Enantioselective Recognition of Mandelic Acid
A R T I C L E S
in hexane to give 4 as a bright yellow solid in 92% yield (4.2 g). mp
102-105 °C. 1H NMR (CDCl3, 300 MHz): δ 2.57 (m, 2H), 2.67 (m,
2H), 3.06 (s, 6H), 3.58 (m, 4H), 4.88 (d, J ) 6.9 Hz, 2H), 4.99 (d, J
) 6.9 Hz, 2H), 7.01-7.48 (m, 18H), 7.81-7.92 (m, 10H). 13C NMR
(CDCl3, 75 MHz): δ 47.0, 55.9, 68.0, 95.3, 114.3, 117.5, 119.6, 121.4,
124.0, 124.3, 125.3, 125.5, 126.6, 127.8, 127.9, 129.3, 129.4, 129.6,
129.8, 133.9, 146.0, 149.4, 153.7, 154.5. ESI-MS m/z: 915 (M + H+).
HRMS (FAB) calcd for C54H46N2O10NaS (M + Na+): 937.2771.
Found: 937.2776.
workup, the crude product was purified by column chromatography
on silica gel eluted with 30% ethyl acetate in hexane to give 6 as a
bright yellow solid in 83% yield. mp 107-110 °C. [R]D ) +48.9 (c )
1
0.90, CH2Cl2). H NMR (CDCl3, 300 MHz): δ 2.47-2.55 (m, 2H),
2.68-2.76 (m, 2H), 3.07 (s, 6H), 3.51-3.66 (m, 4H), 4.87 (d, J ) 6.9
Hz, 1H), 4.99 (d, J ) 6.9 Hz, 1H), 6.84 (d, J ) 9.0 Hz, 2H), 6.93 (d,
J ) 9.0 Hz, 2H), 7.04 (d, J ) 9.3 Hz, 2H), 7.24 (dd, J ) 1.8, 9.0 Hz,
2H), 7.29 (dd, J ) 1.8, 9.0 Hz, 2H), 7.46-7.51 (m, 4H), 7.75 (d, J )
9.0 Hz, 2H), 7.85 (d, J ) 9.0 Hz, 2H), 7.95-7.98 (m, 4H), 8.04 (d, J
) 1.8 Hz, 2H). 13C NMR (CDCl3, 75 MHz): δ 47.4, 56.3, 68.1, 95.3,
115.4, 118.2, 118.5, 119.4, 121.0, 124.3, 127.1, 127.3, 128.0, 128.8,
129.3, 130.1, 130.2 (br), 130.7, 130.9, 132.5, 145.8, 149.8, 153.2, 153.8.
APCI-MS m/z: 1225.8 (M). HRMS (MALDI) calcd for C54H42N2O10-
NaSBr4 (M + Na+): 1252.9150. Found: 1252.9275.
Preparation and Characterization of (S,S)-Bis-[2-(2′-hydroxy-
[1,1′]binaphthalenyl-2-yloxy)-ethyl]-amine, 1. Under nitrogen, to a
solution of 4 (0.914 g, 1.0 mmol) in DMF (30 mL) were added K2CO3
(0.420 g, 3.0 mmol) and 4-methylbenzenethiol (0.150 g, 1.2 mmol)
sequentially. The mixture was stirred at room temperature for 4 h and
monitored by TLC. Water (30 mL) was then added to quench the
reaction, and the aqueous layer was extracted with ethyl acetate (3 ×
20 mL). The combined organic solution was washed sequentially with
1 N NaOH, water, and then dried over Na2SO4. After the solvent was
removed, the residue was purified by flash chromatography on silica
gel eluted with 20-40% ethyl acetate in hexane to give a nitrogen
deprotected product in 94% yield. This compound (1.5 g, 2.0 mmol)
was dissolved in ethanol (20 mL) and combined with 4 N HCI (10
mL). After degassed by bubbling nitrogen through, the acidic mixture
was heated at 40-50 °C for 4 h. The mixture was then neutralized at
room temperature with Na2CO3 and extracted with diethyl ether (3 ×
30 mL). The combined organic layer was washed with brine and dried
over Na2SO4. After removal of the solvent by evaporation, the residue
was passed through a short silica gel column eluted with 10% methanol
in diethyl ether to afford 1 as a white powder in 78% yield. mp 120-
Preparation and Characterization of (R,R)-N,N-Bis-[2-(2′-meth-
oxymethoxy-6,6′-diphenyi-[1,1′]binaphthalenyl-2-yloxy)-ethyl]-4-ni-
tro-benzenesulfonamide, 7. Under nitrogen, to a 50 mL Schlenk flask
charged with 6 (615 mg, 0.5 mmol) were syringed phenylboronic acid
(377 mg, 3.0 mmol) and Pd(PPh3)4 (116 mg, 0.1 mmol) in aqueous
K2CO3 (2 M, 5 mL, degassed with nitrogen) and dry THF (10 mL).
The reaction mixture was degassed again by three freeze-pump-thaw
cycles and was then refluxed under nitrogen. After 2.5 days, the reaction
mixture was cooled to room temperature. After most of the solvent
was removed under vacuum, the mixture was diluted with CH2Cl2. The
organic layer was washed with 1 N HCl and brine and dried over Na2-
SO4. After removal of the solvent, the residue was purified by column
chromatography on silica gel eluted with 25% ethyl acetate in hexane
to give 7 as an orange solid in 80% yield (490 mg). mp 134-137 °C.
1
[R]D ) +18.7 (c ) 0.40, CH2Cl2). H NMR (CDCl3, 300 MHz): δ
1
123 °C. H NMR (CDCl3, 300 MHz): δ 2.33 (m, 4H), 3.87 (m, 4H),
2.47-2.56 (m, 2H), 2.75-2.83 (m, 2H), 3.11 (s, 6H), 3.51-3.57 (m,
2H), 3.61-3.68 (m, 2H), 4.94 (d, J ) 6.6 Hz, 2H), 5.02 (d, J ) 6.6
Hz, 2H), 7.05 (d, J ) 9.0 Hz, 2H), 7.11 (d, J ) 8.7 Hz, 2H), 7.24 (d,
J ) 8.7 Hz, 2H), 7.28-7.41 (m, 8H), 7.45-7.57 (m, 16H), 7.69 (dd,
J ) 1.2, 8.1 Hz, 4H), 7.85-7.95 (m, 6H), 8.03 (s, 4H). 13C NMR
(CDCl3, 75 MHz): δ 47.1, 56.3, 68.1, 95.5, 115.0, 118.1, 119.6, 121.5,
124.2, 125.8, 126.1, 126.3, 126.5, 127.3, 127.4, 127.5, 128.0, 129.1,
129.1, 129.8, 130.2, 130.3, 133.3, 133.3, 136.8, 137.2, 140.7, 141.1,
146.1, 149.7, 153.0, 153.7. APCI-MS m/z: 1218.1 (M). HRMS
(MALDI) calcd for C78H62N2O10NaS (M + Na+): 1241.4017. Found:
1241.4110.
4.4 (br, 3H), 6.98-7.44 (m, 16H), 7.78 (d, J ) 9.0 Hz, 2H), 7.82 (d,
J ) 9.0 Hz, 2H), 7.89 (d, J ) 9.0 Hz, 2H), 7.98 (d, J ) 9.0 Hz, 2H).
13C NMR (CDCl3, 75 MHz): δ 47.5, 67.6, 115.0, 117.0, 117.9, 119.3,
123.2, 124.1, 124.9, 125.2, 126.3, 126.9, 127.9, 128.0, 129.1, 129.3,
129.5, 130.2, 133.8, 151.7, 154.3. ESI-MS m/z: 642.5 (M + H+). [R]D
) +24.52 (c ) 0.75, CH2Cl2). CD (THF, 1.0 × 10-4 M) [θ]λ 6.2 ×
104 (241 nm), -4.3 × 104 (223 nm). Anal. Calcd for C44H35O4N: C,
82.34; H, 5.50; N, 2.18. Found: C, 82.32; H, 5.57; N, 2.10.
Preparation and Characterization of (R,R)-6,6′-Dibromo-2′-
methoxymethoxy-[1,1′]binaphthalenyl-2-ol, 5. Under nitrogen, a 250
mL flask equipped with an addition funnel was charged with (R)-6,6′-
dibromo-1,1′-bi-naphthol (4.44 g, 10.0 mmol), K2CO3 (6.90 g, 50.0
mmol), and acetone (50 mL). After the mixture was stirred at room
temperature for 5 min, a solution of chloromethyl methyl ether (0.91
mL, 12.0 mmol) in acetone (50 mL) was added dropwise via the
addition funnel. The mixture was stirred at room temperature for 5 h
and quenched with water. Most of the solvent was then removed under
vacuum, and the mixture was diluted with CH2Cl2. The organic layer
was further washed with water and brine and dried over Na2SO4. After
removal of the solvent, the residue was purified by column chroma-
tography on silica gel eluted with 15-20% ethyl acetate in hexane to
give 5 as a pale yellow solid in 75% yield (3.66 g). mp 60-63 °C.
Preparation and Characterization of (R,R)-N,N-Bis-[2-(2′-hy-
droxy-6,6′- diphenyl-[1,1′]binaphthalenyl-2-yloxy)-ethyl]-amine, the
G0 Sensor 8. A procedure similar to the preparation of 1 was applied
to make 8 from the deprotection of 7. After general workup, the crude
product was purified by column chromatography on silica gel eluted
with 2-5% MeOH in ethyl acetate to give 8 as a white solid in 70%
yield. mp 164-167 °C. [R]D ) -251.2 (c ) 0.44, CH2Cl2). 1H NMR
(CDCl3, 300 MHz): δ 2.39-2.44 (m, 2H), 2.58-2.64 (m, 2H), 3.84-
3.89 (m, 2H), 3.95-4.29 (m, 2H), 7.16 (d, J ) 8.7 Hz, 2H), 7.26-
7.42 (m, 16H), 7.48-7.53 (m, 4H), 7.41-7.60 (m, 6H), 7.70-7.73
(m, 4H), 7.91 (d, J ) 8.7 Hz, 2H), 8.04 (d, J ) 9.0 Hz, 2H), 8.07 (d,
J ) 1.8 Hz, 2H), 8.12 (d, J ) 1.5 Hz, 2H). 13C NMR (CDCl3, 75
MHz): δ 48.0, 67.6, 115.5, 117.5, 118.0, 120.3, 125.8, 126.0, 126.2,
126.4, 127.0, 127.2, 127.3, 127.5, 128.6, 129.0, 129.1, 129.7, 130.0,
130.9, 133.3, 136.2, 137.1, 141.1, 152.2, 154.5. APCI-MS m/z: 946.5
(M + 1, 100). HRMS (MALDI) calcd for C68H52NO4 (M + H+):
946.3891. Found: 946.3871.
1
[R]D ) -90.0 (c ) 0.62, CH2Cl2). H NMR (CDCl3, 300 MHz): δ
3.19 (s, 3H), 4.93 (s, br, 1H), 5.08 (d, J ) 6.9 Hz, 1H), 5.11 (d, J )
6.9 Hz, 1H), 6.89 (d, J ) 9.0 Hz, 1H), 7.01 (d, J ) 9.0 Hz, 1H), 7.29
(dd, J ) 2.4, 9.0 Hz, 1H), 7.34 (d, J ) 3.0 Hz, 1H), 7.37 (d, J ) 2.7
Hz, 1H), 7.62 (d, J ) 9.3 Hz, 1H), 7.82 (d, J ) 9.0 Hz, 1H), 7.94 (d,
J ) 9.0 Hz, 1H), 8.01 (d, J ) 2.1 Hz, 1H), 8.07 (d, J ) 2.1 Hz, 1H).
13C NMR (CDCl3, 75 MHz): δ 56.5, 95.1, 115.0, 117.4, 118.2, 119.0,
126.6, 126.9, 129.3, 130.0, 130.3, 130.4 (br), 130.9, 131.4, 132.4, 132.5,
151.8, 154.0. APCI-MS m/z: 457.0 (M - OCH3 + 2, 100). HRMS
(DEI) calcd for C22H16O3Br2: 485.9466. Found: 485.9483.
Preparation and Characterization of (R)-2,2′-Bis-methoxymethoxy-
6,6′-bis- [1,1′;3′,1′′]terphenyl-5′-yl-[1,1′]binaphthalenyl, 11. The reac-
tion was carried out by using 10 (935 mg, 1.8 mmol), 3,5-
diphenylphenylboronic acid (9) (1.900 g, 4.0 mmol), Pd(PPh3)4 (203
mg, 0.2 mmol) in dry THF (16 mL), and aqueous K2CO3 (2 M, 12
mL). The reaction mixture was heated at reflux under nitrogen for 3
days. After general workup, the crude product was passed through a
silica gel column using 25% ethyl acetate in hexane to give 11 as a
white solid in 92% yield (1.34 g). mp 141-144 °C. [R]D ) -118.1 (c
Preparation and Characterization of (R,R)-N,N-Bis-[2-(6,6′-
dibromo-2′- methoxymethoxy-[1,1′]binaphthalenyl-2-yloxy)-ethyl]-
4-nitro-benzenesulfonamide, 6. A procedure similar to the preparation
of 4 was applied to make 6 from the reaction of 5 with 3. After general
9
J. AM. CHEM. SOC. VOL. 124, NO. 47, 2002 14245