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GÖK ET AL.
(CHNS 0932). Melting points were measured with a Thermo Scientific
9200 melting point apparatus.
(=C-H), 2893 (-C-H), 1921, 1487 (-C-H), 1386, 1183, 1081 (-C-O), 749,
688; 1H NMR (400 MHz, DMSO-d6, δ) 7.61 (4H, Ar-H, d, J = 7.2 Hz),
7.52 (4H, Ar-H, d, J = 8.2 Hz), 7.42 (4H, Ar-H, t, J = 7.2 Hz), 7.34-7.27
(6H, Ar-H, m), 5.43 (2H, -CH, s), 4.72 (2H, -OH, s); 13C NMR (100
MHz, DMSO-d6, δ) 141.8 (C), 140.0 (C), 138.4 (C), 128.9 (CH), 127.8
(CH), 127.2 (CH), 126.5 (CH), 125.6 (CH), 77.1 (CH); MS (ES+) MS cal-
culated [M]+, [M+Na]+, [M-OH]+ for C26H22O2: 366.2, 389.2, 349.2 found:
366.2, 389.2, 349.2, respectively.
(E)-3,3’-Dibromostilbene (3). (3-bromobenzyl)phosphonic acid diethyl
ester 1 (12.24 g, 40.0 mmol) was dissolved in dry THF (600 mL) was
added to a solution of 3-bromobenzaldehyde (14.80 g, 80.0 mmol) in dry
THF (300 mL) under an argon atmosphere at room temperature (rt).
Next, t-BuOK (6.73 g, 60 mmol) was added to the reaction mixture. The
resulting reaction mixture was stirred at room temperature for an addi-
tional 40 min. After hydrolysis with water, the mixture was stirred over-
night, and the precipitated solid was filtered off, resulting in 12.5 g
(92%) of 3 as a pure white solid. mp: 100–101°C; IR (KBr) 3056 (=C-H),
3028 (=C-H), 1857, 1591 (-C=C-), 1562, 1471, 1429, 1073, 970, 873, 770,
681; 1H NMR (400 MHz, CDCl3, δ) 7.65 (2H, Ar-H, t), 7.40 (4H, Ar-H,
dd, J = 7.7Hz) 7.22 (2H, Ar-H, t, J = 7.8 Hz) 7.00 (2H, -CH, s); 13C NMR
(100 MHz, CDCl3, δ) 138.9 (C), 130.8 (CH), 130.2 (CH), 129.4 (CH),
128.6 (CH),125.4 (CH), 122.9 (C).
GENERAL PROCEDURE FOR THE ENANTIOSELECTIVE
DIETHYLZINC ADDITION TO ALDEHYDES
Under an argon atmosphere, chiral ligand (0.025 mmol)
was dissolved in dry solvent, Ti(OiPr)4 (0.25 mmol) was
added and stirred for 1 h for the Ti-mediated reactions. Et2Zn
(0.5 mmol, 1 M in hexane) was added, and the resulting
yellow solution was stirred for 20 min at rt. Aldehyde was
then added (0.25 mmol), and the reaction was stirred for
another 24 h. After quenching with 1 mL saturated NH4Cl
solution, 25 mL H2O was added and then extracted with
EtOAc (3 × 25 mL). The combined organic phases were
dried over Na2SO4 and evaporated in vacuo. The crude prod-
uct was purified by flash chromatography to give the corre-
sponding alcohol. Enantiomeric excesses were determined
by high-performance liquid chromatography (HPLC) analy-
sis using a chiral stationary phase column (Chiracel OD-H
or Chiracel OB) or GC analysis with chiral HP-CHIRAL-B20
column.
(1R,2R)-1,2-Bis(3-bromophenyl)-ethane-1,2-diol (5). First, AD-mix-β (48
g) was dissolved in a mixture of tert-butyl alcohol (120 mL) and water (120
mL). Next, methanesulfonamide (2.21 g, 23.06 mmol) was added, and the
reaction mixture was cooled to 0°C, and the inorganic salts were partially
precipitated. (E)-3,3′-dibromo stilbene 3 (6 g, 17.75 mmol) was added in
one portion and the heterogeneous slurry was stirred vigorously at 0°C
for 3 days. The mixture was allowed to warm to rt, and Na2SO3 (29.81 g,
236.5 mmol) was added. The reaction mixture was stirred at rt for an addi-
tional 24 h. Next, EtOAc (100 mL) was added, and the organic phase was
separated, whereupon the aqueous phase was further extracted with
EtOAc (2 × 50 mL). The combined organic phases were washed with 2
M KOH and dried over MgSO4, filtered, and concentrated in vacuo. The
crude product was purified by flash chromatography over silica gel (Hex-
ane/EtOAc, 80:20) resulting in 5.2 g (>99% enantiomeric excess [ee], 79%
20
yield) of pure diol 5 as a white solid. mp: 49–50°C; ½αꢀD ¼+93.98 (c = 1,
RESULTS AND DISCUSSION
CHCl3); IR (KBr) 3399 (OH), 3061 (=C-H), 2897 (-C-H), 1941, 1873, 1569
(-C=C-), 1473 (-C-H), 1426, 1190, 1071(-C-O), 1039, 880, 786, 746; 1H
NMR (400 MHz, CDCl3, δ) 7.40-7.35 (4H, Ar-H, m), 7.10 (2H, Ar-H, t, J =
7.7 Hz), 6.94 (2H, Ar-H, dt, J = 7.7 Hz), 4.61 (2H, -CH, s), 2.96 (2H, -OH,
s); 13C NMR (100 MHz, CDCl3, δ) 141.8 (C), 131.3 (CH), 129.9 (CH),
129.7 (CH), 125.7 (CH), 122.5 (C), 78.2 (CH); MS (ES-) MS calculated
[M-2H]+ for C14H10Br2O2: 369.9 found: 369.0.
The C2-symmetric chiral diols were prepared in good over-
all yields according to the synthetic routes outlined in
Scheme 1. The key compounds dibromo-substituted (E)-stil-
bene 3 and 421,22 were not commercially available and needed
to be synthesized. Dibromo-substituted (E)-stilbene 3 and 4
were synthesized via different methods such as McMurry
coupling23,24 or Wittig reaction25,26 by different research
groups. The harsh reaction conditions, expensive synthetic
steps, or small differences in the E:Z ratio reported in the lit-
erature inspired us to devise a different route with milder and
more economical synthetic steps. Dibromo-substituted (E)-
stilbene 3 and 4 were synthesized via Horner-Wadsworth-
Emmons (HWE) reaction starting from phosphonates 127
and 2,21 respectively. This route could be easily scaled up.
(1R,2R)-1,2-bis(([1,1’-biphenyl]-3-yl)-ethane-1,2-diol (7). To a solution of
5 (2 g, 5.37 mmol) and Pd(PPh3)4 (0.73 g, 0.64 mmol) in toluene (274
mL), phenylboronic acid (1.96 g, 16.11 mmol), EtOH (42 mL), and aq
K2CO3 (2 M, 80 mL) were added. The resulting reaction mixture was
refluxed for 26 h. Water (200 mL) was then added to the reaction mixture.
The aqueous layer was further extracted with CH2Cl2 (3 × 100 mL), and
the combined organic phases were washed with brine (20 mL), dried over
MgSO4, and concentrated in vacuo. The crude product was purified by
flash chromatography over silica gel (CH2Cl2/EtOAc, 95:5) resulting in
20
1.86 g (>99% ee, 96% yield) pure diol 7 as transparent oil. ½αꢀD ¼ +91.97
(c = 1, CHCl3); IR (KBr) 3389 (OH), 3060 (=C-H), 3031 (=C-H), 2902
(-C-H), 1598 (-C=C-), 1574, 1479 (-C-H), 1180, 1046 (-C-O), 895, 803,
758, 701, 615; 1H NMR (400 MHz, CDCl3, δ) 7.47-7.14 (18H, Ar-H,
m), 4.79 (2H, -CH, s), 2.59 (2H, -OH, s); 13C NMR (100 MHz, CDCl3,
δ) 141.2 (C), 140.9 (C), 140.4 (C), 128.7 (CH), 128.6 (CH), 127.3
(CH), 127.2 (CH), 126.8 (CH), 126.0 (CH), 125.8 (CH), 79.3 (CH);
MS (ES+) MS calculated [M]+, [M+Na]+, [M-OH]+ for C26H22O2:
366.2, 389.2, 349.2 found: 366.2, 389.2, 349.2, respectively; Anal. Calcd.
for C26H22O2: C 85.22, H 6.05; found C 84.72, H 6.12.
(1R,2R)-1,2-bis(([1,1’-biphenyl]-4-yl)-ethane-1,2-diol (8). To a solution of
6 (2 g, 5.37 mmol) and Pd(PPh3)4 (0.73 g, 0.64 mmol) in toluene
(274 mL), phenylboronic acid (1.96 g, 16.11 mmol), EtOH (40 mL), and
aq K2CO3 (2 M, 80 mL) were added. The resulting reaction mixture
was refluxed for 26 h. Water (200 mL) was added to the reaction mixture.
The aqueous layer was further extracted with CH2Cl2 (3 × 100 mL), and
the combined organic phases were washed with brine (20 mL), dried over
MgSO4, and concentrated in vacuo. The crude product was purified by
flash chromatography over silica gel (CH2Cl2/EtOAc, 95:5), resulting in
0.91 g (>99% ee, 52% yield) pure diol 8 as a white solid. mp: 242-243°C;
20
½αꢀD ¼ +161.90 (c = 1, THF); IR (KBr) 3400 (OH), 3055 (=C-H), 3030
Scheme 1. Synthesis of optically pure C2-symmetric diols 5-8.
Chirality DOI 10.1002/chir