The Journal of Organic Chemistry
Article
8.5, 2.2 Hz, 2H); 13C NMR (ACN-d3) δ 81.6 118.8, 127.1, 138.3,
139.9, 154.3.
4,4′,6,6′-Tetrabromo-1,1′-dihydroxy-2,2′-biphenyl (10).17 2,2′-
Biphenol (200 mg, 1.07 mmol) was dissolved in 5 mL of anhydrous
methanol. The solution was cooled to 0 °C, and Br2 (0.27 mL, 5.35
mmol) was added. The mixture was allowed to warm to room
temperature and stirred for 8 h. The precipitate was filtered and
washed with cold methanol to give 451 mg (0.96 mmol, 90%) of a
1,1′-Biphenyl-4,4′-diiodo-2,2′-diacetate (5).14 Compound 4 (430
mg, 0.98 mmol) and NEt3 were dissolved in 10 mL of dichloro-
methane. The mixture was cooled to 0 °C, and acetyl chloride (0.3
mL, 3.93 mmol) was added. The mixture was allowed to warm to
room temperature and then stirred for 4 h. The reaction was quenched
with water and the mixture extracted with dichloromethane. The
combined organic layers were dried over MgSO4 and concentrated in
vacuo. Purification by flash chromatography on silica gel (4:1 hexanes/
EtOAc) afforded 435 mg (0.83 mmol, 85%) of a white solid: 1H NMR
δ 2.06 (s, 6H), 6.92 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 2.2 Hz, 2H), 7.71
(dd, J = 8.5 Hz, 2.2 Hz, 2H); 13C NMR δ 20.7, 89.8, 124.7, 131.2,
138.3, 139.6, 147.9, 168.7.
1
white solid: H NMR (DMSO-d6) δ 7.26 (s, 2H), 7.70 (s, 2H); 13C
NMR (DMSO-d6) δ 110.9, 113.1, 128.5, 133.3, 134.6, 151.7.
4,4′,6,6′-Tetrabromo-1,1′-dimethoxymethoxy-2,2′-biphenyl (11).
A solution of 10 (400 mg, 0.80 mmol) in 10 mL of anhydrous THF
was cooled to 0 °C. NaH (60% dispersion in mineral oil, 80 mg, 2.00
mmol) was added, and the mixture was allowed to stir for 30 min.
Then, MOMCl (183 μL, 2.40 mmol) dissolved in 5 mL of THF was
added dropwise, and the mixture was stirred overnight at room
temperature. The reaction was quenched with water and the mixture
extracted with dichloromethane. The combined organic layers were
dried over MgSO4 and concentrated in vacuo. Purification by flash
chromatography on silica gel (4:1 hexanes/EtOAc) afforded 448 mg
1,1′-Biphenyl-4,4′-diphenylacetylene-2,2′-diacetate (6). A solu-
tion of 5 (360 mg, 0.69 mmol), phenylacetylene (0.23 mL, 2.07
mmol), Pd(PPh3)4 (80.0 mg, 0.07 mmol), CuI (13.1 mg, 0.07 mmol),
and NEt3 (0.77 mL, 5.52 mmol) in 5 mL of DMF was stirred at room
temperature for 24 h. The reaction was quenched with water and the
mixture extracted with dichloromethane. The combined organic layers
were dried over MgSO4 and concentrated in vacuo. Purification by
flash chromatography (4:1 hexanes/EtOAc) afforded 268 mg (0.57
mmol, 82%) of a light yellow solid: 1H NMR δ 2.08 (s, 6H), 7.17 (d, J
= 8.4 Hz, 2H), 7.34−7.36 (m, 6H), 7.51−7.53 (m, 6H), 7.57 (dd, J =
8.4, 2.1 Hz, 2H); 13C NMR δ 23.5, 90.9, 92.7, 124.1, 125.5, 125.7,
131.1, 132.8, 134.3, 135.0, 137.1, 171.6. Anal. Calcd for C32H26O4: C,
80.99; H, 5.52. Found: C, 80.63; H, 5.48.
1
(0.76 mmol, 95%) of a white crystalline solid: mp 101−104 °C; H
NMR δ 3.07 (s, 6H), 4.86 (s, 4H), 7.47 (s, 2H), 7.75 (s, 2H); 13C
NMR δ 57.2, 99.7, 117.1, 118.8, 133.7, 134.3, 135.7, 151.7. Anal. Calcd
for C16H14Br4O4: C, 32.58; H, 2.39. Found: C, 32.67; H, 2.54.
4,4′,6,6′-Tetraphenylacetylene-1,1′-dimethoxymethoxy-2,2′-bi-
phenyl (12). A solution of 11 (400 mg, 0.68 mmol), phenylacetylene
(0.6 mL, 5.44 mmol), Pd(PPh3)4 (235 mg, 0.20 mmol), CuI (38 mg,
0.20 mmol), and Et3N (1.52 mL, 10.9 mmol) in 10 mL of THF was
stirred at 60 °C for 24 h. The reaction mixture was allowed to cool to
room temperature, the reaction quenched with water, and the mixture
extracted with dichloromethane. The combined organic layers were
dried over MgSO4 and concentrated in vacuo. Purification by flash
chromatography on silica gel (4:1 hexanes/EtOAc) afforded 422 mg
1,1′-Dimethoxymethoxy-2,2′-biphenyl (7).15 2,2′-Biphenol (500
mg, 2.7 mmol) was dissolved in 15 mL of anhydrous THF and cooled
to 0 °C. NaH (161 mg, 6.7 mmol) was added, and the mixture was
stirred at 0 °C for 30 min. MOMCl (0.62 mL, 8.1 mmol) was
dissolved in 3 mL of THF, and the solution was added dropwise. The
reaction mixture was allowed to warm to room temperature and stirred
overnight. The reaction was quenched with water and the mixture
extracted with dichloromethane. The combined organic layers were
dried over MgSO4 and concentrated in vacuo. Purification by flash
chromatography on silica gel (4:1 hexanes/EtOAc) afforded 630 mg
1
(0.63 mmol, 92%) of a yellow crystalline solid: mp 119−121 °C; H
NMR δ 3.12 (s, 6H), 5.16 (s, 4H), 7.34−7.37 (m, 12H), 7.51−7.55
(m, 8H), 7.60 (s, 2H), 7.75 (s, 2H); 13C NMR δ 57.0, 85.1, 87.9, 89.8,
94.2, 99.4, 118.2, 119.3, 122.9, 123.0, 128.4, 128.4, 128.6, 130.0 131.5,
131.6, 132.4, 134.8, 136.1, 156.0. Anal. Calcd for C48H34O4: C, 85.44;
H, 5.08. Found: C, 85.20; H, 5.13.
Enantioselective Sensing Experiments. A stock solution of
sensor 1, 2, or 3 (0.006 M) in THF was prepared, and 0.5 mL portions
were transferred to 4 mL vials. Solutions of the substrates (0.15 M) in
THF were prepared. To each vial containing 0.5 mL of the sensor
stock solution was added 1 equiv (20 μL, 0.003 mmol) of substrates
13 and 14 or 2 equiv (40 μL, 0.006 mmol) of substrates 15−24. To
each vial was then added Et2Zn (3 μL, 0.003 mmol), and the mixtures
were allowed to react for 5 min. CD analysis was conducted by adding
20 μL (sensors 1 and 3, 6.0 × 10−5 M) or 40 μL (sensor 2, 1.2 × 10−4
M) of the mixtures to 2 mL of diethyl ether. The CD spectra were
collected with a standard sensitivity of 100 mdeg, a data pitch of 0.5
nm, a bandwidth of 1 nm, a scanning speed of 500 nm s−1, and a
response of 0.5 s using a quartz cuvette (1 cm path length). All CD
spectra were collected at 25 °C. The data were baseline corrected and
smoothed using a binomial equation.
Quantitative ee Analysis. The CD response of the zinc
biphenolate of 2 or 3 in the presence of 13 with varying ee’s was
determined. Solutions of the biphenol (0.5 mL, 0.006 M in THF) and
of the analyte (0.5 mL, 0.15 M in THF) were prepared. Mixtures of
the reporter compound and the analyte at varying enantiomeric
compositions (+100, +80, +60, +40, +20, 0, −20, −40, −60, −80, and
−100% ee) were generated by adding 20 μL of the solution containing
13 to a 0.5 mL solution of 2 or 3. Et2Zn (3 μL, 0.003 mmol) was then
added, and the mixtures were allowed to stand for 5 min. CD analysis
was conducted as described above
1
(2.3 mmol, 85%) of a colorless oil: H NMR δ 3.33 (s, 6H), 5.06 (s,
4H), 7.06 (dd, J = 7.3, 7.4 Hz, 2H), 7.20−7.33 (m, 6H); 13C NMR δ
55.6, 95.3, 115.6, 121.8, 128.7, 129.2, 131.5, 154.9.
6,6′-Diiodo-1,1′-dimethoxymethoxy-2,2′-biphenyl (8).16 A solu-
tion of n-BuLi (2.5 M in hexanes, 1.1 mL, 2.7 mmol) and TMEDA
(0.41 mL, 2.7 mmol) was stirred in 10 mL of diethyl ether for 10 min.
Then, 7 (300 mg, 1.1 mmol) dissolved in 10 mL of anhydrous diethyl
ether was added dropwise. The mixture was heated to reflux for 2 h,
and an orange precipitate appeared. The reaction mixture was then
cooled to −78 °C, and I2 (833 mg, 3.3 mmol) dissolved in 10 mL of
diethyl ether was added dropwise. The reaction mixture was allowed to
warm to room temperature and stirred overnight. The reaction was
quenched with water and the mixture extracted with dichloromethane.
The combined organic layers were dried over MgSO4 and
concentrated in vacuo. Purification by flash chromatography (5:1
hexanes/EtOAc) afforded 386 mg (0.73 mmol, 67%) of a light yellow
solid: 1H NMR δ 3.04 (s, 6H), 4.80 (s, 4H), 6.92 (dd, J = 7.8, 7.7 Hz,
2H), 7.35 (dd, J = 7.7, 1.6 Hz, 2H), 7.83 (dd, J = 7.8, 1.6 Hz, 2H); 13C
NMR δ 57.2, 92.9, 99.7, 125.8, 132.2, 133.4, 139.4, 154.7.
1,1′-Dimethoxymethoxy-6,6′-diphenylacetylene-2,2′-biphenyl
(9). A solution of 8 (300 mg, 0.6 mmol), phenylacetylene (0.25 mL,
2.3 mmol), Pd(PPh3)4 (66 mg, 0.06 mmol), CuI (11 mg, 0.06 mmol),
and NEt3 (0.7 mL, 4.6 mmol) was stirred in 10 mL of anhydrous THF
at 60 °C for 12 h. The reaction was quenched with water and the
mixture extracted with dichloromethane. The combined organic layers
were dried over MgSO4 and concentrated in vacuo. Purification by
flash chromatography (4:1 hexanes/EtOAc) afforded 257 mg (0.54
Crystallography. A single crystal of compound 8 was obtained by
slow evaporation of a concentrated chloroform solution. Crystallo-
graphic analysis was performed at 100 K using a Siemens platform
diffractometer with graphite monochromated Mo Kα radiation (λ =
0.71073 Å). Data were integrated and corrected using the Apex 2
program. The structure was determined by direct methods and refined
with full-matrix least-squares analysis using SHELX-97-2. Non-
hydrogen atoms were refined with anisotropic displacement
1
mmol, 95%) of a brown solid: H NMR δ 3.04 (s, 6H), 5.09 (s, 4H),
7.18 (dd, J = 7.7, 7.7 Hz, 2H), 7.34−7.40 (m, 8H), 7.52−756 (m, 6H);
13C NMR δ 56.8, 86.1, 93.6, 99.3, 110.0, 117.8, 123.3, 123.8, 128.4,
131.5, 132.1, 132.9, 133.1, 156.1. Anal. Calcd for C32H26O4: C, 80.99;
H, 5.52. Found: C, 81.22; H, 5.76.
1190
J. Org. Chem. 2016, 81, 1185−1191