L. Liu, L. Pu / Tetrahedron 60 (2004) 7427–7430
7429
has been observed for the reaction of phenylacetylene with
aromatic aldehydes, especially with the ortho-substituted
benzaldehydes. Application of this ligand to other asym-
metric reactions is currently under investigation.
mixture was stirred at room temperature for 4 h, a saturated
ammonium chloride solution was added to quench the
reaction. The mixture was extracted with methylene
chloride (3£5 mL) and the organic solution was concen-
trated under vacuum. The residue was purified by passing
through a short silica gel column eluted with methylene
chloride/hexane (1:1) which afforded the pure propargylic
alcohol product.
2. Experimental
2.1. General data
2.3.1. 1,3-Diphenylprop-2-yn-1-ol.8 86% yield. 87% ee
determined by HPLC analysis. Retention time: tmajor¼24.0
min and tminor¼13.3 min.
2.3.2. 1-(2-Chlorophenyl)-3-phenylprop-2-yn-1-ol.9 88%
yield. 97% ee determined by HPLC analysis. Retention
time: tmajor¼14.0 min and tminor¼12.0 min.
All reactions were carried out under nitrogen. Unless
otherwise specified, all the reagents were purchased from
Aldrich Chemical Co. and used directly. Diethylzinc (95%)
was purchased from Strem. Toluene was distilled over
sodium under nitrogen. Methylene chloride, diethyl ether
and tetrahydrofuran were dried by passing through activated
alumnia columns under nitrogen. All the solvents were
˚
2.3.3. 1-(2,6-Dichlorophenyl)-3-phenylprop-2-yn-1-ol.
62% yield. 87% ee determined by HPLC analysis. Retention
time: tmajor¼12.2 min and tminor¼8.9 min. [a]2D4¼þ3.67
stored over 4 A molecular sieves before use. Deuterated
˚
chloroform was stored over 4 A molecular sieves before
use. NMR spectra were obtained using the Varian-300 MHz
spectrometer. Mass spectra were recorded either at atmos-
pheric pressure chemical ionization (APCI) or at electro-
spray ionization (ESI) mode. HPLC analyses were carried
out with the Waters 600 by using the Daicel Chiralcel OD
column and eluting with 10% i-PrOH in hexane at
1.0 mL/min unless otherwise indicated, and were detected
at 254 nm by the Waters 486. The optical rotations were
measured on the JASCO DIP-1000 Polarimeter.
1
(c¼1.26, CHCl3). H NMR (300 MHz, CDCl3) d 7.48–
7.43 (m, 2H), 7.36–7.17 (m, 6H), 6.60 (d, 1H, J¼10.2 Hz),
3.40 (d, 1H, J¼10.2 Hz). The large coupling constant
observed here between the hydroxyl proton and the methine
proton is probably due to the intramolecular hydrogen bond
between the hydroxyl group and one of the two chlorine
atoms at the 2,6-positions. This intramolecular hydrogen
bond allows the hydroxyl proton and the methine proton to
form an antiperiplanar conformation as shown by a
PCSpartan-Semi-Empirical AM1 calculation and it signifi-
cantly increases the coupling constant. 13C NMR (75 MHz,
CDCl3) d 135.7, 134.7, 132.1, 130.0, 129.5, 128.9, 128.5,
122.6, 86.9, 86.5, 61.7. MS (FIA-APCI) m/z 258.4
(Mþ2H2O, 100).
2.2. Synthesis and characterization of (S)-1
Paraformaldehyde (6.0 g, 0.20 mol) was placed in a round
bottom flask equipped with a reflux condenser. Morpholine
(17.6 g, 0.20 mol) was added dropwise over 0.5 h with
rigorous stirring. Since this was a strongly exothermic
reaction, the addition rate was adjusted in order to keep
the oil bath temperature at ,60 8C. After the addition, the
reaction mixture was heated at 60 8C for ca. 12 h until the
solution became clear. H8-BINOL (3.0 g, 0.010 mol) and
dioxane (10 mL) were added and the solution was stirred at
60 8C for additional 8 h. The solvent was then removed by
roto-evaporation. The residue was dissolved in CH2Cl2
(50 mL), washed with 1 M HCl (3£10 mL) and water
(3£10 mL), and dried over Na2SO4. After roto-evaporation,
the crude material was purified by using ethylacetate/hexane
(3:1) to elute through a short silicon gel column. This gave
(S)-1 as colorless crystals (3.3 g) in 65% yield. Mp 215.5–
216.5 8C. 1H NMR (300 MHz, CDCl3) d 10.37 (s, 2H), 6.73
(s, 2H), 3.83–3.57 (m, 12H), 2.72–2.13 (m, 16H), 1.72–
1.56 (m, 4H). 13C NMR (75 MHz, CDCl3) d 151.71, 135.5,
128.4, 127.1, 123.6, 117.4, 66.3, 61.6, 52.5, 28.9, 26.9,
22.9, 22.8. [a]D¼215.5 (c¼1.0, CDCl3). Anal. Calcd for
C30H39N2O4: C, 72.84; H, 8.56; N, 5.66. Found: C, 73.22;
H, 8.20; N, 5.66. MS (FIA-ESI) m/z 493.0 (Mþ, 100).
2.3.4. 1-(2-Nitrophenyl)-3-phenylprop-2-yn-1-ol.10 62%
yield. 98% ee determined by HPLC analysis. Retention
time: tmajor¼16.0 min and tminor¼20.6. 1H NMR (300 MHz,
CDCl3) d 8.26–7.80 (m, 2H), 7.77–7.74 (m, 2H),7.51–
7.15(m, 5H), 5.80 (s, 1H), 2.63 (s, 1H). 13C NMR (75 MHz,
CDCl3) d 148.0, 147.6, 132.0, 130.7, 129.3, 128.7, 127.7,
124.51, 124.1, 122.0, 87.8, 87.7, 64.2.
2.3.5. 1-(2,4,5-Trimethylphenyl)-3-phenylprop-2-yn-1-
ol. 68% yield. 96% ee determined by HPLC analysis.
Retention time: tmajor¼34.8 min and tminor¼13.4. [a]2D4¼
1
220.9 (c¼1.38, CHCl3). H NMR (300 MHz, CDCl3) d
7.57–7.53 (m, 3H), 7.39–7.36 (m, 3H), 7.05 (s, 1H), 5.84
(d, 1H, J¼4.8 Hz), 2.95 (d, 1H, J¼4.8 Hz), 2.44 (s, 3H),
2.28 (s, 3H), 2.25 (s, 3H). 13C NMR (75 MHz, CDCl3) d
135.9, 134.9, 133.4, 131.4, 130.8, 127.6, 127.4, 121.8, 88.0,
85.3, 61.9, 28.9, 18.5, 17.5. MS (FIA-APCI) m/z 232.5
(Mþ2H2O, 100). (The starting material contained ,7%
5-bromo-1,2,4-trimethylbenzene which could not be
completely removed from the product.)
2.3. General procedure for the phenylacetylene addition
to aldehydes catalyzed by (S)-1
2.3.6. 1-(2-Ethoxyphenyl)-3-phenylprop-2-yn-1-ol. 83%
yield. 92% ee determined by HPLC analysis. Retention
time: tmajor¼18.4 min and tminor¼12.5 min. [a]2D4¼þ2.92
(c¼1.38, CHCl3). 1H NMR (300 MHz, CDCl3) d 7.64–7.60
(m, 1H), 7.50–7.47 (m, 2H),7.31–7.24 (m, 4H), 7.04–
6.9(m, 2H), 5.85 (d, 1H, J¼4.5 Hz), 4.40–4.03 (m, J¼
6.9 Hz, 2H), 3.29 (d, 1H, J¼4.5 Hz), 1.51–1.46 (t, 3H,
In a 10 mL round-bottom flask, phenylacelylene (1.0 mmol,
113 mL) was dissolved in THF (3 mL) at room temperature.
Et2Zn (1.0 mmol, 110 mL), Ti(OiPr)4 (74 mL, 0.25 mmol),
(S)-1 (12.3 mg, 0.025 mmol) and an aldehyde (0.25 mmol)
were then added sequentially. After the resulting reaction