Asymmetric construction of binaphthyl by the chiral diether-mediated conjugate addition of naphthyllithium to naphthalenecarboxylic acid 2,6-di-t-butyl-4-methoxyphenyl ester

Article abstract of DOI:10.1248/cpb.57.752

Two ways for the synthesis of binaphthyl were examined based on a chiral ligand-mediated asymmetric conjugate addition of 1-naphthyllithium to naththalene-2-carboxylic acid 2,6-di-t-butyl-4-methoxyphenyl esters. The one pot method by conjugate addition-el

Full text of DOI:10.1248/cpb.57.752

752
Notes
Chem. Pharm. Bull. 57(7) 752—754 (2009)
Vol. 57, No. 7
Asymmetric Construction of Binaphthyl by the Chiral Diether-Mediated
Conjugate Addition of Naphthyllithium to Naphthalenecarboxylic Acid
2,6-Di-t-butyl-4-methoxyphenyl Ester
,a
b
b
,b
*
*
Mitsuru SHINDO, Yasutomo YAMAMOTO, Ken-ichi YAMADA, and Kiyoshi TOMIOKA
a Institute for Materials Chemistry and Engineering, Kyushu University; 6–1 Kasugako-en, Kasuga 816–8580, Japan: and
b Graduate School of Pharmaceutical Sciences, Kyoto University; Yoshida, Sakyo-ku, Kyoto 606–8501, Japan.
Received March 18, 2009; accepted April 11, 2009; published online April 14, 2009
Two ways for the synthesis of binaphthyl were examined based on a chiral ligand-mediated asymmetric con-
jugate addition of 1-naphthyllithium to naththalene-2-carboxylic acid 2,6-di-t-butyl-4-methoxyphenyl esters. The
one pot method by conjugate addition-elimination gave a relatively higher enantioselectivity than the two step
synthesis based on addition and subsequent oxidative aromatization.
Key words axial chirality; central chirality; asymmetric addition; chiral ligand
Asymmetric construction of axial chirality represented by the way to binaphthyl to give target 9. Another way is the
biaryl has been the continuing interest of organic chemistry.1) asymmetric conjugate addition and subsequent elimination of
Coupling of two naphthyl groups is the fundamental strategy a leaving group X from 7 to give the target 9 in a one pot. It
for the formation of chiral biaryl bond by using chiral part- is important to point out that the central chirality in 7 and 8
ner(s) or chiral mediator. Practical level of asymmetric ox- should be transferred or converted to axial chirality of 9 in
idative coupling of naphthols to chiral binaphthol has been both of two approaches.
demonstrated by Nakajima et al.2,3) Transition metal-cat-
Asymmetric Conjugate Addition and Subsequent Ox-
alyzed formation of axial chirality has been proven to be in idative Aromatization to Binaphthyl We began our stud-
the reasonably high level of efficiency.4,5) Other interesting ies with two-step procedure, that is, asymmetric conjugate
way is the application of conjugate addition of naphthylmet- addition and subsequent oxidative aromatization to binaph-
als to chiral naphthyl acceptors and subsequent elimination thyl. The reaction of 3 eq of 3 with naphthalenecarboxylic
process as has been demonstrated by Meyers and Lutomski,6) acid BHA ester (6a) in the presence of 3.3 eq of diether lig-
Wilson and Cram,7) and Miyano and colleagues.8) We have and 1 in a mixture of toluene and diethyl ether at ꢁ45 °C for
also developed an efficient asymmetric conjugate addition- 5 h gave, after protonation of an intermediate enolate 7a
elimination of 1-napthyllithium 3 and fluoronaphthylimine 2 (XꢀH) with trifluoroacetic acid, a 1 : 1 olefin isomeric mix-
giving chiral binaphthyls 4 and 5 with 91% ee by setting ture of addition products 8 in 66% yield (Chart 3). Since the
the external chiral diether ligand 19,10) (5 mol%)-catalyzed subsequent in situ treatment of an enolate 7a successively
methodology as shown in Chart 1.11) As part of the continu- with super-hydride, methyl iodide, and finally sodium boro-
ing approach toward conjugate addition-elimination protocol, hydride has been confirmed to give an alcohol 10 with 95%
we selected a naphthyl ester as a directing group in place of enantiomeric excess (ee) in 40% yield,13) the adducts 8
an imine.12) We describe herein the comparison of two ap- should have 95% enantiomeric purity. The central chirality in
proaches to axial chirality of binaphthyl by using asymmetric 8 was then transferred by treating with 2,3-dichloro-5,6-di-
conjugate addition of 1-naphthyllithium 3 to naphthalenecar- cyano-p-benzoquinone (DDQ) in refluxing tetrahydrofuran
boxylic acid BHA (2,6-di-t-butyl-4-methoxyphenol) ester 6 (THF) for 1.5 h into axial chirality in (ꢂ)-(S)-9 in 92%
under the steric control of chiral diether 1.
chemical yield. Enantiomeric purity of (ꢂ)-(S)-9 was, how-
Asymmetric conjugate addition reaction of 3 to 6 is con- ever, disappointingly low, 24% ee.
trolled by a chiral diether 1-chelated complex to give addi-
The referential binaphthyl ester (ꢁ)-(R)-9 with established
tion intermediate 7 as an initial product. Protonation would absolute configuration and specific rotation was synthesized
give us a chiral addition product 8 if X (ꢀH) is not a leaving from the corresponding aldehyde (R)-511) that was obtained
group (Chart 2). Subsequent oxidative aromatization of 8 is
Chart 1
Chart 2
∗ To whom correspondence should be addressed. e-mail: tomioka@pharm.kyoto-u.ac.jp
© 2009 Pharmaceutical Society of Japan

July 2009
753
Discussions
Oxidative aromatization of dihydronaphthalenic com-
pound bearing central chirality is the efficient process to bi-
naphthyl. However, transfer of central chirality to axial chi-
rality involves loss of enantioselectivity in a large extent. Ad-
dition-elimination sequence is a more efficient way for the
transfer of central chirality to axial chirality as well as for
aromatization. It is quite interesting to note that the two ways
gave the antipode each other.
Experimental
All melting points are uncorrected. Silica gel column chromatography
was used for purification. NMR was measured in CDCl3 unless otherwise
noted, and chemical shifts and coupling constants are presented in ppm d
relative to tetramethylsilane and Hz, respectively. Abbreviations are as fol-
lows: s, singlet; d, doublet; t, triplet; q, quartet; sep, septet; m, multiplet; br,
broad. The wave numbers of maximum absorption peaks of IR spectroscopy
are presented in cmꢁ1
.
Chart 3
Synthesis of 2,6-Di-t-butyl-4-methoxyphenyl (S)-1,1ꢀ-binaphthalene-2-
carboxylate ((ꢁ)-9) with 24% ee by Two Step Procedure To a solution
of 0.42 ml (3.0 mmol) of 1-bromonaphthalene in 5 ml of dry ether was added
1.86 ml (3.0 mmol) of a 1.6 M solution of n-butyllithium in hexane at
ꢁ78 °C. The yellow heterogeneous mixture was stirred for 1 h at ꢁ78 °C
and was added via cannula at ꢁ78 °C to a solution of 2-naphthoic acid BHA
ester (391 mg, 1.0 mmol) and 1 (800 mg, 3.3 mmol) in toluene (25 ml). The
orange solution was stirred at ꢁ45 °C for 6 h, and was then quenched with
trifluoroacetic acid (0.77 ml). The mixture was diluted with ether (50 ml),
washed with saturated sodium bicarbonate, brine, and then dried over mag-
nesium sulfate. Concentration and chromatography (hexane/etherꢀ100/1—
5/1) gave a 1 : 1 mixture of 1,2-dihydro- and 1,4-dihydro isomers 8 (344 mg,
66%) as a colorless amorphous and recovered 1 (0.76 g, 95%). 1H-NMR, IR,
and TLC of 8 were identical with those of authentic sample.12—14)
Fig. 1
A mixture of 8 above (164 mg, 0.32 mmol) and 2,3-dichloro-5,6-dicyano-
p-benzoquinone (90 mg, 0.38 mmol) in THF (5 ml) was refluxed for 1.5 h.
The brown mixture was diluted with ether (50 ml) and washed with 15%
NaOH (30 mlꢃ5), brine, and then dried over magnesium sulfate. Concentra-
tion and chromatography (hexane/etherꢀ15/1) gave (ꢂ)-(S)-9 (150 mg,
92%) as colorless solids of mp 190—205 °C and [a]D25 ꢂ18.4 (cꢀ1.24,
CHCl3). Optical purity was 24% (vide infra). 1H-NMR d: 1.19 and 1.28
(each 9H, s, t-Bu), 3.70 (3H, s, OMe), 6.72 and 6.76 (each 1H, d, Jꢀ3), 7.07
(1H, d, Jꢀ8), 7.14 (1H, ddd, Jꢀ7, 7, 1), 7.22—7.30 (4H, m), 7.36 (1H, ddd,
Jꢀ7, 7, 1), 7.48 (1H, m), 7.58 (1H, m), 7.85 (1H, dd, Jꢀ8, 5), 7.99 (1H, d,
Jꢀ8), 8.13 (1H, d, Jꢀ9), 8.62 (1H, d, Jꢀ8). 13C-NMR d: 31.5 (q), 35.5 (q),
55.2 (q), 111.5 (d), 125.1 (d), 125.4 (d), 125.4 (d), 125.5 (d), 125.9 (d),
126.2 (d), 126.3 (d), 126.4 (d), 126.8 (d), 127.6 (d), 127.7 (d), 128.1 (d),
128.3 (d), 128.5 (d), 132.8 (s), 133.3 (s), 133.8 (s), 135.3 (s), 137.0 (s),
141.6 (s), 143.5 (s), 144.2 (s), 156.1 (s), 165.2 (s). IR (KBr): 1740, 1590.
MS m/z: 516 (Mꢂ). Anal. Calcd for C36H36O31/3H2O: C, 82.73; H, 7.07.
Found: C, 82.57; H, 6.94.
1-Methoxy-2-naphthoic acid BHA Ester (6b) To a suspension of NaH
(0.86 g, 21.5 mmol, 60% in mineral oil, washed with hexane) in THF (30 ml)
was added dropwise a solution of 2,6-di-t-butyl-4-methoxyphenol (4.60 g,
19.5 mmol) in THF (20 ml) at 0 °C. After stirring for 10 min at room temper-
ature, a solution of 1-methoxy-2-naphthoyl chloride (6.44 g, 29.2 mmol),
prepared from the corresponding acid15) and thionyl chloride, in THF
(20 ml) was added dropwise to the above green solution at 0 °C. After stir-
ring for 3.5 h at room temperature, 15% NaOH (100 ml) was added, and the
mixture was stirred for another 1 h, and then water (100 ml) was added. The
resulting mixture was extracted with benzene (100 mlꢃ3). The combined or-
ganic layers were washed with water, brine, and then dried over magnesium
sulfate. Concentration and chromatography (benzene then benzene/AcOEtꢀ
10/1) gave 6b (6.75 g, 82%) as colorless needles of mp 181.5—182.5 °C
(AcOEt). 1H-NMR d: 1.37 (18H, s, t-Bu), 3.83 and 4.09 (each 3H, s, OMe),
6.94 (2H, s, ArH), 7.57—8.36 (6H, m, ArH). IR (KBr): 1735, 1640, 1590.
MS m/z: 420 (Mꢂ). Anal. Calcd for C27H32O4: C, 77.11; H, 7.67. Found: C,
77.40; H, 7.86.
Chart 4
by reported catalytic biaryl synthesis shown in Chart 1.
Potassium permanganate oxidation of (R)-5 with 62% ee in a
1 : 1 mixture of acetone and water at reflux for 1.5 h gave the
corresponding carboxylic acid (R)-11. Two step treatment of
11 with thionyl chloride providing an acid chloride and then
with sodium salt of BHA in THF gave the requisite BHA
ester (ꢁ)-(R)-9 of 62% ee.
Asymmetric Conjugate Addition-Elimination to Bi-
naphthyl in One Pot The attempted reaction of 3 with
isopropyl 1-methoxynaphthalene-2-carboxylate, in place of
BHA ester, in THF gave 1,2-addition product without forma-
tion of conjugate addition product. BHA ester 6b was the ap-
propriate acceptor of conjugate addition in THF at ꢁ78 °C
for 1.5 h and further at ꢁ45 °C for 1 h giving addition-elimi-
nation product 9 in 91% yield (Chart 4).
The chiral diether ligand 1-mediated asymmetric reaction
proceeded much more smoothly in toluene at ꢁ78 °C for
0.5 h to give binaphthyl (ꢁ)-(R)-9 with 52% ee in 93% yield.
The absolute configuration was determined to be R by the
comparison of specific rotation.
Asymmetric Synthesis of (ꢂ)-(R)-9 with 52% ee by Addition-Elimina-
tion To a solution of 1-bromonaphthalene (0.42 ml, 3.0 mmol) and 1
(800 mg, 3.3 mmol) in toluene (15 ml) was added at ꢁ78 °C a pentane solu-
tion of tert-butyllithium (1.85 M, 1.62 ml, 3.0 mmol). The mixture was
stirred for 1 h at ꢁ78 °C. A solution of 1-methoxy-2-naphthoic acid BHA
ester (6b, 421 mg, 1.0 mmol) in toluene (5 ml) was added dropwise to the

754
Vol. 57, No. 7
formations of Carbon Resources,” a Grant-in-Aid for Scientific Research
(A), and a Grant-in-Aid for Young Scientist (B) from the Ministry of Educa-
tion, Culture, Sports, Science and Technology-Japan.
yellow solution above at ꢁ78 °C and the pale green solution was stirred at
ꢁ78 °C for 0.5 h. The mixture was added with saturated ammonium chloride
(20 ml) and extracted with ether (25 mlꢃ3). The combined extracts were
washed with brine and dried over magnesium sulfate. Concentration and
chromatography (hexane/etherꢀ15/1) gave (R)-9 with 52% ee (0.48 g, 93%)
as colorless solids of mp 218—221 °C and [a]D25 ꢁ40.0 (cꢀ1.08, CHCl3).
(R)-1,1ꢀ-Binaphthalene-2-carboxylic Acid To a solution of (R)-1,1ꢄ-
binaphthalene-2-carbaldehyde (5)11) (149 mg. 0.528 mmol, [a]D25 ꢂ63.0
(cꢀ1.185, CHCl3), 62% ee) in acetone (4 ml) was added under reflux a solu-
tion of potassium permanganate (0.50 g, 3.17 mmol) in hot water (4 ml).
After reflux for 1.5 h, the mixture was treated with 10% HCl (2 ml) and
sodium bisulfite at room temperature, and then extracted with CHCl3
(15 mlꢃ3). The combined organic layers were washed with water, brine, and
then dried over magnesium sulfate. Concentration and chromatography
(CHCl3/etherꢀ10/1) gave an acid (92.2 mg, 59%) as a powder of mp 177—
References and Notes
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1
184 °C and [a]D25 ꢂ19.0 (cꢀ2.74, benzene). H-NMR (DMSO-d6) d: 7.0—
8.3 (13H, m), 12.44 (1H, s). IR (KBr): 1680. Spectroscopic data were super-
imposable with those reported.16)
(R)-1,1ꢀ-Binaphthalene-2-carboxylic Acid BHA Ester ((ꢂ)-(R)-9 with
62% ee) A mixture of above 1,1ꢄ-binaphthalene-2-carboxylic acid (83.9
mg, 0.28 mmol), pyridine (1 drop), and thionyl chloride (2 ml) was refluxed
for 1.5 h, and then concentrated to afford acid chloride (0.11 g) as a yellow
oil (IR (KBr): 1780). A solution of the chloride in THF (8 ml) was added to
a suspension of sodium salt of BHA, prepared from NaH and BHA in THF
(1 ml). The mixture was stirred for 20 h at room temperature and then treated
with saturated ammonium chloride (10 ml), and then extracted with ether
(20 mlꢃ2). The combined extracts were washed with 15% NaOH, brine, and
then dried over magnesium sulfate. Concentration and chromatography
(hexane/etherꢀ20 : 1) gave (R)-9 with 62% ee (22 mg, 15%) of [a]D25 ꢁ48.1
(cꢀ0.72, CHCl3). Then optically pure (ꢁ)-(R)-9 should show [a]D25 ꢁ77.6.
Acknowledgements This research was partially supported by a Grant-
in-Aid for Scientific Research in Priority Areas “Advanced Molecular Trans-