J.You, H-.M.Gau et al.
[D6]DMSO): d=5.41 (s, 2H), 6.87 (d, J=8.4 Hz, 1H), 6.90 (d, J=8.4 Hz,
1H), 6.97 (s, 1H), 7.15–7.20 (m, 2H), 7.23–7.27 (m, 2H), 7.30 (s, 1H),
7.36 (d, J=9.0 Hz, 1H), 7.55 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.80 (s,
1H), 7.88 (d, J=7.8 Hz, 1H), 7.91 (d, J=9.0 Hz, 1H), 9.11 ppm (brs,
2H); 13C NMR (150 MHz, [D6]DMSO): d=46.1, 113.3, 116.2, 118.8,
119.9, 122.4, 123.0, 124.0, 124.3, 126.0, 126.1, 127.3, 127.7, 127.9, 128.0,
128.2, 128.3, 129.6, 133.6, 134.3, 137.7, 150.7, 154.0 ppm; HRMS (FAB):
calcd for C24H19N2O2 [M++H]: 367.1447, found: 367.1445; elemental
analysis calcd (%) for C24H18N2O2: C 78.67, H 4.95, N 7.65; found: C
78.48, H 5.04, N 7.51.
ether/acetone (1:6) to afford (R)-3 (367 mg, 95%) as a white solid.mp..
55.5–57.08C; [a]2D0 =+106.4 (c=0.5 in CH2Cl2); 1H NMR (400 MHz,
CDCl3): d=5.11 (brs, 1H), 5.43 (brs, 1H), 6.39 (t, J=2.2 Hz, 2H), 7.14–
7.19 (m, 4H), 7.28–7.33 (m, 2H), 7.35–7.43 (m, 3H), 7.87–7.89 (m, 2H),
7.95 (s, 1H), 7.98 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=110.1,
110.9, 113.6, 117.8, 122.2, 124.1, 124.3, 125.1, 127.5, 127.6, 128.2, 128.5,
129.1, 129.5, 129.9, 131.6, 131.8, 133.2, 146.9, 152.6 ppm; HRMS (ESI):
calcd for C24H18NO2 [M++H]: 352.1338, found: 352.1337; elemental anal-
ysis calcd (%) for C24H17NO2: C 82.03, H 4.88, N 3.99; found: C 81.68, H
4.81, N 3.60.
(R)-3-Iodo-2,2’-bis(methoxymethyl)-1,1’-bi-2-naphthol[( R)-14]: A flame-
dried three-necked flask was charged with (R)-13 (7.50 g, 20 mmol) and
dry THF (300 mL) under N2. nBuLi (1.5m in diethyl ether, 16 mL,
24 mmol) was slowly added over a period of 1 h at À788C and the mix-
ture was stirred for 5 h at the same temperature.A solution of iodine
(6.09 g, 24 mmol) in dry THF (30 mL) was then added dropwise to the
chilled solution over a period of 1 h.After being stirred for 1 h at À788C,
the solution was allowed to warm to room temperature and stirring was
continued for 12 h.Aqueous Na 2SO3 solution (5%, 100 mL) was then
slowly added at 08C and the resulting mixture was stirred for 2 h.The
mixture was subsequently concentrated under reduced pressure, and the
residue was partitioned between ethyl acetate (250 mL) and H2O
(100 mL), stirring vigorously until the solid had dissolved.The organic
layer was separated, and the aqueous layer was extracted with ethyl ace-
tate (2100 mL).The combined organic layers were washed with brine
(150 mL) and dried over anhydrous Na2SO4.After removal of the sol-
vent, the residue was purified by recrystallization from hexane/ethyl ace-
tate (8:1) to give (R)-14 (8.21 g, 82%) as white crystals. m.p. 124.0–
(R)-3-(1H-Pyrazol-1-yl)-2’-methoxymethyl-1,1’-bi-2-naphthol[( R)-17]:[10]
A
flame-dried three-necked flask was charged with CuI (570.0 mg,
3.0 mmol), N,N-dimethylglycine (619.0 mg, 6.0 mmol), K2CO3 (16.5 g,
120 mmol), (R)-14 (10.0 g, 20 mmol), pyrazole (2.8 g, 41 mmol), and
DMSO (150 mL) at room temperature under nitrogen.After being
heated at 1108C for 60 h, the mixture was concentrated under reduced
pressure.The resulting residue was then partitioned between water
(100 mL) and CH2Cl2 (200 mL).The organic layer was separated, and the
aqueous layer was extracted with CH2Cl2 (330 mL).The combined or-
ganic layers were dried over Na2SO4 and concentrated in vacuo.The
crude product was purified by chromatography on a silica gel column
eluting with petroleum ether/acetone (6:1 to 3:1).( R)-17 was obtained in
44% yield (3.51 g) as
a
white solid. m.p. 188.0–189.08C; 1H NMR
(400 MHz, CDCl3): d=3.19 (s, 3H), 5.01, 5.14 (AB system, J=6.8 Hz,
2H), 6.56, 6.57 (AB system, J=2.0 Hz, 1H), 7.13–7.37 (m, 6H), 7.59 (d,
J=9.2 Hz, 1H), 7.73 (d, J=1.6 Hz, 1H), 7.83–7.99 (m, 4H), 8.24 (d, J=
2.0 Hz, 1H), 11.36 ppm (brs, 1H); 13C NMR (75 MHz, CDCl3): d=55.9,
95.3, 107.4, 116.4, 117.4, 119.9, 120.6, 124.1, 124.2, 125.1, 125.3, 126.4,
126.5, 127.6, 127.7, 128.0, 128.1, 129.7, 130.1, 132.9, 133.8, 139.6, 145.9,
152.8 ppm; MS (ESI): m/z: 397 [M++H].
1
125.08C; H NMR (400 MHz, CDCl3): d=2.71 (s, 3H), 3.19 (s, 3H), 4.68,
4.72 (AB system, J=5.2 Hz, 2H), 5.03, 5.12 (AB system, J=6.8 Hz, 2H),
7.14–7.19 (m, 2H), 7.24–7.31 (m, 2H), 7.34–7.42 (m, 2H), 7.57 (d, J=
9.2 Hz, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.95 (d, J=
8.8 Hz, 1H), 8.51 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=55.9,
56.7, 92.9, 94.8, 99.1, 116.2, 120.1, 124.1, 125.4, 125.6, 126.1, 126.3, 126.7,
126.8, 126.9, 127.8, 129.5, 130.1, 132.4, 133.8, 139.8, 151.6, 152.9 ppm; MS
(ESI): m/z: 523 [M++Na].
(R)-3-(1H-Pyrazol-1-yl)-1,1’-bi-2-naphthol[( R)-4]: Aqueous HCl (6m,
22.0 mL) was added to a solution of (R)-17 (3.50 g, 8.8 mmol) in THF
(150 mL) and methanol (50 mL).The resulting solution was refluxed for
12 h until the conversion of (R)-17 was complete.The solution was then
cooled to room temperature and neutralized by the addition of saturated
aqueous NaHCO3 solution.The resulting mixture was stirred for a fur-
ther 12 h, then concentrated under reduced pressure, and the residue was
extracted with ethyl acetate (360 mL).The combined organic layers
were dried over anhydrous Na2SO4, filtered, and concentrated to give the
crude product, which was further purified by flash chromatography on
silica gel eluting with petroleum ether/ethyl acetate (1:5 to 1:2) to afford
(R)-4 (3.05 g, 98%) as white crystals. m.p. 188.0–189.08C; [a]2D8 =+82.8
(c=0.5 in CH2Cl2); 1H NMR (400 MHz, CDCl3): d=5.08 (brs, 1H), 6.60
(t, J=2.0 Hz, 1H), 7.15–7.40 (m, 7H), 7.76 (d, J=1.6 Hz, 1H), 7.86 (d,
J=8.0 Hz, 2H), 7.92 (d, J=8.8 Hz, 1H), 8.04 (s, 1H), 8.27 (d, J=2.8 Hz,
1H), 11.63 ppm (brs, 1H); 13C NMR (100 MHz, CDCl3): d=107.6, 114.4,
116.1, 117.3, 117.7, 123.3, 124.6, 124.7, 124.8, 126.6, 127.3, 127.8, 127.9,
128.0, 128.2, 129.2, 130.1, 132.6, 133.5, 139.7, 147.0, 151.4 ppm; HRMS
(ESI): calcd for C23H17N2O2 [M++H]: 353.1290, found: 353.1291; elemen-
tal analysis calcd (%) for C23H16N2O2: C 78.39, H 4.58, N 7.95; found: C
78.44, H 4.49, N 7.77.
(R)-3-(1H-Pyrrol-1-yl)-2’-methoxymethyl-1,1’-bi-2-naphthol[( R)-16]:[9c]
A flame-dried Schlenk test tube fitted with a magnetic stirring bar was
charged with CuI (76.0 mg, 0.4 mmol), pyrrolidinylmethylimidazole 15
(204.0 mg, 0.8 mmol), Cs2CO3 (2.6 g, 8 mmol), pyrrole (0.55 mL, 8 mmol),
(R)-14 (2.0 g, 4 mmol), and DMF (10 mL) under N2.A rubber septum
was replaced with a glass stopper, and the system was evacuated twice
and back-filled with N2.The reaction mixture was stirred for 30 min at
room temperature, and then heated to 1108C for 48 h.It was then cooled
to ambient temperature, diluted with CH2Cl2 (15 mL), and filtered
through a plug of silica gel.The silica was washed with CH 2Cl2 (50 mL)
and the combined filtrate and washing was concentrated.The resulting
residue was purified by column chromatography on silica gel, eluting
with petroleum ether/acetone (8:1) to afford the desired product (R)-16
(506 mg, 32%) as
a
pale-yellow solid. m.p. 49.0–50.58C; 1H NMR
(400 MHz, CDCl3): d=3.21 (s, 3H), 5.09, 5.12 (AB system, J=6.8 Hz,
2H), 5.23 (brs, 1H), 6.39 (t, J=2.2 Hz, 2H), 7.07–7.09 (m, 1H), 7.20–7.26
(m, 4H), 7.29–7.43 (m, 3H), 7.61 (d, J=9.2 Hz, 1H), 7.85 (d, J=8.4 Hz,
1H), 7.90 (s, 1H), 7.91 (d, J=8.0 Hz, 1H), 8.04 ppm (d, J=8.8 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=56.1, 95.0, 109.6, 116.9, 117.3, 117.7,
122.3, 123.7, 124.3, 124.8, 124.9, 125.0, 126.5, 127.4, 127.8, 128.2, 128.7,
129.7, 130.2, 131.1, 132.3, 133.8, 145.5, 153.6 ppm; MS (ESI): m/z: 396
[M++H].
(R)-3-(1H-1,2,4-Triazol-1-yl)-2’-methoxymethyl-1,1’-bi-2-naphthol[( R)-
18]:[10] A flame-dried three-necked flask was charged with CuI (454.0 mg,
2.4 mmol), N,N-dimethylglycine (495.0 mg, 4.8 mmol), K2CO3 (13.2 g,
96 mmol), (R)-14 (8.0 g, 16 mmol), triazole (2.3 g, 33 mmol), and DMSO
(150 mL) at room temperature under nitrogen.After being heated at
1108C for 60 h, the mixture was concentrated under reduced pressure.
The resulting residue was then partitioned between water (100 mL) and
ethyl acetate/THF (1:3, 200 mL).The organic layer was separated, and
the aqueous layer was extracted with ethyl acetate/THF (1:3, 330 mL).
The combined organic layers were dried over Na2SO4 and concentrated
in vacuo.The residue was loaded onto a silica gel column and eluted
with petroleum ether/acetone (3:1 to 1:1) to afford the corresponding
coupling product (R)-18 (3.88 g, 61%) as a white solid. m.p. 193.5–
195.08C; 1H NMR (400 MHz, CDCl3): d=3.19 (s, 3H), 5.07, 5.12 (AB
system, J=6.8 Hz, 2H), 7.13 (d, J=8.4 Hz, 1H), 7.19 (d, J=8.8 Hz, 1H),
7.27–7.31 (m, 2H), 7.36–7.41 (m, 2H), 7.60 (d, J=9.2 Hz, 1H), 7.91 (t,
J=6.8 Hz, 2H), 8.00 (d, J=9.2 Hz, 1H), 8.13 (s, 1H), 8.22 (brs, 1H), 8.25
(R)-3-(1H-Pyrrol-1-yl)-1,1’-bi-2-naphthol[( R)-3]: Aqueous HCl (6m,
1.1 mL) was added to a solution of (R)-16 (435 mg, 1.1 mmol) in THF
(15 mL) and methanol (3 mL).The resulting solution was refluxed for
12 h until the conversion of (R)-16 was complete.The solution was then
cooled to room temperature and neutralized by the addition of saturated
aqueous NaHCO3 solution.The resulting mixture was concentrated
under reduced pressure, and the residue was extracted with ethyl acetate
(320 mL).The combined organic layers were dried over anhydrous
Na2SO4, filtered, and concentrated to give the crude product, which was
purified by flash chromatography on silica gel eluting with petroleum
2230
ꢀ 2008 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2223 – 2231