Kinetic resolution of d,l-myo-inositol derivatives catalyzed by chiral Cu(II) complex

Article abstract of DOI:10.1016/j.tetlet.2004.10.019

Kinetic resolution of d,l-myo-inositol derivatives having a 1,2-diol functionality by monobenzoylation was achieved using (R,R)-Ph-BOX-Cu(II) as a catalyst. The monobenzoylation preferentially took place at the 1,2-diol functionality via a highly enantiod

Full text of DOI:10.1016/j.tetlet.2004.10.019

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9131–9134
Kinetic resolution of D,L-myo-inositol derivatives catalyzed
by chiral Cu(II) complex
Yoshihiro Matsumura,* Toshihide Maki, Kazuya Tsurumaki and Osamu Onomura
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Received 30 August 2004;revised 1 October 2004;accepted 1 October 2004
Abstract—Kinetic resolution of D,L-myo-inositol derivatives having a 1,2-diol functionality by monobenzoylation was achieved
using (R,R)-Ph-BOX-Cu(II) as a catalyst. The monobenzoylation preferentially took place at the 1,2-diol functionality via a highly
enantiodiscriminatory process, which was largely influenced by a substituent at the position adjacent to the 1,2-diol functionality.
This method was applied to a synthesis of biologically important D-inositol-1-phosphate.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Kinetic resolution has long continued to attract much
interest in asymmetric synthesis because of its simple
process for preparation of enantiomerically enriched
compounds from easily available racemic mixture.1,2
We have recently exploited an efficient method for
kinetic resolution of 1,2-diols using a selective mono-
benzoylation reaction catalyzed by (R,R)-Ph-BOX-
CuCl2.3 As an application of the method, we report
herein a kinetic resolution of D,L-myo-inositol deriva-
tives D,L-1a–d (Eq. 1) and utilization of this kinetic res-
olution to a synthesis of D-inositol-1-phosphate (3), a
biologically important compound related to the intracel-
lular signaling process.4 Although a variety of synthetic
methods for 3 via utilization of chiral starting com-
pounds,5 a resolution of diastereoisomers,6 and an enzy-
matic asymmetric induction7 have been developed, there
have been few reports for its synthesis using chiral
catalysts.8
2+
2Cl-
OH
OH
O
O
OBz
OBn
ROCO
BnO
OH
ROCO
BnO
2
3
5
1
N
N
L-1a-d
D-1a-d
+
6
4
Cu
Ph
Ph
OBn
OH
L-2a-d
+
OH
L-1a-d
+
(R,R)-Ph-BOX-CuCl2
(5 mol%)
BzCl (0.5 equiv.)
OH
ð1Þ
OH
OCOR
OBn
BzO
BnO
i-Pr2NEt
OCOR
OBn
HO
(1 equiv.)
2
5
+
3
4
1
6
at 0
C
°
BnO
OH
OH
D-2a-d
D-1a-d
c : R=t-Bu d : R=p-Ph-Ph
a : R=Me b : R=i-Pr
The racemic inositol derivatives D,L-1a–d were readily
prepared from 4,6-dibenzylated myo-inositol according
to the reported procedure.9 Benzoylation of D,L-1a–d
was carried out as follows. Benzoyl chloride (0.5equiv)
Keywords: Kinetic resolution; myo-Inositol;1,2-Diol;Monobenzoyl-
ation;Inositol-1-phosphate;Chiral copper complex.
*
Corresponding author. Tel.: +81 95 819 2429;fax: +81 95 819
2476;e-mail: matumura@net.nagasaki-u.ac.jp
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.019

9132
Y. Matsumura et al. / Tetrahedron Letters 45 (2004) 9131–9134
Table 1. Benzoylation of myo-inositol derivatives 1a–d
dependent on the kind of the 3-acyl group, and the max-
imum ee (91% ee) was observed in the benzoylation of
1d (entry 4).
Run
R
myo-Inositol Products
2a–d
2a–d
derivatives
1a–d
Yielda (%) % Eeb
On the basis of those results, we propose a working
hypothesis for the reaction mechanism (Fig. 1), in which
the L-intermediate from L-1 is more preferentially
formed than the D-intermediate from D-1 because of
the steric repulsion between Ph of oxazoline ring and
R groups, and BzCl attacks more easily the oxygen atom
at C-3 (between cis and trans adjacent substituents) of
the L-intermediate than the oxygen atom at C-2 (be-
tween cis and cis adjacent substituents).
1
2
3
Me
1a
1b
1c
2a
2b
2c
25
36
37
60
67
74
i-Pr
i-Bu
4
1d
2d
35
91
a Isolated yield based on 1a–d.
b Determined by chiral solid-phase HPLC. For 2a–c: Daicel Chiralcel
OD (4.6mm/ · 25cm), wave length = 254nm, flow rate = 1.0mL/
min, n-hexane–2-propanol = 5:1, retention time: L-2a;11.5min, D-2a;
23.9min, L-2b;9.3min, D-2b;15.1min, L-2c;7.1min, D-2c;9.5min;
for 2d: Daicel Chiralpak AS (4.6mm/ · 25cm), wave
length = 254nm, n-hexane–2-propanol = 5:1, retention time: 19.6min
(for L-2d), 25.2min (for D-2d).
The kinetic resolution of D,L-1e (R = Ph) was ambigu-
ous because the product 2e was a meso isomer but the
enantioselectivity was not low (s = ꢀ9.5)13 (Eq. 2).
This catalytic kinetic resolution was applied to a synthe-
sis of biologically important inositol-1-phosphate (Eq.
3). That is, D,L-1e was subjected to the kinetic resolution
using benzoyl chloride in the presence of (R,R)-Ph-
BOX-CuCl2 (5mol%) and i-Pr2NEt (1.0equiv) at 0ꢁC
in CH2Cl2. Although the benzoylated product 2e was
a meso isomer, the recovered 1e showed optical activity
depending on the amount of BzCl (Eq. 2):14 70% ee for
0.5equiv BzCl;94% ee for 0.5equiv BzCl; ꢀ100% ee15
was added into a solution of D,L-1a–d in CH2Cl2 in the
presence of (R,R)-Ph-BOX-CuCl2 (5mol%)10 and i-
Pr2NEt (1.0equiv) at 0ꢁC to afford 3-monobenzoylated
compounds 2a–d with a recovery of 1a–d.11 The results
are shown in Table 1.
In this benzoylation reaction, the following points were
remarkable. (1) The benzoylation did not occur at the
OH
OH
BzO
BnO
2
5
1
6
3
4
BzCl
OH
OH
OBn
(R,R)-Ph-BOX-CuCl2
OBz
OBn
BzO
OBz
HO
(5 mol%)
OH
+
L-1e
i-Pr2NEt
(1 equiv.)
BnO
BnO
OBn
+
OH
ð2Þ
OH
at 0 °C
OH
2
2e
recovered
OBz
OBn
HO
D-1e
3
4
1
6
BzCl
0.5 equiv.
0.7 equiv.
0.8 equiv.
5
BnO
51%
34%
17%
70%ee
94%ee
~100%ee
OH
D-1e
5-OH group but selectively took place at 2,3-(OH)2.
(2) The reaction mainly gave the 3-O-benzoylated prod-
uct in yields of 25–44% with a small amount of a 2-ben-
zoylated product.12 (3) The enantiomerically enriched
isomer was L with 60–91% ee. (4) The % eeÕs were
for 0.8equiv BzCl. The yields were 51%, 34%, and
17% based on the used D,L-1e, respectively. The opti-
cally pure D-1e was used for a synthesis of D-inositol-
1-phosphate 3 according to procedures similar to
reported ones (3: 100% ee) (Eq. 3).7c
BzCl
L-1
D-1
R
Ph
O
O
N
Ph
O
N
O
O
BnO Ph
N
O
O
O
N
Ph
2
O
Cu
O
Cu
HO
1
4
3
1
D-2
L-2
BnO
HO
6
5
2
O
3
R
6
5
4
BnO
O
BnO
BzCl
L-intermediate
D-intermediate
Figure 1. Working hypothesis for a reaction mechanism.

Y. Matsumura et al. / Tetrahedron Letters 45 (2004) 9131–9134
9133
O
O
OBz
OBn
O
OBz
OBn
O
i
ii
iii
D-1e
95%
97%
93%
BnO
BnO
OH
O
THP
4
5
OH
O
O
O
O
OPO3H2
OH
HO
HO
OBn
ð3Þ
OH
O
P
O
O
v
iv
OBn
100%
97%
BnO
OBn
OBn
THP
BnO
OH
O
THP
3
6
7
(i) 2,2-Dimethoxypropane (6.4 equiv), p-TsOH (2 mol%), acetone, rt. (ii) 3,4-Didehydro-2H-pyran (2.4
equiv), p-TsOH (1.4 mol%), CH2Cl2, rt. (iii) KOH (3 equiv), HOCH2CH2OH, rt. (iv) (a) 1H-Tetrazole (2
equiv), dibenzyl diisopropylphosphoramidite (1.5 equiv), CH Cl , rt; (b) m-CPBA (3 equiv), CH Cl , 0 C.
˚
2
2
2
2
(v) 10% Pd/C, MeOH/H2O (80/20), H2, rt.
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Acknowledgements
Y.M. and T.M. thank the Ministry of Education,
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11. A typical experimental procedure for benzoylation of
D,L-1a–d: Benzoyl chloride (0.5equiv) was added into a

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Y. Matsumura et al. / Tetrahedron Letters 45 (2004) 9131–9134
solution of D,L-1d (1.0mmol) in CH2Cl2 (5mL) in the
12. The amount of byproducts was less than 10% of 2a–
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presence of (R,R)-Ph-BOX-CuCl2 (5mol%) and i-Pr2NEt
(1.0equiv) at 0ꢁC. After stirring for 2h, the reaction
mixture was added onto water (10mL) and the product
was extracted with CH2Cl2 (10mL·3). Combined organic
layers were dried over MgSO4. After removal of organic
solvent, the residue was chromatographed on silica gel to
afford 3-monobenzoylated compound 2d in 35% yield with
a recovery of 1d (51%). The ee of 2d was determined by
chiral solid-phase HPLC, see: footnote of Table 1.
14. Determined by chiral solid-phase HPLC. Daicel Chiralcel
OD (4.6mm/ · 25cm), n-hexane–2-propanol = 3:1, wave-
length = 254nm, flow rate = 1.0mL/min, retention time:
9.3min (for D-1e), 14.9min (for L-1e).
30
15. ½aꢁD ꢂ71.0 (c 1.0, MeOH).