Enantioselective Epoxidation of Electron-Deficient Alkenes Catalyzed by Manganese Complexes with Chiral N4 Ligands Derived from Rigid Chiral Diamines

Article abstract of DOI:10.1002/adsc.201700541

A series of tetradentate sp²N/sp³N hybrid chiral N₄ ligands derived from rigid chiral diamines were synthesized, which enabled the first manganese-catalyzed enantioselective epoxidation of electron-deficient alkenes with hydrogen peroxide (H₂O₂) as an oxidant. The reaction furnishes enantiomerically pure epoxy amides, epoxy ketones as well as epoxy esters in good yields and excellent enantioselectivities (up to 99.9% ee) with lower catalyst loading. Preliminary studies on structure–activity relationship demonstrated that maintaining comparatively lower electron-donating ability of the sp³N and relatively higher electron-donating ability of sp²N of the N₄ ligands is beneficial to getting higher activity and selectivity, thus providing us a new view to understand epoxidation with H₂O₂. (Figure presented.).

Full text of DOI:10.1002/adsc.201700541

Title: Enantioselective Epoxidation of Electron-Deficient Alkenes
Catalyzed by Manganese Complexes with Chiral N4 Ligands
Derived from Rigid Chiral Diamines
Authors: Hanmin Huang, Xiang-Ning Chen, Bao Gao, and yijin Su
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700541
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Enantioselective Epoxidation of Electron-Deficient Alkenes
Catalyzed by Manganese Complexes with Chiral N4 Ligands
Derived from Rigid Chiral Diamines
Xiangning Chen,a Bao Gao,b Yijin Su,a and Hanmin Huanga,b*
a State Key Laboratory for Oxo Synthesis and Selective Oxidation,Lanzhou Institute of Chemical Physics,Chinese
Academy of Sciences,Lanzhou 730000 (China).
bHefei National Laboratory for Physical Sciences at the Microscale, and Department of Chemistry, University of Science
and Technology of China, Hefei 230026, People’s Republic of China.
E-mail: hanmin@ustc.edu.cn; Fax: (+86)-551-6360-1592
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
environment-benign H2O2 to be used as the oxidant
Abstract. A series of tetradentate sp2N/sp3N hybrid chiral
N4 ligands derived from rigid chiral diamines were
synthesized, which enabled the first Mn-catalyzed
enantioselective epoxidation of electron-deficient alkenes
with H2O2 as an oxidant. The reaction furnishes
enantiomerically pure epoxy amides, epoxy ketones as
well as epoxy esters in good yields and excellent
enantioselectivities (up to 99.9% ee) with lower catalyst
loading. Preliminary studies on structure-activity
relationship demonstrated that maintaining comparatively
lower electron-donating ability of the sp3-N and relatively
higher electron-donating ability of sp2-N of the N4
ligands is beneficial to getting higher activity and
selectivity, thus providing us a new view to understand
epoxidation with H2O2.
and allowing the asymmetric epoxidation to proceed
with low catalyst loading is highly desirable. Herein,
we reported a new type of tetradentate sp2N/sp3N
hybrid chiral N4 ligands derived from rigid chiral
diamines with lower electron-donating ability, which
enabled us to establish a highly efficient manganese
catalytic system for enantioselective epoxidation of
alkenyl amides, enones as well as α,β-unsaturated
esters with H2O2 as an oxidant (Scheme 1).
Keywords: enantioselective epoxidation; alkenes;
manganese; chiral N4 ligand; hydrogen peroxide
Scheme 1. Mn-catalyzed enantioselective epoxidation of
electron-deficient alkenes.
Enantioselective epoxidation of C-C double bond with
chiral catalysts in the presence of oxidants provides an
easy and direct access to optically active epoxides and
their derivatives, which has reached a very high level
of development leading to a vast number of
enantiomerically pure epoxy molecules.[1] However, a
limited number of methods have been developed so far
for the selective epoxidation of alkenyl amides,[2] yet
the resulting chiral epoxy amides are versatile starting
materials for the synthesis of functional molecules.[3]
Shibasaki and co-workers realized the enantioselective
epoxidation of α,β-unsaturated amides in the presence
of chiral lanthanide catalysts,[2] but a large amount of
environmentally unfriendly TBHP and high catalyst
loading (5-10 mol%) were required for achieving high
enantioselectivity, which significantly reduced the
appeal of this elegant catalytic epoxidation process and
hindered large-scale applications. Hence, an efficient
and practical catalytic system enabling the
The chiral ligand plays a definitive role cooperated
with the central metal in asymmetric reactions
catalyzed by metal-complexes. Finely tuning the
electron-donating ability of the coordinative atoms of
ligands often revolutionizes the catalytic performance
in terms of reactivity, selectivity and productivity.[4]
Bio-inspired manganese complexes ligated with
tetradentate sp2N/sp3N hybrid chiral N4 ligand have
been identified as effective catalysts for the
enantioselective epoxidation of enones and α,β-
unsaturated esters.[5] However, very few such kind of
catalysts were utilized for epoxidation of the
recalcitrant alkenyl amides due to their low reactivity.
A critical step in this type of catalysis relies on the
ability of the high-valent electrophilic oxidizing
1
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
species LMn=O to transfer the O-atom to the C-C
double bond to allow the catalyst turnover with
enantioselectivity.[6] It is widely appreciated that
appropriate modulation of the electron-donating
ability of the four sp2N/sp3N-atoms of the N4 ligand
could effectively tune the electrophilicity of the active
Mn-oxo species to facilitate the O-atom transfer and
ensure high enantioselectivity. Since the coordinated
sp2N-atom usually could exert stronger influence on
the electron properties of central-metal than that of
sp3N-atom, almost all of the documented works on
modifying chiral Mn-N4 catalysts focused on the
modulation of sp2N moiety by introducing strongly
electron-donating groups to improve the interaction of
the sp2N-atom with the central metal.[5,6] However,
even the strongest electron-donating group NMe2 was
introduced in the backbone of sp2N, the electron-
donating ability of the sp2N-atom still could not meet
the requirement for fulfilling the reactivity of some
formidable substrates. In this context, we envisioned
that appropriate attenuation of the donating ability of
the sp3N-atom might enhance the interaction of the
sp2N-atom of N4 ligand with the central metal to
improve the electrophilicity of the corresponding
active species. In this regard, the benzene-fused chiral
diamine 1,1'-biisoindoline (named BIDN) developed
by our own group appeared to be a suitable diamine
precursor for the chiral N4 ligand. Our previous work
suggested that the presence of fused benzene ring in
BIDN not only made it more rigid, but also could
attenuate the electron-donating ability of the sp3N-
atom due to its π-electron acceptability.[7] Inspired by
the unique nature of this chiral diamine, we anticipated
that it could be evolved into a new class of unique
chiral N4 ligands for Mn-catalyzed epoxidation by
combination of this chiral backbone and an achiral
privileged pyridine or benzoimidazole, in which the
lower electron-donating ability of the sp3N-atom in
BIDN might enhance the interaction of pyridine or
benzoimidazole sp2N-atom with central metal to craft
an effective chiral environment.
to the amino sp3N-atoms [2.363Å, 2.361Å] as a
consequence of the sp2-hybridization of the
benzimidazole N-atom and the metal-benzoimidazole
π-interaction. Moreover, the bond length of the two
Mn-Nsp3 bonds is the longest, but the bond length of
the two Mn-Nsp2 bonds is the shortest in all of the
reported chiral Mn-N4 complexes for catalytic
epoxidation (see SI). These results confirmed our
hypothesis that decreasing the electron-donating
ability of sp3N-atom of the chiral N4 ligands could
indeed enhance the interaction of sp2N-atom with the
central metal. To further validate this concept, the
benzene-fused chiral diamine unit in ligand 2e was
replaced by the commonly used chiral bipyrrolidine to
give the chiral N4 ligand 2i and the corresponding
[Mn(2i)(OTf)2]. Confirmation of the solid-state
structure of the Mn-complex was obtained from single
crystal X-ray diffraction studies (Figure 1).[8] As
expected, the bond length [2.250Å, 2.213Å] of the two
Mn-Nsp2 bonds is much longer than that of
[Mn(2e)(OTf)2], but the bond length [2.322Å, 2.316Å]
of the two Mn-Nsp3 bonds is shorter than that of
[Mn(2e)(OTf)2]. This observation is most likely
resulted from the stronger electron-donating ability of
the sp3N-atom in bipyrrolidine than that of BIDN.
Scheme 2. Synthesis of the chiral ligands.
The development of chiral diamines into a series of
chiral N4 ligands 1 and 2 was successfully achieved in
one step from the chiral diamine BIDN and the
corresponding 2-(chloromethyl)pyridines or N-
substituted
2-(chloromethyl)benzoimidazoles
(Scheme 2). The corresponding Mn(II)-complexes
were obtained in high yields by stirring the mixture of
ligands and Mn(OTf)2 in CH3CN at room temperature
Figure 1. X-ray structure of Mn-N4 complexes.
overnight.
The
solid-state
structures
of
[Mn(2a)(OTf)2] and [Mn(2e)(OTf)2] were confirmed
by X-ray analysis of their single crystals recrystallized
from Et2O/CH3CN and Et2O/CH2Cl2 solvent system,
respectively. The X-ray structures of these two
complexes revealed that the chiral N4 ligand is bound
to a manganese center in a cis-α configuration with
two sp2N-atoms coordinated to the metal center trans
to each other and the two triflate groups bind at the two
remaining coordination sites that are cis to each other
(Figure 2).[8] In the structure of [Mn(2e)(OTf)2], the
metal bonds to the benzoimidazole sp2N-atoms
[2.168Å, 2.155Å] are significantly shorter than those
Encouraged by the successful preparation of the
chiral ligands and their corresponding manganese
complexes, we examined the enantioselective
epoxidation with N,N-dibenzylcinnamamide 3a as a
model substrate for identifying an effective chiral
2
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
catalyst. The reaction was carried out in the presence
of 0.2 mol% of catalyst under acidic condition at -
40 °C for 35 min with H2O2 as the sole oxidant. To our
delight, the asymmetric epoxidation of 3a proceeded
smoothly in the presence of manganese complex
ring of benzoimidazole moiety, giving the
corresponding product with higher enantioselectivity
(99.6% ee, Table 1, entry 11). Finally, among the
series of catalysts examined, excellent results were
observed with the Mn-complexes ligated with 2e and
ligated with 1a, affording the desired product 4a in 66% 2f (Table 1, entries 10 and 11). As expected, the Mn-
isolated yield with 90.9% ee (Table 1, entry 1). This
prompted us to assess other chiral N4 ligands, and we
found that both the yield and enantioselectivity were
affected significantly by the steric bulk and electron-
donating ability of the chiral N4 ligands. For the
pyridine-derived ligand 1, the reaction was virtually
stopped when a methyl group was introduced into the
ortho-position of the pyridine-ring presumably due to
steric hindrance (Table 1, entry 2). In addition, when
electron-donating groups were introduced at the para-
position (R5) of the pyridine, both the yield and
selectivity were improved (Table 1, entry 3).
Interestingly, the ligands 1e and 2h bearing two
electron-donating methoxy groups in the fused
benzene ring of diamine
complex derived from chiral ligand 2i exhibited lower
reactivity and selectivity (Table 1, entry 14).
Having identified the best catalyst and with the
optimal reaction conditions in hand, the scope of this
enantioselective epoxidation was investigated in the
presence of manganese complexes ligated with 2e or
2f as a chiral ligand. As summarized in Table 2,
various types of cinnamamides were found to be
applicable for the reaction with low catalyst loading
(0.3-0.05 mol%). Electronically and sterically diverse
Table 2. Screening of catalyst[a]
Entry R1
R2
Bn
R3
Bn
H
Yield (%) ee (%)
Table 1. Screening of catalyst[a]
1[b]
2
C6H5
C6H5
4a (81)
4b (85)
4c (83)
4d (86)
4e (82)
4f (80)
99.6
98.2
95.1
97.2
97.1
97.7
97.1
99.1
95.7
96.7
98.4
99.4
99.4
99.0
97.7
98.9
95.6
97.7
94.5
99.5
t-Bu
cyclohexylH
Bn
CH3
H
3
C6H5
4[b]
5[c]
6[d]
7[b]
8
C6H5
C6H5
C6H5
C6H5
H
H
H
Ligand
ee (%)
Entry
1
Yield (%)
66
C6H5
i-Pr
CH3 4g (81)
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
2f
90.9
-
C6H5
i-Pr
(CH2)4
(CH2)5
Bn
4h (86)
4i (83)
4j (81)
4k (85)
4l (79)
4m (83)
4n (84)
4o (80)
4p (83)
4q (82)
4r (83)
4s (87)
4a (81)
2
NR
85
9
C6H5
3
94.9
59.9
-
10[b]
11
12
13
14
15
16[e]
17[e]
18
19
C6H5
4
87
4-CH3C6H4
4-BrC6H4
4-ClC6H4
3-CH3C6H4
2-CH3C6H4
3-ClC6H4
2-ClC6H4
3,4-(CH3)2C6H3 Bn
3,4-Cl2C6H3
C6H5
Bn
5
NR
75
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
6
98.0
35.4
93.5
95.4
98.5
99.6
97.6
-
7
35
8
86
9
85
10
11
12
13
87
Bn
Bn
81
20[f]
2g
2h
2i
68
[a]
Unless noted, the reaction was conducted in
NR
69
HOAc/MeCN/CH2Cl2 (0.6 mL/1.2 mL/0.2 mL) with 3 (0.3
mmol) and [Mn(OTf)2/2e] (0.2 mol%) at -40 C, and 360 μL
o
14
81.0
H2O2 (1.2 equiv., 1 M in MeCN, 50% H2O2) was added dropwise
through a syringe pump for 30 min, and additional 5 min of
stirring was allowed. Isolated yields and ee values were
determined by HPLC. The absolute configuration was
determined by comparison of the optical rotation with reported
data.
[a]
Reaction conditions: the reaction was conducted in
HOAc/MeCN/DCM (0.6 mL/1.2 mL/0.2 mL) with 1a (0.3
mmol) and [Mn(OTf)2L*] (0.2 mol%) at -40 oC, and H2O2 (1.2
equiv., 1 M in MeCN, 50% H2O2) was added dropwise through
a syringe pump for 30 min, and additional 5 min of stirring was
allowed, isolated yields, ee values were determined by HPLC.
[b] Using [Mn(OTf)2/2f] as a catalyst.
[c]
The reaction was conducted in HOAc/MeCN/CH2Cl2 (2.0
mL/4.0 mL/1.0 mL) with 3e (1.0 mmol) and [Mn(OTf)2/2e] (0.2
backbone were unable to catalyze the reaction (Table
1, entries 5 and 13). These results indicated that
maintaining comparatively lower electron-donating
ability of the sp3N-atom and relatively higher electron-
donating ability of sp2N-atom was beneficial to getting
higher activity and selectivity, which confirmed our
hypothesis that electrophilicity of the reactive Mn-
species. This tendency was further confirmed by
comparing the catalytic performance of ligand 2e with
2f (99.6% ee (2f) vs 98.5% ee (2e)). The ligand 2f
contains two electron-donating groups in the arene-
mol%) at -30 oC, H2O2 (1.2 equiv., 1 M in MeCN, 50% H2O2).
[d]
The reaction was conducted in HOAc/MeCN/CH2Cl2 (1.0
mL/2.0 mL/0.3 mL) with 3f (1.0 mmol) and [Mn(OTf)2/2e] (0.2
mol%) at -30 oC, and 1.2 mL H2O2 (1.2 equiv., 1 M in MeCN,
50% H2O2).
[e] [Mn(OTf)2/2e] (0.3 mol%).
[f] [Mn(OTf)2/2f] (0.05 mol%), -25 oC.
cinnamamides all participated smoothly to provide the
targets 4a-4s in high yields with excellent
3
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
enantioselectivities. The protocol can be extended to
primary and secondary amides and this enables highly
enantioselective epoxidation of α,β-unsaturated
amides with different substituents at the nitrogen atom,
giving the corresponding epoxides in high yields with
excellent enantioselectivities (Table 2, entries 2-6).
These epoxides can be used directly as key
intermediates for the synthesis of a number of natural
products and bioactive molecules.[9] Furthermore, the
electronic and steric effects on aromatic ring of
cinnamamides were investigated, and we found that
the reactions proceeded in high yields with excellent
enantioselectivities in the presence of both electron-
deficient and electron-rich aromatic systems (94.5-
99.4% ee, Table 2, entries 11-19). Typical functional
groups, such as chloro, and bromo, are also tolerated
well under the reaction conditions. Importantly, the
successful preparation of 4l, 4m, 4p, 4q and 4s with
intact bromine and chlorine provides a good
opportunity for further formation of carbon-carbon or
carbon-heteroatom bonds by transition-metal-
catalyzed coupling and other reactions. Significantly,
the reaction is effectively catalyzed with 0.05 mol% of
the catalyst within 35 min, which represents the lowest
catalyst/substrate ratio and one of the fastest catalytic
system for enantioselective epoxidation of alkenyl
amides (Table 2, entry 20).
behavior of these new chiral Mn-N4 catalytic systems,
we decided to move forwards to the synthesis of epoxy
compounds with a ketone or ester functionality. As
shown in Table 4, a variety of enones were could be
efficiently converted to the desired products in good to
excellent yields (71% to 92% yields) and
enantioselectivities (up to 99% ee) with Mn(OTf)2(2e)
as a catalyst under the optimized reaction conditions.
Excellent performance was observed when electron-
donating or electron-withdrawing substituents were
introduced in the aromatic rings of enones (Table 4,
entries 2-14). Moreover, the sterically hindered enone
7o could also be smoothly transformed to the
corresponding epoxide in good yield with excellent
enantioselectivity (96 % ee). However, no desired
reaction occurred for substrates bearing oxidation
sensitive groups (such as thioether and hydroxyl) on
the phenyl ring of the alkene. For the epoxidation of
cinnamic ester 7p, a good yield was achieved but only
moderate ee value (62% ee) was observed (Table 4,
entry 16). Furthermore, the cyclic enones (Table 4,
entries 17-18) were epoxidized with high yields and
excellent
enantioselectivities
(96-99%
ee).
Unfortunately, no desired epoxy product was observed
when cinnamaldehyde was subjected to the standard
reaction conditions.
Table 4. Substrate scope of enones[a]
Encouraged by the above results, we turned our
attention to the more electron-deficient unsaturated
o
ketoamides. The reactions were conducted at -30 C
for 35 min in the presence of H2O2 with 1c as the best
chiral ligand. As summarized in Table 3, the results
shown that α,β-unsaturated ketoamides 5 were
smoothly epoxidized to afford the corresponding
chiral epoxy amides 6 in moderate yields with nearly
perfect enantioselectivities (ee values range from
98.3% to 99.9% ee) in the presence of 0.1 mol% chiral
Mn-catalyst. Electron-donating substituents as well as
electron-withdrawing groups at the para position of
the phenyl ring exerted little impact on the reactivity
and selectivity (Table 3, entries 1-4).
Entry Ar
R
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
Yield (%)
8a (85)
8b (72)
8c (90)
8d (91)
8e (92)
8f (80)
8g (92)
8h (84)
8i (85)
8j (71)
8k (89)
8l (89)
8m (85)
8n (88)
8o (84)
8p (77)
8q (82)
ee (%)
96
93
93
95
95
95
82
82
93
93
93
92
94
96
96
62
99
1
C6H5
2
4-CH3C6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
3-ClC6H4
2-ClC6H4
2-naphthyl
C6H5
C6H5
C6H5
C6H5
C6H5
3[b]
4[b]
5[b]
6[b]
7
8[c]
9[b]
10[b]
11[b]
12[b]
13
C6H5
4-CH3OC6H4
4-i-BuC6H4
4-ClC6H4
4-BrC6H4
2-CH3OC6H4
2-ClC6H4
t-Bu
Table 3. Substrate scope of unsaturated ketoamides[a]
14
C6H5
C6H5
C6H5
15[d]
16
C6H5O
n = 1
17[b]
Entry
R
C6H5
4-CH3C6H4
4-BrC6H4
4-ClC6H4
Yield (%)
6a (53)
6b(46)
6c(48)
6d (51)
ee (%)
98.3
99.5
99.9
99.4
1
2
3
18[b]
n= 2
8r (84)
96
[a] Unless noted, the reaction was conducted in HOAc/MeCN (0.3
mL/0.6 mL) with 7 (0.3 mmol) and [Mn(OTf)2(2e)] (0.2 mol%)
at -40 oC, and H2O2 (1.2 equiv, 1 M in MeCN, 50% H2O2) was
added dropwise through a syringe pump for 30 min, and
additional 5 min of stirring was allowed; isolated yields and ee
values were determined by HPLC.
4
[a]
All reactions were conducted in HOAc/MeCN/CH2Cl2 (0.6
mL/1.2 mL/0.2 mL) with 5 (0.3 mmol) and [Mn(OTf)2/1c] (0.1
mol%) at -30 oC, and 360 μL of H2O2 (1.2 equiv., 1 M in MeCN,
50% H2O2) were added dropwise via a syringe pump for 30
minutes, and additional 5 minutes of stirring was allowed;
isolated yields and ee values were determined by HPLC.
[b] CH2Cl2 (0.2 mL) was added.
o
[c] 0 C, [Mn(OTf)2(2e)] (0.3 mol%), and CH2Cl2 (0.2 mL) was
added.
[d] [Mn(OTf)2(2e)] (0.3 mol%).
With the success of the Mn-catalysed epoxidation as
a means to provide chiral epoxy compounds with an
amide functionality and to further explore the catalytic
4
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
In order to evaluate the practicability and synthetic
hindrance between two phenyl rings that come from
the substrate and ligand, respectively.
utility of this Mn-catalyzed epoxidation process, the
reactions of 3e and 3f with H2O2 were carried out on a
gram scale in the presence of 0.05 mol% and 0.1 mol%
of catalyst at -30 oC with a reaction time of 2 h and 3
h, respectively. As expected, the reactions underwent
smoothly to afford the corresponding (2R,3S)-N-
methyl-3-phenyloxirane-2-carboxamide
4e
and
(2R,3S)-3-phenyloxirane-2-carboxamide 4f in high
yields with excellent enantioselectivities (S/C = 2000
and 1000, 96.1 and 97.0% ee, respectively). The ee
value can be upgraded to 99% by crystallization from
CH2Cl2/hexane to produce 4e and 4f in high yields.
The product 4e could be converted to the (R)-
fluoxetine according to the method reported by
Shibasaki and co-workers.[2e] On the other hand, the
product 4f, which previously prepared by bio-catalytic
kinetic resolution, is a key intermediate toward a wide
range of natural products. For example, the (+)-ζ-
Clausenamide, (-)-SB-204900 and (-)-Balasubramide
(Scheme 3) could be easily prepared from 4f by using
the reported method.[9]
Scheme 4. Proposed reaction mechanism and transition
state for epoxidation of alkene.
In summary, a novel class of sp2N/sp3N hybrid
chiral N4 ligands derived from rigid chiral diamines as
well as the corresponding chiral Mn-complexes were
designed and synthesized. The structures of these Mn-
N4 complexes were confirmed by X-ray analysis and
identified as effective catalysts for the enantioselective
epoxidation of electron-deficient alkenes with H2O2 as
an oxidant. The established catalytic system has a
broad generality for epoxidation of electron-deficient
alkenes with a nearly stoichiometric amount of H2O2
and low catalyst loading (0.05 mol%). A large number
of chiral α,β-epoxy amides, ketones and esters were
Scheme 3. (2R,3S)-3-phenyloxirane-2-carboxamide 4e and
(2R,3S)-N-methyl-3-phenyloxirane-2-carboxamide 4f as
versatile synthons in organic synthesis.
afforded
in
high
yields
with
excellent
enantioselectivities (up to 99.9% ee). Conceptually, it
is shown that the catalytic behavior of these chiral Mn-
complexes for asymmetric epoxidation could be
modulated by finely tuning the electron-donating
ability of the sp3N-atoms of the chiral N4 ligands.
Therefore, we anticipate that the present results should
significantly expand the range of possibilities in
designing catalysts not only for oxidation but also for
many other reactions.
On the basis of the above results and previous
reports,[6] a plausible reaction mechanism was
proposed (Scheme 4). The manganese complex
Mn(L)(OTf)2
A is initially converted to the
intermediate B in the presence of H2O2. Subsequently,
the active Mn=O complex D is formed via acid-
assisted heterolytic cleavage of the O-O bond of
intermediate C. The active species D epoxidizes the
olefins to the corresponding products. On the basis of
understanding the X-ray structure of the manganese
complex [Mn(OTf)22e], we supposed that when the
cinnamamide approaches to the Mn=O species, the
oxygen should capture the double bond from the Si, Si-
face of the alkene delivering the corresponding epoxy
amides with 2R,3S-configuration. In contrast, the Re,
Re-face attack model would lead to large steric
Experimental Section
General procedure for enantioselective epoxidation
To an oven-dried Schlenk tube equipped with a stir bar was
added alkenyl amide (3a 0.3 mmol), manganese complexes
(0.2 mol%), HOAc (0.6 mL), DCM (0.2 mL) and MeCN
(1.2 mL) under nitrogen atmosphere. The reaction mixture
5
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
was allowed to stir at room temperature for 5 minutes and
then cooled to -40 oC. H2O2 (0.36 mmol, 50% H2O2, 1M in
MeCN) was added by syringe pump for 30 minutes, and an
additional 5 minutes of stirring was allowed at -40 oC. The
resulting mixture was quenched with Et3N (1.0 mL) at -
40 °C, and purified directly by flash column
chromatography on silica gel and eluted with
EtOAc/petroleum ether/DCM (1/3/1 to 1/10/1) to afford the
chiral α,β-epoxy amides.
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Acknowledgements
This research was supported by CAS Interdisciplinary Innovation
Team, the National Natural Science Foundation of China
(21672199 and 21172226) and the Anhui provincial Natural
Science Foundation (1708085MB28).
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[8]
CCDC
1475364
([Mn(2a)OTf2]),
1475388
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([Mn(2e)OTf2]) and 1486425 ([Mn(2i)OTf2]) contain
the supplementary crystallographic data for this paper.
This data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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6
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10.1002/adsc.201700541
Advanced Synthesis & Catalysis
COMMUNICATION
Enantioselective Epoxidation of Electron-Deficient
Alkenes Catalyzed by Manganese Complexes with
Chiral N4 Ligands Derived from Rigid Chiral
Diamines
Adv. Synth. Catal. Year, Volume, Page – Page
Xiangning Chen, Bao Gao, Yijin Su, and Hanmin
Huang*
7
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