Insight into the mechanism of oxidative kinetic resolution of racemic secondary alcohols by using manganese(III)(salen) complexes as catalysts

Article abstract of DOI:10.1002/chem.200400818

The oxidative kinetic resolution of various racemic secondary alcohols with PhI(OAc)₂ catalyzed by chiral [Mn^III(salen)] complexes in the presence of KBr was studied in a water/organic solvent mixture. The dramatic, synergetic effect of additives, organic solvent, and the substituents of chiral salen ligands on the enantioselectivities of the reactions is reported. Results from UV/Vis spectroscopy and ESI-MS studies provide evidence that these reactions are induced by the formation of a high-valent manganese intermediate.

Full text of DOI:10.1002/chem.200400818

Insight into the Mechanism of Oxidative Kinetic Resolution of Racemic
Secondary Alcohols by Using Manganese(iii)(Salen) Complexes as Catalysts
[
a]
Zhen Li, Zhong H. Tang, Xiao X. Hu, and Chun G. Xia*
Abstract: The oxidative kinetic resolution of various racemic secondary alcohols
iii
with PhI(OAc) catalyzed by chiral [Mn (salen)] complexes in the presence of
2
Keywords: alcohols · manganese ·
KBr was studied in a water/organic solvent mixture. The dramatic, synergetic
effect of additives, organic solvent, and the substituents of chiral salen ligands on
the enantioselectivities of the reactions is reported. Results from UV/Vis spectros-
copy and ESI-MS studies provide evidence that these reactions are induced by the
formation of a high-valent manganese intermediate.
mass spectrometry
kinetic resolution
spectroscopy
·
oxidative
UV/Vis
·
[8]
Introduction
dant. Here we report a more efficient and simple method
for the enantioselective oxidation of alcohols catalyzed by
chiral [Mn(salen)] complexes and either PTC or the inex-
The oxidation of alcohols to carbonyl compounds is a key
transformation in organic chemistry, and has attracted much
attention, especially in the search for versatile and selective
pensive inorganic salt KBr, with PhI(OAc) as co-oxidant.
2
We also elucidated the mechanism of the oxidative kinetic
resolution by conducting electrospray ionization mass spec-
trometry (ESI-MS) and UV-visible spectroscopy.
[1]
regents in catalytic reactions. Recently, the oxidizing prop-
erties of hypervalent iodine reagents have been of increasing
interest, as these species have low toxicity, are readily avail-
[2]
able, and are easy to handle. Adama found that Cr(salen)
complexes were effective catalysts for the oxidation of sec-
ondary alcohols to ketones with iodosobenzene (PhI=O)
Results and Discussion
[
3]
and diacetoxyiodobenzene (PhI(OAc) ) as oxidants, and
Effect of additive: To explore the effect of cation and haloid
2
iii
iii
we also reported [Mn (salen)] complexes to be effective cat-
anion we performed an additive screen using the [Mn (sa-
alysts for the oxidation of secondary alcohols to ketones in
len)] complex 1a (the highly enantioselective epoxidation
Jacobsen catalyst ) as catalyst and a-methylbenzyl alcohol
as a model test substrate.
[4]
[9]
the presence of the co-oxidant PhI(OAc)2. We wanted to
extend the scope of this potentially useful reaction to asym-
metric catalysis and its application to the oxidative kinetic
resolution of secondary alcohols; the kinetic resolution of
[5,6]
which has been accomplished through acylation
dation.
and oxi-
[7]
We recently developed a method for the oxidative kinetic
resolution of alcohols in water, catalyzed by chiral [Mn(sa-
len)] complexes and the phase-transfer catalyst (PTC) tet-
raethylammonium bromide, with PhI(OAc) as the co-oxi-
2
[
a] Dr. Z. Li, Z. H. Tang, X. X. Hu, Prof. Dr. C. G. Xia
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences
Lanzhou, 730000, (P. R. China)
Fax : (+86)931-496-8129
E-mail: cgxia@ns.lzb.ac.cn
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
1210
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/chem.200400818
Chem. Eur. J. 2005, 11, 1210 – 1216

FULL PAPER
[
a]
Table 1. Screen with various additives.
Table 2. Oxidative kinetic resolution of a-methylbenzyl alcohol with var-
ious [Mn (salen)] complexes
iii
[a]
[
b]
[c]
[d]
Entry
Catalyst
Conversion [%]
ee [%]
k
rel
[
e]
1
2
3
4
5
6
7
1b
1b
1c
1d
2
18.7
63.0
68.0
68.4
33.2
66.1
57.5
0
1
99.8
99.9
29.1
2.8
81.2
30.8
23.9
23.2
2.0
1.1
5.6
[b]
[c]
[d]
Entry Additive
Conversion [%]
ee [%]
k
rel
1
2
3
4
5
6
7
8
–
12.0
65.0
63.2
62.0
41.5
57.4
56.6
11.6
0
>99
>99
53.7
15.4
92.9
92.9
3.3
1
N(CH
N(C
N(C
3
)
4
Br
>15.6
>18.0
3.2
3a
3b
2
H
H
5
)
)
4
Br
Br
2.1
4
9
4
[
f]
[a] Reaction conditions as in Table 1. [b] Determined by performing GC
analysis using an internal standard. [c] Determined by performing GC
using a CP-Chirasil-Dex CB capillary column. [d] krel =ln[(1ꢀC)(1ꢀee)]/
ln[(1ꢀC)(1+ee)]. [e] In the absence of KBr.
CTAB
1.8
[
[
[
g]
(C
(C
(C
2
4
6
mim)Br
mim)Br
mim)Br
17.9
19.6
1.7
h]
i]
9
62.2
94.1
12.3
1
1
0
1
68.5
62.1
99.9
99.9
17.4
28.4
1
2
59.1
93.0
15.0
13
14
15
16
17
18
NaBr
LiBr
KBr
KBr
KCl
KI
58.5
73.4
64.0
62.8
9.0
95.7
92.0
96.0
95.9
0
19.3
5.7
12.2
13.2
1
[
e]
9.9
0.93
1.2
[
a] Reactions performed at room temperature with Jacobsen catalyst
(
(
2 mol%), additive (4 mol%), substrate (0.25 mmol), PhI(OAc)
0.175 mmol), and H O/CH Cl (1 mL/0.5 mL). [b] Determined by per-
2
2
2
2
Figure 1. Plot of conversion, ee, and krel versus reaction time for the oxi-
dative kinetic resolution of a-methylbenzyl alcohol.
forming GC analysis using an internal standard. [c] Determined by per-
forming GC analysis using CP-Chirasil-Dex CB capillary column.
a
[
d] krel =ln[(1ꢀC)(1ꢀee)]/ln[(1ꢀC)(1+ee)]. [e] After 30 min. [f] Hexade-
cyltrimethylammonium bromide. [g] 1-ethyl-3-methylimidazolium. [h] 1-
butyl-3-methylimidazolium. [i] 1-hexyl-3-methylimidazolium.
after ten minutes, krel remained at a value of around 15
during the course of reaction.
As shown in Table 1, in the absence of additive, the (R,
R) Jacobsen catalyst is inactive in the resolution of a-meth-
ylbenzyl alcohol (Table 1, entry 1). The addition of bromide
salts leads to a substantial increase in enantioselective activi-
ty (Table 1, entries 2, 3, 6, 7, 9–11). The most dramatic effect
was observed upon addition of the inexpensive inorganic
salt KBr (4 mol%); 99.9% ee was obtained in just 0.5 h.
In this system, it is unclear if bromide is acting as a coun-
Effect of counterion: Use of the manganese(iii)(salen) com-
plex with a nonligating counterion, such as PF6 (1d), yield-
ꢀ
ed a conversion of 68.4% and a low k value of only 2. Spe-
rel
ꢀ
cies 1c, which has OAc as a counterion, also resolved effec-
tively; a conversion of 68.0%, an ee value of 99.9%, and a
krel of 23.2 were observed (Table 2, entry 3). Substitution of
the tert-butyl groups at the 5,5’-positions of the Jacobsen cat-
alyst 1a by methyl substituents (2) resulted in low conver-
sion and enantioselectivity (Table 2, entry 5). This indicates
that the steric hindrance at the 5,5’-positions was favourable
iii
terion in the catalyst. To investigate this, [Mn (salen)Br] 1b
was added to the standard reaction conditions in the ab-
sence of KBr. Consequently, a surprisingly low level of cat-
alysis was observed (Table 2, entry 1). However, upon addi-
tion of KBr (4 mol%), catalytic activity was re-established
and good conversion and ee values were obtained (Table 2,
entry 2). This data suggests that KBr is necessary for oxida-
tion, and that the bromide ion does not coordinate to the
manganese atom.
iii
for the catalytic activity of the [Mn (salen)] complex. Com-
plex 3b, derived from (R, R)-diphenylethylenediamine, dis-
played an activity similar to complex 1d; however, in the
ꢀ
case of Cl as a counterion (3a), a moderate result was ob-
tained (Table 2 entry 6).
Effect of organic solvents: Before turning to other sub-
strates, attempts were made to improve the process and to
make it more general. The oxidative kinetic resolution of a-
methylbenzyl alcohol catalyzed by 1a (2 mol%) and
We also investigated the relationship between conversion,
ee, the selectivity factor k , and reaction time, in the kinetic
rel
resolution of a-methylbenzyl alcohol. Figure 1 reveals that,
although the highest conversion and ee values were obtained
PhI(OAc) with KBr (4 mol%) was studied by using a varie-
2
Chem. Eur. J. 2005, 11, 1210 – 1216
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1211

C. G. Xia et al.
[
a]
Table 3. The effect of organic solvent on oxidative kinetic resolution.
aprotic solvents, including MeCN, CHCl , ethyl acetate,
DMF, and THF, gave low krel values (Table 3, entries 7–11).
3
[
b]
[c]
[d]
Entry
Solvent system
Conversion [%]
ee [%]
k
rel
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
H
H
H
H
2
2
2
2
2
2
2
2
2
2
2
2
O/hexane
64.5
61.6
53.0
55.8
64.0
69.0
43.2
68.4
41.3
59.2
54.6
99.3
99.9
91.6
91.1
96.0
99.2
1.4
79.5
19.7
20.3
52.9
–
17.3
29.7
30.8
19.2
12.2
12.4
O/toluene
O/acetone
O/1,4-dioxane
Effect of substrates: The scope of the oxidative kinetic reso-
lution of some other rac-secondary alcohols was explored by
using KBr (4 mol%) as an additive together with 1a
O/CH
O/DCE
O/MeCN
O/CHCl
2
Cl
2
(
2 mol%) (Table 4).
1.05
3
4.8
2.1
1.6
4.1
–
O/ethyl acetate
O/DMF
O/THF
1
1
1
0
1
2
[
e]
O/tBuOH
–
[
a] Reactions performed at room temperature with catalyst (2 mol%),
KBr (4 mol%), substrate (0.25 mmol), PhI(OAc) (0.175 mmol), and
O/organic solvent (1 mL/0.5 mL). [b] Determined by performing GC
analysis using an internal standard. [c] Determined by performing GC
analysis using CP-Chirasil-Dex CB capillary column. [d] krel
ln[(1ꢀC)(1ꢀee)]/ln[(1ꢀC)(1+ee)]. [e] No oxidation.
2
H
2
a
=
ty of organic solvents. As shown in Table 3, the krel of the re-
action depends strongly upon the organic solvent used. In
the case of H O mixed with less polar solvents, the oxidative
2
kinetic resolution reaction exhibited moderate to high enan-
tioselectivity (ee of >90%) (Table 3). No reaction was ob-
served when the protic solvent tBuOH was used. Dipolar
Notably, most of the examples produced enantiomeric ex-
cesses of over 99%. Interesting-
ly, H O/hexane is the best sol-
vent system for the asymmetric
oxidation of aliphatic racemic
[
a]
2
Table 4. Data for the kinetic resolution of rac-secondary alcohols by the 1a/PhI(OAc)
2
/KBr system
[
b]
[c]
[d]
k
rel
Entry
Substrate
Solvent
Conversion [%]
ee [%]
1
2
3
(ꢁ)-1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
O/CH
O/hexane
O/toluene
O/CH
O/CH
O/hexane
O/CH Cl
O/hexane
O/toluene
O/CH
O/hexane
O/toluene
O/CH Cl
2 2
O/hexane
O/toluene
2 2
O/CH Cl
O/hexane
O/toluene
O/CH
O/hexane
O/toluene
O/CH
O/hexane
O/toluene
2 2
O/CH Cl
2
Cl
2
66.1
66.4
29.7
55.1
69.2
53.4
60.6
55.1
59.5
50.4
50.8
58.8
72.2
67.3
69.6
61.3
57.1
62.5
8.2
14.0
31.2
63.4
56.6
70.2
52.2
68.9
71.6
95.3
>99.0
21.7
10.0
>14.2
sec-alcohols, such as (ꢁ)-1,
(
ꢁ)-3, (ꢁ)-4, and (ꢁ)-5 (dl-
3.8
[
e]
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
(ꢁ)-2
(ꢁ)-3
2
Cl
Cl
2
91.2
21.2 menthol), and resulted in the
2
2
>99.9
>99.9
>16.7 kinetic resolution of these sub-
>108
>32.8
>71.3
>37.0
strates with extremely high
enantioselectivity. On the other
hand, hexane and toluene are
[
g]
g]
g]
(ꢁ)-4
2
2
>99.9
>99.9
>99.9
93.5
>99.9
>99.9
96.7
99.5
99.9
92.5
74.3
97.7
–
[
[
[
i]
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
(ꢁ)-5
(ꢁ)-6
(ꢁ)-7
(ꢁ)-8
(ꢁ)-9
2
Cl
2
83.6 not applicable to (ꢁ)-2. Aryl-
>458.0
>40.2
7.8
substituted alcohols are gener-
ally good substrates under these
modified conditions, in which
15.0
16.3 the optimal solvent is depen-
12.0 dent on the substrate. Sub-
[
[
[
[
e]
e]
e]
f]
7.6
15.9
–
–
–
14.9
>54.5
15.7
127.1
strates with a large substituent
group at the ortho site undergo
2
Cl
2
relatively poor oxidation and
kinetic resolution (Table 4, en-
tries 19–21). This observation is
in line with the view that the
difference in size of the sub-
–
–
2
Cl
2
97.8
>99.9
99.9
99.5
99.4
99.6
[
e]
[
[
[
h]
h]
h]
(ꢁ)-10
O/hexane
O/toluene
13.1 stituents plays a significant role
11.9 in the overall efficiency of the
[
a] Reactions were performed at room temperature with catalyst (2 mol%), KBr (4 mol%), substrate kinetic resolution.
(
0.25 mmol), PhI(OAc)
2
(0.175 mmol), H
2
O/organic solvent (2:1, v/v), for 1 h. [b] Determined by performing
To verify the efficiency of
catalyst 1a in the kinetic resolu-
tion of a-methylbenzyl alcohol,
analysis was performed on a
1:500 molar ratio of catalyst/
GC analysis using decane as an internal standard. [c] Determined by performing GC analysis using a CP-Chir-
asil-Dex CB capillary column. [d] krel =ln[(1ꢀC)(1ꢀee)]/ln[(1ꢀC)(1+ee)]. [e] After 0.5 h. [f] KBr 8 mol%.
[
g] Determined by using HPLC with a Chiralcel OJ column (Hex/IPA=75:25). [h] Determined by using
HPLC with a Chiralcel OD-H column (Hex/IPA=95:5). [i] The remaining alcohol is l-menthol according to
the MS spectrum.
1212
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Chem. Eur. J. 2005, 11, 1210 – 1216

Oxidative Kinetic Resolution
FULL PAPER
substrate. This larger scale reac-
tion required a slightly longer
reaction time of 2 h and showed
a slight decrease in krel values
(
9.8 compared to 12.2) and a
reasonable ee of 92%.
Reaction mechanism: Kita and
co-workers reported the oxida-
tion of alcohols by using iodo-
sobenzene (PhI=O) as a co-oxi-
dant and KBr as a catalyst in
water, and thought that PhI=O
and KBr formed a reactive in-
[10]
termediate in water [Eq. (1)].
Electrospray ionization mass
spectrometry (ESI-MS) analysis
of the behavior of PhI=OꢀKBr
in aqueous solution suggested
that the highly reactive iodine
ꢀ
species
formed.
(PhIBrO )
was
[11]
H2O
ꢀ
þ
iii
PhI¼OþKBrƒƒ!PhIBrO þK
Scheme 1. Possible mechanism of the oxidative kinetic resolution of sec-alcohols catalyzed by [Mn (salen)]
complexes and PhI(OAc) in the presence of KBr.
2
ð1Þ
This hypervalent iodine(iii) species may not, however, be
the active intermediate in our reaction system. In fact, the
in situ treatment of a-methylbenzyl alcohol and 1a with
ꢀ
PhIBrO , which had been generated from iodosobenzene
diacetate (IBDA) and KBr in water, resulted in zero enan-
tioselectivity. This differs from Kitaꢁs conclusion that the for-
ꢀ
mation of PhIBrO is very rapid and, once formed, reacts
immediately with alcohol. To clarify this discrepancy, we
considered a possible mechanism involving a ternary com-
pound, which was generated by combining catalyst,
PhI(OAc) , and substrate.
2
We assumed that the adduct A of complex 1a with
PhI(OAc) is formed in the first step, as proposed during
2
III
[12]
the reaction of [(salen)Cr ] with PhI(OAc) , after which
2
this adduct coordinates with the substrate molecule to form
the ternary compound B. Subsequent electronic reorganiza-
tion, with elimination of the CH (O)CC radical and an ace-
3
tate group, generates the high-valent manganese intermedi-
ate C. This hypothesis was supported by the results of UV-
visible and ESI-MS spectroscopic analysis and a possible,
plausible reaction mechanism is proposed in Scheme 1.
Figure 2. Relationship between the conversion and reaction time under
different reaction conditions.
Control experiment: The results of a control experiment
with the enantiomerically enriched a-methylbenzyl alcohol
showed that the (S)-a-methylbenzyl alcohol enantiomer was
oxidized preferentially to the ketone by the (R, R)-Jacobsen
catalyst 1a, with a conversion of 99.0% in 15 min (Figure 2).
In contrast, the (R)-a-methylbenzyl alcohol enantiomer ex-
hibited only 45.2% conversion after the same reaction time
and 66.0% conversion after 1 h. Reactions performed in the
absence of KBr resulted in a poor conversion for both (R)-
and (S)-a-methylbenzyl alcohol, whereas in the absence of
catalyst, two enantiomers were transformed to ketone with
similar conversions of ~60–70%.
This discrepancy may be explained in terms of thermody-
namic or kinetic differences. Initially, as the substrate com-
bines with the catalyst, the binding of the (S)-enantiomer is
favored, which is in accordance with the observation above
that substrates with a bulky group next to the carbonyl
carbon atom do not undergo oxidative kinetic resolution
Chem. Eur. J. 2005, 11, 1210 – 1216
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1213

C. G. Xia et al.
under the present conditions. This suggests that coordination
of a hydroxyl group is essential for oxidation and that this
occurs within the coordination sphere of the manganese ion.
UV-visible spectroscopy of reaction intermediates: To iden-
tify the reactive intermediates in the oxidative kinetic reso-
lution of racemic sec-alcohols using 1a/PhI(OAc) /KBr, we
2
recorded UV/Vis spectra at room temperature by using tolu-
ene as the solvent.
The UV/Vis spectra of 1a in the presence of substrate are
shown in Figure 3. An initial increase in absorbance at
431 nm and a broad band between 600 and 700 nm were ob-
served within 25 min of addition of PhI(OAc) to the so-
2
lution. This indicates that a compound with a broad absorp-
Figure 4. UV/Vis spectra of the organic phase following the addition of
ꢀ2
KBr/H
ratio=1:6.7:20) in toluene. Spectrum 1: catalyst 1a/a-methylbenzyl alco-
hol; spectrum 2: catalyst 1a/a-methylbenzyl alcohol/PhI(OAc) (after
h); spectrum 3: the organic phase following the addition of KBr/H O to
a/a-methylbenzyl alcohol/PhI(OAc) in toluene (after 30 min).
2 2
O (1.68ꢂ10 m) to 1a/a-methylbenzyl alcohol/PhI(OAc) (molar
2
1
2
1
2
complex 1a, a-methylbenzyl alcohol, and PhI(OAc) . In
2
contrast to spectrum 2, spectrum 3 shows the decrease in ab-
sorbance at about 600 nm. Therefore, it can be concluded
that the key step of this kinetic resolution reaction is the at-
ꢀ
tachment of the Br ion to the high-valent manganese inter-
mediate C.
ESI-MS studies of reaction intermediates: The addition of a
solution of complex 1a in toluene to a solution of
PhI(OAc) in toluene resulted in the disappearance of the
2
iii
+
molecular ion [Mn (salen)] (m/z: 599.7). Instead, the mo-
lecular ions [O=Mn (salen)(PhIO)] (m/z: 836.8), [Mn (sa-
len)(OPhIOAc)]
PhI(OAc) }] (adduct A) (m/z: 921.7) dominated (Fig-
v
+
v
+
iii
(m/z:
878.6),
and
[Mn (salen)-
+
{
2
ure 5A).
Results of collision-induced dissociation (CID) experi-
iii
ments performed on the solution showed that the [Mn (sa-
+
len){PhI(OAc) }] ion is stable. The fragment ion [O=
2
v
+
Mn (salen)] (m/z: 615.7) is produced by increasing the
cone energy from 10 V to 20 V, which suggests that this ion
v
+
is a product of the dissociation of [O=Mn (salen)(PhIO)]
v
+
and [Mn (salen)(OPhIOAc)] (Figure 5B).
Addition of a-methylbenzyl alcohol led to the disappear-
ance of the molecular ion [Mn (salen){PhI(OAc) }] (m/z:
iii
+
2
Figure 3. Variation in UV/Vis spectra of 1a/a-methylbenzyl alcohol/
PhI(OAc) (molar ratio=1:6.7:20) in toluene with time.
2
9
21.7) and the appearance of a new ion (m/z: 941.6), which
iii
+
was assigned to the [PhIOMn (salen){OCH(CH )Ph}] ion
C, formed from the [Mn (salen){PhI(OAc) }] ion (Fig-
3
iii
+
2
tion band of around 600 nm was formed. The spectra
changed as the reaction proceeded (Figure 3B). An isosbes-
tic point at 583 nm implies that the initially formed com-
pound is converted to another species, which was assumed
to be the high-valent manganese intermediate C.
ure 6A). A solution of KBr in H O was then added to the
2
above solution and, after being stirred for 5 min, the organic
phase was analyzed by using ESI-MS. The resulting spec-
trum (Figure 6B) is consistent with the data described
above; the catalyst 1a was recovered and the ion (m/z:
283.6) was assigned to the PhIBr cation.
Figure 4 shows the UV/Vis spectra of the organic phase
following the addition of KBr/H O to toluene containing
2
1214
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Chem. Eur. J. 2005, 11, 1210 – 1216

Oxidative Kinetic Resolution
FULL PAPER
Figure 5. Electrospray ionization mass spectrum of the reaction mixture
of 1a with PhI(OAc)
0 V.
2
in toluene. A) cone voltage 10 V; B) cone voltage
2
Conclusion
Figure 6. A) Electrospray mass spectrum of a solution of 1a, a-methyl-
2
benzyl alcohol, and PhI(OAc) in toluene, showing the formation of
We have demonstrated a clean and efficient system for the
enantioselective oxidative kinetic resolution of secondary al-
cohols catalyzed by [Mn (salen)] complexes and PhI(OAc)2
cation C. B) Electrospray mas spectrum of a toluene solution after oxida-
tive kinetic resolution of a-methylbenzyl alcohol.
iii
with KBr as an additive. Analysis of the system by using
ESI-MS enabled us to characterize the detailed mechanism
of oxygen transfer from PhI(OAc)2 to the [Mn (salen)]
complex and to identify for the first time the oxomanganese
species formed during oxidative kinetic resolution. The re-
sults clearly show that the bromide ion plays a key role in
the enantioselective oxidative reaction.
propylmethyl carbinol, (R)-(+)-sec-phenethyl alcohol, (S)-(+)-sec-phe-
nethyl alcohol, PhI(OAc) , and derivatives of benzaldehyde were pur-
2
chased from Acros Chemical Company and used as received. The other
secondary alcohols were prepared from derivatives of benzyldehyde and
iii
CH
3 2 5
MgI or C H MgBr and were subjected to GC-MS analysis. The imi-
dazolium bromine and pyridinium bromine were prepared according to
[
13]
known procedures. Complexes 1b–1d, 2, 3a, and 3b were prepared ac-
[7b,9b,14]
cording to reported procedures.
Equipment: GC analysis was performed by using an HP 6890 gas chro-
matograph with a CP-Chirasil-Dex CB column (25 m long, 0.25 mm inner
diameter), helium as a carrier gas, and a flame ionization detector (see
Supporting Information). The UV/Vis spectra were recorded by using an
HP 8453 UV/Vis spectrometer. ESI-MS analysis was performed by using
Experimental Section
Materials: The Jacobsen ligand, a-methylbenzyl alcohol, 4-methyl-sec-
phenethyl alcohol, 4-fluoro-sec-phenethyl alcohol, 1,2,3,4-tetrahydro-1-
naphthol, dl-2-methoxy-a-methylbenzyl alcohol, dl-2-pentanol, 1,1-di-
phenyl-2-propanol, 1-indanol, dl-menthol, 3,3-dimethyl-2-butanol, cyclo-
2
a Waters micromassZQ alliance spectrometer with acetonitrile/H O
ꢀ
1
(0.2 mLmin , 80:20). GC-MS measurements were obtained by using an
Agilent 6890N/5973N apparatus. Analytical chiral HPLC was performed
by using an HP1090 instrument equipped with Chiralcel OJ and OD-H
Chem. Eur. J. 2005, 11, 1210 – 1216
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1215

C. G. Xia et al.
columns (each 25 cm long, inner diameter of 0.46 cm) obtained from
Daicel Chemical Industries, Ltd (see Supporting Information).
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General procedure for the kinetic resolution of secondary alcohols cata-
iii
lyzed by [Mn (salen)] complexes:
(
(
A
mixture of the substrate
Cl
0.5 mL), and water (1 mL) was stirred in a 5 mL tube for a few minutes
(0.175 mmol) was then
0.25 mmol), catalyst (0.005 mmol), additive (0.02 mmol), CH
2
2
at room temperature. The oxidant PhI(OAc)
2
added and the system was stirred for a further 1 h until completion of the
reaction. The products were extracted by using diethyl ether and the con-
version and ee values were determined by performing GC analysis.
5
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1
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2
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was poured into 10 mm quartz cuvettes, PhI(OAc)
fold excess, and the spectra were recorded.
2
was added in a 20-
Electrospray solutions: The stock solution of 1a containing substrate
(
(
10 equivalents) was diluted with toluene, then a solution of PhI(OAc)
20 equivalents) in toluene was added. The reaction mixture was shaken
2
for 10 s and a sample of the solution was subjected to ESI-MS analysis.
Next, a solution of KBr in H O was added, and a sample from the organ-
ic phase was analyzed by using ESI-MS.
2
Acknowledgements
This work was supported financially by the National Natural Science
Foundation of China. (20373082, 29933050)
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Published online: December 27, 2004
1216
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www.chemeurj.org
Chem. Eur. J. 2005, 11, 1210 – 1216