Williamson Reaction
J . Org. Chem., Vol. 61, No. 8, 1996 2697
24 H; 5.14 (d, 9.0 Hz) and 4.35 (d, 9.0 Hz), 4 H. 13C NMR
both optically pure enantiomers (-)-(S)-2 and (+)-(R)-2
in one step from 3a or 3b, with the need of only one
enantiomer of the resolving agent (-)-(S)-1 or (+)-(R)-1;
(iii) the recovery of the resolving agent; (iv) the op-
portunity of alternate resolution of both the diol 1 and
the dibromide 2; (v) the direct availability of both
enantiomers of the dichloride 5 from the racemic dibro-
mide 2. This new method, which has only limited
interest concerning the diol 1, advantageously competes
for the number of steps and the overall yield, with the
previously described resolution procedures of the dibro-
mide 2.
(CDCl3) δ 152.27-115.15; 70.65. [R]25 ) +707.6°, [R]25
)
578
546
+842.3°, [R]25436 ) +1912.2°, [R]25365 ) +5706.3° (c 0.5; CHCl3).
Anal. Calcd for C42H28O2: C, 89.33; H, 5.00; O, 5.67. Found:
C, 88.61; H, 5.05; O, 5.25. EI+ MS m/ z (relative intensity):
564 (M+) (100); 279 (43); 266 (43), and pure (+)-(R,R,R,S)-4:
0.173 g (6.1%), white solid, mp ) 220-225 °C. Rf ) 0.54 (I),
0.16 (III). 1H NMR (CDCl3) δ 8.2-6.3 (m), 48 H; 4.76 (d, 14.0
Hz) and 4.71 (d, 14.0 Hz), 4 H; 4.40 (d, 15.0 Hz) and 4.16 (d,
15.0 Hz), 4 H. 13C NMR (CDCl3) δ 154.95-113.32; 69.74;
67.71. [R]25 ) +37.7°, [R]25 ) +48.5°, [R]25 ) +144.4°
578
546
436
(c 0.5; CHCl3). Anal. Calcd for C84H56O4: C, 89.33; H, 5.00;
O, 5.67. Found: C, 88.49; H, 5.13; O, 5.79. FAB+ MS (mNBA
matrix/CH2Cl2) m/ z (relative intensity): 1128 (M+) (4.7); 843
(10.3); 564 (13.8); 279 (100).
In a duplicate experiment, reaction of (+)-(R)-1 prepared
Exp er im en ta l Section
by resolution,2e {[R]25
) +49.5° (c 1; THF) (2.964 g, 10.3
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1,1′-Binaphthalene-2,2′-diols (R,S)-1 and (+)-(R)-1 were
purchased from Aldrich. Racemic 2,2′-bis(bromomethyl)-1,1′-
binaphthyl [(R,S)-2] was prepared as previously described.12
Optical rotations were measured with an accuracy of 0.3%, in
a 1 dm thermostated cell. Analytical thin layer chromatog-
raphy (TLC) and preparative column chromatography were
performed on Kieselgel F 254 and on Kieselgel 60 (0.040-0.063
mm) (Merck), respectively, with the following eluent systems:
75% petroleum ether (40-60 °C)-25% ethyl acetate (I), 90%
petroleum ether-5% ethyl acetate-5 % toluene (II), 50%
petroleum ether-50% toluene (III).
mmol)}, (R,S)-2 (4.550 g, 10.3 mmol), and Cs2CO3 (10.5 g) in
refluxing acetone (1 l) for 16 h, followed by the same treatment
as above, gave (-)-(R,S)-3a {2.393 g (82.2%)17 after two
crystallizations, [R]25 ) -206.2° (c 0.5; CHCl3)}, (+)-(R,R)-
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3b {2.378 g (81.7%),17 [R]25 ) +858.0° (c 0.5; CHCl3)}, and
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(+)-(R,R,R,S)-4 {0.471 g (8.1%), [R]25
CHCl3)}.
) +48.5° (c 0.5;
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In the same manner, racemic (R,S)-1 (0.143 g, 0.5 mmol)
was reacted with a sample of optically pure (+)-(R)-2 (0.220
g, 0.5 mmol) and Cs2CO3 (1.6 g) in refluxing acetone (100 mL)
for 15 h. After workup, two consecutive crystallizations from
benzene as above yielded (+)-(S,R)-3a {0.139 g (98.9%),17
P r ep a r a tion of th e Cyclic Dieth er s (-)-(R,S)-3a a n d
[R]25 ) +218.7° (c 0.5; CHCl3)}. Flash-chromatography of
(+)-(R,R)-3b a n d of th e Cyclic Tetr a eth er (+)-(R,R,R,S)-
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4. A mixture of optically pure (+)-(R)-1 {[R]25 ) +50.1° (c
the mother liquor from the first crop on a 1.5 × 41 cm column
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1; THF)2b (0.715 g, 2.5 mmol)}, (R,S)-2 (1.100 g, 2.5 mmol),
and K2CO3 (3.5 g) in acetone (500 mL) was stirred and refluxed
under argon for 24 h. After evaporation of acetone in vacuo,
the residue was solubilized in water (500 mL)/CH2Cl2 (500
mL). The decanted organic phase was extracted with two
portions of 100 mL of aqueous 10% NaOH, 200 mL of aqueous
2N HCl, and 400 mL of H2O, dried over MgSO4, filtered, and
evaporated in vacuo. The crude product was dissolved in CH2-
Cl2 (50 mL), and benzene (50 mL) was added (caution: all
operations involving benzene were conducted in a well venti-
lated hood). The resulting solution was heated at 80 °C and
concentrated to ca. 10 mL. Crystallization occurred during
this process. The mixture was left in a refrigerator overnight,
and the crystals were filtered, washed with cold benzene, and
air-dried to give (-)-(R,S)-3a as white shiny crystals: 0.586 g
of silica gel with eluent (III) yielded pure (+)-(R,R)-3b {0.140
g (99.3%),17 [R]25 ) +790.3° (c 0.5; CHCl3)}.
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Clea va ge of th e Cyclic P olyeth er s 3a , 3b, a n d 4 by
BBr 3 or BCl3. The diether (-)-(R,S)-3a (0.564 g, 1 mmol)
obtained from (+)-(R)-1 and (R,S)-2 was dissolved in CH2Cl2
(50 mL). The solution was cooled to 0 °C, and a solution of
BBr3 (1 M) in CH2Cl2 (10 mL) was added by syringe under an
argon stream. The resulting solution was stirred under argon
atmosphere at 0 °C to room temperature for 1 h and then
quenched with aqueous 10% NaOH. The separated organic
layer was extracted with aqueous 10% NaOH, washed with
water, dried over MgSO4, filtered, and evaporated in vacuo.
The obtained extract (0.406 g) was chromatographed on a 2.3
× 62 cm column of silica gel with CH2Cl2 as eluent, to give
0.324 g (73.6%) of chromatographically pure (-)-(S)-2 [Rf )
0.73 (I), 0.83 (CH2Cl2)] and 0.048 g of a fraction presenting a
single spot [Rf ) 0.43 (I), 0.72 (CH2Cl2)] but corresponding to
a mixture of several compounds resulting from C-alkylation
of binaphthol. The sample of pure dibromide was dissolved
in boiling methyl ethyl ketone and the solution concentrated
to ca. 1.5 mL. Crystallization occurred from the boiling
solution. The mixture was left in a refrigerator overnight, and
the crystals were filtered, washed with cold methyl ethyl
ketone, and air-dried to give 0.240 g (54.5%) optically pure
(-)-(S)-2, pale yellow crystals; mp ) 185.3 °C (3 °C/min),
(83%),17 mp ) 335-345 °C, [R]25 ) -209.1° (c 0.5; CHCl3).
546
In a second identical run, except that Cs2CO3 (8.1 g) was used
instead of K2CO3, 0.707 g (100%)17 of crystalline (-)-(R,S)-3a
{[R]25 ) -210.3° (c 0.5; CHCl3)} was obtained as the first
546
crop. A second crystallization of the combined crystals from
the two runs led to only a slight increase of the optical rotation
(dissolution of the crystals in chloroform was now difficult) of
the obtained analytically pure (-)-(R,S)-3a : 1.075 g (76.2%),17
mp ) 345-350 °C (dec at solid state from ca. 300 °C). Rf )
0.51 (I), 0.13 (III). 1H NMR (CDCl3) δ 8.1-6.8 (m), 24 H; 5.20
(d, 13.6 Hz) and 4.86 (d, 13.6 Hz), 4 H. 1H NMR (DMSO-d6)
δ 5.58 (d, 12.9 Hz) and 4.60 (d, 13.0 Hz), 4 H. 13C NMR (CDCl3)
δ 152.52-118.60; 68.81. 13C NMR (DMSO-d6) δ 152.12-
117.28; 66.89. [R]25 ) -199.4°, [R]25 ) -226.8°, [R]25
[R]23578 ) -170.2°, [R]23546 ) -199.8°, [R]23436 ) -418.3°, [R]23
365
) -1046.8° (c 1; benzene), ≈100% optical purity, lit.14 mp )
185.5-186.5 °C, [R]23
) -169.4°, [R]23
) -199.8 (c 1;
578
546
benzene), lit.12 mp ) 182-184 °C, [R]23578 ) -169.8°/+171.1°,
578
546
436
) -339.8°, [R]25 ) +491.6° (c 0.5; CHCl3). Anal. Calcd for
[R]23
) -198.6°/+200.2°, [R]23
) -415.2°/+420.3° (c 1;
365
546
436
C42H28O2: C, 89.33; H, 5.00; O, 5.67. Found: C, 88.76; H, 5.28;
O, 5.02. EI+ MS m/ z (relative intensity): 564 (M+) (100); 279
(60); 266 (86). The combined mother liquors from the first
crops of the two runs were evaporated, and the residue was
chromatographed on a 3 × 60 cm column of silica gel with
eluent (II), to give 0.464 g of chromatographically pure (+)-
(R,R)-3b and 0.966 g of a fraction in which 3b was ac-
companied by a small proportion of the cyclic tetraether 4 of
close Rf. Attempts for further purification of 3b by crystal-
lization in various solvents failed, as even the pure sample
crystallized as an amorphous powder. Flash-chromatography
of the less pure fraction on a 2.3 × 68 cm column of silica gel
with eluent (III) gave 0.715 g more of analytically pure (+)-
(R,R)-3b: total 1.179 g (83.6%),17 white solid, mp ) 185-190
°C. Rf ) 0.59 (I), 0.23 (III). 1H NMR (CDCl3) δ 7.9-6.9 (m),
benzene). A second crop of crystals was obtained from the
mother liquor: yield 0.046 g (10.5%), [R]23 ) -200.5° (c 1;
546
benzene). The combined initial aqueous 10% NaOH phase (ca.
150 mL) was extracted twice with CH2Cl2, filtered on glass
wool, and acidified with a large excess of concentrated aqueous
HCl. The resulting milky solution was extracted twice with
CH2Cl2, and the combined organic phase was washed with
water, dried, filtered, and evaporated. The obtained extract
presented a single spot of Rf ) 0.33 (I) and was pure by 1H
NMR, showing the exclusive extraction of the diol (+)-(R)-1:
yield 0.208 g (72.7%), white/pale yellow crystalline powder, mp
(crude) ) 210.1 °C (3 °C/min), [R]25
) +36.2°, [R]25
)
578
546
+49.1°, [R]25
) +220.0°, [R]25
) +1356° (c 0.9; THF),
436
365
≈100% optical purity, lit.2b mp ) 207.5-208.5 °C, [R]25
)
578
-37.8°, [R]25 ) +50.9°/-51.3°, [R]25 ) -228° (c 1; THF).
546
436