Asymmetric Halogen/Metal-Exchange Reaction
FULL PAPER
EtOAc 98:2) provided the title compound (fractions 31–45, 1.55 g, 93%)
as a colorless solid. Melting range 68–878C; [a]2D0 = +96.2 (c=1.16 in
CHCl3); >99 ee;[58] 1H NMR (400 MHz, CDCl3/TMS): d=AB signal
(dA =4.16, dB =4.30, JAB =10.1 Hz, OCH2), 5.39 (s, OH), 6.36–6.39 (m, 2ꢀ
ArH), 6.97 (tt, 3J=8.2, 4J=1.7 Hz, 2ꢀp-C6H4-H), 7.05 (tt, 3J=6.3, 4J=
1.3 Hz, p-C6H4-H), 7.19 (ddd, 3J=8.5, 4J=4J=0.7 Hz, ArH), 7.25 (ddd,
3J=3J=8.5 Hz, 4J=1.4, ArH), 7.30–7.35 (m, 2ꢀArH), 7.36–7.43 (m, 3ꢀ
ArH), 7.43–7.49 (m, 5ꢀArH), 7.64–7.67 (m, 2ꢀArH), 7.75–7.78 (m, 2ꢀ
ArH), 7.89 (d, 3J=8.1 Hz, ArH), 7.96 (d, 3J=8.2 Hz, ArH), 7.97 (s, HC=
CPh), 8.06 ppm (s, HC=CPh); 13C NMR (100 MHz, CDCl3): d=75.16
(OCH2), 116.47, 123.80, 124.15, 125.07, 125.81, 125.83, 126.74, 126.99,
127.62, 127.66, 127.68, 127.95, 128.19, 128.26, 128.37, 128.40, 128.52,
129.18, 129.73, 130.20, 130.86, 131.38, 131.52, 133.50, 133.68, 136.00,
136.58, 138.04, 138.40, 149.09 (COMe), 153.80 ppm (COH); IR (film): n˜ =
3530, 3055, 2985, 1740, 1715, 1620, 1600, 1495, 1455, 1420, 1375, 1360,
1305, 1245, 1220, 1185, 1150, 1130, 1075, 1050, 1005, 895, 850, 785, 750,
130.48, 133.42, 133.53, 136.98, 140.50, 140.68, 143.33, 143.56, 151.90
(OCAr), 155.54 ppm (OCAr); IR (film): n˜ =3295, 3060, 2940, 2825, 1625,
1600, 1495, 1450, 1425, 1400, 1335, 1310, 1280, 1220, 1150, 1105, 1060,
1035, 1000, 945, 910, 890, 850, 815, 750, 700 cmꢀ1; HRMS (EI, 70 eV):
m/z: calcd for C48H36O3 [MꢀMeOH+]: 660.266445; found: 660.266802
(+0.5 ppm).
(S)-1-[2-(Benzyloxy)-3-(methoxydi-
phenylmethyl)naphthalen-1-yl]-3-(me-
thoxydiphenylmethyl)-2-naphthol
(19c): Benzyl alcohol (0.480 mL,
502 mg, 4.64 mmol, 1.55 equiv) and
DIAD (0.650 mL, 663 mg, 3.28 mmol,
1.09 equiv) were added to a solution
of diol 19a (2.04 g, 3.00 mmol) and
PPh3 (884 mg, 3.37 mmol, 1.12 equiv)
in THF (18 mL) and the mixture was
stirred at RT for 27 h. KOH (1.79 g,
31.9 mmol, 10.6 equiv) in H2O (1 mL)
730, 700 cmꢀ1
528.208930; found: 528.208202 (ꢀ1.4 ppm).
(S)-3,3’-Bis(methoxydiphenylmethyl)-
;
HRMS (EI, 70 eV): m/z: calcd for C39H28O2 [M+]:
was added and the mixture was stirred at RT for further 19 h. The reac-
tion was quenched by the addition of satd. aq. KH2PO4 (26 mL). The
phases were separated and the aqueous phase was extracted with CH2Cl2
(3ꢀ15 mL). The combined organic phases were dried over MgSO4. Re-
moval of the solvent under reduced pressure and flash chromatography
(7ꢀ20 cm, 100 mL, cyclohexane/EtOAc 98:2) provided the title com-
pound (fractions 37–58, 1.78 g, 77%) as a colorless solid. M.p. range 84–
1178C; [a]2D0 =ꢀ110 (c=3.01 in CHCl3); >99 ee;[58] 1H NMR (400 MHz,
CDCl3/TMS): d=3.12 (s, CH3), 3.13 (s, CH3), AB signal (dA =3.72, dB =
4.09, JAB =11.4 Hz, CH2), 5.89 (dd, 3J=7.0, 4J=0.9 Hz, 2ꢀArH), 6.78–
6.83 (m, 3ꢀArH), 6.94 (dddd, 3J=3J=7.3, 4J=4J=1.1 Hz, p-C6H4-H),
7.04–7.11 (m, 2ꢀArH), 7.13–7.25 (m, 14ꢀArH), 7.27–7.37 (m, 4ꢀArH),
7.39–7.42 (m, 2ꢀArH), 7.51 (m, 2ꢀArH), 7.54–7.59 (m, 4ꢀArH), 7.91
(dd, 3J=8.1, 4J=0.5 Hz, ArH), 8.45 (s, HC=C-CPh2OMe)*, 8.72 ppm (s,
OH)*; * assignment interchangeable; 13C NMR (100 MHz, CDCl3): d=
52.17 (CH3), 52.91 (CH3), 72.97 (CH2), 86.27 (Ar3C), 90.29 (Ar3C),
118.36, 123.35, 124.68, 124.92, 124.97, 125.13, 126.15, 126.30, 126.46,
126.54, 126.71, 126.80, 127.12, 127.40, 127.62, 127.70, 127.79, 127.94,
128.06, 128.19, 128.22, 128.78, 128.97, 129.09, 129.16, 129.92, 130.27,
130.49, 133.39, 133.60, 137.74, 137.92, 140.48, 141.19, 142.65, 142.70,
151.73 (OCAr), 153.76 ppm (OCAr); IR (film): n˜ =3295, 3060, 3025, 2940,
2825, 2250, 1955, 1710, 1625, 1600, 1495, 1450, 1425, 1365, 1335, 1310,
1280, 1255, 1220, 1195, 1150, 1105, 1060, 1035, 1000, 945, 930, 905, 890,
850, 815, 750, 720, 700 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C54H40O3
[MꢀMeOH+]: 736.297745; found: 736.297300 (ꢀ0.6 ppm).
1,1’-bi-2-naphthol (19a):[30] A solution
of conc. H2SO4 (0.500 mL, 0.883 g,
9.01 mmol, 0.495 equiv) in MeOH
(180 mL) was added to a solution of
diol 24 (13.4 g, 18.2 mmol) and tri-
methyl orthoformate (18.0 mL, 17.5 g,
165 mmol, 9.04 equiv) in CH2Cl2
(180 mL) and the mixture was stirred
at RT. After 1.5 h, the reaction was
quenched by the addition of NEt3
(6.00 mL,
2.38 equiv). Removal of the solvent under reduced pressure and flash
chromatography (7ꢀ20 cm, 100 mL, cyclohexane/EtOAc 90:10 1%
4.38 g,
43.3 mmol,
+
NEt3, from fraction 41 80:20 + 1% NEt3, from fraction 61 70:30 + 1%
NEt3) provided the title compound (fractions 14–78, 11.6 g, 94%) as a
colorless solid. 1H NMR (300 MHz, CDCl3/TMS): d=3.29 (s, 2ꢀCH3),
3
3
4
6.98 (d, J=8.2 Hz, 2ꢀArH), 7.11 (ddd, J=3J=8.4, J=1.2 Hz, 2ꢀArH),
7.20 (ddd, 3J=3J=7.9, 4J=1.0 Hz, 2ꢀArH), 7.28–7.40 (m, 12ꢀArH),
7.45–7.51 (m, 8ꢀArH), 7.64 (s, 2ꢀHC=C-CPh2OMe), 7.65 (d, J=6.2 Hz,
3
2ꢀArH), 8.44 ppm (s, 2ꢀOH).
(S)-1-[2-Methoxy-3-(methoxydiphenyl-
methyl)naphthalen-1-yl]-3-(methoxydi-
phenylmethyl)-2-naphthol
(19b):
MeOH (0.200 mL, 158 mg, 4.94 mmol,
1.53 equiv) and DIAD (0.700 mL,
714 mg, 3.53 mmol, 1.09 equiv) were
added to a solution of diol 19a (2.19 g,
(S)-1-[2-(Dimethylamino)naphthalen-
1-yl]-2-naphthol (20a):[31]
A solution
of amine 26 (1.28 g, 3.87 mmol) in
HCO2H (14 mL) and an aq. formalde-
hyde solution (37%, 14 mL) were
heated under reflux for 9 h. After
cooling, satd. aq. NaHCO3 (200 mL)
was added. The phases were separated
3.23 mmol)
3.59 mmol,
and
1.11 equiv)
PPh3
(941 mg,
in THF
(20 mL) and the mixture was stirred at
RT for 27 h. KOH (1.78 g, 31.7 mmol,
9.82 equiv) in H2O (1 mL) was added
and the mixture stirred at RT for further 19 h. The reaction was
quenched by the addition of satd. aq. KH2PO4 (24 mL). The phases were
separated and the aqueous phase was extracted with CH2Cl2 (3ꢀ15 mL).
The combined organic phases were dried over MgSO4. Removal of the
solvent under reduced pressure and flash chromatography (7ꢀ20 cm,
100 mL, cyclohexane/EtOAc 98:2) provided the title compound (fractions
35–53, 1.93 g, 86%) as a colorless solid. M.p. 170–1738C (decomp.);
[a]2D0 =ꢀ163 (c=2.66 in CHCl3); >99 ee;[58] 1H NMR (400 MHz, CDCl3/
TMS): d=2.33–2.33 (m, possibly interpretable as s, CH3), 3.17 (s, CH3),
3.26 (s, CH3), 6.87 (d, 3J=8.5 Hz, ArH), 7.07–7.40 (m, 19ꢀArH), 7.47–
7.49 (m, possibly interpretable as dd, 3J=8.3, 4J=1.8 Hz, 2ꢀArH), 7.52–
7.54 (m, possibly interpretable as dd, 3J=8.6, 4J=1.3 Hz, 2ꢀArH), 7.61–
and the aqueous phase was extracted
with Et2O (3ꢀ50 mL). The combined
organic phases were dried over MgSO4. Removal of the solvent under re-
duced pressure and flash chromatography (6ꢀ5 cm, 100 mL, cyclohex-
ane/EtOAc 90:10 + 1% NEt3) provided the title compound (fractions 5–
19, 1.03 g, 85%) as a colorless solid. 1H NMR (300 MHz, CDCl3/TMS):
d=2.64 (s, 2ꢀCH3), 7.02–7.22 (m, 4ꢀArH), 7.31 (m, possibly interpreta-
ble as dd, 3J=3J=7.4 Hz, 2ꢀArH), 7.37 (d, 3J=8.9 Hz, ArH), 7.50 (d,
3J=8.9 Hz, ArH), 7.83 (d, 3J=8.5 Hz, ArH), 7.85 (d, 3J=8.4 Hz, ArH),
3
3
7.88 (d, J=8.8 Hz, ArH), 7.95 ppm (d, J=9.1 Hz, ArH).
(S)-1-[2-(N,N-Dibenzylamino)naph-
thalen-1-yl]-2-naphthol (20b): Conc.
aqueous HCl (0.5 mL) was added to a
solution of methoxymethyl ether 27
(94.6 mg, 0.186 mmol) in MeOH
(3 mL) and the mixture was heated
under reflux for 7 h. After cooling,
3
7.66 (m, 4ꢀArH), 7.87 (d, J=8.1 Hz, ArH), 8.35 (s, HC=C-CPh2OMe)*,
8.82 ppm (s, OH)*; * assignment interchangeable; 13C NMR (100 MHz,
CDCl3): d=52.53 (AlkOCH3), 53.05 (AlkOCH3), 59.22 (ArOCH3), 86.29
(Ar3C), 90.59 (Ar3C), 118.60, 123.48, 124.09, 124.56, 124.69, 126.22,
126.51, 126.62, 126.79, 127.60, 127.71, 127.76, 127.93, 128.01, 128.12,
128.27, 128.35, 128.39, 128.61, 128.71, 128.90, 129.19, 129.93, 130.17,
Chem. Eur. J. 2009, 15, 6688 – 6703
ꢄ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6699