A practical synthesis of C2-symmetric chiral binaphthyl ketone catalyst

Article abstract of DOI:10.1055/s-2000-8197

A practical synthesis of 11-membered C₂-symmetric binaphthyl ketone (R)-1, a catalyst for asymmetric epoxidation, was developed. (±)-1,1'-Binaphthyl-2,2'-dicarboxylic acid [(±)-6] was efficiently resolved by (R)-(-)-1-cyclohexylethylamine to give (R)-6 in >99% ee and in 38% yield. Condensation of the acid chloride derived from (R)-6 with 1,3-dihydroxyacetone dimer at 60-70 °C provided the desired chiral ketone (R)-1 in 61-63% yield without need for high dilution techniques.

Full text of DOI:10.1055/s-2000-8197

PAPER
1677
A Practical Synthesis of C2-Symmetric Chiral Binaphthyl Ketone Catalyst
Masahiko Seki,* Shin-ichi Yamada, Tooru Kuroda, Ritsuo Imashiro, Toshiaki Shimizu
Product & Technology Development Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa-ku, Osaka 532-8505, Japan
Fax +81(6)63002816; E-mail: m-seki@tanabe.co.jp
Received 12 June 2000; revised 27 July 2000
memberd ring via condensation of the acid chloride from
Abstract: A practical synthesis of 11-membered C2-symmetric bi-
(R)-6 with 1,3-dihydroxyacetone dimer.
naphthyl ketone (R)-1, a catalyst for asymmetric epoxidation, was
developed. (±)-1,1’-Binaphthyl-2,2’-dicarboxylic acid [(±)-6] was
efficiently resolved by (R)-( )-1-cyclohexylethylamine to give (R)-
6 in >99% ee and in 38% yield. Condensation of the acid chloride
derived from (R)-6 with 1,3-dihydroxyacetone dimer at 60 70 °C
provided the desired chiral ketone (R)-1 in 61 63% yield without
need for high dilution techniques.
(±)-1,1’-Binaphthyl-2,2’-dicarboxylic acid [(±)-6], the
substrate for the optical resolution, was prepared from
commercially available 1-bromo-2-methylnaphthalene
(2) with some modification of the reported procedures3,4
(Scheme). Oxidation of the methyl group of 2 to the cor-
responding carboxylic acid 3 was carried out by treatment
with molecular oxygen with cobalt(II) acetate as a cata-
lyst. A reported procedure3 in which oxygen is bubbled
into a mixture of 2 and cobalt(II) acetate (20 mol%) in
acetic acid and butan-2-one at 90 100 °C needs a long re-
action period (9 h) and a large excess of oxygen to com-
plete the reaction. In order to reduce the reaction period
and the consumption of the oxygen, the reaction was con-
ducted in an autoclave under 3.5 kg/cm2 of oxygen at
100 109 °C for 1 hour to provide the desired carboxylic
acid 3 in 87% yield. The compound 3 was esterified4 and
was allowed to react with copper powder in refluxing
DMF4 and subsequent hydrolysis4 provided (±)-1,1’-bi-
naphthyl-2,2’-dicarboxylic acid [(±)-6] in 70% yield
based on 2 without any tedious purification such as silica
gel column chromatography.
Key words: catalysts, asymmetric epoxidation, dioxiranes, macro-
cycles, optical resolution
Development of a practical synthetic method for chiral
catalysts is one of the most important criteria for a catalyt-
ic asymmetric synthesis to become a commercial process
for large-scale preparation. In search of an epoxidation
that can be applied to an industrial synthesis, we have fo-
cused on chiral dioxirane-mediated asymmetric epoxida-
tion catalyzed by chiral C2-symmetric binaphthyl ketone
(R)-1.1 The original synthetic method of the chiral ketone
(R)-1, however, suffers from such drawbacks as 1) han-
dling highly toxic alkaloids for the optical resolution of
(±)-1,1’-binaphthyl-2,2’-dicarboxylic acid [(±)-6];4,5 and
2) a poor yield (28%) to construct the 11-membered ring
using 2-chloro-1-methylpyridinium iodide (Mukaiyama
reagent) and a high dilution method [reaction solvent: ca
300 volume of the solvent per weight of the substrate (300
v/w)].1
Optical resolution of (±)-1,1’-binaphthyl-2,2’-dicarboxy-
lic acid [(±)-6] was then investigated. So far known re-
solving agents for (±)-6 are the highly toxic quinine and
brucine.4,5 We tried a number of chiral amines for the op-
tical resolution and eventually found that the non-toxic
(R)-( )-1-cyclohexylethylamine [(R)-CHEA] (2.0 equiv)
could effectively resolve (±)-6 to give (R)-6 in >99% ee
and in 38% yield. In order to reduce the amount of the re-
solving agent, addition of achiral amine in the optical res-
olution was tested. As the result of the screening,
dimethylamine (0.9 equiv) was found to be effective to re-
duce the resolving agent to give (R)-6 in 38% yield by the
use of 1.2 equivalents of (R)-CHEA. Dimethylamine has
additional advantages of high water solubility and a low
boiling point (bp = 7 °C), which enabled facile and high-
yielding recovery (90%) of (R)-CHEA free from contam-
ination by dimethylamine.
O
O
O
O
O
(R)-1
We have recently described some improvements in the
synthesis of (R)-1, which involved an intramolecular Ull-
mann reaction, a Co(salen)-catalyzed macrolactonization
and an enzymatic resolution.2 However, a practical use of
these methods has hitherto been restricted by the multi-
steps (8 steps or more) and the low concentration of the
substrates in the enzymatic resolution. Reported herein is
a more efficient synthesis of the chiral ketone (R)-1
through a novel optical resolution of (±)-1,1’-binaphthyl-
2,2’-dicarboxylic acid [(±)-6] and the formation of the 11-
Condensation of (R)-6 with 1,3-dihydroxyacetone dimer
was then investigated via formation of its acid chloride.
The acid chloride was prepared by treatment of (R)-6 with
thionyl chloride (4 equiv) in the presence of pyridine (0.96
equiv) and was allowed to react with 1,3-dihydroxyace-
tone dimer (1.2 equiv) at 20 °C in the presence of trieth-
ylamine (3 equiv) in dichloromethane. A high dilution
method (reaction solvent: 320 v/w) was again needed to
Synthesis 2000, No. 12, 1677–1680 ISSN 0039-7881 © Thieme Stuttgart · New York

1678
M. Seki et al.
PAPER
c4
a
b4
CO2Me
CO2Me
quant.
96%
87%
Me
CO2H
CO2Me
Br
Br
Br
(±)-5
2
3
4
d4
e
f
CO2H
CO2H
CO2H
CO2H
(R)-1
84%
38%
63%
(R)-6
(±)-6
Reagents and conditions: a) O2 (3 kg/cm2)/Co(OAc)2•4H2O (0.2 equiv)/butan-2-one (0.3 equiv)/AcOH, 100 109 °C, 1 h; b) MeOH/SOCl2
(1.2 equiv), reflux, 3 h; c) Cu (1.7 equiv)/DMF, 125 °C, 3 h; d) KOH (3.8 equiv), MeOH/H2O, reflux, 2 h then HCl; e) (R)-CHEA (1.2 equiv)/
Me2NH (0.9 equiv)/MeOH, H2O, then HCl; f) i. SOCl2 (4 equiv)/pyridine (0.96 equiv)/CHCl3 ii. 1, 3-dihydroxyacetone dimer (1.2 equiv)/
Et3N (3 equiv)/toluene, 60 °C, 2 h
Scheme
obtain 53% yield of (R)-1 (Table, Entries 1, 2). This may cause of the low solubility of the reactants (acid chloride
be due to the poor reactivity of 1,3-dihydroxyacetone and 1,3-dihydroxyacetone dimer). When the reaction was
dimer. Indeed, a dramatic improvement in the yield with conducted at 50 °C, a remarkable decrease in the yield
considerably reduced amount of the reaction solvent was was observed (63 to 16%) (Table, Entries 6 and 7). Under
achieved by elevating the reaction temperature: addition the best reaction conditions (Table, Entry 6), almost all
of 1,3-dihydroxyacetone dimer and Et3N to the solution of the dicarboxylic acid (R)-6 was consumed. While the
the acid chloride in 1,2-dichloroethane (total volume of structure of the byproducts in the cyclization reaction has
the reaction solvent: 50 v/w) at 70 °C over 1.5 hours pro- not been determined yet, alkaline hydrolysis of the mother
vided (R)-1 in 61% yield (Table, Entry 4). Under the same liquor of (R)-1 regenerated (R)-6 in 34% yield based on
reaction conditions except the reaction temperature (60 the initially added (R)-6.
°C), environmentally acceptable toluene (60 v/w) could
In conclusion, the 11-membered binaphthyl ketone (R)-1
also be used to give good yield (63%) of the coupling
was synthesized from readily accessible 1-bromo-2-meth-
product (R)-1 (Table, Entry 6). Further investigations to
ylnaphthalene in 6 steps and in 17% overall yield through
the novel and efficient optical resolution with the non-tox-
reduce the amount of toluene were not undertaken be-
ic resolving agent and the formation of the 11-membered
ring without using the high dilution method. Simple oper-
ations, ready availability of the reagents and short steps of
the present synthesis permit a practical access to the chiral
ketone catalyst of recent interest.
Table Optimization of the Synthesis of (R)-1
Entry
Solvent
(v/w)a
Conditions
Yield
(%)c
Temp
Addition
(°C)
Time (h)b
1
2
3
4
5
6
7
CH2Cl2 (320)
CH2Cl2 (50)
20
20
9
53
12
60
61
49
63
16
Melting points were measured using a Yamato melting point appa-
ratus and are uncorrected. IR were taken by the use of a Perkin Elm-
er 1600 infrared spectrometer. 1H NMR were recorded on a Bruker
AC-200 (200 MHz) spectrometer and are reported in values. Mass
spectra were taken by using a Hitachi M-2000A mass spectrometer
at an ionizing potential of 70 eV. Microanalyses were performed by
a Perkin-Elmer 2400 Series II CHNS/O analyser. Optical rotations
were measured on a Perkin-Elmer 243 polarimeter and [ ]D-values
9
ClCH2CH2Cl (100) 70
1.5
1.5
1.5
1.5
1.5
ClCH2CH2Cl (50)
ClCH2CH2Cl (22)
toluene (60)
70
70
60
50
1
are given in 10 1 deg cm2 g . TLC was performed on E. Merck 0.25
mm precoated glass backed plates (60 F254). Development was ac-
complished using either 5% phosphomolybdic acid in EtOH-heat or
visualized by UV-light where feasible. Flash chromatography was
accomplished using Kieselgel 60 (230 400 mesh, E. Merck). The
copper powder (particle size: 100 200 mesh) was purchased from
Kanto Chemicals Co., Lnc. and used without further purification.
toluene (60)
a Volume of the solvent per weight of (R)-6.
b Addition time of a mixture of 1,3-dihydroxyacetone dimer and Et3N
to the solution of the acid chloride of (R)-6.
c Isolated yield.
Synthesis 2000, No. 12, 1677–1680 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Practical Synthesis of C2-Symmetric Chiral Binaphthyl Ketone Catalyst
1679
1
1-Bromo-2-naphthoic Acid (3)
IR (KBr): = 1696 cm .
A mixture of 1-bromo-2-methylnaphthalene (106.5 g, 0.482 mol),
Co(OAc)2•4H2O (24 g, 0.096 mol) and butan-2-one (13 mL, 0.145
mol) in AcOH (400 mL) was stirred at 100 109 °C under O2 atom-
osphere (3 kg/cm2) in an autoclave for 1 h. After cooling the mixture
to 30 °C, the mixture was poured into ice-water (2 L). The crystals
formed were collected, washed with H2O (5 × 300 mL ) and dried
at 60 °C for 17 h to give 3 (105.3 g, 87%) as slightly brown crystals;
mp 187 189 °C (Lit.4 mp 186 188 °C).
Anal. calcd for C22H14O4: C, 77.18; H, 4.12. Found: C, 77.15; H,
3.99.
The mother liquor of the optical resolution was evaporated and
treated with 1 N aq NaOH solution (47 mL). The mixture was ex-
tracted with CH2Cl2 (2 × 5 mL) and combined with the CH2Cl2 ex-
tracts obtained in the decomposition of the (R)-CHEA•(R)-6 salt.
The organic solution was treated with active charcoal (0.3 g), dried
(MgSO4) and evaporated to give (R)-CHEA (4.1 g, 90%) as color-
less liquid which could be used without further purification.
1
IR (KBr): = 1692 cm .
1H NMR (DMSO-d6): = 7.68 7.81 (m, 3 H), 8.04 8.09 (m, 2 H),
8.31 8.35 (m, 1 H), 13.6 (br s, 1 H).
MS: m/z = 251 (M+).
(R)-5H-Dinaphtho[2,1-g:1’,2’-i][1,5]dioxacycloundecin-
3,6,9(7H)-trione [(R)-1]
To a suspension of (R)-6 (5.0 g, 14.6 mmol) and pyridine (300 mg,
14 mmol) in CHCl3 (stabilized with amylenes, 100 mL) was added
SOCl2 (4.26 mL, 58.4 mmol) at 25 °C and the mixture was stirred
at 25 °C for 2 h. The mixture was evaporated to give the correspond-
ing acid chloride. To a suspension of 1,3-dihydroxyacetone dimer
(306 mg, 1.8 mmol) in toluene (150 mL) were simultaneously add-
ed the acid chloride in toluene (100 mL) and Et3N (6.1 mL, 43.8
mmol) in toluene (50 mL) at 60 °C for 1.5 h. During the reaction,
1,3-dihydroxyacetone dimer (4 × 306 mg, 7.2 mmol) was added
portionwise at an interval of 15 min. After the addition was com-
pleted, the mixture was further stirred at 60 °C for 30 min. The mix-
ture was washed with brine (50 mL) and the aqueous layer was
extracted with toluene (50 mL). The combined extracts were
washed with H2O (2 × 50 mL), dried (MgSO4) and evaporated. To
the residue was added acetone (15 mL) and the mixture was stirred
at 25 °C for 20 min. The crystals formed were collected and washed
with acetone to provide (R)-1 (3.64 g, 63%); mp 300 °C (dec.);
[ ]D25 +10.9 (c = 1.0, CHCl3); optical purity: >99% ee [HPLC:
Chiralcel OD (Daicel), hexane /propan-2-ol = 10:1, 1 mL/min, 40
°C, 224 nm).
(±)-1,1’-Binaphthyl-2,2’-dicarboxylic Acid [(±)-6]
To a mixture of 3 (105.3 g, 0.419 mol) in MeOH (350 mL) was add-
ed SOCl2 (36.7 mL, 0.503 mol) over 10 min under cooling with ice-
water. The mixture was refluxed for 3 h and evaporated. The residue
was dissoved in toluene (300 mL) and washed successively with
H2O (300 mL), sat. aq NaHCO3 300 mL) and brine (300 mL), treat-
ed with active charcoal (25 g), dried (MgSO4) and evaporated to
give 4 (106.3 g, 96%) as brown crystals. A mixture of the crude 4
(106.3 g) and copper powder (43.3 g, 0.682 mol) in DMF (150 mL)
was stirred at 117 120 °C for 3 h. The mixture was filtered through
a pad of Celite and the undissolved materials were washed with
DMF (2 × 30 mL). The filtrate and the washings were combined and
evaporated. The solid formed was washed with H2O (3 × 250 mL)
and dried at 90 °C for 17 h to give 5 (74 g, quant.) as brown crystals.
To the crude 5 (74 g) were added MeOH (570 mL), H2O (110 mL)
and KOH (85%, 50.7 g, 0.768 mol) and the mixture was refluxed for
2 h. After evaporating the solvent, the residue dissolved in H2O (300
mL) was washed with toluene (3 × 300 mL) and acidified (pH 1.0)
by concd HCl (75 mL). The mixture was extracted with EtOAc (2 ×
300 mL), washed with brine (300 mL), treated with active charcoal
(10 g), dried (MgSO4) and evaporated. The crystals formed were
collected by adding hexanes and dried at 90 °C for 17 h to give (±)-
6 (57.6 g, 84%) as slightly yellow crystals; mp 277 278 °C (Lit.4
272 274 °C).
1
IR (KBr): = 1755, 1730, 1593 cm .
1H NMR (CDCl3): = 8.04 (d, J = 8.5 Hz, 2 H), 7.97 (d, J = 8.2 Hz,
2 H), 7.66 (d, J = 8.5 Hz, 2 H), 7.56 (dd, J = 1.5, 6.6 Hz, 2 H), 7.30
7.37 (m, 2 H), 7.25 (d, J = 14.1 Hz, 2 H), 5.56 (d, J = 15.4 Hz, 2 H),
4.20 (d, J = 15.4 Hz, 2 H).
1
IR (KBr): = 1691 cm .
MS: m/z = 396 (M+).
1H NMR (DMSO-d6): = 7.04 7.26 (m, 4 H), 7.44 7.53 (m, 4 H),
7.89 8.00 (m, 4 H), 8.11 8.15 (m, 2 H).
MS: m/z = 342 (M+).
Anal. calcd for C25H16O5: C, 75.71; H, 4.07. Found: C, 75.42; H,
3.99;
Recovery of (R)-6
The filtrate and washings were combined and evaporated and the
residue was dissolved in 1,4-dioxane (17 mL). To the solution were
added H2O (3 mL) and KOH (2 g, 30 mmol) and the mixture was
refluxed for 2 h. The mixture was evaporated and H2O (20 mL) was
added. The mixture was washed with EtOAc (2 × 10 mL), acidified
with concd HCl (2.4 mL) and extracted with EtOAc (2 × 10 mL).
The extracts were combined, washed with H2O, treated with active
charcoal (0.5 g), dried (MgSO4) and evaporated. The crystals
formed were collected and dried at 90 °C for 17 h to provide (R)-6
[1.7 g, 34% based on the initially added (R)-6]. The product was
identical to an authentic sample of (R)-6 with respect to mp, IR, 1H
NMR, mass spectrum and specific rotation.
(R)-1,1’-Binaphthyl-2,2’-dicarboxylic Acid [(R)-6]
To a suspension of (±)-6 (10.3 g, 30 mmol) in MeOH (22 mL) were
added Me2NH (50 wt% solution in H2O, 2.44 g, 27 mmol) and (R)-
CHEA (4.58 g, 36 mmol) and the mixture was dissolved at 65 °C.
To this mixture was added boiling water (50 mL) and the mixture
was gradually cooled down to 25 °C under mechanical stirring for
2.5 h. After further stirring at 25 °C for 1 h, the crystals formed were
collected, washed with 40% MeOH/H2O (20 mL) and dried at 60 °C
for 5 h to give (R)-6•[( R)-CHEA]2 (6.85 g) as colorless crystals.
The salt (R)-6•[(R)-CHEA]2 (6.85 g, 11.5 mmol) was dissolved in 1
N aq NaOH solution (25.3 mL, 25.3 mmol) and washed with
CH2Cl2 (2 × 5 mL). The aqueous layer was acidified by concd HCl
and extracted with EtOAc (20 mL). The organic layer was washed
with H2O, treated with active charcoal (0.1 g), dried (MgSO4) and
evaporated. The crystals formed were dried at 90 °C for 17 h to pro-
vide (R)-6 (3.91 g, 38%) in colorless crystals: the product (R)-6
References
(1) (a) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.; Zheng,
J.-H.; Cheung, K.-K. J. Am. Chem. Soc. 1996, 118, 491.
(b) Yang, D.; Wang, X.-C.; Wong, M.-K.; Yip, Y.-C.; Tang,
M.-W. J. Am. Chem. Soc. 1996, 118, 11311.
1
showed the same H NMR and mass spectra as (±)-6; mp 200 °C
(dec.) [Lit.5 mp 197 199 °C (dec.)]; [ ]54625 +127.0 (c = 1.0, 0.1 N
NaOH)(Lit.5 [ ]54625 +127.0 (c = 1.0, 0.1 N NaOH). Optical purity:
>99% ee [HPLC: Chiralcel OD (Daicel), hexane/EtOH/trifluoro-
acetic acid = 90:10:0.1, 1 mL/min, 35 °C, 254 nm].
(c) 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.
Synthesis 2000, No. 12, 1677–1680 ISSN 0039-7881 © Thieme Stuttgart · New York

1680
M. Seki et al.
PAPER
(2) (a) Seki, M.; Furutani, T.; Hatsuda, M.; Imashiro, R.
Tetrahedron Lett. 2000, 41, 2149.
(5) Kanoh, S.; Hongoh, Y.; Motoi, M.; Suda, H. Bull. Chem. Soc.
Jpn. 1988, 61, 1032.
(b) Kuroda, T.; Imashiro, R.; Seki, M. J. Org. Chem. 2000, 65,
4213.
(3) Hellwinkel, D.; Bohnet, S. Chem. Ber. 1987, 120, 1151.
(4) Hall, D. M.; Turner, E. E.; J. Chem. Soc. 1955, 1242.
Article Identifier:
1437-210X,E;2000,0,12,1677,1680,ftx,en;F03400SS.pdf
Synthesis 2000, No. 12, 1677–1680 ISSN 0039-7881 © Thieme Stuttgart · New York