Practical synthetic protocols of enantiopure 1,1′-binaphthyl-2, 2′-dicarboxylic acid and 2,2′-dicyano-1,1′-binaphthyl starting from optically active dibromide precursor

Article abstract of DOI:10.1016/j.tetlet.2004.02.156

Dilithiation of optically active 2,2^′-dibromo-1,1 ^′-binaphthyl 2 with t-BuLi followed by carboxylation of the resulting dilithio-intermediate 3 with CO₂ gave optically active 1,1^′-binaphthyl-2,2^′-dicarboxylic acid 1, which was further transformed to its dicyano derivative 4. Both of these transformations were carried out in a one-pot operation and the products were obtained in excellent yields with no observable racemization.

Full text of DOI:10.1016/j.tetlet.2004.02.156

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3485–3487
Practical synthetic protocols of enantiopure 1,10-binaphthyl-2,20-
dicarboxylic acid and 2,20-dicyano-1,10-binaphthyl starting from
optically active dibromide precursor
Takashi Hoshi,a,* Eiji Nozawa,b Masayoshi Katano,b Toshio Suzukia and
Hisahiro Hagiwarab,*
aFaculty of Engineering, Niigata University, 2-Nocho, Ikarashi, Niigata 950-2181, Japan
bGraduate School of Science and Technology, Niigata University, 2-Nocho, Ikarashi, Niigata 950-2181, Japan
Received 22 January 2004; revised 25 February 2004; accepted 27 February 2004
Abstract—Dilithiation of optically active 2,20-dibromo-1,10-binaphthyl 2 with t-BuLi followed by carboxylation of the resulting
dilithio-intermediate 3 with CO2 gave optically active 1,10-binaphthyl-2,20-dicarboxylic acid 1, which was further transformed to its
dicyano derivative 4. Both of these transformations were carried out in a one-pot operation and the products were obtained in
excellent yields with no observable racemization.
Ó 2004 Elsevier Ltd. All rights reserved.
Enantiopure 1,10-binaphthyl-2,20-dicarboxylic acid 1 has
received much attention as a versatile synthetic inter-
mediate in the preparation of a variety of chiral catalysts
and ligands in enantioselective processes.1 Since its first
preparation by Kuhn and Albrecht,2 several practical
synthetic routes have been reported: (1) Optical resolu-
tion of racemate (Æ)-1 or its precursors.3 (2) Inter- or
intramolecular diastereoselective Ullmann coupling of
optically active 2-halonaphthalene derivatives.4 (3) Pal-
ladium-catalyzed methoxycarbonylation of enantiopure
2,20-bis(triflate)-1,10-binaphthyl.5 However, the optical
resolution and Ullmann coupling protocols require
multi-pot operations starting from the key intermedi-
ates. Though methoxycarbonylation directly affords the
dimethyl ester of 1 in high yield, highly toxic CO gas
must be handled with care in the laboratory. Because it
is well precedented that carboxylation of organometallic
reagents with CO2 directly affords carboxylic acids
without any toxic reagents,6 we report herein a novel
practical synthesis of enantiopure 1 via a one-pot
operation of the dilithiation followed by carboxylation
of optically active 2,20-dibromo-1,10-binaphtyl 2, which
is easily available according to our recently reported
procedure.7 We also describe a one-pot, quantitative
and racemization-free transformation from 1 to 2,20-
dicyano-1,10-binaphthyl 4 as a novel synthetic applica-
tion of enantiopure 1.
The synthetic studies of optically active (R)-1 are sum-
marized in Table 1. Initially, we chose n-BuLi as
dilithiation reagent. Dilithiation of optically active (R)-2
(97% ee) with 2.4 equiv of n-BuLi was complete in less
than 30 min at )72 °C under N2. After the atmosphere
was exchanged from N2 to CO2, carboxylation of the
resulting dilithio-intermediate (R)-3 with atmospheric
CO2 was carried out at this temperature for 17 h to
afford (R)-1 in 65% yield and 86% ee (entry 1). The
chemical yield was at a satisfactory level. However,
decrease in enantiopurity, which was repeatedly
observed in this reaction condition (entry 2), suggested
that racemization of the axial chirality slowly but surely
occurred during the transformation. Incorporation of
sterically demanding substituents into 2,20-positions of
optically active binaphthyl compounds is a well-recog-
nized strategy for restricting racemization of its axial
chirality. Then, we investigated the chelating effect
of TMEDA (N,N,N0,N0-tetramethylethylenediamine)
and PMDTA (N,N,N0,N00,N00-pentamethyldiethylenetri-
amine) with the expectation that their chelating effects
would increase steric bulk of the lithium substituents of
nucleophilic binaphthyl intermediates.8 However, no
detectable improvement of the retention of the axial
chirality was observed when 2.4 equiv of TMEDA was
added to the reaction mixture (entry 3). Though the
* Corresponding authors. Tel.: +81-25-262-7401; fax: +81-25-265-
7339; e-mail: hoshi@gs.niigata-u.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.156

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T. Hoshi et al. / Tetrahedron Letters 45 (2004) 3485–3487
Table 1. Synthetic study of (R)-1 via dilithiation followed by carboxylation of (R)-2a;b
RLi, THF
additive, –72 °C
CO2, –72 °C
Br
Br
Li
Li
CO2H
CO2H
(R)-2
(R)-3
(R)-1
Entry
ee of (R)-2f (%)
RLi (equiv)
Additive (equiv)
ee of (R)-1g (%)
Yield of (R)-1 (%)
1c
97
94
94
94
94
92
92
n-BuLi (2.4)
n-BuLi (2.4)
n-BuLi (2.4)
n-BuLi (2.4)
n-BuLi (2.4)
t-BuLi (4.8)
n-BuLi (2.7)
––
––
86
82
81
90
85
91
89
65
61
70
21
65
90
43
2d
3d
4d
5d
6c;e
7c
TMEDA (2.4)
TMEDA (20)
PMDTA (2.4)
––
LiBr (2.8)
a The reaction scales were in the range from 0.60 to 7.3 mmol.
b The reaction times of carboxylation were in the range from 17 to 24 h.
c The dilithiation reaction was carried out for 30 min.
d The dilithiation reaction was carried out for 1 h.
e Average of two runs.
f The enantiopurity of (R)-2 was estimated based on the specific rotation value (Ref. 10).
g The enantiopurity of (R)-1 was determined by HPLC using a Daicel Chiralcel OD-H (Ref. 9).
1) DCC
2)
retention of enantiopurity was gradually improved as
the amount of TMEDA was increased, the complete
retention of enantiopurity was not realized even through
H
•CH3CN
H2N
C
CH3
CO2H
H
CO2H
CO2H
Ph
the use of 20 equiv of TMEDA and the chemical yield
was significantly decreased (entry 4). The tridentate
chelating agent PMDTA was also ineffective for the
complete retention of the axial chirality (entry 5). For-
tunately, in contrast to n-BuLi, t-BuLi was found to be
sufficient to effect the transformation from (R)-2 to (R)-1
(entry 6). Actually, the complete retention of the axial
chirality was reproductively achieved through the use of
t-BuLi. Though no explanation for this excellent result
can be offered at this time, we felt that it was reasonable
to assume that the LiBr byproduct may play an
important role in the retention of the axial chirality. In
fact, the improvement of the retention of the axial chi-
rality was also observed when n-BuLi was used in the
presence of LiBr (entry 7). In addition, it is noteworthy
that not only the enantiopurity but also the chemical
yield of (R)-1 were remarkably improved when t-BuLi
was used as the dilithiation reagent. Since the racemate
(Æ)-1 crystallized preferentially from an ether solution,3d
the contamination of the minor enantiomer (S)-1 could
be removed by recrystallization followed by filtration of
the resulting nearly racemic precipitates to afford
enantiopure (R)-1 confirmed by HPLC analysis.9
CONH
C
CH3
3) CH3CN
Ph
43%, >99% de
(3 steps)
5
( )-1
1) SOCl2
2) NH3
3) SOCl2
CN
CN
50%
(3 steps)
(s)-4 (>99% ee)
Scheme 1.
thetic protocol requires multi-pot operations starting
from racemate (Æ)-1 and the chemical yield derived
from the enantiopure intermediate 5 is moderate. Thus,
in order to find a convenient synthetic protocol for
enantiopure 4 and a novel synthetic application of
enantiopure 1, we investigated the synthesis of enan-
tiopure (R)-4 starting from enantiopure (R)-1 with the
expectation that the axial chirality would be completely
retained during the transformation (Scheme 2). Because
the transformation from a carboxylic acid to a nitrile
consists of three steps in which an acyl chloride and an
amide are consecutively produced as intermediates, we
carried out a one-pot operation without isolation of the
two intermediates (R)-6 and (R)-7 in order to simplify
this protocol. A solution of enantiopure (R)-1 in SOCl2
was heated to reflux for 10 min. After evaporation of
residual SOCl2, THF and NH3 were sequentially added
Enantiopure 2,20-dicyano-1,10-binaphthyl 4 would be a
prospective candidate for a versatile synthetic interme-
diate of chiral ligands because the cyano group is con-
vertible into not only a variety of other functional
groups but also heterocycles containing nitrogen as the
ligating donor in transition metal complexes.11;12 To the
best of our knowledge, only one effective synthetic
protocol of enantiopure 4 has been reported by Von-
denhof and Mattay (Scheme 1).11a However, their syn-

T. Hoshi et al. / Tetrahedron Letters 45 (2004) 3485–3487
3487
References and notes
b
a
1. (a) Ooi, T.; Uematsu, Y.; Maruoka, K. J. Org. Chem.
2003, 68, 4576–4578, and references cited therein; (b)
Yang, D.; Wong, M.-K.; Yip, Y.-C.; Wang, X.-C.; Tang,
M.-W.; Zheng, J.-H.; Cheung, K.-K. J. Am. Chem. Soc.
1998, 120, 5943–5952, and references cited therein; (c)
Trost, B. M.; Lee, D. C.; Rise, F. Tetrahedron Lett. 1989,
30, 651–654; (d) Groves, J. T.; Myers, R. S. J. Am. Chem.
Soc. 1983, 105, 5791–5796; (e) Mazaleyrat, J.-P.; Cram, D.
J. J. Am. Chem. Soc. 1981, 103, 4585–4586.
COCl
COCl
(R)-1 (>99% ee)
(R)-6
c
CONH2
CONH2
(R)-4 (>99% ee)
2. Kuhn, R.; Albrecht, O. Justus Liebigs Ann. Chem. 1928,
465, 282–287.
3. (a) Seki, M.; Yamada, S.-I.; Kuroda, T.; Imashiro, R.;
Shimizu, T. Synthesis 2000, 1677–1680; (b) Furutani, T.;
Hatsuda, M.; Imashiro, R.; Seki, M. Tetrahedron: Asym-
metry 1999, 10, 4763–4768; (c) Oi, S.; Matsuzaka, Y.;
Yamashita, J.; Miyano, S. Bull. Chem. Soc. Jpn. 1989, 62,
956–957; (d) Kanoh, S.; Hongoh, Y.; Motoi, M.; Suda, H.
Bull. Chem. Soc. Jpn. 1988, 61, 1032–1034; (e) Colter, A. K.;
Clemens, L. M. J. Am. Chem. Soc. 1965, 87, 847–852; (f)
Hall, D. M.; Turner, E. E. J. Chem. Soc. 1955, 1242–1251.
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2655–2658; (b) Miyano, S.; Shimizu, K.; Sato, S.;
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1346; (c) Miyano, S.; Tobita, M.; Hashimoto, H. Bull.
Chem. Soc. Jpn. 1981, 54, 3522–3526.
(R)-7
Scheme 2. Reagents and conditions: (a) SOCl2 (excess), reflux, 10 min;
(b) NH3 (excess), THF, 0 °C, 15 min; (c) NEt3 (excess), Tf2O (excess),
0 °C, 40 min, 97% (three steps).
to the crude product at 0 °C. Then, the reaction mixture
was stirred at this temperature for 15 min. After evap-
oration of THF and excess NH3, the residue was diluted
with CH2Cl2 and then reacted with large excess of Et3N
and Tf2O at 0 °C for 40 min. Concentration of the
reaction mixture and subsequent purification by chro-
matography on silica gel afforded the desired enantio-
pure (R)-4 in 97% overall yield with no observable
racemization confirmed by HPLC analysis.13
5. Ohta, T.; Ito, M.; Inagaki, K.; Takaya, H. Tetrahedron
Lett. 1993, 34, 1615–1616.
6. Hattori, T.; Suzuki, Y.; Miyano, S. Chem. Lett. 2003, 32,
454–455, and references cited therein.
7. Hoshi, T.; Shionoiri, H.; Suzuki, T.; Ando, M.; Hagiwara,
H. Chem. Lett. 1999, 28, 1245–1246.
In conclusion, our present study demonstrated novel
practical protocols for the synthesis of enantiopure 1,10-
binaphthyl-2,20-dicarboxylic acid (R)-1 and its dicyano
derivative (R)-4 starting from optically active dibromide
precursor (R)-2. We also found that the employment of
t-BuLi as dilithiation reagent is crucial for the retention
of the axial chirality during the transformation from
(R)-2 to (R)-1. Synthetic application of these enantio-
pure functional binaphthyl compounds to the prepara-
tion of chiral catalysts and ligands is under way in our
laboratory.
8. For chelating effects of TMEDA and PMDTA with an
aryllithium, see: Reich, H. J.; Goldenberg, W. S.; Sanders,
A. W.; Jantzi, K. L.; Tzchucke, C. C. J. Am. Chem. Soc.
2003, 125, 3509–3521, and references cited therein.
9. Daicel Chiralcel OD-H (0.46 cm / Â 25 cm), hexane/
EtOH/TFA ¼ 90:10:0.1, wavelength: 254 nm, flow rate:
1.0 mL/min, retention time: 7.8 min (R), 11.8 min (S).
10. Brown, K. J.; Berry, M. S.; Waterman, K. C.; Lingenfel-
ter, D.; Murdoch, J. R. J. Am. Chem. Soc. 1984, 106,
4717–4723.
11. For the preparation of enantiopure 4, see: (a) Vondenhof,
M.; Mattay, J. Chem. Ber. 1990, 123, 2457–2459; (b) Kurz,
L.; Lee, G.; Morgans, D., Jr.; Waldyke, M. J.; Ward, T.
Tetrahedron Lett. 1990, 31, 6321–6324.
ꢀ
12. For the preparation of optically active 4, see: (a) Karak,
Acknowledgements
P.; Putala, M. Collect. Czech. Chem. Commun. 2000, 65,
729–740; (b) Hoshi, T.; Katano, M.; Nozawa, E.; Suzuki,
T.; Hagiwara, H. Tetrahedron Lett. 2004, 45 following
paper. doi: 10.1016/j.tetlet.2004.02.156.
This work was partially supported by a Grant-in-Aid for
Young Scientists (B) (no 1474033) from the Ministry of
Education, Culture, Sports, Science and Technology of
Japan and Grant for Promotion of Niigata University
Research Projects (to T.H.).
13. Daicel Chiralcel OD-H (0.46 cm / Â 25 cm), hexane/
i-PrOH ¼ 3:1, wavelength: 254 nm, flow rate: 0.2 mL/min,
retention time: 34.8 min (R), 38.7 min (S).