Manganese complex-catalyzed oxidation and oxidative kinetic resolution of secondary alcohols by hydrogen peroxide

Article abstract of DOI:10.1039/c7sc00891k

The highly efficient catalytic oxidation and oxidative kinetic resolution (OKR) of secondary alcohols has been achieved using a synthetic manganese catalyst with low loading and hydrogen peroxide as an environmentally benign oxidant in the presence of a small amount of sulfuric acid as an additive. The product yields were high (up to 93%) for alcohol oxidation and the enantioselectivity was excellent (>90% ee) for the OKR of secondary alcohols. Mechanistic studies revealed that alcohol oxidation occurs via hydrogen atom (H-atom) abstraction from an α-CH bond of the alcohol substrate and a two-electron process by an electrophilic Mn-oxo species. Density functional theory calculations revealed the difference in reaction energy barriers for H-atom abstraction from the α-CH bonds of R- and S-enantiomers by a chiral high-valent manganese-oxo complex, supporting the experimental result from the OKR of secondary alcohols.

Full text of DOI:10.1039/c7sc00891k

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ARTICLE
Manganese Complex-Catalyzed Oxidation and Oxidative Kinetic
Resolution of Secondary Alcohols by Hydrogen Peroxide
Received 00th January 20xx,
Accepted 00th January 20xx
ab‡
ac‡
c
a
a
ac
Chengxia Miao, Xiao-Xi Li, Yong-Min Lee, Chungu Xia, Yong Wang, Wonwoo Nam,* and
a
Wei Sun*
DOI: 10.1039/x0xx00000x
A highly efficient catalytic oxidation and oxidative kinetic resolution (OKR) of secondary alcohols has been achieved using a
synthetic manganese catalyst with a low loading and hydrogen peroxide as an environmentally benign oxidant in the
presence of a small amount of sulfuric acid as an additive; the product yields were high (up to 93%) in the alcohol
oxidation and the enantioselectivity was excellent (>90% ee) in the OKR of secondary alcohols. Mechanistic studies
revealed that the alcohol oxidation occurs via a hydrogen atom (H-atom) abstraction from an α-CH bond of alcohol
substrate and a two-electron process by an electrophilic Mn-oxo species. Density functional theory calculations revealed
the difference of reaction energy barriers for the H-atom abstraction from α-CH bonds of R- and S-enantiomers by a chiral
high-valent manganese-oxo complex, supporting the experimental result of the OKR of secondary alcohols.
www.rsc.org/
metalꢀhydroperoxo species to form highꢀvalent metalꢀoxo
3
ꢀ5
Introduction
intermediates.
Very recently, we have reported that a
manganese complex bearing a tetradentate N4 ligand is an
efficient catalyst in the asymmetric epoxidation of olefins by
aqueous H O in the presence of a small amount of H SO ,
2 2 2 4
The selective oxidation of organic substrates using earthꢀ
abundant transition metal catalysts (e.g., manganese and iron)
and environmentally benign oxidants (e.g., molecular oxygen
and hydrogen peroxide) is fundamentally important in
enzymatic/biomimetic reactions and immensely useful in
affording high product yields with excellent stereoꢀ and
7
enantioselectivities. In the latter reaction, it has been shown
1
,2
that carboxylic acid can be replaced by H SO in activating
2
4
organic synthesis. Therefore, tremendous efforts have been
exerted on elucidating the biomimetic oxidation reactions and
developing highly efficient, selective (asymmetric) oxidation
reactions using the earthꢀabundant transition metal catalysts and
2 2
H O by manganese complexes and generating highꢀvalent
7
manganeseꢀoxo species as active oxidants, although the role of
SO remains elusive.
H
2
4
2
ꢀ7
the environmentally benign oxidants under mild conditions.
Another important research area in oxidation reactions is the
8
,9
As a result, great advance has been achieved recently in the
catalytic (asymmetric) epoxidation and hydroxylation reactions
oxidation of alcohols to aldehydes or ketones. Recently,
nonporphyrinic manganese complexes have been employed as
catalysts in developing efficient catalytic systems for the
using synthetic iron and manganese catalysts and aqueous H
2 2
O
as an environmentally benign oxidant in the presence of
2 2
alcohol oxidation reactions, especially using H O as an
2
ꢀ6
carboxylic acid as an additive. In these reactions, it has been
proposed that highꢀvalent metalꢀoxo intermediates are the
active oxidants that effect the (asymmetric) epoxidation and
hydroxylation reactions and that the role of the carboxylic acid
is to facilitate the heterolytic OꢀO bond cleavage of putative
environmentally benign oxidant in the presence of carboxylic
acid; mechanistic studies have been performed to elucidate the
9
alcohol oxidation reactions using synthetic metalꢀoxo
1
0
complexes. In the alcohol oxidation chemistry, oxidative
kinetic resolution (OKR) of racemic secondary alcohols has
attracted much attention to develop efficient catalytic systems
1
1ꢀ13
to obtain enantioꢀenriched alcohols,
since chiral secondary
a.
Key Laboratory for Oxo Synthesis and Selective Oxidation
alcohols are valuable synthetic intermediates in pharmaceutical
and fine chemical industries. In the OKR of racemic secondary
alcohols, chiral metal complexes (e.g., Mn(III) salen complex)
with artificial oxidants (e.g., iodobenzene diacetate and sodium
Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP),
Chinese Academy of Sciences, Lanzhou 730000, China. E-mail: wsun@licp.cas.cn
College of Chemistry and Material Science, Shandong Agricultural University,
b.
Tai’an 271018, China
Department of Chemistry and Nano Science, Ewha Womans University, Seoul
c.
0
3760, Korea. E-mail: wwnam@ewha.ac.kr
Electronic Supplementary Information (ESI) available: Tables S1 – S4 and
hypochlorite) have been used to produce chiral secondary
†
12d,13
alcohols.
However, to the best of our knowledge, the OKR
additional data: NMR spectra of the products, GC and HPLC chromatograms in the
OKR of the secondary alcohols, key geometric information for DFT and so on. See
DOI: 10.1039/x0xx00000x
of secondary alcohols has never been explored using synthetic
mononuclear manganese catalysts and aqueous H
terminal oxidant.
2 2
O as the
‡
These authors contributed equally to this work.
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Table 1 Optimization of reactions conditions for the oxidation of 1ꢀ
a,b
2 2
phenylethanol by manganese complexes and H O
entry
catalyst (mol%)
1 (0.20)
2 (0.20)
3 (0.20)
-----
additive (mol%)
H
2
O
2
(equiv.)
1.5
yield (%)
90
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
2
2
2
2
2
2
2
SO
SO
SO
SO
SO
SO
SO
4
(1.0)
4
(1.0)
4
(1.0)
4
(1.0)
4
(1.0)
4
(1.0)
4
(1.0)
(0.50)
(0.30)
(0.10)
1.5
91
c
1.5
trace
d
1.5
ND
1 (0.30)
1 (0.40)
1 (0.30)
1 (0.30)
1 (0.30)
1 (0.30)
1 (0.30)
1 (0.30)
1 (0.30)
1 (0.30)
1.5
95
95
94
93
93
62
13
18
1.5
1.2
H
2
H
2
H
2
SO
SO
SO
4
4
4
1.2
1.2
1
1
0
1
1.2
HClO
4
(1.0)
1.5
Scheme 1 (A) Schematic structures of manganese complexes bearing N4
II
12
H PO (1.0)
1.5
ligands: Mn (PꢀMCP)(OTf)
2
(1; PꢀMCP = (1R,2R)ꢀN,N’ꢀdimethylꢀN,N’ꢀbisꢀ
3
4
–
–
(
phenylꢀ2ꢀpyridinylmethyl)cyclohexaneꢀ1,2ꢀdiamine and OTf = CF
3
SO
(1R,2R)ꢀN,N’ꢀdiꢀ methylꢀN,N’ꢀ
bis((R)ꢀ(3,5ꢀdiꢀtertꢀbutylphenyl)ꢀ2ꢀpyridinylmethyl)cycloꢀhexaneꢀ1,2ꢀ
3
);
c
1
3
HCl (1.0)
CF SO H (1.0)
1.5
trace
II
2
Mn (DpbꢀMCP)(OTf) (2; DbpꢀMCP =
c
14
3
3
1.5
trace
II
2
diamine); Mn (MCP)(OTf) (3; MCP = (1R,2R)ꢀN,N’ꢀdimethylꢀN,N’ꢀbis(2ꢀ
a
pyridinylmethyl)cyclohexaneꢀ1,2ꢀdiamine). (B) Summary of the alcohol
oxidation. (C) Summary of the oxidative kinetic resolution (OKR) of
secondary alcohols.
Reaction conditions: An CH
was added dropwise into an CH
phenylethanol (0.50 mmol), catalyst, and additive by using a syringe pump
3
CN (0.50 mL) solution containing 30% H
2 2
O
3
CN (1.0 mL) solution containing 1ꢀ
o
b
c
at 25 C for 1 h. Yields were determined by GC. Yields were less than 5%.
d
Not detected.
Herein, we report that manganese complexes bearing substrate (see Experimental Section). Among the tested
tetradentate N4 ligands, such as Mn(II)(PꢀMCP)(OTf) ( ) and manganese catalysts (see Scheme 1A for structures), Mn(II)(Pꢀ
) (Scheme 1A), are highly efficient MCP)(OTf) ( ) and Mn(II)(DbpꢀMCP)(OTf) ( ) exhibited a
catalysts in the oxidation of alcohols by aqueous 30% H O in high catalytic activity (Table 1, entries 1 and 2), whereas
1
2
7
Mn(II)(DbpꢀMCP)(OTf)2 (
2
1
2
2
2
2
2
the presence of a catalytic amount of H SO (Scheme 1B). Mn(II)(MCP)(OTf) (3) was a poor catalyst (Table 1, entry 3).
2
4
2
Further, to the best of our knowledge, the present study reports In the absence of the manganese catalyst, the oxidation of 1ꢀ
the first example of using a chiral manganese catalyst with a phenylethanol to acetophenone was not observed (Table 1,
low loading, aqueous H O as the terminal oxidant, and a entry 4). Since
1
can be prepared easily and costꢀeffectively,
1
2
2
catalytic amount of H SO as an additive in the OKR of was used as the catalyst in determining reaction conditions, by
2
4
racemic secondary alcohols (Scheme 1C). Density functional varying the amounts of catalyst (Table 1, entries 5 and 6), H O
2
2
theory (DFT) calculations reveal that energy barriers for the
CH bond activation of the chiral 1ꢀphenylethanol ( ꢀ and
enantiomers) by a highꢀvalent manganeseꢀoxo complex are nonporphyrinic Mn catalysts and H O , other Brønsted acids,
α
S
ꢀ
ꢀ
(Table 1, entries 5 and 7), and H SO (Table 1, entries 7 – 10).
2 4
R
In addition, as reported in the olefin epoxidation reactions by
7
2
2
significantly different, explaining the experimental observation such as HClO , H PO , HCl, and CF SO H, were turned out to
4
3
4
3
3
of the high enantioselectivity in the OKR of racemic secondary be poor additives (Table 1, entries 11 – 14).
alcohols.
After optimizing reaction conditions (Table 1, entry 9), we
investigated the substrate scope in the oxidation of secondary
alcohols by and H O in the presence of H SO (Table 2); 1ꢀ
phenylethanol derivatives with electronꢀdonating and
withdrawing substituents at the paraꢀposition of the phenyl
group were oxidized to their corresponding ketones with good
yields (e.g., >80%) (Table 2, left column). However, the
1
2
2
2
4
Results and discussion
ꢀ
First, reaction conditions for the catalytic oxidation of alcohols
by manganese complexes and aqueous H O in the presence of
2
2
H SO were optimized using 1ꢀphenylethanol as a model
2
4
2
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a,b,c
Table 3 Substrate scope of oxidative kinetic resolution of secondary alcohols
using the 2/H O /H SO catalytic system
2 2 2 4
Table 2 Substrate scope in the oxidation of secondary alcohol
a,b
entry
substrate
H
2
O
2
(equiv.)
conv. (%)
ee (%)
c
1
R = H
0.8
0.8
0.9
0.9
0.9
0.9
69
74
69
68
60
65
90
92
92
96
96
93
2
3
4
R = p-Cl
R = m-Cl
R = o-Cl
d
5
R = p-NO
2
d
6
R = p-Ph
a
Reaction conditions: An CH
3
CN (0.50 mL) solution containing 30% H
CN (1.0 mL) solution containing substrate
(0.30 mol%) by using a syringe pump at
2 2
O (1.2
equiv.) was added dropwise into an CH
(
2
3
0.50 mmol), 1 (0.30 mol%), and H
2
SO
5 C for 1 h. Yields were determined by GC. Numbers in parenthesis are
4
o
b
c
d
2 4
product yields. 1.0 mol% H SO was used.
7
8
9
R = H
R = p-Br
R = p-Cl
R = p-F
R = m-F
R = o-F
0.8
0.8
0.7
0.8
0.9
0.8
71
69
62
68
69
61
92
96
90
96
94
90
1
1
1
0
1
2
1
1
1
3
4
5
0.8
0.8
0.8
66
65
64
92
92
93
Fig. 1 Plots of the conversion yields (black triangles) of 1ꢀphenylethanol and
the ee values (red circles) of unreacted 1ꢀphenylethanol against equivalents
of H
by 2 (0.20 mol%) and H
substrate) in the presence of H
2
O
2
obtained in the catalytic oxidation of 1ꢀphenylethanol (0.50 mmol)
2 2
O
(0 – 1.0 equiv. based on the concentration of
o
2 4 3
SO (1.0 mol%) in CH CN at 0 C for 1 h.
a
Reaction conditions: An CH
0.90 equiv.) was added dropwise into an CH
secondary alcohol (0.50 mmol), 2 (0.20 mol%), and H
syringe pump at 0 C for 1 h. Conversion yields and ee values were determined
3
CN (0.50 mL) solution containing 30% H
CN (1.0 mL) solution containing
SO (1.0 mol%) by using a
2 2
O (0.70
–
3
product yields were moderate (e.g., ~50%) in the oxidation of
ꢀphenylethanol derivatives with steric hindrance at the orthoꢀ
2
4
o
b
1
c
by GC with a CPꢀChirasilꢀDex CB column. When 1 was used as a catalyst under
position of the phenyl group (Table 2, left column). Similarly,
increasing the chain length and steric hindrance on the methyl
side of 1ꢀphenylethanol derivatives, such as 1ꢀphenylbutanꢀ1ꢀ
ol, 2ꢀmethylꢀ1ꢀphenylpropanꢀ1ꢀol, and 2,2ꢀdimethylꢀ1ꢀ
phenylpropanꢀ1ꢀol, decreased the product yields (Table 2,
the identical reaction conditions, the conversion yield and ee value were 66% and
d
6
5%, respectively. Conversion yields were calculated from the isolated products
and the ee values were determined by HPLC with IA column.
We then investigated the OKR of secondary alcohols
middle column). On the other hand,
a
series of
utilizing the manganese catalyst, H
additive system. First, we optimized reaction conditions by
varying the amounts of catalyst, oxidant, and H SO and the
2 2 2 4
O oxidant, and H SO
diphenylmethanol derivatives were converted to the desired
products with the yields of >80% (Table 2, middle column).
Unactivated aliphatic secondary alcohols were also oxidized to
their corresponding ketones with moderate to high yields (Table
2
4
reaction temperature (see Fig. 1; also see Tables S1 and S2,
ESI†). Obviously, the conversion of 1ꢀphenylethanol would be
2
, right column).
raised with increasing the amount of H
Due to the preference of oxidation towards
2
O
2
as shown in Fig. 1.
ꢀenantiomer in
S
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OKR of racemic secondary alcohols by sulfuric acidꢀenabled
manganese system, the ee value would be improved with
increasing the equivalent of H
significant change occurred with further increasing the
equivalent of H up to 1.0. Therefore, the oxidant amount
was chosen to be 0.80 equiv. for OKR of 1ꢀphenylethanol as a
result of an excellent ee with lower conversion. Besides, was
chosen as a catalyst since afforded a higher enantiomeric
excess (ee) value (90%) than (65%) in the oxidation of 1ꢀ
2 2
O from 0 to 0.80, while no
2
O
2
2
Scheme 2 Oxidation of cyclobutanol to cyclobutanone.
2
1
the detailed method), implying suggesting that a hydrogen atom
Hꢀatom) abstraction from an αꢀCH bond may be the rateꢀ
determining step, as observed in other manganese complexꢀ
phenylethanol (Table 3, entry 1 and footnote c). Under the
optimized catalytic conditions, we obtained high ee values
(
(>90% ee) irrespective of the substituents on the phenyl group
8
b,8c
catalyzed alcohol oxidation reactions.
It is also notable that
of benzylic alcohols (i.e., no effects on the steric hindrance and
electronic nature of substrates) (Table 3, entries 2 – 6).
Importantly, 1ꢀphenylpropanꢀ1ꢀol derivatives, which were
reported to be poor substrates in most of manganese salen
KIE values determined in CꢀH bond activation reactions by
synthetic metalꢀoxo complexes under stoichiometric conditions
1
0,15
(
e.g., KIE values of >10)
are much higher than those
1
2d,13,14
obtained in metal complexꢀcatalyzed oxidation reactions under
systems,
manganese system; ee values were >90% (Table 3, entries 7 –
2). In addition, increasing the steric hindrance and the chain
also worked well in this sulfuric acidꢀenabled
8
b,8c
catalytic conditions (e.g., KIE values of <4);
interest to understand the difference of the KIE values obtained
under the stoichiometric and catalytic reactions e.g.
it would be of
1
(
,
length in 1ꢀphenylpropanꢀ1ꢀol derivatives did not affect the ee
involvement of different metalꢀoxygen intermediates in
catalytic oxidation reactions). Thirdly, since cyclobutanol was
often used as a substrate probe to distinguish oneꢀelectron
values either (Table 3, entries 13 – 15).
In order to gain mechanistic insights into the manganeseꢀ
catalyzed alcohol oxidation reactions, we first investigated the
effect of paraꢀsubstituents on the reactivity of benzyl alcohol,
by carrying out a competitive alcohol oxidation of benzyl
alcohol against paraꢀsubstituted benzyl alcohols (see
Experimental Section). A good linear correlation was obtained
when the krel values were plotted against Hammett parameters
versus
reactions,
twoꢀelectron
process
in
alcohol
oxidation
10a,10c,16
we performed the oxidation of cyclobutanol
and found that cyclobutanone was yielded exclusively and a
ring opened product, 4ꢀhydroxylbutyraldehyde, was not
detected (Scheme 2). Based on the mechanistic studies
discussed above, we conclude that the alcohol oxidation by an
of the substituents (Fig. 2); the small but negative
.58 indicates that the active intermediate possesses
electrophilic character, as reported in the oxidation of benzyl
ρ value of –
electrophilic manganeseꢀoxo species was
a twoꢀelectron
0
process. Such reactive manganeseꢀoxo intermediate has been
proposed previously in the asymmetric epoxidation of olefins
1
0
alcohol derivatives by synthetic metalꢀoxo complexes.
Secondary, when an intermolecular competitive oxidation of 1ꢀ
phenylethanol or its αꢀdeuterated compound (1ꢀdeuterated 1ꢀ
2 2
by the manganese catalyst (2) and H O in the presence of
7
H
2
SO
4
.
Then, density functional theory (DFT) computations were
phenylethanol) was carried out together with 1ꢀ(
chlorophenyl)ethanol as a mediation, a kinetic isotope effect
KIE) value of 1.8 was obtained (see Experimental Section for
pꢀ
carried out to explore the enantioselectivity in the
activation of the chiral 1ꢀphenylethanols (both
α
R
+
ꢀCH bond
ꢀ and
Sꢀ
(
enantiomers) by a chiral [(PꢀMCP)Mn(V)(O)(SO
4
)] complex
(
I
), which was proposed previously as the reactive intermediate
7
in the reaction of
Computational results reveal that the Hꢀatom abstraction from
the ꢀCH bond of the ꢀenantiomer with an energy barrier of
.7/5.5 kcal/mol for the triplet/quintet spin state is easier than
that of the ꢀenantiomer with an energy barrier of 10.6/6.8
2 2 2 4
1 and H O in the presence of H SO .
α
S
7
R
kcal/mol for the triplet/quintet spin state (Table S3, ESI†). This
reactivity trend could be obtained by comparing the geometric
characters of these two transition states, in which TSS with rCꢀH
=
1.203 Å has a smaller elongation of the CꢀH bond, while TSR
with rCꢀH = 1.240 Å has a larger elongation of the CꢀH bond for
the quintet ground state (Fig. S32, ESI†). In addition, the
energy barrier difference for two isomers might be due to the
nonꢀcovalent anionꢀπ interaction between the phenyl group of
the substrate and the sulfuric acid anion ligand, which can
stabilize the transition state lowering the energy barrier. Such
kind of interaction just exists for TSS with a distance of ca. 3.4
Fig. 2 Hammett plot of log krel against the Hammett parameter σ value for the
catalytic oxidations of paraꢀsubstituted benzyl alcohols by 1 (0.30 mol%)
with H
2 2
O (0.40 equiv. based on the concentration of substrate) as an oxidant
o
2 4 3
in the presence of H SO (0.30 mol%) in CH CN at 25 C.
Å between two groups. Thus, we may conclude that
Sꢀ
4
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enantiomer is an easier substrate than
R
ꢀenantiomer for the Instrumentation
1
13
oxidation by the highꢀvalent Mnꢀoxo intermediate regardless of
the spin states; therefore, ꢀenantiomer remains in the reaction
H and C NMR spectra were recorded on a Bruker AVANCE
o
R
3
III 400 MHz spectrometer in CDCl at 25 C. Reactions were
solution. Based on the Arrhenius equation, an energy barrier
difference of 1.3 kcal/mol will give a rate constant ratio
(k /k(S)) of 0.112, which corresponds to a high ee value (~80%)
(R)
as obtained in experiments (vide supra). Inspection of the spin
densities (Table S4 and Figs. S32 and S33, ESI†), we can see
monitored using thin layer chromatography (TLC). Commercial
TLC plates (silica gel GF254) were developed and the spots
were visualized under UV light at 254 or 365 nm. Silica gel
column chromatography was performed with silica gel (particle
size 200–300 mesh). Product analysis was performed on an
Agilent Technologies 6890N gas chromatograph [GC; HPꢀ5
column (length = 30 m and i.d. = 0.32 mm with 0.25 ꢁm film
thickness)] with a flamedꢀionization detector and a Thermo
Finnigan (Austin, Texas, USA) FOCUS DSQ (dual stage
quadrupole) mass spectrometer interfaced with Finnigan
FOCUS gas chromatograph (GCꢀMS). Gas chromatograph
that for the quintet spin state, the sulfuric acid group has a spin
5
density of ca. 0.5 in the
I+Sub species and that of ca. 0.0 in the
transition state. This indicates that the sulfuric acid group
should be nonꢀinnocent to the reaction and the nonꢀinnocence
of the sulfuric acid group may make the reaction on the quintet
spin state approachable. In addition, the low energy barrier
indicates the high electrophilicity of the highꢀvalent
manganeseꢀoxo species, which may originate from the
existence of a low lying σ* that can accept electronic density
from the CꢀH bond (Fig. S33, ESI†).
(
GC) analysis was performed on an Agilent Technologies 7890
with a flamedꢀionization detector and a CPꢀChirasilꢀDex CB
column (length = 25 m and i.d. = 0.32 mm with 0.25 ꢁm film
thickness). High Performance Liquid Chromatography (HPLC)
analysis was performed on WatersꢀBreeze (2487 Dual λ
Absorbance Detector and 1525 Binary HPLC Pump) equipped
with a variable wavelength UVꢀ220 detector. Chiralpak IA was
Conclusions
In summary, we have reported the first example of sulfuric purchased from Daicel Chemical Industries, LTD.
acidꢀenabled chemoselective oxidation of secondary alcohols
Typical procedure for the oxidation of 1-phenylethanol
by manganese catalysts and hydrogen peroxide; secondary
All reactions were performed under an Ar atmosphere using a
alcohols were oxidized to their corresponding ketones with
dried solvent and a standard Schlenk techniques. Catalyst (0.30
good yields and an efficient OKR of racemic secondary
2 4
mol%), 1ꢀphenylethanol (0.50 mmol) as a substrate, and H SO
alcohols was achieved with excellent enantioselectivities
>90% ee). Mechanistic studies revealed that the active
manganese oxidant possesses electrophilic character, an Hꢀ
atom abstraction from an ꢀCH bond of alcohol substrate is the
rateꢀdetermining step, and the alcohol oxidation occurs via
(
0.30 mol%) were added into a Schlenk tube containing an
(
o
CH
3
CN (1.0 mL) at 25 C. Subsequently, an CH
(1.2 equiv.) was added dropwise by using
a syringe pump for 1 h. Then, the reaction solution was
quenched with NaHCO and Na , and ꢀdecane was added
3
CN (0.50 mL)
2 2
containing 30% H O
α
a
3
2
S
2
O
3
n
twoꢀelectron process. DFT calculations revealed that the
difference of reaction energy barriers for the Hꢀatom
into the solution as an internal standard. The yields were
determined by GC.
abstraction from
putative highꢀvalent manganeseꢀoxo intermediate is significant
i.e., 1.3 kcal/mol), affording the enantioselectivity in the OKR
αꢀCH bonds of Rꢀ and Sꢀenantiomers by a
Typical procedure for the OKR of 1-phenylethanol
(
All reactions were performed under an Ar atmosphere using a
dried solvent and a standard Schlenk techniques. Catalyst (0.20
mol%), racemic 1ꢀphenylethanol (0.50 mmol) as a substrate,
of racemic secondary alcohols. Future studies will be focused
on the improvement of the catalytic activity as well as the
enantioselectivity in the OKR of secondary alcohols using
synthetic nonheme iron and related manganese catalysts and
environmentally benign oxidants such as molecular oxygen and
hydrogen peroxide.
and H
containing an CH
CH CN (0.50 mL) containing 30% H
added dropwise by using a syringe pump for 1 h. Then, the
reaction solution was quenched with NaHCO and Na
and ꢀdecane was added into the solution as an internal
2 4
SO (1.0 mol%) were added into a Schlenk tube
o
3
CN (1.0 mL) at 0 C. Subsequently, an
(0.80 equiv.) was
3
2 2
O
3
2 2 3
S O ,
Experimental Section
n
standard. The yields were determined by GC (see Fig. 1 and
Table 3; see also Tables S1 and S2, ESI†).
Materials
All chemicals were purchased from Aldrich, Alfa Aesar, and
TCI, which were the best available purity and were used Determination of relative rate constants (krel
)
without further purification unless otherwise indicated.
An CH
added dropwise into an CH
mixture of 1ꢀphenylethanol (0.50 mmol) and paraꢀsubstituted
ꢀphenylethanol (0.50 mmol), catalyst ( , 0.30 mol%), and
SO (0.30 mol%) by using a syringe pump at 25 C for 1 h.
Then, the reaction solution was quenched with NaHCO and
Na , and ꢀdecane was added into the solution as an
internal standard. The yields were determined by GC. The
3
CN (0.50 mL) containing 30% H
2
O
2
(0.40 equiv.) was
Solvents were dried according to published procedures and
3
CN solution (1.0 mL) containing a
1
7
distilled under argon prior to use. PhCD(OH)CH
3
was
prepared from acetophenone according to the literature
1
H
1
1
8
method. Ligands, MCP, PꢀMCP, and DbpꢀMCP compounds,
o
2
4
II
II
2
and their corresponding Mn complexes, Mn (MCP)(OTf) ,
3
II
II
Mn (PꢀMCP)(OTf)
2 2
, and Mn (DbpꢀMCP)(OTf) were prepared
2
S
2
O
3
n
7
,19
according to the reported methods.
k
rel
1
8a
values were calculated using eqn (1),
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ARTICLE
Journal Name
k
rel
=
k
R
/
k
H
= ln([R]
and [R]
paraꢀsubstituted 1ꢀphenylethanol, respectively, and [H]
H] are the initial and final concentrations of 1ꢀphenylethanol,
f
/[R]
are the initial and final concentrations of
and
i
)/ln([H]
f
/[H]
i
)
(1) Notes and references
1
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,
where [R]
i
f
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i
M. Bollinger, Jr., Acc. Chem. Res., 2007, 40, 484; (c) W. Nam,
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and W. Nam, Curr. Opin. Chem. Biol., 2015, 25, 159; (h) X.
[
f
respectively.
Determination of KIE value
An CH
3
CN (0.50 mL) containing 30% H
2 2
O (0.40 equiv.) was
Engelmann, I. MonteꢀPérez and K. Ray, Angew. Chem. Int. Ed.
,
added dropwise into an CH
mixture of substrate (0.50 mmol; 1ꢀphenylethanol or 1ꢀ
deuterated 1ꢀphenylethanol) and 1ꢀ(4ꢀchlorophenyl)ethanol
3
CN solution (1.0 mL) containing a
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(
0.50 mmol),
a syringe pump at 25 C for 1 h. Then, the reaction solution was
quenched with NaHCO and Na , and ꢀdecane was added
2 4
1 (0.30 mol%), and H SO (0.30 mol%) by using
o
3
2
S
2
O
3
n
2
3
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into the solution as an internal standard. The yields were
determined by GC. The KIE values were calculated using eqn
1
8a
(2) – (4),
k
k
Cl
Cl
/
/
k
k
H
D
= ln([Cl]
f
/[Cl]
/[Cl]
)/(
and [Cl]
i
)/ln([H]
)/ln([D]
) =
f
/[H]
i
)
(2)
(3)
(4)
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i
f
i
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KIE = (
k
Cl
/
k
D
k
Cl
/
k
H
k
H
/
k
D
where [Cl]
i
f
are the initial and final concentrations of
and [H] are the
initial and final concentrations of 1ꢀphenylethanol, respectively,
and [D] and [D] are the initial and final concentrations of 1ꢀ
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ꢀ(4ꢀchlorophenyl)ethanol, respectively, [H]
i
f
2
3
i
f
4
5
deuterated 1ꢀphenylethanol, respectively.
(
5
Computational details
Density functional theoretical calculations were performed
3
2
0
1
using Gaussian 09 software.
The highꢀvalent [(Pꢀ
5
+
2–
2–
+
MCP)Mn (O )(SO
4
)] species (
I
) was chosen as the reactive
2
intermediate, and two enantiomers of the chiral 1ꢀphenylethanol
ꢀ and ꢀenantiomers) were used as the substrates. The spinꢀ
unrestricted B3LYP (UB3LYP) functional
with two basis sets: (1) the LACVP basis set for Mn and 6ꢀ
1G* basis set for the rest atoms, denoted as B1, are used to
(
S
R
,
2
1,22
was employed
,
2
3
2
1
017, 7, 60; (f) K. P. Bryliakov, Chem. Rev., 2017. DOI:
0.1021/acs.chemrev.7b00167
optimize the minima and transition states; (2) the LACV3P
basis set for Mn and 6ꢀ311+G** basis set for the rest atoms,
denoted as B2, are used for obtaining single point energy
.
6
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2
We acknowledge financial support for this work from the
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A highly efficient catalytic oxidation and oxidative kinetic
resolution of secondary alcohols has been achieved using
mononuclear Mn(II) catalysts and H O .
2 2
8
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