Pinacol Coupling of Aryl Aldehydes
purified by flash chromatography on silica gel using hexanes-
EtOAc as the eluent.
afforded 1,2-di(p-chlorophenyl)ethane-1,2-diol within 4 h at
-10 °C. [R]D ) +63.3 (c ) 1, EtOH). Mp: 130 °C [lit.27 [R]D
)
Liga n d -2. A mixture of (1R,2S)-norephedrine (1.51 g, 10
mmol) and salicaldehyde (1.2 mL, 10 mmol) in CH2Cl2 (15 mL)
in the presence of anhydrous Na2SO4 (3 g) afforded ligand 2
almost quantitatively as a viscous liquid within 2 h of stirring
+93 (c ) 1, EtOH) for 100% ee R,R-enantiomer. Mp: 127 °C)].
NMR shows a dl/meso ratio of 89:11.
(R,R)-(+)-1,2-Di(p-flu or op h en yl)eth a n e-1,2-d iol. Accord-
ing to the general protocol, p-fluorobenzaldehyde (0.43 mL, 4
mmol), Ti-4 (0.18 g, 0.4 mmol, 10 mol %), Zn (0.52 g, 8 mmol),
and TMSCl (0.76 mL, 6 mmol), followed by desilylation,
afforded 1,2-di(p-fluorophenyl)ethane-1,2-diol within 5 h at
-10 °C. [R]D ) +36.0 (c ) 1, EtOH) [lit.5b [R]D ) +53 (c )
1.10, EtOH) for 100% ee R,R-enantiomer]. Mp: 134-135 °C
(lit.28 mp: 108-110 °C). NMR shows a dl/meso ratio of 90:10.
(R,R)-(+)-1,2-Di(1′-n a p h th yl)eth a n e-1,2-d iol. According
to the general protocol, 1-naphthaldehyde (0.54 mL, 4 mmol),
Ti-4 (0.36 g, 0.8 mmol, 20 mol %), Zn (0.52 g, 8 mmol), and
TMSCl (0.76 mL, 6 mmol), followed by desilylation, afforded
1,2-di(1′-naphthyl)ethane-1,2-diol within 5 h at -10 °C. [R]D
) +58.5 (c ) 1, THF) [lit.29 [R]D ) +68 (c ) 0.86, THF) for
100% ee R,R-enantiomer]. Mp: 174-175 °C. NMR shows a
dl/meso ratio of 91:9. 1H NMR (200 MHz, CDCl3): δ 2.60
1
at room temperature. [R ]D ) +152.21 (c ) 7.17; MeOH). H
NMR (200 MHz, CDCl3): δ 1.29 (d, J ) 6.84 Hz, 3 H, CH3),
2.06 (bs, 1 H, OH), 3.64 (m, 1 H, CH), 4.80 (d, J ) 5.38 Hz, 1
H, CH), 6.8-6.94 (m, 2 H, HAr), 7.14-7.36 (m, 6 H, HAr), 8.21
(s, 1 H, CH), 13.24 (bs, 1 H, OH) ppm. 13C NMR (50 MHz,
CDCl3): δ 17.93, 70.09, 77.74, 96.19, 117.03, 118.50, 118.76,
126.88, 127.91, 128.28, 131.44, 132.32, 141.03, 161.18, 164.67
ppm. IR (neat): ν˜ (cm-1) ) 3417, 3060, 3029, 2974, 2873, 1631.
Anal. Calcd for C16H17N02: C, 75.26; H, 6.72; N, 5.49. Found:
C, 75.48; H, 6.76; N, 5.52.
Ti-4 Com p lex. According to the general protocol, SALEN
(ligand 4) (1.61 g, 5 mmol), Ti(OiPr)4 (5 mL, 1 M in toluene, 5
mmol), and TMSCl (1.3 mL, 10 mmol) afforded Ti-4 within 8
h at room temperature. [R]D ) +514.3 (c ) 0.014, CHCl3).
Mp: 330-350 °C dec. 1H NMR (500 MHz, CDCl3): δ 1.43-
1.47 (m, 2 H, CH2), 1.61-1.67 (m, 2 H, CH2), 2.10-2.16 (m, 2
H, CH2), 2.59-2.61 (m, 2 H, CH2), 4.06-4.08(m, 2 H, CH2),
6.9 (d, J ) 8.26 Hz, 2 H. HAr), 7.12-7.15 (m, 2 H, HAr), 7.56-
7.62 (m, 4 H, HAr), 8.39 (s, 2 H, CH) ppm. 13C NMR (500 MHz,
CDCL3): δ 24.11, 28.69, 67.75, 116.42, 122.71, 125.45, 135.00,
136.40, 159.59, 162.52. Anal. Calcd. for C20H20N2O2Cl2Ti: C,
54.72; H 4.60; N, 6.38. Found: C, 54.84; H, 4.61; N, 6.40.
(R,R)-(+)-1,2-Dip h en yleth a n e-1,2-d iol. According to the
general protocol, benzaldehyde (0.42 mL, 4 mmol), Ti-4 (0.18
g, 0.4 mmol, 10 mol %), Zn (0.52 g, 8 mmol), and TMSCl (0.76
mL, 6 mmol), followed by desilylation, afforded 1,2-diphenyl-
ethane-1,2-diol within 4 h at -10 °C. [R]D ) +89.4 (c ) 1,
EtOH). Mp: 148-150°C [lit.5a [R]D ) -94.5 (c ) 1, EtOH) for
100% ee S,S-enantiomer. Mp: 148-150 °C]. NMR shows a dl/
meso ratio of 98:2.
(R,R)-(+)-1,2-Di(p -m et h ylp h en yl)et h a n e-1,2-d iol. Ac-
cording to the general protocol, p-methylbenzaldehyde (0.48
mL, 4 mmol), Ti-4 (0.18 g, 0.4 mmol, 10 mol %), Zn (0.52 g, 8
mmol), and TMSCl (0.76 mL, 6 mmol), followed by desilylation,
afforded 1,2-di(p-methylphenyl)ethane-1,2-diol within 4 h at
-10 °C. [R]D ) +98.4 (c ) 1, EtOH). Mp: 105-107°C [lit.5a
[R]D ) -102.5 (c ) 1, EtOH) for 100% ee S,S-enantiomer. Mp:
105-107 °C)]. NMR shows a dl/meso ratio of 91:9.
(R,R)-(+)-1,2-Di(o-m et h ylp h en yl)et h a n e-1,2-d iol. Ac-
cording to the general protocol, o-methylbenzaldehyde (0.46
mL, 4 mmol), Ti-4 (0.36 g, 0.8 mmol, 20 mol %), Zn (0.52 g, 8
mmol), and TMSCl (0.76 mL, 6 mmol), followed by desilylation,
afforded 1,2-di(o-methylphenyl)ethane-1,2-diol within 4 h at
-10 °C. [R]D ) +53.3 (c ) 1, EtOH). Mp: 108-110 °C. [lit.1g
[R]D ) -64.8 (c ) 0.83, EtOH) for 100% ee S,S-enantiomer.
Mp: 109-110 °C]. NMR shows a dl/meso ratio of 96:4.
(R,R)-(+)-1,2-Di(p-m eth oxylp h en yl)eth a n e-1,2-d iol. Ac-
cording to the general protocol, p-methoxybenzaldehyde (0.48
mL, 4 mmol), Ti-4 (0.18 g, 0.4 mmol, 10 mol %), Zn (0.52 g, 8
mmol), and TMSCl (0.76 mL, 6 mmol), followed by desilylation,
afforded 1,2-bis(paramethoxyphenyl)ethane-1,2-diol within 3
h at -10 °C. [R]D ) +92.3 (c ) 1, EtOH). Mp: 132-134 °C
[lit.5a [R]D ) -118.3 (c ) 1, EtOH) for 100% ee S,S-enantiomer.
Mp: 132-134 °C)]. NMR shows only dl isomer.
(bs, 2 H, OH), 5.73 (s, 2 H, CH), 7.21-7.83 (m, 14 H, HAr
)
ppm. 13C NMR (50 MHz, CDCl3): δ 74.50, 123.02, 124.86,
125.12, 125.34, 125.74, 128.57, 128.68, 133.72, 136.14 ppm.
IR (Nujol): ν˜ (cm-1) ) 3339. Anal. Calcd for C22H1802: C, 84.04;
H, 5.78. Found: C, 84.10; H, 5.76.
(R,R)-(+)-1,2-Di(2′-n a p h th yl)eth a n e-1,2-d iol. According
to the general protocol, 2-naphthyldehyde (0.63 g, 4 mmol),
Ti-4 (0.36 g, 0.8 mmol, 20 mol %), Zn (0.52 g, 8 mmol), and
TMSCl (0.76 mL, 6 mmol), followed by desilylation, afforded
1,2-di(2′-naphthyl)ethane-1,2-diol within 4 h at -10 °C. [R]D
) +203.8 (c ) 1, THF). Mp: 243 °C [lit.29 [R]D ) +224 (c ) 1,
THF) for 100% ee R,R-enantiomer. Mp: 242-244 °C)]. NMR
shows a dl/meso ratio of 94:6.
(R,R)-(+)-1,2-Di(2′-fu r yl)eth a n e-1,2-d iol. According to the
general protocol, 2-furaldehyde (0.33 mL, 4 mmol), Ti-4 (0.18
g, 0.4 mmol, 10 mol %), Zn (0.52 g, 8 mmol), and TMSCl (0.76
mL, 6 mmol), followed by desilylation, afforded 1,2-di(2′-furyl)-
ethane-1,2-diol within 3 h at -10 °C. [R]D ) +15.5 (c ) 1,
EtOH) [lit.5a [R]D ) -31.0 (c ) 1, EtOH) for 100% ee
S,S-enantiomer]. NMR shows a dl/meso ratio of 93:7. The
compound is a viscous liquid and deteriorates rapidly at
ambient temperature. Therefore, it was difficult to crystallize.
Ack n ow led gm en t. We are thankful to Department
of Science and Technology for financial support and one
of us (A.C.) would like to thank CSIR for a Research
Fellowship.
Note Ad d ed a fter ASAP P ostin g. Structure 2 in
Figure 1 had errors in the version posted ASAP on J une
12, 2003; the corrected version was posted J une 16, 2003.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
all the reported products. This material is available free of
J O0342875
(27) Brienne, M. J .; Collet, A. J . Chem Res. Synop. 1978, 60.
(28) Fu¨rstner, A.; Csuk, R.; Rohrer, C.; Weidmann, H. J . Chem. Soc.,
Perkin Trans. 1 1988, 1729.
(29) Rosini, C.; Scamuzzi, S.; Uccello-Barretta, G.; salvadori, P. J .
Org. Chem. 1994, 59, 7395.
(R,R)-(+)-1,2-Di(p -ch lor op h en yl)et h a n e-1,2-d iol. Ac-
cording to the general protocol, p-chlorobenzaldehyde (0.56 g,
4 mmol), Ti-4 (0.18 g, 0.4 mmol, 10 mol %), Zn (0.52 g, 8
mmol), and TMSCl (0.76 mL, 6 mmol), followed by desilylation,
J . Org. Chem, Vol. 68, No. 14, 2003 5671