.4 Hz,
2H), 5.65 (d, J = 6.0 Hz, 1H), 3.83 (s, 3H), 2.24 (d, J = 6.0 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 160.1, 133.4, 132.2, 129.0,
128.7, 128.6, 122.9, 114.4, 89.4, 86.8, 65.1, 55.7.
propanol–hexane = 20 : 80). Retention time: tmajor = 5.85, tminor
=
1
8.55. H NMR (400 MHz, CDCl3) d 7.50–7.45 (m, 3H), 7.34–
7.33 (m, 3H), 6.53 (d, J = 2.8 Hz, 1H), 6.39 (s, 1H), 5.69 (d, J =
6.8 Hz, 1H), 2.44 (d, J = 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
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d 153.3, 143.5, 132.2, 129.2, 128.7, 122.5, 110.9, 108.3, 86.6, 86.1,
59.0.
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HPLC analysis (Chiralcel OD-H column, isopropanol–hexane =
1
20 : 80). Retention time: tmajor = 6.34, tminor = 9.40. H NMR
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(400 MHz, CDCl3) d 7.44 (t, J = 7.2 Hz, 2H), 7.33–7.19 (m, 8H),
4.60 (q, J = 5.6 Hz, 1H), 2.87 (t, J = 8.0 Hz, 2H), 2.15 (q, J =
3.6 Hz, 2H), 1.95 (d, J = 5.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 141.7, 132.1, 128.9, 128.8, 128.7, 126.4, 123.0, 90.3, 85.7, 62.6,
39.7, 31.9.
1-(Naphthalen-6-yl)-5-phenylpent-2-yn-1-ol. 67% yield. 83%
ee determined by HPLC analysis (Chiralcel OD-H column, iso-
propanol–hexane = 20 : 80). Retention time: tmajor = 9.67, tminor
=
1
17.74. H NMR (400 MHz, CDCl3) d 7.86 (s, 1H), 7.79 (d, J =
6.4 Hz, 3H), 7.55 (d, J = 8.4 Hz, 1H), 7.47–7.45 (m, 2H), 7.25–7.18
(m, 5H), 5.54 (s, 1H), 2.84 (t, J = 7.2 Hz, 2H), 2.56 (t, J = 7.2 Hz,
2H), 2.46 (s, 1H); 13C NMR (100 MHz, CDCl3) d 140.9, 138.7,
133.5, 133.4, 129.1, 129.0, 128.9, 128.8, 128.6, 128.1, 126.8, 126.6,
125.7, 125.1, 87.4, 81.1, 65.2, 35.2, 21.4.
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3-(Trimethylsilyl)-1-(naphthalen-6-yl)prop-2-yn-1-ol. 53%
yield. 88% ee determined by HPLC analysis (Chiralcel AD-H
column, isopropanol–hexane = 15 : 85). Rentention time: tminor
=
1
4.65, tmajor = 5.91. H NMR (400 MHz, CDCl3) d 7.96 (s, 1H),
7.88–7.84 (m, 3H), 7.54 (d, J = 8.4 Hz, 1H), 7.50 (dd, J = 6.4 Hz,
J = 3.2 Hz, 2H), 5.62 (d, J = 5.2 Hz, 1H), 2.46 (d, J = 5.2 Hz,
1H), 0.23 (s, 9H); 13C NMR (100 MHz, CDCl3) d 139.0, 138.6,
133.5, 129.0, 128.7, 128.1, 126.8, 126.7, 126.0, 125.1, 105.3, 92.3,
65.6, 0.31.
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Acknowledgements
We are grateful to the grants from the Natural Science Foundation
of Education Committee of Jiangsu Province (06KJB150099) and
the Key Laboratory of Organic Synthesis of Jiangsu Province for
financial support.
9 P. Lehr, A. Billich, B. Charpiot, P. Ettmayer, D. Scholz, B. Rosenwirth
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