Kinetic resolution of racemic secondary alcohols catalyzed by chiral diaminodiphosphine-Ir(I) complexes

Article abstract of DOI:10.1021/ol062244f

Chiral diaminodiphosphine-Ir(I) complexes were found to efficiently catalyze enantioselective oxidation of racemic secondary alcohols in acetone. In the presence of base, oxidative kinetic resolution of the alcohols proceeded smoothly with excellent enantioselectivity (up to 98% ee) under mild conditions.

Full text of DOI:10.1021/ol062244f

ORGANIC
LETTERS
2
006
Vol. 8, No. 24
565-5567
Kinetic Resolution of Racemic
Secondary Alcohols Catalyzed by Chiral
5
Diaminodiphosphine−Ir(I) Complexes
Yan-Yun Li, Xue-Qin Zhang, Zhen-Rong Dong, Wei-Yi Shen, Gui Chen, and
Jing-Xing Gao*
State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of
Chemistry, College of Chemistry and Chemical Engineering, Xiamen UniVersity,
Xiamen 361005, Fujian, Peoples Republic of China
cuihua@jingxian.xmu.edu.cn; jxgao@xmu.edu.cn
Received September 10, 2006
ABSTRACT
Chiral diaminodiphosphine−Ir(I) complexes were found to efficiently catalyze enantioselective oxidation of racemic secondary alcohols in
acetone. In the presence of base, oxidative kinetic resolution of the alcohols proceeded smoothly with excellent enantioselectivity (up to 98%
ee) under mild conditions.
Optically active alcohols are extremely useful starting
materials and intermediates in synthetic organic chemistry
and the pharmaceutical industry. For the past 10 years, highly
efficient asymmetric hydrogenation, involving asymmetric
transfer hydrogenation of prochiral ketones catalyzed by
metal complexes to attain chiral alcohols, has made great
progress.1 Besides that, oxidative kinetic resolution of
racemic alcohols is also another feasible approach giving
enzymatic catalysts for the oxidative kinetic resolution of
racemic alcohols have been reported. Sigman’s group and
3
Stoltz’s group intensively studied aerobic oxidative kinetic
resolution of secondary alcohols catalyzed by (-)-sparteine/
Pd(II) to conveniently access enantiomerically enriched
3
a,b
secondary alcohols, respectively.
Nishibayashi and co-
workers employed [RuCl (PPh )(ferrocenyloxazolinylphos-
2
3
phine)] to catalyze the oxidative kinetic resolution of racemic
1-indanol, obtaining an optically active 1-indanol in good
2
optically active alcohols. Recently, several effective non-
-
1
yield (turnover frequency exceeds 80 000 h ) with high
(
1) For recent reviews, see: (a) Gladiali, S.; Alberico, E. Chem. Soc.
ReV. 2006, 35, 226. (b) Samec, J. S. M.; B a¨ ckvall, J.-E.; Andersson, P. G.;
Brandt, P. Chem. Soc. ReV. 2006, 35, 237. (c) Clapham, S. E.; Hadzovic,
A.; Morris, R. H. Coord. Chem. ReV. 2004, 248, 2201. (d) Blaser, H. U.;
Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studen, M. AdV. Synth. Catal.
003, 345, 103. (e) Fan, Q. H.; Li, Y. M.; Chan, A. S. C. Chem. ReV.
002, 102, 3385. (f) B a¨ ckvall, J. E. J. Organomet. Chem. 2002, 652, 105.
(3) (a) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221. (b)
Stoltz, B. M. Chem. Lett. 2004, 33, 362. (c) Nishibayashi, Y.; Yamauchi,
A.; Onodera, G.; Uemura, S. J. Org. Chem. 2003, 68, 5875. (d) Sun, W.;
Wang, H.; Xia, C.; Li, J.; Zhao, P. Angew. Chem., Int. Ed. 2003, 42, 1042.
(e) Faller, J. W.; Lavoie, A. R. Org. Lett. 2001, 3, 3703. (f) Masutani, K.;
Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron Lett. 2000, 41, 5119. (g)
Nishibayashi, I.; Takei, I.; Uemura, S.; Hidai, M. Organometallics 1999,
18, 2291. (h) Gross, Z.; Ini, S. Org. Lett. 1999, 1, 2077. (i) Hamada, T.;
Irie, R.; Mihara, J.; Hamachi, K.; Katsuki, T. Tetrahedron 1998, 54, 10017.
(j) Hashiguchi, S.; Fujii, A.; Haack, K.-J.; Matsumura, K.; Ikariya, T.;
Noyori, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 288.
2
2
(
g) Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045. (h)
Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97.
(
2) (a) Keith, J. M.; Larrow, J. F.; Jacobsen, E. N. AdV. Synth. Catal.
2
2
001, 343, 5. (b) Robinson, D. E. J. E.; Bull, S. D. Tetrahedron: Asymmetry
003, 14, 1407.
1
0.1021/ol062244f CCC: $33.50
© 2006 American Chemical Society
Published on Web 10/27/2006

enantioselectivity (up to 94% ee).3c Recently, Sun et al.
reported chiral Mn(salen)-complex catalyzed kinetic resolu-
tion of secondary alcohols with excellent enantioselectivity
Table 1. Kinetic Resolution of Racemic 1-Phenylethanol
Catalyzed by Chiral PNNP and Various Metal Complex
Systemsa
(
up to 98% ee) in water.3d
In the past several years, we successfully prepared a class
of chiral diaminodiphosphine (PNNP) ligands possessing the
dual property of two “soft” phosphorus atoms and two “hard”
nitrogen donor atoms, which display rich coordination
chemistry and easily modify the steric and electronic
4
properties of the resulting metal complexes. On the basis
of these ligands, the chiral PNNP-Ru(II), -Rh(I), and -Ir-
(
I) complexes were prepared and used as catalysts in the
5
asymmetric transfer hydrogenation of aromatic ketones.
These metal complexes have proved to be excellent catalyst
precursors for the enantioselective reduction of a series of
aromatic ketones, leading to corresponding chiral alcohols
with up to 99% ee and the molar ratio of ketone to catalyst
up to 10 000:1. Recently, other groups employed ruthenium
complexes with these chiral PNNP ligands to catalyze
asymmetric epoxidation and asymmetric cyclopropanation
of olefins. Encouraged by these findings, we extended our
study to develop the enantioselective oxidation of racemic
secondary alcohols catalyzed by chiral PNNP metal com-
plexes.
run
M
sub:[M]:L*:KOH conv (%) ee (%) confc
b
b
1
2
[IrCl(COD)]2
200:1:1:2
200:1:1:2
200:1:1:6
200:1:1:6
200:1:1:6
63
68
44
3
98
79
24
R
R
S
[IrHCl2(COD)]2
Ru(DMSO)4Cl2
RuCl2(PPh3)3
[RhCl(COD)]2
d
5d
3
d
4
d
5
4
6,7
a Reaction conditions: racemic 1-phenylethanol (1 mmol); L* ) (R,R)-
1
; solvent: anhydrous acetone (10 mL); time: 8 h; temperature: 25 °C.
Determined by GC using a chiral column (Chiraldex G-TA column).
Determined by comparison of the retention times of enantiomers on the
b
c
GC traces with literature values. d Temperature: 50 °C.
In our continuing study, we have successfully found chiral
PNNP/Ir(I) complex as a versatile catalyst for the enanti-
oselective redox reaction of ketones and alcohols. The
combinations of chiral PNNP ligand with various Rh(I), Ru-
species to promote the reaction. No reaction occurred if the
base was absent. However, excess base caused serious side
reactions including the aldol reaction of acetone, which
(II), or Ir(I) complexes have been tested as catalyst precursors
3
j
would hamper the catalytic cycle. The oxidation with Ru-
II), Rh(I)-based catalyst systems proceeded more slowly.
for the kinetic resolution of racemic 1-phenylethanol and the
results are summarized in Table 1. The enantioselective
oxidation of 1-phenylethanol was carried out in anhydrous
acetone, using chiral PNNP metal complexes prepared in situ
(
Even in the presence of a large excess of KOH (6 equiv to
the catalyst), the oxidation of 1-phenylethanol catalyzed by
the Ru(DMSO) Cl /(R,R)-1 catalyst system at 50 °C for 8 h
4 2
only gave 44% conversion and 24% ee (Table 1, run 3). It
is noteworthy that the opposite configuration of the chiral
alcohol was produced by changing Ir to Ru. Under the same
reaction conditions, RuCl (PPh ) and [RhCl(COD)] were
2 3 3 2
almost inert to the enantioselective oxidation of 1-phenyl-
ethanol.
8
as catalysts. In the presence of KOH, the chiral PNNP/Ir(I)
catalyst systems proved to be efficient in catalytic oxidative
kinetic resolution of racemic 1-phenylethanol. Especially, the
catalyst system generated from [IrCl(COD)] and (R,R)-1
2
exhibited high catalytic activity and enantioselectivity (63%
conversion, 98% ee; Table 1, run 1). The role of base is
presumed to form metal hydride complex, which is a key
Table 1 indicated the chiral PNNP/Ir(I) catalyst systems
were the most effective for the oxidative kinetic resolution
of racemic 1-phenylethanol under mild conditions. This
preliminary result prompted us to investigate oxidative kinetic
resolution of other racemic alcohols in more detail. In our
earlier studies, we observed that the preformed chiral PNNP-
Ir(I) complexes were excellent catalyst precursors for asym-
(
4) Gao, J.-X.; Zhang, H.; Yi, X.-D.; Xu, P.-P.; Tang, C.-L.; Wan, H.-
L.; Tsai, K.-R.; Ikariya, T. Chirality 2000, 383.
5) (a) Gao, J.-X.; Ikariya, T.; Noyori, R. Organometallics 1996, 15,
1
1
(
087. Wong, W.-K.; Chik, T.-W.; Feng, X.; Mak, T. C. W. Polyhedron
996, 15, 3905. (b) Zhang, H.; Yang, C.-B.; Li, Y.-Y.; Dong, Z.-R.; Gao,
J.-X.; Nakamura, H.; Murata, K.; Ikariya, T. Chem. Commun. 2003, 142.
c) Gao, J.-X.; Yi, X.-D.; Xu, P.-P.; Tang, C.-L.; Zhang, H.; Wan, H.-L.;
Ikariya, T. J. Mol. Catal. A: Chem. 2000, 159, 3. (d) Chen, J.-S.; Li, Y.-Y.;
Dong, Z.-R.; Li, B.-Z.; Gao, J.-X. Tetrahedron Lett. 2004, 45, 8415. (e)
Xing, Y.; Chen, J.-S.; Dong, Z.-R.; Li, Y.-Y.; Gao, J.-X. Tetrahedron Lett.
(
9
metric transfer hydrogenation of aromatic ketones. In this
work, we examined the chiral PNNP-Ir(I) complex catalyst
for enantioselective oxidation of a variety of secondary
alcohols; typical results are shown in Table 2. It could be
seen that for the oxidative kinetic resolution of racemic
1-phenylethanol (2a), the preformed chiral PNNP-Ir(I)
complexes exhibited better reactivity and excellent enanti-
oselectivity (69% yield, 98% ee; Table 2, run 1). The kinetic
resolution of 1-phenyl-1-propanol (2b), 1-phenyl-1-butanol
2
006, 47, 4501. (f) Dong, Z.-R.; Li, Y.-Y.; Chen, J.-S.; Li, B.-Z.; Xing, Y.;
Gao, J.-X. Org. Lett. 2005, 7, 1043.
6) Stoop, R. M.; Bachmann, S.; Valentini, M.; Mezzetti, A. Organo-
metallics 2000, 19, 4117.
7) (a) Bonaccorsi, C.; Mezzetti, A. Organometallics 2005, 24, 4953.
b) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001, 20, 2102.
8) A typical experimental procedure of oxidative kinetic resolution of
-phenylethanol is as follows. To a mixture of (R,R)-1 (0.005 mmol) and
(
(
(
(
1
[
Ir(COD)Cl]2 (0.0025 mmol) was added anhydrous acetone (10 mL) under
nitrogen. After the solution was stirred for 1 h at 25 °C, a solution of KOH
i
in PrOH and then racemic 1-phenylethanol (1 mmol) were slowly added.
The solution was stirred at the desired temperature for the required reaction
time. The chemical yield and ee of products were determined by chiral GC
ananlysis on a Chiraldex G-TA column.
(9) Li, Y.-Y.; Zhang, H.; Chen, J.-S.; Liao, X.-L.; Dong, Z.-R.; Gao,
J.-X. J. Mol. Catal. A: Chem. 2004, 218, 153.
5566
Org. Lett., Vol. 8, No. 24, 2006

lective oxidation of phenylethanol derivatives was also
investigated. Introduction of an electron-donating methyl to
the ortho position of the aromatic ring would sharply decrease
the reactivity and enantioselectivity of the reaction. Even with
an extreme excess of KOH (20 equiv to the catalyst), the
oxidation of racemic 1-(2-methylphenyl)ethanol (o-2f) for
Table 2. Kinetic Resolution of Racemic Secondary Alcohols
Catalyzed by Preformed Chiral PNNP-Ir(I) Complexesa
2
0 h hardly occurred (8% yield, 4% ee; Table 2, run 6). On
the other hand, the oxidative kinetic resolution of racemic
1-(3-methylphenyl)ethanol (m-2f) was carried out easily with
9
7% ee (Table 2, run 7). Introduction of an electron-
withdrawing group such as an chloro substituent to the meta-
position of the aromatic ring would decrease the enantiose-
lectivity (61% yield, 88% ee; Table 2, run 8), while the
enantioselective oxidation of racemic 1-(4-chlorophenyl)-
ethanol (p-2g) exhibited a high chiral efficiency, with up to
b
b
run alcohol
catalyst
time (h) conv (%) ee (%)
s
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
o-2f
m-2f
[IrCl-(R,R)-1]
[IrCl-(S,S)-1]
[IrCl-(S,S)-1]
[IrCl-(S,S)-1]
[IrCl-(S,S)-1]
[IrCl-(S,S)-1]
[IrCl-(S,S)-1]
3
8
8
20
24
20
3
69
59
56
63
14
8
62
61
75
98
98
98
97
13
4
97
88
97
10
23
34
14
10
3
15
10
7
c
7
5% yield and 97% ee (Table 2, run 9).
d
e
In summary, this work presents the first successful use of
chiral PNNP-Ir(I) complex catalyst for the oxidative kinetic
resolution of racemic secondary alcohols with up to 98%
ee. The kinetic resolution reactions are carried out under mild
conditions, and the workup procedure is simple. This result
provides a useful index for designing efficient catalyst
systems in achieving optically active alcohols.
m-2g [IrCl-(R,R)-1]
p-2g [IrCl-(R,R)-1]
2
5
a
Reaction conditions: racemic secondary alcohol (1 mmol); catalyst
0.005 mmol); solvent: anhydrous acetone (10 mL); sub:cat.:KOH ) 200:
:2; temperature: 25 °C. Determined by GC using a chiral column
(
1
b
c
d
(
2
Chiraldex G-TA column). Sub:cat.:KOH ) 200:1:6. Sub:cat.:KOH )
e
00:1:10. Sub:cat.:KOH ) 200:1:20.
Acknowledgment. We would like to thank the National
Natural Science Foundation of China (20373056, 20423002)
and the Fujian Provincial Science and Technology Commis-
sion (2005YZ1020) for financial support.
(
2c), and 1-phenyl-1-pentanol (2d) also proceeded smoothly
with 97-98% ee (Table 2, runs 2-4). However, when the
alkyl substituent group of the substrate was changed to
bulkier isopropyl, the reaction proceeded slowly with low
enantioselectivity (14% yield, 13% ee; Table 2, run 5). The
decrease of reactivity and enantioselectivity may be caused
by space handicap. The steric repulsion between alcohol and
catalyst might prevent the formation of a favorable transition
Supporting Information Available: Typical procedures
for oxidative kinetic resolution of racemic secondary alcohols
and GC analytical data for chiral aromatic alcohols. This
material is available free of charge via the Internet at
http://pubs.acs.org.
3c
state, which gives high enantioselectivity. Next, enantiose-
OL062244F
Org. Lett., Vol. 8, No. 24, 2006
5567