Facile synthesis of chiral 2-formyl-1,1′-binaphthyl via lipase-catalyzed acylation and hydrolysis of 1,1′-binaphthyl oximes

Article abstract of DOI:10.1016/j.tetlet.2003.09.061

Lipase-catalyzed acylation of 2-hydroxyiminomethyl-1,1′-binaphthyl [(±)-1] and hydrolysis of 2-acetoxyiminomethyl-1,1′-binaphthyl [(±)-2] yielded optically active oximes 1 and 2 with high enantiomeric excess. Successful synthesis of the optically active aldehyde 4 from chiral O-acetyl oxime 2 occurred without a decrease of enantiomeric excess.

Full text of DOI:10.1016/j.tetlet.2003.09.061

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8269–8272
Facile synthesis of chiral 2-formyl-1,1%-binaphthyl via
lipase-catalyzed acylation and hydrolysis of 1,1%-binaphthyl
oximes
Naoto Aoyagi,* Tomoyuki Ohwada and Taeko Izumi
Department of Chemistry and Chemical Engineering, Graduate School of Science and Engineering, Yamagata University, Jyonan,
Yonezawa, Yamagata 992-8510, Japan
Received 22 July 2003; revised 5 September 2003; accepted 10 September 2003
Abstract—Lipase-catalyzed acylation of 2-hydroxyiminomethyl-1,1%-binaphthyl [(±)-1] and hydrolysis of 2-acetoxyiminomethyl-
1
,1%-binaphthyl [(±)-2] yielded optically active oximes 1 and 2 with high enantiomeric excess. Successful synthesis of the optically
active aldehyde 4 from chiral O-acetyl oxime 2 occurred without a decrease of enantiomeric excess.
2003 Elsevier Ltd. All rights reserved.
©
Lipases in organic solvents have been employed as
catalysts in the synthesis of extensive optically active
compounds. Typical substrates used for lipase-cata-
Although lipase-catalyzed esterification and hydrolysis
of biaryls has been reported for the synthesis of chiral
biaryl alcohols, enzymatic kinetic resolutions of biaryl
1
7
lyzed resolutions include alcohol, amine, carboxylic
acid and ester. Recently, it was reported that oxime
derivatives were resolved by lipase-catalyzed acylation
and hydrolysis. However, little is known about the
lipase-catalyzed resolution of oxime derivatives of axial
biaryl compounds.
aldehydes proved to be extremely challenging. For
example, kinetic resolution of racemic 2-formyl-1,1%-
binaphthyls by baker’s yeast reduction yielded chiral
2-hydroxymethyl-1,1%-binaphthyls, leaving chiral alde-
2
8
hydes with low enantioselectivities. Chiral binaphthyl
aldehydes are generally synthesized by oxidation of
7c,9
chiral binaphthyl alcohols.
However, it is well
Recently, chiral biaryl derivatives have received much
known that these alcohols were previously reduced
from binaphthyl esters, after which chiral alcohols must
be oxidized by a large excess of manganese(IV) oxide,
3
attention in the context of chiral ligands, pharmaceuti-
4
5
6
7c
cal products, natural products, and liquid crystals.
Scheme 1. Synthesis of racemic oximes (±)-1ꢀ2.
Keywords: binaphthyl; Suzuki cross-coupling; oxime; lipase; acylation; hydrolysis.
*
Corresponding author. Tel.: +81-238-26-3126; fax: +81-238-26-3413; e-mail: tp455@dip.yz.yamagata-u.ac.jp
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.061

8
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N. Aoyagi et al. / Tetrahedron Letters 44 (2003) 8269–8272
Scheme 2. Lipase-catalyzed resolution of oxime (±)-1ꢀ2.
9
10
toxic Jones reagent, or expensive Fetizon reagent in
order to yield chiral aldehydes. Therefore, a novel,
facile synthesis of chiral biaryl aldehydes was
developed.
An efficient resolution of 1,1%-binaphthyl amine and
1
,1%-binaphthyl ester using lipase-catalyzed amidations
1
1
was previously reported. Consequently, the applicabil-
ity of these reactions using binaphthyl oxime deriva-
tives and synthesis of the chiral 2-formyl-1,1%-
binaphthyl from 1,1%-binaphthyl oximes became an area
of research interest.
Scheme 3. Synthesis of known configuration (R)-3.
As shown in Table 1, Pseudomonas species lipases (LIP,
14
AH and PS) were found to give the most effective
selectivity for esterification (entries 1ꢀ3). Although the
esterification reactions catalyzed by Candida antarctica
lipases (NOVOZYM 435 and CHIRAZYME L-2) pro-
ceeded at a high reaction rate, the enantioselectivities
were relatively low, the highest being 31% ee (entries 4
and 5). Selectivity for the opposite enantiomer of the
axial binaphthyl ring was shown by C. antarctica lipase
against Pseudomonas lipase-catalyzed esterification
1
2
Racemic mixtures of oximes (±)-1ꢀ2 were obtained
in high yields using the Suzuki cross-coupling reaction
Scheme 1). The enzymatic resolution of (±)-1ꢀ2 was
conducted under esterification and hydrolysis condi-
tions, using 13 commercially available lipase prepara-
1
3
(
14
tions (Scheme 2).
(
entries 1ꢀ5).
In a typical experiment, lipase (40 mg) and vinyl acetate
0.202 mmol) [or n-butanol (0.0672 mmol)] were added
(
As with the lipase-catalyzed esterification of (±)-1,
Pseudomonas species lipases (LIP, AH and PS) were
found to yield the most effective selectivity for hydroly-
sis (Table 2, entries 1, 3, 5). Passing over this convers-
ing of hydrolysis reaction, leave chiral oxime ester (R)-2
was obtained with high enantiomeric excess using LIP
to a solution of oxime (±)-1 (20 mg, 0.0672 mmol) [or
O-acetyl oxime (±)-2 (23 mg, 0.0672 mmol)] and 2%-ace-
tonaphthone (1.0 mg, standard substance) in tert-butyl
methyl ether (4 mL) (MTBE). The resulting mixture
was shaken (150 cycles/min) at 30°C, during which the
course of the reaction was monitored by a high perfor-
mance liquid chromatograph (HPLC) equipped with a
UV detector (GL Sciences, Column: Inertsil ODS-2,
Mobile phase: acetonitrile/water=8:2, Flow rate: 0.8
mL/min, Wavelength-UV: 254 nm). Upon completion,
the reaction was stopped by filtering to remove the
lipase enzyme. The lipase portion was washed with
MTBE (10 mL). The combined filtrate and wash were
evaporated at 30°C, and the resulting crude residue was
purified by silica gel column chromatography (Mobile
phase: chloroform) to yield the chiral O-acetyl oxime 2
and oxime 1. Enantiomeric excess (ee) values were
determined using HPLC (Daicel, Column: Chiralcel
OD, Mobile phase: hexane/2-propanol=100:1, Flow
rate: 0.4 mL/min (0–50 min)—1.4 mL/min (50–80 min),
Wavelength-UV: 254 nm). E Values were calculated
(
99% ee, 36% yield; entry 2) and AH (98% ee, 41%
yield; entry 4). In general, hydrolysis reactions of (±)-2
were much more reactive than esterification reactions of
(
±)-1.
The hydrolysis of the O-acetyl oxime (R)-2 to the
aldehyde (R)-4 was then investigated. We found that
synthesis of the chiral aldehyde (R)-4 from (R)-2 with
acetic acid and 8N hydrochloric acid in acetone at
ambient temperature (99% yield) was successful without
a decrease of enantiomeric excess (Scheme 4).
In conclusion, the efficient chiral synthesis of 2-formyl-
1
,1%-binaphthyl (R)-4 was accomplished using a combi-
nation of the Suzuki cross-coupling reaction and the
lipase-catalyzed kinetic resolution of (±)-2. Pseu-
domonas species lipases (LIP, AH and PS) served as
effective catalysts for the kinetic resolution of (±)-1 and
1
5
according to the literature. Absolute configurations of
the products were determined using their circular
dichromism spectra (dihedral angles of the binaphthyl
backbones were calculated by WinMOPAC.). These
determinations were confirmed by converting chiral
O-acetyl oxime 2 to (R)-(+)-2-hydroxymethyl-1,1%9-
binaphthyl 3 by the established mechanism (Scheme 3).
(
±)-2. The present synthetic methodology offers the
following two advantages: (1) simplicity of operation,
and (2) high yields of the lipase-catalyzed resolution
without the use of toxic resolving agents. Currently, the
applicability of this method is being extended to the
lipase-catalyzed resolution of 2,2%-diformyl-1,1%-biaryls.
16

N. Aoyagi et al. / Tetrahedron Letters 44 (2003) 8269–8272
Table 1. Acylation of racemic-1 a using lipase catalyst
8271
Entry
Lipasea,b
Time (h)
Acetyloxime 2
Oxime 1
E valuee
Yield (%)c
E.e. (%)d
Config.
Yield (%)c
E.e. (%)d
Config.
1
2
3
4
5
6
LIP
AH
PS
24
24
24
24
45
32
10
38
35
10
73
84
63
29
S
S
S
R
R
38
68
87
47
40
80
84
39
7
31
R
R
R
S
S
–
17
17
5
2
2
NOVOZYM 435
CHIRAZYME L-2 24
AK 24
23
31
Racemate
Racemate
–
a
Another seven commercially lipases (Ref. 14) were not reacted.
NOVOZYM 525L and Thermomyces lanuginosus lipases adsorbed on Celite; see Ref. 17.
Determined by internal standard method of HPLC using ODS-2 (254 nm, 0.8 mL/min, CH CN/H O=8:2).
b
c
3
2
d
e
Determined by HPLC using Chiralcel OD (254 nm, 0.4 mL/min (0–50 min)–1.4 mL/min (50–80 min), n-hexane/IPA=100:1).
−1
−1
E=ln[(ee (1−ee ))(ee +ee ) ]/ln[ee (1+ee ))(ee +ee ) ]; see Ref. 15.
p
s
p
s
p
s
p
s
Table 2. Hydrolysis of racemic-2 by lipase catalyst
Entry
Lipase
Time (h)
Oxime 1
Acetyloxime 2
E valuec
Yield (%)a
E.e. (%)b
Config.
Yield (%)a
E.e. (%)b
Config.
1
2
3
4
5
6
7
8
9
LIP
LIP
AH
AH
PS
PS
1
2
1
2
7
15
0.1
24
0.1
24
24
15
8
57
64
47
59
55
75
42
76
63
78
68
44
24
38
S
S
S
S
S
S
R
–
R
–
–
S
–
S
–
42
36
52
41
45
22
57
98
>99
62
98
48
R
R
R
R
R
R
S
–
S
–
–
R
–
R
–
33
>22
15
23
4
5
3
–
3
–
–
<1
–
1
94
37
NOVOZYM 435
NOVOZYM 525L
CHIRAZYME L-2
d
Not detected
45
Not detected
Not detected
48
53
51
53
50
Recovery
36
55
29
d
10
11
12
13
14
15
16
Thermomyces lanuginosus
Recovery
Recovery
PPL
CCL
AK
AY
OF
MY
11
51
42
48
46
50
<1
Racemate
5
Racemate
8
Racemate
24
Racemate
6
15
4
15
–
1
S
R
a
b
c
Determined by internal standard method of HPLC using ODS-2 (254 nm, 0.8 mL/min, CH CN/H O=8/2).
3
2
Determined by HPLC using Chiralcel OD (254 nm, 0.4 mL/min (0–50 min)—1.4 mL/min (50–80 min), n-hexane/IPA=100/1).
−1
−1
E=ln[(ee (1−ee ))(ee +ee ) ]/ln[ee (1+ee ))(ee +ee ) ]; see Ref. 15.
p
s
p
s
p
s
p
s
d
These lipases adsorbed on Celite; see Ref. 17.
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3
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1
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7
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(
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2. (±)-1: mp 155–157°C; IR wmax (KBr)/cm 3300 (OH); H
−
1
1
1
NMR (CDCl ) l 7.20 (2H, d, J=7.5 Hz, ArH), 7.25–7.51
3