Stereoselective epoxidation of alkenes with hydrogen peroxide using a bipyrrolidine-based family of manganese complexes

Article abstract of DOI:10.1002/adsc.201100409

Novel manganese complexes containing N₄-tetradentate ligands derived from chiral bipyrrolidinediamines catalyze the stereoselective epoxidation of a wide array of alkenes using low catalyst loadings (0.1 mol%) and hydrogen peroxide (1.2 equiv.) as terminal oxidant. This family of catalysts affords good to excellent yields (80-100%) and moderate to good ees (40-73%) in short reaction times (30 min) making efficient use of hydrogen peroxide.

Full text of DOI:10.1002/adsc.201100409

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DOI: 10.1002/adsc.201100409
Stereoselective Epoxidation of Alkenes with Hydrogen Peroxide
using a Bipyrrolidine-Based Family of Manganese Complexes
Isaac Garcia-Bosch,a Laura Gꢀmez,a Alfonso Polo,b Xavi Ribas,a,*
and Miquel Costasa,*
a
QBIS Group, Departament de Quꢁmica, Universitat de Girona, Campus Montilivi, E-17071 Girona, Catalonia, Spain
E-mail: xavi.ribas@udg.edu or miquel.costas@udg.edu
Departament de Quꢁmica, Universitat de Girona, Campus Montilivi, E-17071 Girona, Catalonia, Spain
b
Received: May 18, 2011; Revised: July 29, 2011; Published online: November 29, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100409.
Abstract: Novel manganese complexes containing
N4-tetradentate ligands derived from chiral bipyrro-
lidinediamines catalyze the stereoselective epoxida-
tion of a wide array of alkenes using low catalyst
loadings (0.1 mol%) and hydrogen peroxide
(1.2 equiv.) as terminal oxidant. This family of cata-
lysts affords good to excellent yields (80–100%)
and moderate to good ees (40–73%) in short reac-
tion times (30 min) making efficient use of hydro-
gen peroxide.
minal oxidant.[11] In addition, Beller and co-workers
have also described a Fe-based methodology for
asymmetric epoxidation of alkenes, which exhibits
high stereoselectivities for stilbenes.[12,13] Both of these
methodologies have a somewhat limited substrate
scope and therefore the development of environmen-
tally benign technologies capable of producing a wide
range of enantiomerically pure epoxides, remains a
challenge of academic interest and technological sig-
nificance. Selected manganese complexes relying on
N-rich ligands were first described by Stack and co-
workers as very active catalysts in the epoxidation of
a wide range of olefins using peracetic acid as oxi-
Keywords: alkene epoxidation; green chemistry;
hydrogen peroxide; manganese catalysts; stereose-
lective reactions
dant.[14,15] The complex L-[Mn
ACHTUNGRTENN(UG CF3SO3)2HCATUNGTREN(NNGU (S,S)-MCP)]
(L-1) was particularly interesting because its chiral
nature converted it into a promising candidate as ste-
reoselective epoxidation catalysts (Scheme 1). Un-
fortunately, it affords very modest ees, and structural
Epoxides play an important role as polyvalent build- modifications on the catalyst structure resulted in a
ing blocks in a wide range of chemical transforma- loss of activity, which severely challenged further im-
tions.[1,2] Because of that, chemoselective and enantio- provement. Following on from these results, the
selective epoxidations constitute important reactions Mn-N4 catalysts {Mn
ACHTUTGNRENNU(G CF3SO3)2ACHTUTGNREN[NUGN (S,S,R)-MCPP]} (L-2),
for synthetic organic chemistry.[3,4] Extensive work has and {Mn
G
CHTUNGTRENNUNG
been done in order to obtain catalysts which could pinene groups attached to positions 4 and 5 of the
perform asymmetric epoxidations with high enantio- pyridine rings were designed. Introduction of these
selectivities.[5] In this regard, Mn-Salen catalysts[6–8] groups does not erase the catalytic activity, and the
and Shiꢂs ketone-based systems[9] are excellent meth- complex mediates the epoxidation of a wide range of
ods to epoxidize a wide range of olefins with high olefins in moderate ees (30–40%) using low catalyst
enantioselectivity (>90% ee), yet substantial room loadings (0.5 mol%) and peracetic acid as oxidant.[16]
for improvement remains in terms of catalyst load- In parallel we also described a TACN-based complex
ings, and use of oxidants with high atom economy. [MnACTHNUTRGNEUNG
(CF3SO3)2(H,MePyTACN)] as an excellent catalyst
Because of environmental considerations, catalytic for the selective and efficient epoxidation of a wide
systems that use H2O2 as oxidant, and non-toxic first range of olefins using very low catalyst loadings
row transition metal ions catalysts are particularly ap- (0.05–0.1 mol%). Our initial report made use of per-
pealing.[5,10] State of the art methodologies include the acetic acid as oxidant,[17] but in a subsequent work we
Ti-Salalen catalysts developed by Katsuki and co- indentified reaction conditions that allowed the use of
workers, that catalyze the epoxidation of alkenes with a small excess of H2O2 (1.2 equiv.), in the presence of
high enantioselectivities (>96% ee) using H2O2 as ter- acetic acid (14 equiv.) as additive.[18] These experimen-
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Isaac Garcia-Bosch et al.
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Scheme 1. Selected ligands for the Mn-catalyzed steroselective epoxidation of alkenes.
tal conditions were then used by Xia, Sun and co- composed by a bipyrrolidine backbone and two 4,5-
workers, who designed a novel MCP-type of complex pinene-appended pyridine rings. This new family of
[Scheme 1, (R,R,R,R)-BPMCP] that epoxidizes a,b- catalysts has been studied in the stereoselective epoxi-
enones with good enantiomeric excesses (70–80%).[19] dation of alkenes, using H2O2 as oxidant, and acetic
Very recently, Talsi and co-workers have also used the acid as additive. These catalysts require a minimum
H2O2/AcOH conditions to epoxidize alkenes using excess of H2O2 as oxidant and low catalyst loadings
the complex [MnACTHNUTRGENNUG(CF3SO3)2ACHTUNTGREN(NUGN (S,S)-BPBP)] (L-4) (0.1 mol%) to perform the rapid stereoselective epox-
(Figure 1). Using this catalyst, the authors achieved idation of a wide range of substrates. We also show
high ees (70–80%) for electron-deficient substrates, that the H2O2/AcOH methodology affords significant-
but more moderate ees were measured with other ly better stereoselectivities than the previously em-
substrates such as styrene (39% ee).[20]
ployed peracetic acid method.[16] The present work
In this work, we develop a novel family of manga- makes a further step in the development of these se-
nese complexes that contain N4-tetradentate ligands lective epoxidation technologies.
The novel ligands (S,S,R)-BPBPP and (R,R,R)-
BPBPP are structurally related to our previously de-
scribed MCPP system, by replacing the diaminocyclo-
hexane backbone by a more rigid bipyrrolidine. The
two new ligands were obtained by the direct alkyla-
tion of the pinene-pyridine picolyl chloride with the
desired 2,2’-bypirrolidine enantiomer (Scheme 1).
Complexes L-{Mn
L-[Mn(CF3SO3)2A[(S,S,R)-BPBPP]}
D-{Mn(CF3SO3)2A[(R,R,R)-BPBPP]} (D-6) were syn-
thesized by reacting Mn(CF3SO3)2 with 1 equivalent
ACHUGTTRENNG(U CF3SO3)2ACHTNUGTR[EUNNNG (S,S)-BPBP]} (L-4),
A
CHTUNGTRENNUNG
(L-5) and
A
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
of ligand in THF under an anaerobic atmosphere (see
Supporting Information). The manganese complexes
have been characterized by X-ray diffraction analysis,
ESI-MS, combustion analysis and FT-IR.
The solid state structure established by X-ray dif-
fraction analysis shows that the coordination geome-
try of the manganese center is distorted octahedral
for all complexes, and that the ligand adopts a C2-
symmetrical cis-a topology (Figure 1). In an analo-
gous manner to the Mn-MCP complexes L-1, L-2 and
D-3, all of which contain a cyclohexyl-diamine back-
bone, the chirality of complexes L-4, L-5 and D-6 is
determined by that of the backbone diamine; S,S- and
Figure 1. Thermal ellipsoid diagram at 50% probability level
of the crystal structure of L-4, L-5 and D-6. For clarity, H
atoms and CF3SO3 are omitted except for the O bonded to
the Mn(II) center.
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Stereoselective Epoxidation of Alkenes with Hydrogen Peroxide
Table 1. Stereoselective epoxidation of styrene (R=H) and
cis-b-methylstyrene (R=Me) performed by complexes 1–6.
R,R-diamines exclusively afford to L and D stereoiso-
mers, respectively. Combination of the chiral nature
of the diamine backbone, and the pinene group ren-
ders L-5/D-6, and L-2/D-3 as two pairs of complexes
that are diastereoisomerically related. On the other
hand, with regard to the first coordination sphere of
the manganese ions, 1–6 share very common structur-
al features. Four coordination positions are occupied
by the four N atoms of the ligand, and two triflate
groups bind at the two remaining positions, cis with
Entry Cat.[a]
R
H
Conv. [%][b] Yield [%][b] ee [%][b]
1
L-1
L-2
D-3
L-4
L-5
D-6
89
77
78
100
83
87
47
48
65
91
85
95
87
32
32
42
23
48
54
20
43
34
13
46
52
2
3
4
5
Me 83
H
Me 97
H
Me 100
H
Me 96
H
100
100
6
7
8
95
À
À
respect to each other. Mn N and Mn Npy distances
are 2.2 ꢄ and 2.3 ꢄ, which fall in the range of distan-
ces observed in related complexes.[14,16,19] A close in-
spection in their respective structures evidences that
in the L isomers the CH3 groups of the pinene rings
are oriented towards the triflate groups, but are in the
opposite direction in the D isomers.
9[c]
10
11
12
100
Me 99
H
Me 99
100
[a]
Catalyst (0.1 mol%), H2O2 (1.2 equiv.) and AcOH
(14 equiv.).
Epoxide yields, substrate conversions and ees were deter-
mined by GC (see Supporting Information for details of
chiral GC).
[b]
The solution behaviour of the complexes was ana-
lyzed by ESI-MS. The spectra of complexes L-4, L-5
and D-6 shows a cationic peak at m/z=526.1 and
m/z=714.3, respectively, whose mass and isotopic pat-
tern could be satisfactorily assigned to the monocat-
[c]
A control experiment without acetic acid led to low con-
version (<5%) and yields (<5%).
ionic [LMnACHTUNGTRENNUNG
(CF3SO3)]+ ion. These observations sug-
gest that the mononuclear solid state structure of the
complexes is retained in solution.
moderate yields (48–65%). This finding reflects that
The catalysts were tested in the epoxidation of al- the former catalyst is somewhat less selective than
kenes by using H2O2 (1.2 equiv.) as oxidant and L-5 and D-6. In all cases, epoxidation of cis-b-methyl-
AcOH (14 equiv.) as additive (Scheme 2). In a first styrene occurs with lack of epimerization. Enantio-
approach, complexes L-1, L-2, D-3, L-4, L-5 and D-6 meric excesses show a somewhat more complex de-
were tested in the catalytic epoxidation of styrene, pendence on catalyst structure and substrate nature.
and cis-b-methylstyrene (Table 1). In general, the For both styrene and cis-b-methylstyrene, catalysts
pinene-containing complexes L-2, D-3 and L-5, D-6 D-3 and D-6 exhibit the highest enantiometic excesses
showed better product yields than the simpler L-1, (46–54% ee). Complexes L-2 and L-5 also show
and L-4. Particularly significant is the comparison be- better enantiomeric excess than L-1 and L-4, respec-
tween the performance of catalyst L-4 with regard to tively, in the epoxidation of styrene. However, L-2
L-5 and D-6; the three catalysts afford very high and L-5 exhibit poor stereoselectivity when using cis-
ACHTUNGTRENNUNG(>95%) substrate conversions, L-5 and D-6 provide b-methylstyrene as substrate.
high epoxide yields (>85%), but L-4 only reaches
Reactions of catalysts 1–3 with H2O2/AcOH
(Table 1) can be compared with the previously de-
scribed reactions with peracetic acid.[16] Product yields
and stereoselectivities obtained with L-2 are basically
the same for both oxidants. Instead, D-3 afforded
better ees than L-2 when H2O2 is used as oxidant. On
the other hand, these reactions appear to be slower
than those originally reported by Stack by using 1 and
peracetic acid (5 min).[14] Compared with the
{MnACHTUNTRGENN(UG CF3SO3)2ACHUTNGTRENN[UGN (R,R,R,R)-BPMCP]} catalyst described
by Xia and co-workers, the present family of catalysts
provides comparable epoxide yields and stereoselec-
tivities, but our system employs smaller catalyst
(0.1 mol% vs. 1 mol%) and oxidant loadings
(1.2 equiv. vs. 6 equiv.).
Novel complexes L-5 and D-6 were studied in the
asymmetric epoxidation of a wide range of substrates
(Table 2). Moderate to excellent product conversion
(60–100%) and epoxide yields (49–100%) are ob-
tained. Moreover, complex D-6 showed a fair enantio-
Scheme 2. Manganese catalysts used (1–6) and catalysis con-
ditions for the stereoselective epoxidation of alkenes.
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Table 2. Stereoselective epoxidation of various alkenes per-
formed by complexes L-5 and D-6.
Table 2. (Continued)
Entry Substrate
Catalyst[a] Conv./
ee [%]
Catalyst[a] Conv./
yield
ee [%]
yield
(conf.)[b]
Entry Substrate
[%][b]
(conf.)[b]
[%][b]
73[d]
(3S,4S)
15[c]
16
D-6
D-6
100/98[d]
100/83
1
D-6
D-6
100/95
83/72
46 (S)
54 (S)
14
2[c]
17
18
D-6
D-6
84/84
97/75
48
53
3
4
5
D-6
D-6
D-6
100/94
100/94
100/60
41 (S)
41 (S)
43 (S)
19[c]
D-6
94/65
60
20
21
D-6
D-6
90/85[d]
100/100
38[d]
n.d.
6
D-6
100/92
38 (S)
22
D-6
76/49
34
7
D-6
D-6
99/87
99/88
52
66
[a]
Catalyst (0.1 mol%), H2O2 (1.2 equiv.) and AcOH
(14 equiv.), temperature: 08C.
8[c]
[b]
Yields, conversions and ees were determined by GC (see
Supporting Information for details on chiral GC). The re-
sults shown are an average of two experiments, and devi-
ations in yields and ees are below 5 and 2%, respectively.
Product configurations were determined by comparison
with analogous described systems (refs.[16,17,20]
Temperature: À408C.
9
L-5
D-6
100/100
99/71
23
[c]
[d]
1
10
4 (S)
Yields, conversions and ees were determined by H NMR
(see Supporting Information).
8[d]
(1R,2R)
11
12
L-5
D-6
100/100[d]
95/95[d]
selectivity for substrates such as styrene (entry 1, 46%
ee), 2-cyclohexene-1-one (entry 18, 53% ee) cis-b-
methylstyrene (entry 7, 52% ee), trans-chalcone
(entry 12, 66% ee) and DBPCN (entry 14, 66% ee);
moderate enantiomeric excesses for substrates such as
p-substituted styrenes (entries 3–6, 38–43% ee), cou-
marin (entry 20, 38% ee) trans-b-methylstyrene (com-
plex L-5, entry 9, 23% ee) and low enantiomeric ex-
cesses for substrates such as 1,2-dihydronaphthalene
(entry 10, 4% ee), trans-stilbene (complex L-5,
entry 11, 8% ee) and for the epoxidation of the ali-
phatic alkene moiety of 1-phenyl-1-cyclohexene
(entry 16, 14% ee). Remarkably, when reactions were
carried out at low temperature (À408C) with complex
66[d]
(2S,3R)
72[d]
(2S,3R)
13[c]
14
D-6
D-6
93/93[d]
66[d]
(3S,4S)
100/85[d]
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Stereoselective Epoxidation of Alkenes with Hydrogen Peroxide
1
quently rinsed with 2ꢅ1 mL AcOEt. In the case of H NMR
D-6, the catalyst retain its activity, and chemo- and
stereoselectivities are improved. At this low tempera-
ture, styrene is obtained in 54% ee, 2-cyclohexen-1-
one in 60% ee, cis-b-methylstyrene in 66% ee, trans-
chalcone in 72% ee and DBPCN in 73% ee. As men-
tioned before, complex L-4 afforded good enantiose-
lectivities for substrates like trans-chalcone (78% ee)
and DBPCN (76% ee), better values than the com-
plexes which contain pinene rings in their structure,
but their stereoselectivity drops substantially in other
substrates such as styrene (39% ee).[19]
The regioselectivity of the epoxidation performed
by complex D-6 was also tested using substrates
which contained two olefin moieties. In the oxidation
of 1-vinyl-1-cyclohexene, the oxidation occurred in
the cis-internal olefin, achieving a meritorious enan-
tioselectivity (Table 2, entry 17, 48% ee) for an ali-
phatic substrate. To test the preference for cis-alkenes
over trans-alkenes, trans,cis-2,6-nonadienyl acetate
was also oxidized (Table 2, entry 21). Again, the com-
plex showed an exquisite regioselectivity towards ep-
oxidation of the internal cis-olefin. Interestingly, the
epoxidation of 4-vinylpyridine (Table 2, entry 22) was
also achieved in moderate yield and stereoselectivity.
The lack of catalyst inhibition by this pyridine sub-
strate is remarkable and may be tentatively explained
since the pyridine ring is likely to be protonated by
the acetic acid and, because of that, it does not bind
and poison the catalyst.
analysis, a portion of reaction crude was taken from which
the solvents were eliminated under vacuum and the internal
standard (mesitylene) was added. The mixture was dissolved
1
in CDCl3 and analyzed by H NMR. See Supporting Infor-
mation for further details.
Acknowledgements
M.C. thanks MICINN (CTQ2009-08464/BQU and PhD
grants to I.G.-B.) and the European Research Council (ERC-
StG-239910). M.C. and X. R. acknowledge ICREA-Academ-
ia Awards, and SGR 2009-SGR637.
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Experimental Section
See Supporting Information for experimental details, synthe-
sis and characterization of ligands and complexes, and catal-
ysis conditions.
General Procedure for Alkene Epoxidation
An acetonitrile solution (7.5 mL) of the specific olefin
(0.12M) and complex 1–6 (0.12 mM) was prepared in a 25-
mL round-bottom flask equipped with a stir bar and cooled
in an ice bath. Acetic acid (0.7 mL, 14 equiv.) was added di-
rectly to the solution. Then, 0.19 mL of 1:1 v:v acetonitrile:
hydrogen peroxide solution 35% (1.2 equiv.) was added by
syringe pump over a period of 30 min. The solution was fur-
ther stirred at 08C for 5 min. In the case of GC analysis, the
internal standard (biphenyl) was added and the solution was
filtered through a basic alumina plug, which was subse-
Adv. Synth. Catal. 2012, 354, 65 – 70
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Isaac Garcia-Bosch et al.
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