Highly diastereoselective synthesis of the 1,1'-binaphthol unit on a bile acid template

Article abstract of DOI:10.1021/jo000703z

The use of 7-deoxycholic acid as a chiral template in the asymmetric syntheses of 1,1'-binaphthyl-2,2'-diol derivatives is reported. Intramolecular coupling of compounds 7 and 11 have been carried out with Mn(acac)₃ in CH₃CN to afford coupled binaphthol products 8 and 12 with 65% and >99% diastereoselectivity, respectively. In both cases the predominant formation of the (S) isomers were predicted by computer modeling studies. This was confirmed in the case of compound 12.

Full text of DOI:10.1021/jo000703z

J . Org. Chem. 2000, 65, 8239-8244
8239
High ly Dia ster eoselective Syn th esis of th e 1,1′-Bin a p h th ol Un it on
a Bile Acid Tem p la te
Achintya K. Bandyopadhyaya, N. M. Sangeetha, and Uday Maitra*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
maitra@orgchem.iisc.ernet.in
Received May 8, 2000
The use of 7-deoxycholic acid as a chiral template in the asymmetric syntheses of 1,1′-binaphthyl-
2,2′-diol derivatives is reported. Intramolecular coupling of compounds 7 and 11 have been carried
out with Mn(acac)3 in CH3CN to afford coupled binaphthol products 8 and 12 with 65% and >99%
diastereoselectivity, respectively. In both cases the predominant formation of the (S) isomers were
predicted by computer modeling studies. This was confirmed in the case of compound 12.
In tr od u ction
A number of methods for the optical resolution of
binaphthols have been reported to date.14 Kazlauskas
used pancreas acetone powder for the resolution of
Binol.15 Periasamy and co-workers have used (S)-pro-
line,16 and more recently a combination of boric acid and
(R)-(+)-R-methylbenzylamine17 for the resolution of 1,1′-
binaphthyl-2,2′-diol. Even though a number of methods
are available for the resolution, only a few attempts to
synthesize Binol or its derivatives by asymmetric syn-
thesis have been known in the literature at the time our
work was initiated. A few approaches which have ap-
peared since then do not use inexpensive source of
chirality and these are also not recovered at the end of
the synthesis.18-20
Chiral auxiliaries and catalysts derived from optically
active 1,1′-binaphthyl-2,2′-diol (Binol) have been utilized
extensively in asymmetric synthesis in recent years.1
Intramolecular Ullman coupling2 and alkylation of eno-
lates3 have been demonstrated to show high diastereo-
selectivity using chiral Binol as the auxiliary. Enantio-
selective reduction of ketones,4 asymmetric Diels-Alder
reactions,5 Michael and nitroaldol condensations,6 enan-
tioselective protonation of silyl enol ethers and ketene
bis(trialkylsilyl)acetals,7 enantioselective aldol addition
reactions,8 enantioselective Mannich-type reactions,9 enan-
tioselective hydrophosphonylation of cyclic imides,10 and
enantioselective six-membered ring synthesis through
catalytic metathesis11 represent some of the applications
of chiral Binol. Enantiomerically pure binaphthols have
also been used extensively for preparing a large number
of chiral synthetic receptors12 and chiral dendrimers.13
Central to the success of these chemistry is the avail-
ability of homochiral Binol.
As part of a program aimed at the applications of bile
acids in organic synthesis,21 we decided to explore the
possibilities of synthesizing derivatives of 1,1′-binaph-
thyl-2,2′-diol on a 7-dexoycholic acid template.22 The full
details of this study are described below.
Resu lts a n d Discu ssion
The geometrical features of 7-deoxycholic acid have
been described earlier.18 Our approach to the asymmetric
(1) Pu, L. Chem. Rev. 1998, 98, 2405. For the use of BINOL for
optical resolution of phosphine oxides and aryl haloalkyl sulfoxides,
see: Toda, F.; Mori, K. Chem. Abstr. 1989, 111, 134477. Toda, F.;
Tanaka, K. Chem. Abstr. 1987, 106, 49772.
(2) Miyano, S.; Tobita, M.; Nawa, M.; Sato, S.; Hashimoto, H. J .
Chem. Soc., Chem. Commun. 1980, 1233.
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Nakayama, M.; Taga, T.; Fuji, K. J . Am. Chem. Soc. 1995, 117, 12159.
(4) (a) Noyori, R.; Tomino, I.; Tanimoto, Y. J . Am. Chem. Soc. 1979,
101, 3129. (b) Nishizawa, M.; Yamada, M.; Noyori, R. Tetrahedron Lett.
1981, 247. (c) Yamamoto, K.; Fukushima, H.; Nakazaki, M. J . Chem.
Soc., Chem. Commun. 1984, 1490. (d) Noyori, R. Chem. Soc. Rev. 1989,
18, 187. (e) Ma, M. F. P.; Li, K.; Zhou, Z.; Tang, C.; Chan, S. C.
Tetrahedron: Asymmetry 1999, 10, 3259.
(5) (a) Maruoka, K.; Concepcion, A. B.; Yamamoto, H. Bull. Chem.
Soc. J pn. 1992, 65, 3501. (b) Yamamoto, H.; Ishihara, K. J . Am. Chem.
Soc. 1994, 116, 1561. (c) Mikami, K.; Motoyama, Y.; Terada, M. J . Am.
Chem. Soc. 1994, 116, 2812.
(12) (a) Cram, D. J .; Cram, J . M. Science 1974, 183, 803. (b) Cram,
D. J .; Cram, J . M. Acc. Chem. Res. 1978, 11, 8. (c) Lehn, J .-M.; Simon,
J .; Moradpour, A. Helv. Chim. Acta 1978, 61, 2407. (d) Souza, L. R.;
Sogah, G. D. Y.; Hoffman, D.; Cram, D. J . J . Am. Chem. Soc. 1978,
100, 4569. (e) Hester, M. R.; Uyeki, M. A.; Diedrich, F. Isr. J . Chem.
1989, 29, 201. (f) Reeder, J .; Castro, P. P.; Knobler, C. B.; Martinbor-
ough, E.; Owens, L.; Diedrich, F. J . Org. Chem. 1994, 59, 3151.
(13) Peerlings, H. W. I.; Meijer, E. W. Eur. J . Org. Chem. 1998, 573.
(14) (a) J acques, J .; Fouquey, C. Tetrahedron Lett. 1971, 4617. (b)
Toda, F.; Tanaka, K.; Nagamatsu, S. Tetrahedron Lett. 1984, 4929. (c)
Toda, F.; Tanaka, K. J . Org. Chem. 1988, 53, 3607. (d) Toda, F.;
Tanaka, K.; Stein, Z.; Goldberg, I. J . Org. Chem. 1994, 59, 5748.
(15) Kazlauskas, R. J . Org. Synth. 1991, 70, 60.
(16) Periasamy, M.; Venkatraman, L.; Thomas, K. R. J . J . Org.
Chem. 1997, 62, 4302.
(6) (a) Sasai, H.; Arai, T.; Shibasaki, M. J . Am. Chem. Soc. 1994,
116, 1571. (b) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1236.
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1994, 116, 11179.
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117, 3649.
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119, 7153.
(10) Groeger, H.; Saida, Y.; Sasai, H.; Yamaguchi, K.; Martens, J .;
Shibasaki, M. J . Am. Chem. Soc. 1998, 120, 3089.
(11) Zhu, S. S.; Cefalo, D. R.; La, D. S.; J amieson, J . Y.; Davis, W.
M.; Hoveyda, A. H.; Schrock, R. R. J . Am. Chem. Soc. 1999, 121, 8251.
(17) Periasamy, M.; Venkatraman, L.; Sivakumar, S.; Sampathku-
mar, N.; Ramanathan, C. R. J . Org. Chem. 1999, 64, 7643.
(18) (a) Meyers, A. I.; Lutomsky, K. A., J . Am. Chem. Soc. 1982,
104, 879. (b) Lipshutz, B. H.; Kayser, F.; Liu, Z. P., Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1842. (c) Sugimura, T.; Yamada, H.; Inoue, S.;
Tai, A. Tetrahedron: Asymmetry 1997, 8, 649.
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J . Org. Chem. 1992, 57, 1917.
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(21) (a) Maitra, U.; Bag, B. G. J . Org. Chem. 1992, 57, 6979. (b)
Mathivanan, P.; Maitra, U. J . Org. Chem. 1995, 60, 364.
(22) For our preliminary communication, see: Maitra, U.; Bandyo-
padhyay, A. K. Tetrahedron Lett. 1995, 36, 3749.
10.1021/jo000703z CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/01/2000

8240 J . Org. Chem., Vol. 65, No. 24, 2000
Bandyopadhyaya et al.
Sch em e 2a
F igu r e 1. Schematic representation of the template coupling.
Sch em e 1a
a
Key: (a) BnBr, K2CO3, DMF; (b) BrCH2CO2Et, K2CO3, ac-
a
Key: (a) methyl 7-deoxycholate, CaH2, BnEt3N+Cl-, PhCH3,
etone; (c) NaOH, MeOH/H2O; (d) C6H6, (COCl)2, DMF (cat.).
∆, 85%; (b) 10% Pd/C, AcOH/EtOAc, 90%; (c) Mn(acac)3/CH3CN,
50%, 65%, de 65%; (d) CuSO4‚5H2O, pyridine, MeOH, 65 °C, 34%,
de 45%; (e) LAH/THF then Ac2O.
synthesis of derivatives of 1,1′-binaphthyl-2,2′-diol is
schematically shown in Figure 1. We chose 2,7-dihydroxy-
naphthalene as the substrate so that one end of it could
be easily attached to the steroid. To determine the
spacers that would lead to an optimum distance between
atoms 1 and 1′, detailed modeling studies were performed
using PCMODEL and InsightII.23 These studies sug-
gested that a glycolate unit can be used as a spacer.
2,7-Dihydroxynaphthylene (1) was monobenzylated to
2 following a literature procedure,12e and the subsequent
alkylation of 2 with ethyl bromoacetate afforded com-
pound 3 in an overall yield of 40%. Ester 3 was hydro-
lyzed to acid 4 in 98% yield (Scheme 1).
Ta ble 1: In tr a m olecu la r Bin a p h th ol Cou p lin g on th e
Ster oid a l Bisn a p h th ol 8
coupling reagent
temp. (°C)
de (HPLC) (%)
CuCl2/tBuNH2/MeOH
CuCl2/tBuNH2/MeOH
CuSO4‚5H2O/C5H5N/MeOH
Mn(acac)3/MeCN
27
5
65
50
19
33
45
65
column). The diastereomeric excess was also estimated
from the integrations of the methyl ester signals which
was in close agreement with the HPLC data.
To optimize the reaction, the coupling was subse-
quently carried out under various conditions, and the best
result was obtained (Table 1) when a 10 mM solution of
7 was heated at 50 °C with 1.53 equiv of Mn(acac)3 in
MeCN12f for 45 h to yield 65% of 8 with a de of 65%.
The purified diastereomeric mixture obtained from the
coupling reaction was removed from the steroid by LiAlH4
(LAH) reduction. In situ acetylation afforded the acety-
lated binaphthol 9. An authentic sample of racemic 9 was
prepared from compound 3 (overall yield 37%) for the full
characterization of the cleaved binaphthol (Scheme 3).
This product was found to be identical (TLC, IR, NMR,
UV, HPLC) to the product derived from the reduction and
acetylation of 8.
Compound 4 was converted to the acid chloride (5) and
then subjected to Oppenauer esterification with methyl
deoxycholate to yield 85% of the diester 6 after purifica-
tion (Scheme 2). Hydrogenolysis of compound 6 in the
presence of 10% Pd/C in acetic acid/ethyl acetate (1:9)
afforded steroidal bis(naphthol) 7 in 90% yield after
purification.
Compound 7 upon reaction with CuSO4‚5H2O/pyridine
complex24 in dry methanol underwent intramolecular
coupling to yield diastereomeric binaphthols 8 in 34%
yield (Scheme 2). The diastereoisomeric excess (45%) was
calculated by HPLC and NMR. Retention times for the
major and the minor diastereomers were 25.3 and 34.8
min, respectively (85:15 MeOH/H2O in a 250 mm C18
Enantiomerically enriched products 9 (obtained from
a diastereomeric mixture 8 having 65% de) showed a
positive specific rotation ([R]24D ) +57.6° (c 1.51, CHCl3))
and a CD spectrum with a positive Cotton effect with ∆ꢀ
+52.5 (238 nm) and -22.5 (225 nm). Compound 9
(obtained from a diastereomeric mixture 8 having 45%
(23) Modeling studies using PCMODEL and DTMM were performed
in the same way as discussed in ref 21a and that suggested the
feasibility of the template synthesis. This was further supported by
InsightII (Biosym Technologies version 2.3.5) calculations. Both the
diastereomers for 8 and 12 were constructed and minimized using the
CVFF force-field. The two diastereomeric structures having (S) and
(R) configuration around the biaryl bond for 8 and 12 showed a
de) showed a positive specific rotation ([R]24 ) +36.9°
D
difference of
8 and 14 kcal/mol in the gas phase, respectively,
(c 1.22, CHCl3)) and a positive Cotton effect with ∆ꢀ +35.1
(239 nm) and -15.2 (226 nm).25 The CD spectrum
suggesting the greater stability of the (S) isomer.
(24) Feringa, B.; Wynberg, H. Tetrahedron Lett. 1977, 4447.

Diastereoselective Synthesis of 1,1′-Binaphthol
J . Org. Chem., Vol. 65, No. 24, 2000 8241
Sch em e 3a
Sch em e 4a
a
Key: (a) 10% Pd/C, EtOAc/MeOH, 99%; (b) CuCl2/tBuNH2,
MeOH; (c) LAH/THF then Ac2O, 37% overall.
of the enantiomeric mixture was compared with the CD
data reported for (S)-1,1′-binaphthyl-2,2′-diol.26 Three
other biaryl compounds having (S) configurations (in-
cluding (S)-1,1′-binaphthyl-2,2′-diol) have also been re-
ported to have similar CD spectral properties.19 Addi-
tionally, (S)-7,7′-bis(benzyloxy)-2,2′-dihydroxy-1,1′-bi-
naphthyl was reported to have a positive specific
rotation.12f Therefore, on the basis of these similar
spectral properties of the similar types of binaphthols,
the absolute configuration of the major enantiomer was
assigned to be (S).
To further improve the diastereoselectivity other spacer
groups were examined. We felt that a carbonate linkage
instead of a glycolate can bring the bond forming sites
closer to the steroid and this might enhance the selectiv-
ity. Computer modeling with InsightII suggested the
feasibility of the template synthesis.21
Bis(imidazolide) 10 was prepared from methyl deoxy-
cholate by heating with N,N′-carbonyl diimidazole (CDI)
and CaH2 at 65-8 °C in 86% yield.27 The yield of this
reaction showed a marked dependence on the reaction
temperature. A mixture of bis(imidazolide) 10 and 2,7-
dihydroxynaphthalene was dissolved in the minimum
volume of THF and heated in an oil-bath at 148-152 °C
for 5 h. The desired biscarbonate 11 was isolated in 77%
yield.28
a
Key: (a) PhCH3, CaH2, CDI, 65-68%; (b) 2,7-dihydroxynaph-
thalene, [THF], 148-52 °C, 77%; (c) Mn(acac)3/CH3CN, 65 °C, 35%;
(d) LiOH, MeOH then 3 N HCl, 77%.
on neutral alumina. An authentic sample of racemic
binaphthol29 13 was found to be identical (TLC, IR, NMR,
UV) to the product derived from the template coupling.
The enantiomerically enriched product 13 showed
negative specific rotation ([R]26D ) -89.8° (c 0.86, CHCl3))
and a CD spectrum with positive Cotton effects [∆ꢀ +82.1
(242 nm) and -72.1 (226 nm)]. The binaphthol derivative
9 was also found to show a similar CD spectrum.
Therefore, on the basis of these similar spectral proper-
ties of the similar binaphthols the absolute configuration
of binaphthol 13 was initially assigned to be (S), which
was confirmed by conversion of 12 to a binol derivative
of known absolute configuration (Scheme 5).
The intramolecular coupling of 11 to produce 1212e was
accomplished, albeit in a moderate yield (Scheme 4).
Attempts made to couple the template-bound naphthols
under conditions such as CuSO4‚5H2O/pyridine26 in
MeOH and with CuCl2/tBuNH2 in MeOH were unsuc-
12f
cessful and did not yield the expected product. Under the
best condition, we have been able to get an isolated yield
of 36% based on the recovered starting material (70%
conversion). Typically a 7 mM solution of 11 in acetoni-
trile was heated at 65 °C with 6.85 equiv of Mn(acac)3
1
for 62 h. Compound 12 was characterized by LRMS, H
and 13C NMR, UV, and IR spectroscopies. This steroidal
binaphthol 12 showed a single peak in reverse phase
HPLC (tR 14.2 min, 250 mm C18 column, MeOH/H2O
93:7), and 1H NMR of this material was again in
agreement with the presence of a single diastereomer
(estimated de > 99%). Compound 12 when stirred with
LiOH in MeOH at room temperature under argon
atmosphere for 16 h afforded binaphthol 13 in 77%
isolated yield after column chromatographic purification
Binaphthol 12 was methylated by reacting with MeI
in the presence of K2CO3 in DMF at 50 °C for 2 days to
yield 14 (87%). The methylated steroidal binaphthol was
then hydrolyzed by stirring with LiOH in MeOH for 12
h to yield compound 1512f in 95% yield. This compound
gave a positive specific rotation ([R]26 ) + 48.3° (c 2.4,
D
DMF)) which was compared to the literature value ([R]26
D
) + 45.9° (c 1, DMF))12f which confirmed the stereochem-
istry to be (S) with an enantioselectivity of >99%.
Con clu sion s
(25) These numbers are internally consistent and shows that the
low yield in the conversion of 8 to 9 is not associated with the
preferential loss of one diastereomer/enantiomer.
This work demonstrates the first application of the bile
acid template for asymmetric binaphthol coupling. The
(26) Vo¨gtle, F.; Aigner, A.; Thomessen, R. Phys. Scr. 1987, 35, 463.
(S)-1,1′-Binaphthyl-2, 2′-diol was reported to show a positive Cotton
effect with ∆ꢀ +1300 (231 nm) and -1300 (225 nm).
(27) Staab, H. A.; Albrecht, M. Ber. 1962, 95, 1284.
(29) Sakamoto, T.; Yonehara, H.; Pac, C. J . Org. Chem. 1994, 59,
(28) Staab, H. A. Liebigs Ann. Chem. 1957, 609, 75.
6859.

8242 J . Org. Chem., Vol. 65, No. 24, 2000
Bandyopadhyaya et al.
Sch em e 5a
Hz, 3H), 4.30 (q, J ) 7.2 Hz, 2H), 4.72 (s, 2H), 5.18 (s, 2H),
7.00 (d, J ) 2.2 Hz, 1H), 7.01-7.17 (m, 3H), 7.28-7.55 (m,
5H), 7.69 (d, J ) 8.3 Hz, 2H); 13C NMR (22.5 MHz, CDCl3) δ
14.0, 61.0, 65.0, 70.0, 107.0, 116.0, 117.0, 125.0, 127.5-129.5,
135.4, 136.9, 156.7, 157.8, 169.0; LRMS m/z 336 (M+, 21);
HRMS m/z 336.1359 (calcd for C21H20O4 336.1362). Anal. Calcd
for C21H20O4: C, 74.97; H, 5.99. Found: C, 74.69; H, 5.91.
2-((7-Ben zyloxy)n a p h t h yloxy)a cet ic Acid (4). Com-
pound 3 (0.35 g, 1.02 mmol) was dissolved in MeOH/H2O
mixture (9:1 v/v, 25 mL) by heating, and solid NaOH (1.62 g,
40.5 mmol) was added. The mixture was refluxed for 19 h,
cooled (ice-bath), and acidified with 6 M aqueous HCl (5 mL).
Methanol was removed under reduced pressure, and the
residue was filtered and washed thoroughly with water and
dried in vacuo. Traces of water was removed azeotropically,
and the product was dried in vacuo. This crude product (0.317
g, quantitative) was pure enough for the further reactions: mp
158-61 °C; IR (Nujol) 1700, 1720, 2500-2700 cm-1; 1H NMR
(90 MHz, CDCl3) δ 4.81 (s, 2H), 5.21 (s, 2H), 7.00-7.62 (m,
9H), 7.75 (d, J ) 7.7 Hz, 2H).
a
Key: (a) MeI, K2CO3/DMF, 50 °C, 87%; (b) LiOH, MeOH-
THF, rt, 89%.
de in the coupling reaction was increased from 65% to
99% by optimizing the spacer. We believe that further
work to improve the coupling yield and to use compound
12 as a new asymmetric catalyst can lead to practical
benefits. Some of these possibilities are being examined
in our laboratory, and these results will be published in
due course.
Meth yl 3r, 12r-Bis(2-((7-ben zyloxy)n aph th yloxy)acetyl-
oxy)-5â-ch ola n -24-oa te (6). To a stirred suspension of com-
pound 4 (0.268 g, 0.87 mmol) in dry benzene (2.6 mL) was
added oxalyl chloride (0.16 mL, 1.83 mmol) followed by the
addition of 1 drop of dry DMF. The resulting mixture was then
heated to ca. 45 °C for 2.5 h. Excess oxalyl chloride and solvent
were removed under vacuum, and the acid chloride (5) was
dried in vacuo for 2 h.
Exp er im en ta l Section
The crude acid chloride (5) was dissolved in dry toluene (2
mL), and CaH2 (0.165 g, 3.92 mmol) and methyl deoxycholate
(0.161 g, 0.40 mmol) were successively added to the solution
followed by the addition of benzyltriethylammonium chloride
(0.01 g, 0.04 mmol). The mixture was refluxed for 18 h. The
flask was cooled, the suspension was filtered to remove
inorganic materials, and the residue was washed with CHCl3.
The combined organic layer was washed with 7% NaHCO3
solution, water, and brine and finally dried over anhyd Na2-
SO4. The solvent was removed in vacuo. The crude product
was purified by column chromatography on silica gel (100-
200 mesh, 18.0 cm × 2.2 cm, 22 g) using 15% ethyl acetate
(EA)/hexanes as the eluent. The pure product (0.327 g, 83.8%)
was isolated as a foam. Several attempts for crystallization
Gen er a l. All reactions were carried out in oven-dried
glasswares unless otherwise stated. Moisture sensitive reac-
tions were protected with a CaCl2 drying tube or were carried
out under a dry nitrogen atmosphere. Solid reactants were
recrystallized, checked by melting points, and used for the
reaction whereas the liquids were distilled. Distilled com-
mercial grade solvents were used for crystallization, extraction,
and column chromatography. Analytical TLC were performed
on homemade plates made from Acme silica gel or on precoated
silica gel plates purchased from Aldrich. Visualization was
done under UV (shortwave or longwave) radiation or by
dipping the plates in 5% ethanolic phosphomolybdic acid or
methanolic Ac2O/H2SO4 solution or anisaldehyde/H2SO4 in
acetic acid and heating on a hot plate. Columns for chroma-
tography were made from 100-200 mesh silica gel. Toluene,
benzene, tetrahydrofuran were distilled from sodium/ben-
zophenone ketyl. Methanol, methylene chloride, and acetic
anhydride were distilled from magnesium methoxide, calcium
hydride, and phosphorus pentoxide, respectively. Pyridine and
triethylamine were stored over KOH and distilled from CaH2.
Dimethyl formamide (DMF) was preliminarily dried by azeo-
tropic distillation with benzene and then distilled from BaO
under vacuum. Acetonitrile was distilled from CaH2. All
melting points reported are uncorrected. Optical rotations were
measured at 589 nm at the specified temperatures. IR spectra
were recorded on NaCl cells. NMR spectra were measured at
60, 90, 200, 270, and 400 MHz instruments in deuterated
solvents as indicated; TMS or the residual solvent peaks were
used as internal standards. FAB mass spectra were recorded
using argon/xenon (6 KV, 10 mA) as a fab gas and using
m-nitrobenzyl alcohol as a matrix. HPLC analysis were
performed using a C18 column (250 mm × 4.6 mm). MeOH/
H2O of various proportions were used as mobile phases at a
flow rate of 1 mL/min. Samples were detected at 254 nm unless
otherwise mentioned. Retention times of the compounds
reported typically had a standard deviation of (0.20 min.
Eth yl 2-(((7-Ben zyloxy)n a p h th a len e)oxy)a ceta te (3). In
a 10-mL round-bottom (rb) flask were mixed compound 2 (0.30
g, 1.20 mmol), K2CO3 (0.12 g, 0.85 mmol), and dry acetone (3
mL), and the mixture was refluxed for 1 h under a N2
atmosphere. Ethyl bromoacetate (0.16 mL, 1.44 mmol) was
added, and the mixture was refluxed for an additional 21 h.
After filtration and removal of the solvent the crude product
was crystallized from ethanol to get 0.39 g (96%) of the pure
product: mp 100-101 °C; IR (Nujol) 1203, 1377, 1446, 1608,
1752, 2854 cm-1; 1H NMR (270 MHz, CDCl3) δ 1.31 (t, J ) 7.1
with different solvents were unsuccessful: mp 65-67 °C. [R]28
D
) +8.3° (c 3.14, CHCl3); IR (Nujol) 1725 cm-1; UV λmax (log ꢀ)
0.04% CHCl3/EtOH v/v (c 1.27 × 10-5 M) 234.3 (5.34), 325.2
(3.90); 1H NMR (400.1 MHz, CDCl3) δ 0.649 (s, 3H), 0.731 (d,
J ) 6.4 Hz, 3H), 0.869 (s, 3H), 1.18-2.23 (m, steroidal CH
and CH2), 3.619 (s, 3H), 4.657 (d, J ) 15.9 Hz, 1H), 4.677 (s,
2H), 4.728 (d, J ) 15.9 Hz, 1H), 4.883 (m, 1H), 5.099 (s, 2H),
5.114 (s, 2H), 5.170 (s, 1H), 6.95-7.21 (m, 8H), 7.30-7.51 (m,
10H), 7.598 (d, J ) 8.9 Hz, 1H), 7.612 (d, J ) 2.7 Hz, 1H),
7.634 (d, J ) 2.7 Hz, 1H), 7.690 (d, J ) 8.9 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3) δ 12.18, 17.40, 22.86, 23.20, 25.49, 25,57,
26.73, 27.21, 30.57, 31.00, 32.05, 33.91, 34.17, 34.64, 35.39,
41.70, 45.04, 47.38, 48.86, 51.39, 65.37, 65.72, 69.92, 75.48,
77.31, 106.63, 106.75, 107.31, 115.47, 114.85, 116.92, 124.84,
127.40, 127.47, 127.93, 128.54, 129.19, 129.38, 129.51, 135.57,
136.84, 156.37, 157.58, 168.30, 168.47, 174.43. LRMS (FAB)
m/z 986 (M+, 35). Anal. Calcd for C63H70O10: C, 76.64; H, 7.15.
Found: C, 76.95; H, 7.27.
Meth yl 3r, 12r-bis(2-((7-Hyd r oxy)n a p h th yloxy)a cetyl-
oxy)-5â-ch ola n -24-oa te (7). In a 20 mL two-necked rb flask
was dissolved 6 (0.100 g, 0.10 mmol) in 10% AcOH/EtOAc (1
mL), evacuated, and purged with N2. Pd/C (10%, 0.080 g) was
added under a N2 atmosphere and flushed with H2, and the
reaction was stirred at room temperature under 1 atm pres-
sure of H2. Hydrogenolysis was complete after 2 days. The
solution was filtered through a Celite pad and dried in vacuo
to afford the crude product (0.092 g, 100%) which was purified
by column chromatography on silica gel (100-200 mesh, 14.5
cm × 1.3 cm, 6 g) using 10% EA/CHCl3 as the eluent. This
compound (0.073 g, 90%) was characterized by 1H NMR
spectrum which showed the absence of the benzyl groups: 1H
NMR (60 MHz, CDCl3) δ 0.64 (s, 3H), 0.70-0.98 (m, 6H), 1.00-
2.22 (m, steroidal CH and CH2), 3.66 (s, 3H), 4.76 (complex,

Diastereoselective Synthesis of 1,1′-Binaphthol
J . Org. Chem., Vol. 65, No. 24, 2000 8243
4H), 5.20 (complex, 1H), 5.60 (complex, 1H), 6.70-7.20 (m, 8H),
7.40-7.80 (m, 4H).
with the following [R]D and CD data (1H NMR, IR, UV identical
with 9 prepared in the previous experiment): [R]24 ) +36.9°
D
P r ep a r a tion of Ster oid a l Bin a p h th ol 8 Usin g Mn -
(a ca c)3/MeCN. To a stirred solution of compound 7 (0.067 g,
0.08 mmol) in MeCN (8.3 mL) was added Mn(acac)3 (0.045 g,
0.12 mmol) under N2 atmosphere, and the reaction was stirred
at 50 °C for 45 h. The inorganic residue was filtered and
washed with MeCN, and the solvent was evaporated in vacuo.
The crude product was purified by column chromatography
on silica gel (100-200 mesh, 16.0 cm × 1.2 cm, 5 g) using 5%
EA/CHCl3 as the eluent. The purified product (0.044 g, 65%)
was a mixture of two diastereomers. HPLC analysis of this
sample showed a de of 65%. Retention times for the major and
the minor diastereomers were 25.3 and 34.8 min, respectively
(MeOH/H2O in a ratio of 85:15 was used as the mobile phase).
(c 1.22, CHCl3); CD ∆ꢀ M-1 cm-1 (λmax nm) 0.12% CHCl3/MeCN
v/v (c 1.02 × 10-5 M) +35.1 (239), -15.2 (226).
(()-7,7′-Bis(2-acetoxyeth oxy)-2,2′-diacetoxy-1,1′-bin aph -
th yl (9). Compound 3 (0.307 g, 0.91 mmol) was dissolved in a
1:1 mixture of EtOAc/MeOH (10 mL) and degassed. Pd/C (10%,
0.031 g) was added, and the flask was immediately flushed
with H2. The reaction was stirred at 27 °C for 8 h. The mixture
was filtered, and the crude product (0.224 g, 99%) was used
for the next step: mp 97-8 °C; IR (Nujol) 1730, 1745, 3360-
1
3400 cm-1; H NMR (60 MHz, CDCl3) δ 1.30 (t, J ) 6.8 Hz,
3H), 4.30 (q, J ) 6.8 Hz, 2H), 4.70 (s, 2H), 5.00 (s, 1H), 6.83-
7.19 (m, 4H), 7.68 d, J ) 9.0 Hz, 2H); LRMS m/z 246 (M+,
100); HRMS m/z 246.0914 (calcd for C14H14O4 246.0892).
To a stirred solution of crude product (0.204 g, 0.82 mmol)
and CuCl2 (0.266 g, 1.68 mmol) in degassed dry MeOH (12
For 8: mp 170-2 °C; [R]25 ) +144.8° (c 1.25, CHCl3); IR
D
(Nujol) 1720, 3200-3500 cm-1; UV λmax (log ꢀ) 0.15% CHCl3/
EtOH v/v (c 1.22 × 10-5 M) 234.1 (5.00), 305.9 (3.88), 328.1
mL) was added BuNH2 (0.70 mL, 6.66 mmol), and the mixture
t
1
(3.78); H NMR (400.1 MHz, CDCl3) (resolved minor diaste-
was stirred at 27 °C under N2 for 26 h. The ice-cold solution
was acidified with dilute HCl and extracted with EtOAc. The
combined organic layer was washed with water and brine and
finally dried over anhydrous Na2SO4. The solvent was removed
in vacuo to yield the crude product (0.197 g), which was
subjected to LAH reduction without further purification.
To a solution of the crude product (0.197 g, 0.40 mmol) in
dry THF (4 mL) was added LAH (0.033 g, 0.87 mmol), and
the resulting mixture was refluxed for 20 h. To the cold
reaction at 0 °C was added Ac2O (1 mL, 10.6 mmol), and the
solution was stirred for 18 h. The solution was filtered, and
the residue was washed with ethyl acetate. Solvents were
removed to yield the crude product, which was purified by
column chromatography on silica gel (100-200 mesh, 20.0 cm
× 1.5 cm, 12 g) using 30-40% of EA/hexanes as the eluent.
The pure product weighed 0.084 g (37%): HPLC of this
compound was identical with the enantiomerically enriched
binaphthol; IR (neat) 1740 cm-1; 1H NMR (400.1 MHz, CDCl3)
δ 1.79 (s, 6H), 2.01 (s, 6H), 3.81 (m, 2H), 3.90 (m, 2H), 4.26 (t,
J ) 4.5 Hz, 4H), 6.51 (d, J ) 2.3 Hz, 2H), 7.14 (d, J ) 2.4 Hz,
2H), 7.18 (d, J ) 2.4 Hz, 2H), 7.28 (d, J ) 8.7 Hz, 2H), 7.84 (d,
J ) 9.0 Hz, 2H), 7.92 (d, J ) 8.8 Hz, 2H); 13C NMR (100.61
MHz, CDCl3) δ 20.47, 20.69, 62.49, 65.60, 105.29, 116.93,
118.51, 119.61, 121.32, 121.83, 122.37, 127.08, 129.18, 129.47,
129.65, 134.40, 147.28, 157.07, 169.27, 170.73; EIMS m/z 574
(M+, 5).
reomer signals are indicated in italics) δ: 0.71 (s), 0.72 (s),
0.79 (s), 0.81 (s), 0.85 (s), 0.87 (s), 0.88-2.09 (m, steroidal CH
and CH2), 2.10-2.41 (m), 3.61 (s), 3.68 (s), 3.85 (d, J ) 15.5
Hz), 4.07 (s), 4.31 (d, 15.5 Hz), 4.59 (s), 4.60 (s), 4.61 (s), 4.70-
4.79 (m), 4.80-4.95 (m), 5.09 (br s), 5.13 (br s), 5.23 (br s),
5.28 (br s), 6.32 (d, J ) 2.4 Hz), 6.64 (d, J ) 2.5 Hz), 6.66 (d,
J ) 2.5 Hz), 6.85 (dd, J ) 9.0, 2.6 Hz), 7.10 (dd, J ) 9.0, 2.6
Hz), 7.20 (d, J ) 2.5 Hz), 7.22 (d, J ) 2.5 Hz), 7.25 (d, J ) 8.9
Hz), 7.26 (d, J ) 8.9 Hz), 7.32 (d, J ) 8.8 Hz), 7.81 (d, J ) 9.0
Hz), 7.82 (d, J ) 8.9 Hz), 7.89 (d, J ) 8.9 Hz), 7.90 (d, J ) 8.9
Hz), 8.00 (br s), 8.01 (d, J ) 8.9 Hz); the diastereomeric excess
was calculated on the basis of integrations of methyl ester
signals and found to be 62.5%; 13C NMR (100.61 MHz, CDCl3)
(resolved minor diastereomer signals are indicated in italics)
δ 12.3, 17.4, 17.6, 22.8, 23.2, 23.3, 25.3, 25.8, 26.0, 26.5, 27.3,
30.7, 30.8, 31.6, 31.9, 33.8, 33.9, 34.2, 34.6, 35.5, 36.5, 40.7,
41.5, 41.7, 44.8, 44.9, 47.0, 47.5, 49.0, 49.8, 51.4, 53.8, 60.8,
64.1, 65.1, 65.7, 69.2, 71.8, 75.9, 76.7, 77.0, 77.3, 92.3, 95.4,
97.7, 98.9, 103.0, 105.2, 108.8, 109.5, 110.0, 110.4, 112.0, 115.6,
115.9, 116.1, 116.4, 117.2, 121.5, 125.1, 125.3, 130.0, 130.3,
131.0, 131.1, 131.4, 135.1, 135.2, 153.2, 153.3, 156.9, 162.6,
166.8, 169.4, 174.5; the diastereomeric excess calculated from
13C NMR was 63%; FABMS m/z 804 (M+, 79). Anal. Calcd for
C
49H56O10‚H2O: C, 71.51; H, 7.10. Found: C, 71.57; H, 7.17.
P r op er ty of 8 Syn th esized Usin g Cu SO4‚5H2O/P yr i-
d in e. This product, isolated in 34% yield, showed de of 45.3%
by HPLC and 42% by NMR.
Meth yl 3r,12r-Bis(1-im idazolylcar bon yloxy)-5â-ch olan -
24-oa te (10). In a 20-mL rb flask were dissolved methyl
deoxycholate (1.151 g, 2.83 mmol) and N,N′-carbonyldiimida-
zole (1.168 g, 7.20 mmol) in dry toluene (14.0 mL), and CaH2
(0.270 g, 6.41 mmol) was added. The reaction mixture was
stirred at 65-68 °C for 50 h. The mixture was cooled and
filtered, and the residue was washed with CHCl3. Volatiles
were removed in vacuo, and the crude product was purified
by column chromatography on silica gel (100-200 mesh, 21.5
cm × 2.2 cm, 25 g) using 30-50% EA/hexanes as the eluent.
The pure bisimidazolide 10 weighed 1.440 g (86%); mp 55-6
Clea va ge of th e Bin ol Un it fr om 8. 7,7′-Bis(2-a cetoxy-
eth oxy)-2,2′-d ia cetoxy-1,1′-bin a p h th yl (9) fr om th e Dia -
ster eom er s Obta in ed Usin g Mn (a ca c)3. A mixture of
diastereomers 8 (0.067 g, 0.08 mmol) obtained from the Mn-
(acac)3/CH3CN coupling was dissolved in dry THF (10 mL) and
flushed with N2. LAH (0.050 g, 1.32 mmol) was added, and
the mixture was refluxed for 72 h. After the completion of the
reaction, the flask was cooled in an ice-bath, Ac2O (0.3 mL)
was added and stirring was continued for 24 h. The mixture
was filtered and washed with MeOH and ethyl acetate, and
the volatiles were removed in vacuo. The crude product was
purified by column chromatography on silica gel (100-200
mesh, 8.0 cm × 1.2 cm, 3.0 g) using 30% EA/hexanes as the
eluent. The partially purified product (0.012 g) was further
purified by preparative TLC, developing with 30% EA/hexanes
four times to yield 0.00452 g of the product 9. This compound
was analyzed by HPLC (tR ) 8.9 min, MeOH/H2O in a ratio of
75:25 was used as the mobile phase, and the sample was
°C; [R]26 ) +78.0° (c 1.87, CHCl3); IR (neat) 1750 cm-1; UV
D
λ
max (log ꢀ) 3.2% CHCl3/EtOH v/v (c 1.50 × 10-5 M) 230.2 (4.02);
1H NMR (270 MHz, CDCl3) δ 0.82 (s, 3H), 0.84 (d, J ) 6.7 Hz,
3H), 0.97 (s, 3H), 1.08-1.93 (m, steroidal CH and CH2), 2.02-
2.40 (m), 3.63 (s, 3H), 4.83 (m, 1H), 5.35 (s, 1H), 7.04 (s, 1H),
7.13 (s, 1H), 7.36 (s, 1H), 7.48 (s, 1H), 8.09 (s, 1H), 8.21 (s,
1H); 13C NMR (100.6 MHz, CDCl3) δ 12.5, 17.6, 22.9, 23.4, 25.7,
25.9, 26.3, 26.6, 27.0, 27.2, 30.7, 31.0, 31.3, 32.0, 33.8, 34.0,
34.5, 34.7, 35.6, 41.6, 45.5, 48.3, 50.0, 51.5, 78.6, 81.2, 116.7,
117.1, 130.5, 130.9, 136.9, 137.1, 148.0, 148.2, 174.3; LRMS
m/z 594 (M+, 4). Anal. Calcd for C33H46O6N4‚0.5H2O: C, 65.63;
H, 7.85; N, 9.28. Found: C, 65.94; H, 7.80; N, 8.92.
detected at 230 nm). For 9: [R]24 ) +57.62° (c 1.51, CHCl3);
D
IR (neat) 1741 cm-1; UV λmax (log ꢀ) 0.12% CHCl3/MeCN v/v (c
1.05 × 10-5 M) 232.1 (4.95), 328.9 (3.73); CD ∆ꢀ M-1 cm-1 (λmax
nm) 0.12% CHCl3/MeCN v/v (c 1.05 × 10-5 M) +52.5 (238),
Met h yl 3r,12r-Bis((2-(7-h yd r oxyn a p h t h yl)oxy)ca r b -
on yloxy)-5â-ch ola n -24-oa te (11). In a flask (10 mL) fitted
with an 18-cm air condenser (N2 atmosphere) were dissolved
bisimidazolide 10 (0.250 g, 0.42 mmol) and 2,7-dihydroxynaph-
thalene (0.500 g, 3.12 mmol) in 1 mL of THF; the flask was
flushed with N2 and immersed in an oil-bath (148-52 °C) for
5 h 15 min. Traces of solvent was removed under vacuum, and
the crude product was purified by column chromatography on
1
-22.5 (225); H NMR (270 MHz, CDCl3) δ 1.80 (s, 6H), 2.02
(s, 6H), 3.81 (m, 2H), 3.90 (m, 2H), 4.27 (t, J ) 4.5 Hz, 4H),
6.51 (d, J ) 2.3 Hz, 2H), 7.14 (d, J ) 2.4 Hz, 2H), 7.18 (d, J )
2.4 Hz, 2H), 7.28 (d, J ) 8.7 Hz, 2H), 7.84 (d, J ) 9.0 Hz, 2H),
7.92 (d, J ) 8.8 Hz, 2H).
In an analogous manner, compound 8 (0.033 g) obtained
from the CuSO4‚5H2O/pyridine coupling yielded 9 (0.0041 g)

8244 J . Org. Chem., Vol. 65, No. 24, 2000
Bandyopadhyaya et al.
silica gel (100-200 mesh, 14.5 cm × 2.2 cm, 15 g) using 15-
neutral alumina (4.2 cm × 1.2 cm, 5 g) using 40-80% EA/
hexanes as the eluent, to yield 0.005 g (77%) of 13: mp 130-2
°C (lit.51 151-2 °C for racemic mixture); [R]26D ) -89.8° (c 0.86,
CHCl3); IR (neat) 1690, 3350 cm-1; UV λmax (log ꢀ) 0.08%
CHCl3/MeCN v/v (c 1.21 × 10-5 M) 233.7 (4.88); CD ∆ꢀ M-1
cm-1 (λmax nm) 0.4% CHCl3/MeCN v/v (c 1.21 × 10-5 M) +82.1
(242), -72.1 (226); 1H NMR (200 MHz, CDCl3) δ 5.03 (s, 2H),
5.10 (s, 2H), 6.43 (d, J ) 2.5 Hz, 2H), 6.98 (dd, J ) 8.76, 2.5
Hz, 2H), 7.21 (d, J ) 8.87 Hz, 2H), 7.79 (d, J ) 8.78 Hz, 2H),
7.88 (d, J ) 8.86 Hz, 2H).
Con ver sion of Com p ou n d 12 to Com p ou n d 14. In a 10-
mL rb flask, compound 12 (0.023 g, 0.03 mmol) and K2CO3
(0.025 g, 0.18 mmol) in DMF (0.3 mL) was treated with MeI
(0.3 mL, 4.8 mmol) in three 0.1 mL portions at intervals of
about 10 h. The reaction mixture was stirred for 40 h at 50°
C. The solvent was evaporated in vacuo, and the residue was
extracted with ethyl acetate and washed with dilute HCl,
water, and brine and dried over Na2SO4. The crude product
obtained on evaporation of the volatiles was purified on a silica
gel column (1.2 cm × 18 cm) using 4% EA/CHCl3 to yield 0.021
mg (87%) of 14: [R]23D ) + 33.5 (c 1.13, CHCl3); IR (neat) 1759
cm-1; UV λmax (log ꢀ) 0.02% CHCl3/MeCN v/v (c 1.04 × 10-5
M) 233.5 (5.07), 284.0 (3.97), 335.0 (3.82); 1H NMR (300 MHz,
CDCl3) δ 0.72 (s, 3H), 0.86 (s, 3H), 0.91 (d, J ) 6.3 Hz, 3H),
1.04-2.3 (m, steroidal CH and CH2), 3.62 (s, 3H), 3.72 (s, H),
3.78 (s, 3H), 4.59 (m, 1H), 4.85 (s, 1H), 6.8 (dd, J ) 6.6 and
2.4 Hz, 2H), 7.03 (dd. J ) 8.7 and 2.7 Hz, 1H), 7.43 (dd, J )
9 Hz and 2.4 Hz, 2H), 7.86-8.03 (m, 5H); 13C NMR (300 MHz,
CDCl3) δ 12.27, 17.46, 22.43, 23.27, 23.46, 25.74, 25.87, 26.52,
27.19, 30.66, 30.88, 33.12, 33.67, 34.39, 34.81, 34.41, 41.52,
45.23, 47.23, 48.80, 51.46, 56.83, 56.87, 79.34, 81.27, 113.51,
113.93, 114.10, 115.11, 116.69, 118.34, 118.99, 119.29, 126.86,
127.35, 129.23, 129.49, 129.69, 134.43, 134.58, 149.93, 150.19,
151.07, 151.61, 155.90, 155.92, 174.53.
25% EA/hexanes as the eluent, to yield 0.252 g (77%) of the
title compound: mp 212-4 °C; [R]24 ) +73.8° (c 0.596, 1:4
D
CH3CN/CHCl3); IR (neat) 1710, 1730, 1760, 3410 cm-1; UV λmax
(log ꢀ) 0.16% CHCl3/MeCN v/v (c 1.50 × 10-5 M) 228.5 (5.16),
1
276.4 (3.85), 327.8 (3.52); H NMR (270 MHz, CDCl3) δ 0.72
(s, 3H), 0.94 (s, 3H), 0.96 (d, J ) 6.7 Hz, 3H), 1.20-2.10 (m,
steroidal CH and CH2), 2.22-2.54 (m), 3.63 (s, 3H), 4.76 (m,
1H), 5.05 (s, 1H), 5.70 (br s, OH), 6.00 (br s, OH), 6.98-7.20
(m, 6H), 7.35-7.50 (m, 2H), 7.62-7.86 (m, 4H); 13C NMR
(100.6 MHz, CDCl3) δ 12.3, 12.4, 14.2, 17.7, 22.9, 23.0, 23.3,
25.4, 25.8, 25.9, 26.5, 26.8, 27.2, 30.8, 31.1, 32.0, 34.0, 34.3,
34.4, 34.7, 34.8, 35.6, 35.8, 41.8, 45.4, 47.5, 48.9, 49.1, 51.6,
60.5, 72.2, 79.5, 81.2,109.4, 116.7, 118.0, 118.2, 126.9, 129.5,
129.6, 129.7, 135.1, 149.3, 149.5, 153.1, 153.4, 154.4, 154.5,
174.8; FABMS m/z 778 (M+, 7). Anal. Calcd for C47H54O10: C,
72.47; H, 6.99. Found: C, 72.32; H, 7.09.
Cou p lin g of Com p ou n d 11 to Ster oid a l Bin ol 12. To a
20-mL two-necked flask were added bis(carbonate) 11 (0.055
g, 0.071 mmol) and dry CH3CN (10 mL). To the almost
homogeneous solution at 65 °C under N2 atmosphere Mn(acac)3
(0.170 g, 0.483 mmol) was added. The reaction was stirred at
65 °C for 62 h and filtered, and volatiles were removed. The
crude product was purified by column chromatography on
silica gel (100-200 mesh, 11.5 cm × 1.2 cm, 5 g) using 2-8%
EA/hexanes as the eluent. The yield from the reaction was
41%(0.018 g), based on recovered starting material (0.011 g,
20%). Purity of this material was different for different batches
of samples. However, the reaction was optimized to afford pure
coupled product 12 in 35-41% yield based on the recovery of
the starting material (20-30%). HPLC analysis of 12 showed
a single peak at 14.2 min (MeOH/H2O in a ratio of 93:7 was
used as the mobile phase): mp 180-2 °C; [R]23 ) +63.5° (c
D
0.504, CHCl3); IR (Nujol) 1760, 3100-3500 cm-1; UV λmax (log
ꢀ) 0.16% CHCl3/MeCN v/v (c 0.973 × 10-5 M) 230.8 (5.08), 280.9
(3.96), 331.6 (3.80); 1H NMR (400.1 MHz, CDCl3) δ 0.72 (s,
3H), 0.85 (s, 3H), 0.90 (d, J ) 6.4 Hz, 3H), 1.00-2.30 (m,
steroidal CH and CH2), 3.61 (s, 3H), 4.59 (m, 1H), 4.85 (s, 1H),
5.02 (s, OH), 5.12 (s, OH), 6.785 (d, J ) 2.2 Hz, 0.5H), 6.818
(br s, 0.5H), 7.076 (dd, J ) 8.8, 2.3 Hz, 1H), 7.352 (d, J ) 8.9
Hz, 1H), 7.368 (d, J ) 9.0 Hz, 1H), 7.894 (d, J ) 9.0 Hz, 1H),
7.907 (d, J ) 1.3 Hz, 3H), 7.981 (d, J ) 9.1 Hz, 1H), 8.013 (d,
J ) 8.9 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) δ 12.3, 17.5,
22.5, 23.3, 23.6, 25.8, 26.0, 26.6, 27.2, 30.7, 31.0, 33.3, 33.8,
34.4, 34.9, 35.5, 41.6, 45.3, 47.3, 48.9, 51.5, 79.7, 81.5, 110.3,
111.1, 113.3, 114.9, 117.2, 117.8, 117.9, 119.3, 127.1, 127.6,
129.6, 130.1, 131.4, 134.6, 134.8, 150.6, 150.9, 151.0, 151.5,
153.5, 153.6, 174.6; LRMS m/z 776 (M+, 0.5). Anal. Calcd for
(S)-(-)-7,7′-Dih yd r oxy-2,2′-d im et h oxy-1,1′-b in a p h t h -
yl (15). Compound 14 (0.021 g, 0.026 mmol) was dissolved in
degassed MeOH/THF (3:1) (2.0 mL), and LiOH (0.011 g, 0.46
mmol) was added under an argon atmosphere. The reaction
mixture was stirred at room temperature for 16 h and acidified
with 3 M HCl solution. Volatiles were removed under reduced
pressure, and the crude product was purified by column
chromatography on a silica gel column (21 cm × 1.2 cm) using
8-12% EA/CHCl3 as the eluent to yield 0.008 g (90%) of 15:
[R]26 ) + 48.3° (c 2.4, DMF); lit.12f [R]26 ) + 45.9° (c 1.0,
D
D
DMF) for the (S) isomer: 1H NMR (300 MHz, CDCl3) δ 3.76
(s, 6H), 4.78 (s, 2H), 6.34 (d, J ) 2.7 Hz, 2H), 6.94 (d, J ) 2.4
Hz, 2H), 7.29 (d, J ) 3.0 Hz, 2H), 7.77 (d, J ) 9.0 Hz, 2H).
7.89 (d, J ) 9.0 Hz, 2H).
C
47H52O10‚1.5H2O: C, 70.22; H, 6.90. Found: C, 70.28; H, 6.93.
(S)-(-)-1,1′-Bin a p h th yl-2,2′,7,7′-tetr ol (13). The coupled
Ack n ow led gm en t. We thank the Department of
Science & Technology, New Delhi, for support of this
work (grant no. SP/S1/G-08/96). A.K.B. and N.M.S.
thank the UGC and the CSIR, respectively, for financial
support.
steroidal binaphthol 12 (0.016 g, 0.021 mmol) was dissolved
in degassed MeOH (1.0 mL), and LiOH (0.010 g, 0.416 mmol)
was added under argon atmosphere. The reaction was stirred
at room temperature for 16 h and acidified with 3 N HCl
solution. Volatiles were removed under reduced pressure, and
the crude product was purified by column chromatography on
J O000703Z