Synthesis and resolution of racemic 2-amino-2′-hydroxy-1,1′-binaphthyl

Article abstract of DOI:10.1135/cccc19961520

The title compound 3 has been prepared via a highly selective, Cu(II)-mediated cross-coupling of 2-aminonaphthalene 1 and 2-naphthol 2 and resolved into enantiomers via crystallization of diastereoisomeric salts with (1S)-(+)-10-camphorsulfonic acid. The method has been optimized and the use of chromatography eliminated.

Full text of DOI:10.1135/cccc19961520

1520
Smrcina, Vyskocil, Polivkova, Polakova, Kocovsky:
SYNTHESIS AND RESOLUTION OF RACEMIC
2-AMINO-2′-HYDROXY-1,1′-BINAPHTHYL
a
a
a
Martin SMRCINA , Stepan VYSKOCILa,b1, Jana POLIVKOVA , Jana POLAKOVA
b2
and Pavel KOCOVSKY
a Department of Organic Chemistry, Charles University, 128 40 Prague 2, Czech Republic
b Department of Chemistry, University of Leicester, U.K.; e-mail: 1 sv9@le.ac.uk, 2 pk10@le.ac.uk
Received July 1, 1996
Accepted July 12, 1996
Dedicated to the memory of Dr Zdenek Arnold.
The title compound 3 has been prepared via a highly selective, Cu(II)-mediated cross-coupling of
2-aminonaphthalene 1 and 2-naphthol 2 and resolved into enantiomers via crystallization of
diastereoisomeric salts with (1S)-(+)-10-camphorsulfonic acid. The method has been optimized and
the use of chromatography eliminated.
Key words: Binaphthyls; Oxidative coupling; Resolution.
C2-Symmetrical, 2,2′-disubstituted 1,1′-binaphthyls, such as BINOL 5, BINAP, etc.,
which all have identical groups in positions 2 and 2′, are established ligands for use in
asymmetric catalysis1. On the other hand, their congeners with non-identical substi-
tuents in these positions (which are no longer C2-symmetrical) have only recently
emerged. Among them, Hayashi’s MOP (with OMe and PPh2 groups)2 and our amino
alcohol 3 (NOBIN) (refs3–5), have risen to prominence2,6. Whereas C2-symmetrical
1,1′-binaphthyls, such as BINOL 5, are readily synthesized via an efficient oxidative
coupling of the appropriate naphthol (e.g. 2) (refs1,7), non-symmetrical derivatives are
generally more difficult to obtain since their preparation requires a selective transfor-
mation of one of two identical functional groups2,8
.
Recently, we have described a highly chemoselective oxidative cross-coupling between
two different naphthyl derivatives3–5,9 and rationalized the observed selectivity in terms
of frontier orbital theory5. In short, the most selective cross-coupling can be expected
for those pairs of reactants where one component is electron-rich (and, therefore, easily
oxidized), whereas the other partner is relatively electron-poor (e.g., due to an electron-
withdrawing group)5. Thus, for instance, typical pairs for successful cross-coupling are
2-aminonaphthalene and 3-methoxycarbonyl-2-naphthol (71%) (ref.5), 2-naphthol and
3-methoxycarbonyl-2-naphthol (81%) (refs5,9), or 2-aminonaphthalene and 2-naphthol
(85%) (refs3,5). For further examples of selective cross-coupling see ref.9. The latter
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

Short Communication
1521
coupling (1 + 2 → 3; Scheme 1) can be modified to produce the amino alcohol 3 in an
enantiomerically enriched form (46% ee), by carrying out the oxidative coupling with a
complex of CuCl2 and a chiral amine, such as α-methylbenzylamine4. Enantiomerically
pure 3 is then obtained by recrystallization4.
The amino alcohol 3 proved to be an excellent scaffold for building chiral tita-
nium(IV) complexes that have been shown to be superior to other catalysts in aldol-
type condensations, such as the Mukaiyama reaction6. However, a drawback, which
attenuates the wider use of 3, is the practicality of its preparation. Clearly, the asymmetric
coupling process (1 + 2) (ref.4), although excellent on a small scale, may appear less
suitable for larger-scale operations. Therefore we explored an alternative route, namely
the resolution of the racemic 3 into enantiomers. Herein, we describe an optimized
procedure for obtaining larger quantities of (R)-(+)-3 and (S)-(–)-3 via the latter approach.
RESULTS AND DISCUSSION
The oxidative cross-coupling of 2-aminonaphthalene 1 and 2-naphthol 2 was carried
out at room temperature for 48 h in the presence of a stoichiometric amount of an in
situ generated complex of copper(II) chloride and benzylamine in methanol. The amino
alcohol 3 (NOBIN) thus obtained was contaminated by small quantities of the products
arising from self-coupling of each of the starting materials, i.e., the diamine 4 and diol 5,
NH2
OH
+
1
2
CuCl , C H CH NH
6 5 2
2
2
CH OH, r.t., 48h
3
X
NH2
OH
+
X
3
4
5
X = NH
2
X = OH
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1522
Smrcina, Vyskocil, Polivkova, Polakova, Kocovsky:
and by other impurities (mainly of inorganic nature). Although these byproducts can be
easily separated by flash chromatography3, for the large-scale synthesis of 3 an alterna-
tive method was required. We reasoned that the individual components may be separ-
ated owing to their different acid-basic properties.
As expected, the diamine 4 was separated as an insoluble solid by digesting the crude
coupling product with concentrated methanolic KOH, which converted 3 and 5 into the
soluble naphtholates. The pH of the solution was then adjusted to ≈8 in order to precipi-
tate a mixture of 3 and 5. The latter precipitate was treated with concentrated HCl in
ethanol and the resulting hydrochloride of 3 and the neutral 5 were partitioned between
water and toluene. The amino alcohol 3 was then released from its water-soluble hydro-
chloride by treatment with aqueous ammonia and crystallized from toluene to give the
product of sufficient purity for further resolution into enantiomers.
Originally, good resolution of (±)-3 was attained by fractional crystallization of the
diastereoisomeric salts with (1S)-(+)-10-camphorsulfonic acid (CSA). However, on a
larger scale, the latter procedure proved capricious. After numerous experiments, it
turned out that the efficiency of the resolution was crucially dependent on the source
and quality of the CSA used, the best specimen originating from Fluka which, appar-
ently, contains least water. The success of the resolution has been found to be depend-
ent on the batch of camphorsulfonic acid used. Furthermore, the chemical purity of
(±)-3 proved to be no less important. Thus, in particular, 4 has to be completely
removed prior to the resolution, since this byproduct, even if present in quantities as
low as 1%, not only co-crystallizes with the desired salt, but also nucleates the crystal-
lization of its diastereoisomer(!), which substantially lowers the diasteroisomeric purity
of the final crop.
The amount of the solvent (chlorobenzene and ethanol in a 10 : 1 ratio) required has
to be tested first on a small scale before scaling up. We have noticed that if the resolu-
tion gave more than ca 60% of the salt precipitate, related w/w to the starting (±)-3, the
resulting enantiomeric purity of NOBIN was lower.
In an optimized procedure, solid (+)-CSA (Fluka) was added to a suspension of (±)-3
of >99% purity in a chlorobenzene–ethanol mixture (10 : 1), preheated to 110 °C. The
suspension had quickly dissolved and within 10–15 min at 110 °C the salt begun to
precipitate. The heating was then discontinued and the stirred mixture was allowed to
cool to room temperature. The desired optically active base was liberated from the
precipitated salt on treatment with pyridine; single recrystallization of the crude base
from benzene produced the enantiomerically pure (S)-(–)-3 in 30% overall yield. De-
composition of the diastereoisomeric salt that remained in the solution afforded (R)-(+)-3 of
75% enantiomeric purity in 66% yield12.
In conclusion, we have developed an optimized procedure for an alternative prepara-
tion of both enantiomers of the amino alcohol 3 via the cross-coupling of 1 and 2
followed by purification of the crude, racemic product and its resolution into enantiomers
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

Short Communication
1523
by means of camphorsulfonic acid. The importance of the quality of the resolving agent
and of the chemical purity of (±)-3 to be resolved has been demonstrated. Since chro-
matographic purification has been avoided, this protocol is suitable for a large-scale
preparation of NOBIN 3.
EXPERIMENTAL
Optical rotations were measured with an error of <±0.5°. All solvents used for the reactions or for
crystallization experiments were degassed by purging with argon (20 min; 60 ml/min). (1S)-(+)-10-
Camphorsulfonic acid was purchased from Fluka.
2-Amino-2′-hydroxy-1,1′-binaphthyl (±)-3
Preparation of the crude 2-amino-2′-hydroxy-1,1′-binaphthyl (±)-3. To a stirred solution of copper(II)
chloride dihydrate (50 g, 0.3 mol) in degassed methanol (250 ml) was added a solution of benzyl-
amine (128.6 g, 1.2 mol) in degassed methanol (250 ml). The resulting solution was purged with
argon for 5 min and a mixture of 2-aminonaphthalene (14.3 g, 0.1 mol) and 2-naphthol (14.4 g, 0.1 mol)
in degassed methanol (1 l) was then added. After stirring at room temperature for 48 h under argon,
the mixture was first acidified with concentrated HCl (150 ml), stirred for 10 min, then treated with
concentrated aqueous ammonia (200 ml), and finally poured into water (4.5 l). The resulting precipi-
tate was isolated by suction and washed with methanol (100 ml). After air-drying, ca 28 g of the
crude product was obtained. This procedure was repeated for 8 times to give 224 g of the crude
product in total.
Removing 2,2′-diamino-1,1′-binaphthyl 4 from the crude NOBIN 3.To a suspension of crude
NOBIN (224 g) in methanol (500 ml) was added a 20% solution of KOH in methanol (1 700 ml).
The mixture was stirred at room temperature for 5 h and then filtered through celite. The solid ma-
terial was washed with methanol (100 ml) and the filtrate was poured into a vigorously stirred 15%
aqueous HCl (1.5 l). The resulting suspension was neutralized by adding concd aqueous ammonia
(100 ml) to reach pH ≈8 and the precipitate was isolated by suction and washed with methanol (100 ml).
Air-drying of the latter material yielded 125 g of crude NOBIN 3.
Removing BINOL 5 from NOBIN 3. Water (950 ml) was added to a solution of NOBIN (125 g),
free of the diamine 4, in a mixture of ethanol (2.5 l) and concentrated HCl (300 ml), and the solution
was extracted with toluene (3 × 1 l). The aqueous phase was then poured into a mixture of water (4 l)
and concentrated aqueous ammonia (500 ml), and the resulting precipitate was isolated by suction.
Air-drying of the latter material afforded 103 g of purified NOBIN 3 contaminated by 2,2′-diamino-
1,1′-binaphthyl 4 (3%) and BINOL 5 (≤1%), as revealed by GCMS.
Crystallization of NOBIN 3 from toluene. The purified NOBIN (103 g) was refluxed in toluene (5 l)
for 30 min and the hot solution was filtered. On cooling to room temperature, the filtrate furnished
pure, crystalline NOBIN (85 g). Concentration of the mother liquors yielded a second crop of crys-
talline NOBIN (13 g). In total, this whole procedure afforded 98 g (43%) of pure (>99%), racemic
NOBIN 3.
Resolution of Racemic NOBIN 3
To a stirred suspension of (±)-NOBIN 3 (5.70 g) in a mixture of chlorobenzene (160 ml) and ethanol
(16 ml), preheated to 110 °C, was added solid (1S)-(+)-10-camphorsulfonic acid (5.00 g). The result-
ing clear solution was further stirred at 110 °C until a precipitate begun to form (10–15 min); heating
was then discontinued and the mixture was stirred overnight. The precipitate was isolated by suction
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1524
Smrcina, Vyskocil, Polivkova, Polakova, Kocovsky:
and washed with dichloromethane (20 ml) and dried to afford the corresponding salt (3.53 g). The
latter salt was dissolved in pyridine (5 ml) and the solution was poured into hot water (300 ml, 70 °C).
Hot water is essential for obtaining a solid product. If cold water is used, a less easy-to-handle paste
is formed. The product was isolated by suction, washed with water (50 ml), and air-dried to yield
(S)-(–)-NOBIN (1.88 g; 33%): [α]D –116° (c 1.5; THF). Crystallization from benzene (40 ml) afforded
the enantiomerically pure (S)-(–)-3 (1.71 g; 30 %): [α]D –120° (c 1.5; THF, ≈100% ee).
The diastereoisomeric salt obtained from the solution (7.06 g) was worked up in the same manner
to yield (R)-(+)-3 (3.76 g; 66%): [α]D +87 (c 1.5; THF; 75% ee). Enantiomerically pure (R)-(+)-NOBIN
can be obtained from this material via fractional crystallization of this product from benzene4.
We thank The Grant Agency of the Czech Republic for grant No. 203/96/0694 and The Grant Agency
of the Charles University for grant No. 86/95 and the University of Leicester for additional support.
REFERENCES
1. For recent reviews on binaphthyls, see: a) Rosini C., Franzini L., Raffaelli A., Salvadori P.:
Synthesis 1992, 503. b) Noyori R: Asymmetric Catalysis in Organic Synthesis. Wiley and Sons,
New York 1994.
2. a) Uozumi Y., Hayashi T.: J. Am. Chem. Soc. 113, 9887 (1991). b) Ozawa F., Kubo A., Hayashi
T.: Tetrahedron Lett. 33, 1485 (1992). c) Uozumi Y., Lee S.-Y., Hayashi T.: Tetrahedron Lett.
33, 7185 (1992). d) Uozumi Y., Tanahashi A., Lee S.-Y., Hayashi T.: J. Org. Chem. 58, 1945
(1993). e) Hayashi T., Iwamura H., Uozumi Y., Matsumoto Y., Ozawa F.: Synthesis 1994, 526.
f) Hayashi T., Iwamura H., Naito M., Matsumoto Y., Uozumi Y.: J. Am. Chem. Soc. 116, 775
(1994).
3. Smrcina M., Lorenc M., Hanus V., Kocovsky P.: Synlett 1991, 231.
4. a) Smrcina M., Lorenc M., Hanus V., Sedmera P., Kocovsky P.: J. Org. Chem. 57, 1917 (1992).
b) Smrcina M., Polakova J., Vyskocil S., Kocovsky P.: J. Org. Chem. 58, 4535 (1993).
5. Smrcina M., Vyskocil S., Maca B., Polacek M., Claxton T. A., Abbott A. P., Kocovsky P.:
J. Org. Chem. 59, 2156 (1994).
6. a) Carreira E. M., Singer R. A., Lee W.: J. Am. Chem. Soc. 116, 8837 (1994). b) Carreira E. M.,
Lee W., Singer R. A.: J. Am. Chem. Soc. 116, 3649 (1994). c) Singer R. A., Carreira E. M.:
J. Am. Chem. Soc. 117, 12360 (1995).
7. a) Feringa B., Wynberg H.: Bioorg. Chem. 7, 397 (1978). b) Brusse J., Groenendijk J. L. G.,
te Koppele J. M., Jansen A. C. A.: Tetrahedron 41, 3313 (1985).
8. Green J., Woodward S.: Synlett 1995, 155.
9. a) Yamamoto K., Yumioka H., Okamoto Y., Chikamatsu H.: J. Chem. Soc., Chem. Commun.
1987, 168. b) Hovorka M., Gunterova J., Zavada J.: Tetrahedron Lett. 31, 413 (1990). c)
Hovorka M., Zavada J.: Org. Prep. Proced. Int. 23, 200 (1991). d) Hovorka M., Scigel R.,
Gunterova J., Tichy M., Zavada J.: Tetrahedron 48, 9503 (1992). e) Hovorka M., Zavada J.:
Tetrahedron 48, 9517 (1992).
Collect. Czech. Chem. Commun. (Vol. 61) (1996)