New Methods of Resolution and Enrichment of Enantiomeric Excesses of 1,1′-Bi-2-naphthol

Article abstract of DOI:10.1021/jo961937e

Partial resolution of racemic 1,1′-bi-2-naphthol (1) was readily achieved to obtain enriched (scalemic) 1 using (S)-proline (2), The structure of the complex 3 formed between 1 (2 equiv) and (S)-proline (1 equiv) was characterized by an X-ray diffraction method. Enantiomeric excesses of the incompletely resolved 1 were enriched to obtain essentially pure (R)- and (S)-1 following a simple procedure using B(OH)₃ and TMEDA.

Full text of DOI:10.1021/jo961937e

4
302
J . Org. Chem. 1997, 62, 4302-4306
New Meth od s of Resolu tion a n d En r ich m en t of En a n tiom er ic
Excesses of 1,1′-Bi-2-n a p h th ol
,
†
†
‡
Mariappan Periasamy,* Lakshmanan Venkatraman, and K. R. J ustin Thomas
School of Chemistry, University of Hyderabad, Central University P.O., Hyderabad 500 046, India, and
RSIC, Indian Institute of Technology, Madras 600 036, India
Received October 16, 1996 (Revised Manuscript Received April 1, 1997X
)
Partial resolution of racemic 1,1′-bi-2-naphthol (1) was readily achieved to obtain enriched (scalemic)
using (S)-proline (2). The structure of the complex 3 formed between 1 (2 equiv) and (S)-proline
1 equiv) was characterized by an X-ray diffraction method. Enantiomeric excesses of the
incompletely resolved 1 were enriched to obtain essentially pure (R)- and (S)-1 following a simple
procedure using B(OH) and TMEDA.
1
(
3
In tr od u ction
2
-symmetric chiral 1,1′-bi-2-naphthol (1) is useful
form. The most widely used method of synthesis of chiral
involves optical resolution through formation of dia-
1
The C
stereomeric complexes using a chiral source. The pro-
cedures developed in this way often require expensive
chiral sources, and the experimental parts are highly
complicated. This inspired us to look for a simple way
of resolving racemic 1 using readily available and inex-
pensive amino acids. We describe here results of this
study.
in getting higher levels of asymmetric induction in
asymmetric synthesis.1 Many chiral auxiliaries devel-
oped from this compound are highly efficient in stoichio-
metric and catalytic processes like asymmetric reduc-
2
3
4
tions, Diels-Alder reactions, glyoxylate-ene reactions,
5
Mukaiyama aldol-ene reactions, aza Diels-Alder reac-
tions, Michael reactions, enantioselective protonations,
6
7
8
9
and nitroaldol reactions.
Resu lts a n d Discu ssion
P a r tia l Resolu tion of 1,1′-Bi-2-n a p h th ol Usin g (S)-
P r olin e. Initially, it was discovered in this laboratory
that racemic 1 upon refluxing with (S)-proline (2) in
benzene leads to precipitate and filtrate fractions that
1
4
after dilute HCl treatment give partially resolved 1.
Repetition of the experiment successively three times
resulted in essentially complete resolution. Since ben-
zene is not an acceptable solvent, we were looking for an
alternative solvent.
The enantiodifferentiating property of 1 has been found
to be outstanding. However, applications of chiral aux-
iliaries incorporating this material are hindered because
of the expense of the chiral 1 and the difficulties involved
in getting it in enantiomerically pure forms. Several
methods such as optical resolutions through formation
Comparable results were obtained using solvents such
as methanol, dichloromethane, and methanol-dichlo-
romethane mixtures (Scheme 1, Table 1). It appears that
the complex formation is essentially complete in 0.5 h in
methanol (Table 1, entry 2). Filtering the reaction
mixture under hot conditions gave the (S)-(-)-isomer
with 59% ee but only in 7% yield. The results of reaction
for 3 and 12 h are similar in dichloromethane. Also,
refluxing the mixture for 36 h in dichloromethane
resulted in slight improvement in the ee of the (S)-(-)-
isomer.
of diastereomers,10 enzymatic resolution, resolution
11
1
2
through inclusion complexes and asymmetric synthesis
from 2-naphthol13 are available to obtain 1 in enantiopure
X
†
Abstract published in Advance ACS Abstracts, May 15, 1997.
University of Hyderabad.
Indian Institute of Technology.
‡
(
1) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis
992, 503.
2) Noyori, R.; Tomino, I.; Tanimoto, Y.; Nishigava, M. J . Am. Chem.
Soc. 1984, 106, 6709.
3) (a) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007. (b) Bao,
J .; Wulff, W. D.; Rheingold, A. L. J . Am. Chem. Soc. 1993, 114, 3814.
1
(
The effect of concentration of the chiral source used
was studied to find out the optimum amounts of resolving
agent required for the resolution. The use of 1 and 2 in
a 1:1 ratio gives better results (Table 2, entries 1-4).
(
(
(
(
c) Kobayashi, M.; Araki, M.; Hachiya, I. J . Org. Chem. 1994, 59, 3758.
d) Ishihama, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 1561.
e) Kaufmann, D.; Boese, R. Angew. Chem., Int. Ed. Engl. 1990, 29,
Since amino acids exist in the form of zwitterion (i.e.,
5
45.
2
a ), it was obviously of interest to study the effect of
(
4) Van der Meer, F. T.; Feringa, F. L. Tetrahedron Lett. 1992, 33,
deprotonated (2b) and protonated (2c) forms toward
complexation with 1. To examine this, experiments were
6
695.
(
(
(
5) Mikami, K.; Matsukawa, S. J . Am. Chem. Soc. 1993, 115, 7309.
6) Hattori, K.; Yamamoto, H. J . Org. Chem. 1992, 57, 3264.
7) Kobayashi, S.; Suda, S.; Yamada, M.; Mukaiyama, T. Chem. Lett.
1
994, 97, 1.
8) Ishihara, K.; Kaneeda, M.; Yamamoto, H. J . Am. Chem. Soc.
994, 116, 11179.
9) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J . Am.
Chem. Soc. 1992, 114, 4418.
10) (a) J acques, J .; Fouquey, C.; Viterbo, R. Tetrahedron Lett. 1971,
617. (b) J acques, J .; Fouquey, C. Org. Synth. 1988, 67, 13. (c) Gong,
(12) (a) Kawashima, M.; Hirayama, A. Chem. Lett. 1990, 2299. (b)
Tanaka, K.; Okada, T.; Toda, F. Angew. Chem., Int. Ed. Engl. 1993,
32, 1147. (c) Toda, F.; Tanaka, K.; Stein, Z.; Goldberg, I. J . Org. Chem.
1994, 59, 5748. (d) Hu, Q. S.; Vitharna, D.; Pu, L. Tetrahedron:
Asymmetry 1995, 6, 2123.
(13) (a) Brussee, J .; J ansen, A. C. A. Tetrahedron Lett. 1983, 24,
3261. (b) Smrcina, M.; Lorenc, M.; Hanus, V.; Sedmera, P.; Kocovsky,
P. J . Org. Chem. 1992, 51, 1917.
(
1
(
(
4
B.; Chen, W.; Hu, B. J . Org. Chem. 1991, 56, 423. (d) Brunel, J . M.;
Buono, G. J . Org. Chem. 1993, 58, 7313.
(14) Periasamy, M.; Prasad, A. S. B.; Kanth, J . V. B.; Reddy, Ch. K.
Tetrahedron: Asymmetry 1995, 6, 341.
(11) Kazlauskas, R. J . J . Am. Chem. Soc. 1989, 111, 4953.
S0022-3263(96)01937-8 CCC: $14.00 © 1997 American Chemical Society

Enantiomeric Excesses of 1,1′-Bi-2-naphthol
J . Org. Chem., Vol. 62, No. 13, 1997 4303
Sch em e 1
Sch em e 2
Ta ble 1. P a r tia l Resolu tion of Ra cem ic
1
,1′-Bi-2-n a p h th ol (1) Usin g (S)-P r olin e in Va r iou s
a
Solven ts
Ta ble 3. En r ich m en t of En a n tiom er ic Excesses of
P a r tia lly Resolved (Sca lem ic) (1) Usin g (S)-P r olin e
1
,1′-bi-2-naphthol from
precipitate filtrate
% ee % yield % ee % yield
a
reaction
S. no. time (h)
1
,1′-bi-2-naphthol (1) from
precipitate filtrate
% ee % yield
solvent
CH3OH
CH3OH
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
CHCl3
1
,1′-bi-2-naphthol
(1) (% ee)
b
1
2
3
4
5
6
7
8
12
0.5
12
3
36
12
12
12
S, 46
S, 50
S, 52
S, 46
S, 66
S, 52
S, 49
49
55
49
56
52
43
48
32
R, 54
R, 66
R, 70
R, 73
R, 63
R, 52
R, 58
R, 49
43
38
40
35
38
40
39
52
S. no.
% ee
% yield
b
c
c
c
d
e
f
b
1
2
3
4
5
6
S, 47
S, 57
R, 47
R, 73
S, 69
S, 66
S, 70
S, 83
S, 43
62
69
12
00
70
62
R, 03
R, 40
R, 71
R, 73
S, 18
S, 09
27
14
73
100
17
21
c
c
d
e
S, 85
S, 81
f
CH3OH +CH2Cl2 S, 78
a
a
All experiments were performed using racemic 1,1′-bi-2-
In all experiments, 1,1′-bi-2-naphthol (5 mmol) and (S)-proline
(5 mmol) were used. b The components were dissolved in methanol
(15 mL), heated at 60 °C for 10 min, and left at 25 °C for 12 h.
b
naphthol (5 mmol) and (S)-proline (5 mmol). The substrate was
taken in methanol (15 mL), and the contents were heated at 60
C for 10 min and left at 25 °C. The substrate was taken in
dichloromethane (20 mL), and the contents were refluxed. The
substrate was taken in acetonitrile (15 mL), and the contents were
heated at 60 °C for 10 min and left at 25 °C. The substrate was
taken in chloroform (30 mL), and the contents were heated at 60
C for 10 min and left at 25 °C. Dichloromethane (10 mL) and
c
c
°
Refluxed in dichloromethane (25 mL) for 12 h (in entry 3, 20 mL
d
d
of dichloromethane was used). Refluxed in dichloromethane (20
mL) for 12 h. e Refluxed in acetonitrile (20 mL) for 12 h. Refluxed
f
e
in methanol (1 mL) and dichloromethane (10 mL) mixture for 12
h.
f
°
methanol (1 mL) were added, and the contents were refluxed.
An interesting observation was made when (S)-proline
(10 mmol) was taken in methanol and portions of 1 were
Ta ble 2. P a r tia l Resolu tion of Ra cem ic
added successively to obtain the complex as precipitate
that on ether/dilute HCl treatment gave partially re-
solved 1 (Scheme 2). In this way, mixtures of 1 enriched
in the S isomer were obtained in 49-56% ee (43% yield),
and the 1 enriched in the R isomer (45% ee) was obtained
in 77% yield.
1
,1′-Bi-2-n a p h th ol: Effect of Con cen tr a tion of (S)-P r olin e
a
a n d th e Ad d itives KOH a n d P TSA
1
,1′-bi-2-naphthol from
precipitate filtrate
S. no. (S)-proline (mmol) % ee % yield
% ee
% yield
1
2
3
4
5
6
2.5
5.0
7.5
10
5
S, 46
S, 52
S, 52
S, 49
S, 60
49
49
43
48
25
R, 54
R, 70
R, 52
R, 58
R, 21
R,S, 00
43
40
40
39
69
En r ich m en t of En a n tiom er ic Excesses of P a r -
t ia lly R esolved (Sca lem ic) 1 Usin g (S)-P r olin e.
After recrystallization of the complex obtained between
racemic 1 and (S)-proline in methanol followed by dilute
HCl treatment, the (S)-(-)-isomer was obtained in 81%
ee (12% yield). The (S)-(-)-isomer with 37% ee (24%
yield) was recovered from the solution. Since this
crystallization method was not satisfactory, we decided
to repeat the experiments starting from the partially
resolved 1 using an equivalent amount of (S)-proline
again. The results are summarized in Table 3. The ee
of the S isomer could be further enhanced in this way
b
c
5
100
a
All the experiments were carried out using racemic 1,1′-bi-2-
naphthol (1) (5 mmol) in methanol. In entries 1 and 2, methanol
15 mL) and in other entries 25 mL of methanol was used. The
components were heated at 60 °C for 10 min and left at 25 °C for
(
2 h. KOH (1.5 mmol) was added to the reaction mixture. c p-
b
1
Toluenesulfonic acid (5 mmol) was added to the reaction mixture.
(
Table 3, entries 1 and 2, 5 and 6).
Str u ctu r al Ch ar acter ization of th e In clu sion Com -
carried out in the presence of KOH and p-toluenesulfonic
acid (PTSA) in methanol (Table 2, entries 5 and 6).
Addition of KOH, which is expected to favor the formation
of 2b, gave results without improvement. Interestingly,
in the presence of PTSA, no precipitation occurred,
indicating that the carboxylate form may be necessary
for the resolution (Table 2, entries 5 and 6).
p lex. The crystals obtained in the reaction of racemic 1
and (S)-proline in methanol were not suitable for X-ray
crystal structure analysis. Fortunately, the crystals
obtained from (S)-(95% ee)-1 and (S)-proline could be
analyzed using the X-ray diffraction method.
Final atomic coordinates of the complex 3 prepared by
the reaction of (S)-(-)-1 and (S)-proline in methanol,
along with lists of anisotropic thermal parameters,
hydrogen coordinates, bond lengths, and bond angles,
have been deposited with the Cambridge Crystallo-
graphic Data Centre. They can be obtained, on request,

4
304 J . Org. Chem., Vol. 62, No. 13, 1997
Periasamy et al.
prevent a simultaneous close approach of the two bi-
naphthols near the proline molecule. There is also an
another hydrogen-bonding interaction between the two
binaphthols where one CH group of the naphthyl ring
acts as a proton donor and the oxygen site of the hydroxyl
group acts as a proton acceptor at a CH‚‚‚O distance of
2
.715 Å.
En h a n cem en t of En a n tiom er ic Excesses of Sca le-
m ic 1,1′-Bi-2-n a p h th ol Usin g B(OH)
3
a n d TMEDA.
Although the (S)-proline used in the resolution and
enrichment procedures can be recovered easily, it would
be better if the partially resolved 1 could be enriched
further without using another chiral source. Some time
ago, Horeau reported that chemical duplication of a
nonracemic(scalemic) substrate, for example, through
formation of two diastereomeric carbonate diesters from
a scalemic alcohol, separation of the homochiral (RR, SS),
chiral dimer and the achiral (RS) meso dimer, and
regeneration of the alcohol from the homochiral dimer,
provided the scalemic alcohol with amplified enantio-
meric excess.1
5a
This idea was recently applied by
Fleming to enrich the enantiomeric excess of a scalemic
1
5c
alcohol using oxalyl chloride from 92.6% to 99.6%.
Fleming has also shown that if there is no stereoselection,
the derivative ML will be formed following the algebraic
F igu r e 1. Perspective view of the complex 3.
2
2
2
expression, X :Y :2XY. If the starting enantiomeric
excess is 80%, (i.e., X:Y ) 90:10, X,Y are the concentra-
2
2
tions of R and S, respectively) and since (X + Y ) and
2
XY are diastereomers, separation of the RR and SS
2
2
diastereomers (X + Y ) from the above mixture and
regeneration of R and S enantiomers should give R:S in
the ratio (X :Y ) 8100:100 ) 98.8:1.2, corresponding to
an ee of 97.6%.
2
2
We were interested in adopting a similar idea for the
enrichment of the enantiomeric excess of scalemic 1.
Since 1 is a bifuntional molecule it can form a complex
2 3
of the type B L (L ) 1,1′-bi-2-naphthyloxy) (4a ).
F igu r e 2. Packing diagram of the crystal structure of the
complex 3.
from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 1EZ, UK. The
intermolecular organization and association in the inclu-
sion complex are depicted in Figures 1 and 2. The
structural parameters exhibited for the various moieties
in the inclusion complex are in good agreement with that
of the standard values. Minor deviations can be at-
tributed to the packing of these molecules in the unit cell.
The carboxylate and quaternary ammonium groups of
the proline molecule make T-shaped hydrogen bonds with
the hydroxyl group of the one binaphthol with the OH‚‚‚N
and O‚‚‚HO distances of 2.088 and 2.109 Å, respectively,
leading to the locally hydrogen-bonded 1:1 host-to-guest
complex. The host-guest interaction between one bi-
naphthol and proline is complemented by a π-π stacking
interaction between the binaphthols C21C22C23C24-
C26C27C28C29C30 and C11C12C13C14C15C16C17-
C18C19C20. Within the binaphthol that exhibits hydro-
gen-bonding interactions with the proline molecule the
two naphthyl moieties are nearly perpendicular to each
other with the dihedral angle between the mean planes
Four isomers derived from RRR, SSS, RRS, and RSS
combinations of binaphthol would be expected in the ratio
3
3
2
2
of X :Y :3X Y:3XY . An initial ratio of R:S (i.e., X:Y) 90:
3
3
1
9
(
0 (i.e., 80% ee), would lead to the R:S ratio of X :Y (i.e.,
9.86:0.14, 99.72% ee) after separation of RRR and SSS
X + Y ) isomers and regeneration of R and S. However,
3
3
it should be pointed out that this product distribution
can be expected only if there is no stereoselectivity in the
formation of RRR, SSS or RRS, SSR.
We have carried out a series of experiments to examine
these possibilities. Initially, we have attempted to
2 3 3
prepare the B L complex from B(OH) and 1 in benzene
using a Dean-Stark apparatus. Unfortunately, the
enriched enantiomer was obtained only in low yields
16
(
Table 4, entry 1).
Fortunately, better results were
were taken in a 3:2 ratio in
obtained when 1 and B(OH)
3
(15) (a) Vigneron, J . P.; Dhaenens, M.; Horeau, A. Tetrahedron 1973,
29, 1055. (b) Rautenstrauch, V.; Megard, P.; Bourdin, B.; Furrer, A. J .
Am. Chem. Soc. 1992, 114, 1418. (c) Fleming, I.; Ghosh, S. K. J . Chem.
Soc., Chem. Commun. 1994, 99.
9
4.0°. However, in the other binaphthol the dihedral
angle between the mean planes of the naphthyl rings is
3.5°. Here, the larger binaphthyl groups probably
(16) Venkatraman, L.; Periasamy, M. Tetrahedron: Asymmetry
7
1996, 7, 2471.

Enantiomeric Excesses of 1,1′-Bi-2-naphthol
J . Org. Chem., Vol. 62, No. 13, 1997 4305
Ta ble 4. En h a n cem en t of En a n tiom er ic Excesses of
1
Unfortunately, the nature of the TMEDA complex of the
borate obtained under the present conditions is not
clearly understood. The complex is not crystalline enough
for X-ray crystal structure analysis, and we could not
arrive at a molecular formula on the basis of elemental
,1′-Bi-2-n a p h th ol (1) Usin g B(OH)3 a n d TMEDAa
product (1) obtained from
precipitate
(% ee) (mmol) % ee yieldd (%)
filtrate
yield (%)
entry
no.
(1)
B(OH)3
% ee
1
analysis and H NMR spectral data. However, we have
1
2
3
4
S, 47
R, 62
R, 34
R, 16
S, 28
S, 18
R, 34
R, 17
R, 34
R, 52
R, 68
R, 75
S, 18
S, 34
S, 52
S, 69
S, 85
R, 79
S, 75
2.0
2.0
2.0
2.0
2.0
2.0
2.0
0.57
1.14
1.80
2.30
2.50
0.60
1.10
1.80
2.30
2.90
2.67
2.50
S, 91
R, 73
R, 51
R, 41
S, 58
S, 31
R, 88
R, 88
R, 92
R, 95
R, 94
R, 93
S, 89
S, 95
S, 95
S, 93
S, 93
R, 93
S, 95
20
78
47
28
38
57
38
11
31
30
41
48
13
28
38
52
53
77
77
S, 38
R, 40
S, 03
R, 01
R, 03
S, 05
R, 12
R, 03
S, 05
R, 20
R, 52
R, 63
S, 05
S, 01
S, 16
S, 34
S, 73
S, 06
R,S, 00
69
06
33
56
52
30
48
76
55
53
45
39
75
54
47
36
33
10
10
observed that the reaction of racemic 1 (3 equiv) and boric
acid (2 equiv) in refluxing benzene (Dean-Stark setup)
b
b
3
resulted in the formation of Kaufmann’s C symmetric
b
17
5
RRR and SSS propeller 4b.
6
7
8
9
Exp er im en ta l Section
c
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
Racemic 1,1′-bi-2-naphthol was prepared by coupling â-naph-
thol using FeCl in water followed by recrystallization from
benzene or toluene.
Aldrich was used. Enantiomeric excesses were calculated from
3
18
Commercial (S)-proline supplied by
25
R
D
values measured on a Autopol-II automatic polarimeter.
It was also confirmed for a few samples of 1,1′-bi-2-naphthol
by HPLC analysis using chiralpak OP column with methanol
as solvent. Elemental analyses were performed on a Perkin-
Elmer elemental analyzer model 240C.
c
Resolu tion of Ra cem ic 1,1′-Bi-2-n a p h th ol Usin g (S)-
P r olin e. Typ ica l P r oced u r e. 1,1′-Bi-2-naphthol (5 mmol,
a
All experiments were carried out using 5 mmol of (1) in
acetonitrile (20 mL). In entries 1-3, 3 mmol of (1) was used. In
1
.43 g) and (S)-proline (5 mmol, 0.58g) were taken in methanol
entries 1-17, 1 mmol of TMEDA and in entries 18 and 19 5 mmol
(20 mL). The contents were heated at 60 °C for 12 h. Then
b
of TMEDA was used. In these experiments, benzene (40 mL) was
the reaction mixture was brought to 25 °C and filtered.
Methanol was evaporated to obtain a residue. The precipitate
and the residue were treated with diethyl ether (100 mL) and
dilute HCl (3 N, 20 mL) in separate runs. The organic layer
was separated, washed successively with water (2 × 10 mL)
c
used as solvent, and the contents were refluxed for 12 h. HPLC
analysis on a chiralpak OP using methanol as eluent did not detect
d
the presence of the other enantiomer. Yields are based on the
amount of scalemic (1) used.
and brine (10 mL) and dried over anhydrous MgSO
4
. The
Sch em e 3
solvent was evaporated to obtain 1,1′-bi-2-naphthol. The ee
2
5
values are based on R
D
) 34.5 (C1, THF) for the compound
with 100% ee.19
Since the complex formed between 1 and 2 in methanol was
not soluble in most of the solvents, NMR spectra of the complex
could not be recorded. However, elemental analysis of the
complex had revealed that 1 and 2 are present in the ratio of
2
5
:1 in the complex (Anal. Calcd for C45NO
.42; N, 2.46. Found: C, 78.36; H, 5.50, N, 2.04). This was
6
H37: C, 78.58; H,
also confirmed by X-ray diffraction analysis.
acetonitrile and TMEDA was used to precipitate the
complex (Table 4, entries 2 and 3). However, the results
were still poor. Better results were obtained when the
En r ich m en t of En a n tiom er ic Excesses of P a r tia lly
Resolved 1,1′-Bi-2-n a p h th ol Usin g (S)-P r olin e. Partially
enriched 1 (5 mmol, 1.43 g) and (S)-proline (5 mmol, 0.58 g)
were taken in dichloromethane (20 mL), and the contents were
refluxed for 12 h. The reaction mixture was brought to 25 °C
and filtered. The solvent was evaporated to obtain a residue.
The precipitate and the residue were stirred in diethyl ether
3
scalemic 1 and B(OH) were taken in 5:2 ratio (Table 4,
entries 4-7; Scheme 3). It was clear from the results
that the precipitate fraction contains the enriched isomer,
leaving behind the mixture with low ee in solution. So,
(100 mL) and dilute HCl (3 N, 20 mL) in separate runs. The
it was decided to use B(OH)
omer present in excess over the racemic to form the B
complex. This led to very good results (Table 4, entries
-17). In the experiments using mixtures with high ee,
3
equivalent to the enanti-
organic layer was separated, washed successively with water
2
L
3
(2 × 10 mL) and brine (10 mL), and dried over anhydrous
MgSO
4
. The solvent was evaporated to isolate 1.
8
En h a n cem en t of En a n tiom er ic Excesses of P a r tia lly
Resolved (Sca lem ic) 1,1′-Bi-2-n a p h th ol. Scalemic 1 (5
mmol), B(OH) , and TMEDA (1 mmol) were taken in acetoni-
3
trile (20 mL). The resulting suspension was refluxed for 12
h. The reaction mixture was cooled to 25 °C and filtered. The
filtrate was concentrated to obtain a residue. In separate runs,
the precipitate and the residue were treated with diethyl ether
the yields of enriched material were somewhat low and
more amounts were left in solution (Table 4, entries 11
and 12, 16 and 17). This problem was rectified by using
an excess of TMEDA (5 equiv) to precipitate the B
complex (Table 4, entries 18 and 19).
2 3
L
The results are in accordance with the selective forma-
tion of RRR or SSS complexes derived from the enanti-
omer present in excess over the racemic mixture. The
(
100 mL) and dilute HCl (3 N, 20 mL) for 10 min, washed
successively with water (2 × 10 mL) and brine (10 mL), and
4
dried over anhydrous MgSO . The solvent was removed to
obtain 1.
3
poor results obtained when scalemic 1 and B(OH) were
used in a 3:2 ratio further illustrates the point that the
RRS and RSS isomers might not have formed in these
experiments. Kaufmann has previously noted that the
1
(17) The
reported data (ref 3e).
18) Vogel, A. I. Text Book of Practical Organic Chemistry; Long-
H NMR (400 MHz) spectral data were identical to the
(
reaction of racemic 1 with BrBH
2
2
‚SMe results in the
man: Birmingham, AL, 1978.
2
5
formation of enantiomers of the C
3
-symmetric propeller
D
(19) Various authors report the values of R from 33.2 (ref 12b) to
compound (4b).3 It appears that the 1,1′-bi-2-naphthol
e
35.2 (ref 12d) (C1, THF) for 1,1′-bi-2-naphthol of 100% ee. The Fluka
25
catalog (1995-96) reports the R
D
value of 34.5 ( 1 for a sample of
tends to form the symmetric RRR and SSS compounds
rather than the unsymmetrical SRR and RSS isomers.
purity >99% ee (HPLC). We have calculated the ee values on the basis
2
5
of the value of R
D
) 34.5 (C1, THF) for 100% ee.

4
306 J . Org. Chem., Vol. 62, No. 13, 1997
Periasamy et al.
X-r a y Cr ysta l Str u ctu r e An a lysis. Suitable crystals of
,1′-bi-2-naphthol-(S)-proline complex were obtained as fol-
significant information, and the residual density had a maxi-
3
3
1
mum peak 0.314e Å and minimum trough at -0.245eÅ .
Crystal data for 3 (C NO H37): θ range 3.22-59.93°;
lows. (S)-(-)-1 (5 mmol) was dissolved in methanol (20 mL).
To the solution, was added 2 (5 mmol). The contents were
heated at 60 °C gently for 10 min and left at 25 °C for 12 h.
The precipitated complex was redissolved in hot methanol (20
mL) and left at room temperature for 12 h to obtain the
crystals of the complex.
4
5
6
formula weight 687.76, orthorhombic, space group P21 21 21,
a ) 9.0610(10) Å, b ) 13.943(2) Å, c ) 27.480(4) Å, V )
3
-3
-1
3471.8(8) Å , Z ) 4, D
calc
) 1.316 g cm , µ
calc
) 6.99 cm ,
F(000) ) 1448, index ranges 0 e h e 10, 0 e k e 15, 0 e l e
30, S ) 1.144.
A colorless prismatic crystal of dimensions 0.35 × 0.25 ×
0
.52 mm suitable for X-ray diffraction was mounted on a glass
Con clu sion
capillary using glue and transferred to an automated Enraf-
Nonius CAD4 diffractometer equipped with a graphite mono-
chromator. Cell dimensions were obtained by the least-
squares refinement of well centered 25 reflections in the θ
range 2.5-60.0°. Intensity data were collected using Cu KR
Simple and efficient procedures for resolving racemic
1
,1′-bi-2-naphthol (1) and enrichment of enantiomeric
excesses of scalemic mixtures of 1 were developed. The
2:1 complex obtained by the interaction of (S)-(-)-1 and
(S)-proline was characterized by X-ray diffraction analy-
sis. Besides being useful for the synthesis of chiral 1,1′-
bi-2-naphthol, the methods described here should also
stimulate further work in this area.
(
λ ) 1.541 84 Å) radiation by the ω - 2θ scan mode with a
constant scan speed of 4 deg/min. Decay of the crystal during
the measurement was monitored by measuring the intensity
of two standard reflections at regular intervals, and no
appreciable deterioration of the crystal was noticed. 2933
unique data were collected out of which 2839 reflections had
I >2σ(I) and were flagged observed for subsequent calculations.
The data were corrected for Lorentz and polarization effects.
The structure was solved by direct methods (SIR92) and
Ack n ow led gm en t. We are thankful to the UGC,
New Delhi, for support under a Special Assistance
Program. We thank Prof. P. T. Manoharan, RSIC, IIT,
Madras, for extending us the use of the X-ray diffraction
facilities.
2
refined on F using a full-matrix least-squares technique
(
SHELXL92). All of the hydrogens were located directly in
different Fourier maps and refined isotropically. Convergence
was achieved at R ) 0.0280 and wR ) 0.0756 for 2839 observed
reflections. The final difference map revealed no chemically
J O961937E