Synthesis of new macrocyclic chiral manganese(III) Schiff bases as catalysts for asymmetric epoxidation

Article abstract of DOI:10.1021/jo052113c

We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III) salen complexes. The developed reaction pathway allows the modulation of the different key groups, namely, the chiral diimine, the bulky substituents in positions 3 and 3′, and the linker used in the macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available structural variations. The catalytic properties of the catalysts (5 mol %) were improved for the asymmetric epoxidation of 2,2′-dimethylchromene with NaOCl or H₂O ₂ as oxygen atom donor. A large range of enantiomeric excesses was obtained (ee values from 30% to 96%), depending on the features and the stability of the complexes. The most efficient catalyst, in terms of stereoinduction (ee value = 96%), contains a diiminocyclohexyl moiety, ethyl groups in positions 3 and 3′, and a short polyether junction arm.

Full text of DOI:10.1021/jo052113c

Synthesis of New Macrocyclic Chiral Manganese(III) Schiff Bases as
Catalysts for Asymmetric Epoxidation
Alexandre Martinez, Catherine Hemmert,* Christophe Loup, Guillaume Barre´, and
Bernard Meunier*
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne,
31077 Toulouse cedex 4, France
hemmert@lcc-toulouse.fr, bmeunier@lcc-toulouse.fr
ReceiVed October 10, 2005
We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III)
salen complexes. The developed reaction pathway allows the modulation of the different key groups,
namely, the chiral diimine, the bulky substituents in positions 3 and 3′, and the linker used in the
macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available
structural variations. The catalytic properties of the catalysts (5 mol %) were improved for the asymmetric
epoxidation of 2,2′-dimethylchromene with NaOCl or H2O2 as oxygen atom donor. A large range of
enantiomeric excesses was obtained (ee values from 30% to 96%), depending on the features and the
stability of the complexes. The most efficient catalyst, in terms of stereoinduction (ee value ) 96%),
contains a diiminocyclohexyl moiety, ethyl groups in positions 3 and 3′, and a short polyether junction
arm.
Introduction
used catalysts for asymmetric synthesis. This is mainly due to
their facile preparation, the easy construction of a highly
asymmetric coordination sphere, and their versatile catalytic
activity, depending on the nature of the metal chelated by the
salen ligands. At about the same time, Jacobsen10 and Katsuki11
have reported the use of chiral manganese(III)-salen catalysts
in asymmetric epoxidations. The Jacobsen-Katsuki reaction is
universally recognized as one of the most useful and widely
applicable methods for the epoxidation of unfunctionalized
olefins, and Jacobsen’s catalyst (Figure 1) is now commercially
available. Enantiomerically pure epoxides are key intermediates
in organic chemistry because they can undergo stereospecific
ring-opening reactions, giving rise to a wide range of biologi-
cally and pharmaceutically active compounds.5-7,12 During the
past 15 years, many different chiral manganense-salen catalysts
have been reported for homogeneous or supported asymmetric
Cytochrome P-450 enzymes represent a class of biological
oxidation catalysts able to perform enantioselective epoxidation
of prochiral olefins.1,2 Synthetic metalloporphyrins3,4 have been
developed for enantioselective epoxidation, and in the same way,
metallosalens,4-9 since Schiff bases and porphyrin ligands have
common features such as planar structures and electronic
properties. Optically active metallosalens are among the widely
(1) Cytochrome P-450: Structure, Mechanism and Biochemistry, 2nd ed.;
Ortiz de Montellano, P. R., Ed., Plenum Press: New York, 1995.
(2) Meunier, B. Chem. ReV. 1992, 92, 1411-1456.
(3) Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105, 5791-
5796.
(4) Jacobsen, E. N. and Wu, M. H. Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; Wiley-VCH: New York, 1993; pp 159-202.
(5) Katsuki, T. Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-
VCH: New York, 2000; pp 287-325.
(6) Jacobsen, E. N.; Wu, M. H. ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer, New York, 1999;
pp 649-675.
(10) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am.
Chem. Soc. 1990, 112, 2801-2803.
(7) Jacobsen, E. N. ComprehensiVe Organometallic Chemistry II; Per-
gamon: Oxford, 1995; Vol. 12, pp 1097-1135.
(11) Irie, R.; Noda, K.; Yto, Y.; Matsumoto, N.; Katsuki, T. Tetrahedron
Lett. 1990, 31, 7345-7348.
(8) Katsuki, T. Synlett 2003, 281-297.
(12) Taylor, M. S.; Jacobsen, E. N. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5368-5373.
(9) Katsuki, T. AdV. Synth. Catal. 2002, 344, 131-147.
10.1021/jo052113c CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/25/2006
J. Org. Chem. 2006, 71, 1449-1457
1449

Martinez et al.
FIGURE 1. Jacobsen’s catalyst.
FIGURE 3. Macrocyclized Schiff base catalyst of first generation.
substrate and iodosylbenzene as oxidant. This result was
probably due to the absence of bulky substituents in the close
proximity of positions 3 and 3′. Moreover, the presence of two
oxygen atoms on the aromatic entities of the ligand, making an
electron-rich easily oxidable ligand, could explain the fragility
of the complexes under oxidative conditions.
This prompted us to develop a new and more elaborated
synthetic strategy. The synthetic pathway for the synthesis of
one representative complex of the second generation (complex
7) is illustrated in Scheme 1 and involves seven steps. The
aromatic electrophilic substitution (compound 1) was already
described in the literature.20 In the next step, the protection of
the phenol function (compound 2) was necessary for the further
introduction of the bridging linker leading to compound 4, thus
avoiding the formation of undesired intracyclic byproduct. The
choice of this group, allyl in our case,21 was important because
the deprotection conditions have to be mild. First attempts
involving a methoxymethyl as protecting group were disap-
pointing. All the experimental methods reported in the literature
for the deprotection of this group22-27 were unsuccessful (HBr
6 M, MeOH, rt; BF3/Et2O, MeOH, rt; BBr3, CH2Cl2, -78 °C;
Ph3CBF4, rt; LiCl, collidine, 160 °C; AcOH 0.2 M, MeOH,
reflux) and led either to the deprotected starting material 1 or
to complicated unseparable mixtures. Compound 3 was obtained,
after a metal-halogen exchange, by the addition of a ketone,
acetone in this case.28 This is the key step in the preparation of
these macrocyclic chiral salen ligands, since it corresponds to
the insertion of the bulky substituents in positions 3 and 3′ of
the final complex. The introduction of the junction arm was
performed by a Williamson reaction.18 The formylation step
required the presence of TMEDA to obtain the dialdehyde 5.20
The deprotection of the phenol group was achieved under mild
conditions at room temperature, 29 and the reaction was highly
chimioselective since no cleavage of the ether bond of the linker
was observed. Finally, the template synthesis of complex 7 was
achieved by mixing stoechiometric amounts of the dialdehyde
6, the chiral diamine, and manganese(II) diacetate. An air
oxidation, followed by NaCl treatment to introduce a chloro
axial ligand, produced complex 7.
FIGURE 2. Design of the macrocyclic chiral Mn(III)-salen.
epoxidation.5,6,13-17 However, the design of new salen ligands
is still an active domaine because their structural, conforma-
tional, and electronic properties strongly influence the tuning
of the catalytic activity of these metallosalen complexes.
In the present work, we describe the preparation of a series
of original chiral macrocyclic manganese-salen complexes,
where each building block of the salen molecule, i.e., bulky
substituents, bridging linker, and chiral diimine, can be easily
tuned (Figure 2). The catalytic activity of these new chiral
complexes was evaluated in the asymmetric epoxidation of 2,2′-
dimethylchromene with sodium hypochlorite or hydrogen
peroxide as oxygen atom donors.
Results and Discussion
The scaffold of these macrocyclic salen complexes contains
a linker between the 3 and 3′ positions, a chiral diimine, and
bulky substituents in the “south part” of the ligand, in positions
3, 3′ and 5, 5′, to induce the approach of the olefin by the “north
face” in the vicinity of the chiral diimine. The ligands retain a
C2 symmetry to have the same stereoinduction on both faces
of the catalyst.
The macrocyclization of the Schiff bases was generated by
introducing a symmetrical junction arm in the 3 and 3′ positions.
Reinhoudt et al. have previously reported macrocyclic achiral
Schiff bases containing aliphatic polyether linkers.18 However,
such a strategy has not been employed for chiral Mn(III)-salen
catalysts. The macrocyclization of the ligand is expected to
increase the stability of the corresponding complexes in asym-
metric catalysis due to the macrocyclic effect. We have
previously prepared a first generation of macrocyclic chiral
Mn(III)-salen catalysts (one example is depicted in Figure 3).19
The synthesis of this first generation of chiral macrocyclic
complexes was convenient and was realized in three steps,
starting from 4-tert-butylcatechol. Unfortunately, the enantio-
meric excess values obtained in the asymmetric epoxidation of
cis-disubstituted olefins were modest for these catalysts; the
highest ee value was 74% with 2,2′-dimethylchromene as
(20) Chan, K. S.; Xu, J. X.; Lam, F. J. Org. Chem. 1996, 61, 8414-
8418.
(21) Chu, C.; Ramamurthy, A.; Makriyannis, A.; Tius, M. A. J. Org.
Chem. 2003, 68, 55-61.
(22) Ljubovic, E.; Sunjie´, V. Tetrahedron Lett. 2000, 41, 9135-9138.
(23) Marzi, E.; Mongin, F.; Spitaleri, A.; Schlosser, M. Eur. J. Org.
Chem. 2001, 2911-2915.
(24) Demuynck, M.; De Clercq, P.; Vandewalle, M. J. Org. Chem. 2001,
44, 4863.
(13) McMorn, P.; Hutching, G. J. Chem. Soc. ReV. 2004, 33, 108-122.
(14) Song, C. E.; Lee, S.-G. Chem. ReV. 2002, 102, 3495-3524.
(15) Bra¨se, S.; Lauterwasser, F.; Ziegert, R. E. AdV. Synth. Catal. 2003,
345, 869-829.
(16) Canali, L.; Sherrington, D. C. Chem. Soc. ReV. 1999, 28, 85-93.
(17) Heckel, A.; Seebach, D. HelV. Chim. Act. 2002, 85, 913-926.
(18) Jha, S. C.; Joshi, N. N. J. Org. Chem. 2002, 67, 3897-3899.
(19) Martinez, A.; Hemmert, C.; Gornitzka, H.; Meunier, B. J. Organo-
met. Chem. 2005, 690, 2163-2171.
(25) Nakata, T.; Schmid, G.; Vranesic, B.; Okigawa, M.; Smith-Palmer,
T.; Kishi, Y. J. Am. Chem. Soc. 1978, 100, 2933-2935.
(26) Colombo, L.; Gennari, C.; Santandrea, M.; Narisano, E.; Scolastico,
C. J. Chem. Soc., Perkin Trans. 1 1980, 136-140.
(27) Daly, A. M.; Renehan, M. F., Gilheany, D. G. Org. Lett. 2001, 3,
663-666.
(28) Talley, J. J.; Evans, I. A. J. Org. Chem. 1984, 49, 5267-5269.
(29) Vutukuri D. R.; Bharathi, P.; Yu, Z.; Rajasekaran, K.; Tran, M.-
H.; Thayumanavan S. J. Org. Chem. 2003, 68, 1146-1149.
1450 J. Org. Chem., Vol. 71, No. 4, 2006

Macrocyclic Catalysts for Asymmetric Epoxidation
SCHEME 1. Synthesis of Complex 7
SCHEME 2. General Synthetic Pathway Allowing Modulation of the Different Building Blocks of These Macrocyclic Schiff
Base Complexes
J. Org. Chem, Vol. 71, No. 4, 2006 1451

Martinez et al.
SCHEME 3. Complexes 8, 11, 12, 16, 21, 26, and 30
diaminocyclohexane, to study the influence of the carboxylate
group in asymmetric epoxidation reactions. Complex 8 involved
a ligand without a C2 symmetry. Finally, three different chiral
C2-symmetric amines (namely, (1R,2R)-(-)-1,2-diaminocyclo-
hexane or (1S,2S)-(+)-1,2-diaminocyclohexane, (1R,2R)-(+)-
1,2-diphenylethylenediamine, and (S)-(-)-1,1′-binaphthyl-2,2′-
diamine) have been used in the template synthesis of these chiral
macrocyclic manganese(III) Schiff bases (complexes 11, 12, and
30 for example, Scheme 3). These three complexes differed in
terms of size and rigidity, and one can expect to observe
different behaviors in catalytic reactions.
In Table 1 are summarized the comparative catalytic activities
of the various macrocyclic Schiff base complexes in the
asymmetric epoxidation of three cis-disubstituted olefins, namely,
2,2′-dimethylchromene, cis-â-methylstyrene, and 1,2-dihydro-
naphthalene and sodium hypochlorite as oxygen atom donor
(except for catalyst 8). The epoxidations reactions were typically
performed with a substrate/oxidant/catalyst molar ratio of 1/2/
0.05 in a biphasic system, in the presence of an excess of
4-phenylpyridine-N-oxide (5 equiv with respect to the caralyst,
except for catalyst 8) at 0 °C. In the case of complex 8, involving
a carboxylate on the diethylene diimine moiety, no additional
axial ligand was used and the reaction was conducted in an
organic medium with the attractive hydrogen peroxide oxidant
(3.4 equiv with respect to the substrate). As expected for these
chiral macrocyclic metallosalen catalysts of second generation,
the asymmetric induction is efficiently increased, giving rise to
enantiomeric excesses up to 96% (Table 1, entry 6), when
compared to those of the first series (ee ) 74% with iodosyl-
benzene as oxidant).19 This a general trend with the three
substrates employed. Complex 7, with methyl groups as bulky
substituents, a short polyether bridging arm and a cyclohexyl
diimine, gave a highly selective epoxidation reaction (entry 1,
yield and selectivity of the epoxychromane derivative )
100%).31 The best stereoinduction was achieved with the
efficient catalyst 26, analogous to complex 7 but bearing ethyl
groups instead of methyl groups (entry 6, ee ) 96%). Moreover,
the asymmetric epoxidation proceeded more rapidly with catalyst
26 (30 min) than with the other complexes, whereas 2 h were
required to obtain a complete conversion of the olefin. By
lengthening the linker of the catalyst in order to study the
influence of the flexibility of the macrocycle in the high-valent
salen-MnV ) O species, the selectivity in epoxide remained
excellent (100%) but the ee value slightly decreased (entry 2,
ee ) 85%, catalyst 11). In the same way, the presence of an
aromatic linker gave similar results (entry 4, ee ) 85%, catalyst
16). In addition, catalyst 16 is interesting because the phenol
group could act as an axial ligand while still keeping the C2
symmetry for enantioselective epoxidation. This functionalized
linker could also serve to graft the corresponding catalyst on a
solid support for heterogeneous asymmetric catalysis. Introduc-
ing the bulkier diiminodiphenylethylene entity has not a strong
influence on the enantioselectivity (entries 2 and 3 to be
compared, ee ) 83% and 85% for catalysts 11 and 12,
respectively). However, complex 30 containing the bulk and
rigid diiminobinaphthyl backbone showed a poor catalytic
activity (entry 7), when compared to the cyclohexyl-based
analogues. Surprisingly, catalyst 21 with bulky fluorinated
aromatic groups in 3 and 3′ positions gave a significantly lower
enantiomeric excess (ee value ) 59%, entry 5, catalyst 21).
This general strategy is original because it made it possible
to modulate the different building blocks of the molecule,
namely, the ketone with bulky substituents, the ditosylate
containing the junction arm, and the chiral diamine (Scheme
2), and thus gives rise to a new family of chiral macrocyclic
salen complexes (Scheme 3). For example, bulky substituents
such as methyl (complexes 8, 11, 12, and 16), ethyl (complexes
26 and 30) or halogenated aryl (complex 21, Scheme 3) can be
introduced. In the same way, simple polyether linkers of
different lengths (see complexes 8 and 11 for example, Scheme
3) can be employed for homogeneous catalysis. A functionalized
linker can also be included (complex 16, Scheme 3) in order to
have the possibility of grafting the corresponding catalyst on
solid supports such as silica or dendrimers. Katsuki et al. have
reported a metallosalen catalyst having a carboxylate group on
the ethylene diimine moiety.30 This catalyst associated with
iodosylbenzene as oxidant was found to be efficient for the
asymmetric epoxidation of 2,2′-chromene derivatives (ee values
up to 99%) with a very high turnover number of 9200. The
high catalytic activity of this complex was partly explained by
the fact that it does not require any additional axial ligand,
generally used in excess, and thus it possesses a free axial
coordination site. This prompted us to synthesize complex 8
(Scheme 3), starting from (S)-2,3-diaminopropionic acid hy-
drogen chloride instead of the most common (1S,2S)-(+)-1,2-
(31) Martinez, A.; Hemmert, C.; Meunier, B. J. Catal. 2005, 234, 205-
255.
(30) Ito, Y. N.; Katsuki, T. Tetrahedron Lett.1998, 39, 4325-4328.
1452 J. Org. Chem., Vol. 71, No. 4, 2006

Macrocyclic Catalysts for Asymmetric Epoxidation
TABLE 1. Asymmetric Epoxidation of 2,2′-Dimethylchromene with Catalysts 7, 8, 11, 12, 16, 21, 26, and 30e
entry
catalyst
substrate
conversion(%)
yield (%)
selectivity (%)
eea (%)
131
2
3
7
11
12
16
21
26
30
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
2,2′-dimethylchromene
cis-â-methylstyrene
100
100
95
100
99
99
5
100
80
39
67
99
92
96
14
99
95
80
100
100
93
80
98
73
3
87
100
100
98
80
99
93
85
83
85
59
96
4
5
6b
79
7
8
Jacobsen’s catalyst
87
79
92
76
48
46
58
36
75
93
69
63
35
80
56
57
64
60
96
84
30
73
67
74
73
39
91
85
60
11
57
61
57
38
78
86
9c
7
8
7
11
12
16
21
26
63
36
10c
1131d
12d
13d
14d
15d
16d
17
51 (11)
47 (25)
42 (10)
55 (18)
5 (3)
74 (25)
88 (7)
55 (23)
60 (11)
22 (10)
74 (13)
56 (20)
31 (10)
64 (16)
60 (25)
cis-â-methylstyrene
cis-â-methylstyrene
cis-â-methylstyrene
cis-â-methylstyrene
cis-â-methylstyrene
Jacobsen’s catalyst
cis-â-methylstyrene
1831,
19d
20d
21d
22d
23d
24d
25d
d
7
8
11
12
16
21
26
1,2-dihydronaphthalene
1,2-dihydronaphthalene
1,2-dihydronaphthalene
1,2-dihydronaphthalene
1,2-dihydronaphthalene
1,2-dihydronaphthalene
1,2-dihydronaphthalene
1,2-dihydronaphthalene
95
63
92
100
54
100
100
Jacobsen’s catalyst
a ee values were determined by chiral GC; ee values are given for the major enantiomer. b After 30 min. c H2O2 (0.34 mmol) was used as oxidant instead
of NaOCl. d Epoxide yield (naphthalene or trans-â-methylstyrene yield). e Reactions were carried out with substrate (0.1 mmol), catalyst (5 µmol), and
NaOCl as oxidant (0.2 mmol) at 0 °C in the presence of 5 equiv of 4-PPNO with respect to the catalyst.
This unexpected result could be explained by the presence of
these sterically hindered substituents that probably block the
C2 axis of the ligand by conformational constraints and create
the possibility of having diastereomeric complexes. The less
efficient catalyst was the unsymmetrical complex 8 with the
carboxylate group on the diethylenediamine (entry 10 to be
compared with entry 9 or entry 19 to be compared with entry
18). These two later results suggested that the C2 symmetry of
the ligand constitutes one of the key factors to have a good
stereoinduction with these chiral macrocyclic metallosalen
catalysts. To summarize these results, complexes 7 and 26 are
the most efficient in terms of stereoinduction (entries 1 and 6,
11 and 16, and 18 and 24) for the asymmetric epoxidation of
cis-disubstituted olefins and can be compared to the com-
mercially available Jacobsen’s catalyst (entries 8, 17, and 25).
for a good orientation of the olefin and the bridging linker, which
can be more or less flexible or functionalized for the fixation
on a solid support.
Experimental Section
Synthesis of Ligands and Complexes. 1,3-Dibromo-5-(1,1-
dimethylethyl)-2-(2-propen-1-yloxy)benzene (2). To a solution
of 1 (3.82 g, 0.0124 mol) in 30 mL of CH2Cl2/H2O (10/7 v/v) and
8.52 mL of a 40 wt % solution of nBu4NOH in water was added
an excess of allylbromide (13.4 mL, 0.062 mol) at room temper-
ature. The reaction mixture was stirred vigorously for 24 h. Addition
of 200 mL of NaOH 1 M was followed by extraction with CH2Cl2
(3 × 100 mL). The combined organic extracts were washed with
NaOH 1 M (100 mL) and water (2 × 200 mL), dried (MgSO4),
filtered, and concentrated. The crude product was dissolved in
CH2Cl2 and the ammonium salt was precipitated by addition of
Et2O. After filtration, the liquid layer was dried under vacuum to
give a colorless oil (4.1 g, 95%). 1H NMR (CDCl3): δ 1.3 ppm (s,
9H), 4.5 (m, 2H), 5.4-5.5 (m, 2H), 6.3 (m, 1H), 7.5 (s, 2H). 13C
NMR (63 MHz, CDCl3): δ 31.2, 34.6, 73.9, 118.5, 133.2.
C13H16O1Br2 (348): calcd C 44.86, H 4.63; found C 44.57, H 4.55.
MS (EI): m/z ) 348 [M], 333, 307, 267, 226, 147, 132, 91, 77,
57, 41.
Conclusion
In summary, we have developed a new family of macrocyclic
chiral manganese(III) Schiff bases. The strategy consists of the
macrocyclization of the ligand via the 3 and 3′ positions, to
have efficient and robust catalysts in oxidative conditions.
Enantiomeric excesses up to 96% have been obtained in the
asymmetric epoxidation of 2,2′-dimethylchromene with NaOCl
as oxidant, associated with a quantitative conversion of the
olefin. Moreover, the same synthetic pathway allowed the
modulation of the key groups of the molecule: the bulky
substituents in the south part of the catalyst, which are necessary
2-[3-Bromo-5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)phenyl]-
2-propanol (3). To a solution of 2 (6.05 g, 0.017 mol) in anhydrous
diethyl ether (20 mL) under nitrogen at -78 °C was added dropwise
n-BuLi (1.6 M, 13 mL, 0.0204 mol). After stirring for 1 h at -78
°C, acetone (1.65 mL, 0.0221 mol) in anhydrous Et2O (10 mL)
was added dropwise at -78 °C. The solution was allowed to warm
J. Org. Chem, Vol. 71, No. 4, 2006 1453

Martinez et al.
to room temperature and stirred for 1 h. Water (15 mL) was added
to the solution at 5 °C. The mixture was extracted with ether (3 ×
100 mL), and the combined organic layers were washed with water
(2 × 100 mL) and dried over MgSO4. The solvent was removed
and the crude product was purified by column chromatography
using hexane/ethyl acetate (9/1) as the eluent to give a colorless
ppm (s, 18H), 1.64 (s, 12H), 3.54 (t, J ) 5.0 Hz, 4H), 3.73 (t, J )
5.0 Hz, 4H), 7.50 (d, J ) 2.4 Hz, 2H), 7.66 (d, J ) 2.4 Hz, 2H),
10.07 (s, 2H), 10.66 (s, 2H). 13C NMR (63 MHz, CDCl3): δ 26.6,
31.3, 34.5, 62.1, 70.75, 78.0, 121.5, 127.1, 128.4, 131.8, 142.1,
157.5, 194.8. C32H46O7 (542): calcd C 70.82, H 8.54; found C
70.46, H 8.62. MS (ES) m/z ) 565.25 [M + Na+].
1
MnIII-Salen Complex 7. The compound 6 (80 mg, 0.148 mmol)
was dissolved in 50 mL of EtOH under nitrogen. To the resulting
solution was added successively (1R,2R)-(+)-1,2-diaminocyclo-
hexane (17 mg, 0.148 mmol) and manganese(II) diacetate tetra-
hydrate (36.4 mg, 0.148 mmol). After stirring overnight, air was
bubbled through the solution for 4 h. The reaction mixture was
concentrated to 20 mL, treated with 20 mL of brine, and extracted
with 2 × 50 mL of CH2Cl2. The organic layer was washed with
100 mL of H2O and dried over Na2SO4. After evaporation of the
solvent and drying under vacuum, 85 mg (82%) of complex 7 was
obtained as a dark brown microcrystalline solid. C38H54N2O5ClMn
(709): calcd C 64.35, H 7.67, N 3.95, Mn 7.75, Cl 5.00; found C
64.66, H 7.61, N 3.54, Mn 7.75, Cl 5.39. MS (ES): m/z ) 673.55
[M - Cl-]+. IR (KBr, cm-1): 1631(CdN). UV-vis (CH3OH): λ
(ꢀ) ) 274 nm (14000 L mol-1 cm-1), 290 (13210), 318 (8928),
354 (5714), 416 (4103). [R]20D ) -0.0231 (589 nm, 0.039 g/dm-3
in CH3OH, 10 cm path).
oil (3.7 g, 65%). H NMR (CDCl3): δ 1.3 ppm (s, 9H), 1.6 (s,
6H), 3.8 (s, 1H), 4.5 (m, 2H), 5.4-5.5 (m, 2H), 6.3 (m, 1H), 7.32
(d, J ) 2.3 Hz, 1H) 7.44 (d, J ) 2.3 Hz, 1H). 13C NMR (63 MHz,
CDCl3): δ 31.2, 34.3, 73.2, 74.3, 117.2, 118.3, 122.9, 129.8, 133.0,
142.2, 148.2, 150.9. C16H23O2Br1 (328): calcd C 58.72, H 7.08;
found C 58.49, H 7.09. MS (EI): m/z ) 328 [M], 311, 270, 255,
91, 77, 43.
1,1′-[Oxybis(2,1-ethanediyloxy-2,2-propanediyl)]bis[3-bromo-
5-(1,1-dimethylethyl)-2-(vinyloxy)benzene] (4). NaH (0.78 g,
20.34 mmol, 60% dispersion in oil) was washed with pentane (3
× 4 mL) and a solution of 3 (3.7 g, 11.3 mmol) in THF (15 mL)
was then added dropwise under nitrogen. The reaction mixture was
stirred for 3 h at room temperature. To the resulting suspension
was added a solution of diethylene glycol ditosylate (2.86 g, 6.9
mmol) in anhydrous DMF (10 mL) in one portion and the mixture
was stirred for 48 h. The reaction was quenched by addition of
brine (100 mL) and extracted with CH2Cl2 (3 × 100 mL). The
organic layer was washed with H2O (2 × 100 mL), dried over
Na2SO4, filtered and evaporated to dryness. The residue was purified
by column chromatography using hexane/ethyl acetate (96/4) as
the eluent to obtain a colorless oil (2.3 g, 55%). 1H NMR
(CDCl3): δ 1.26 ppm (s, 18 H), 1.62 (s, 6H), 3.43 (t, J ) 5.5 Hz,
4H), 3.66 (t, J ) 5.5 Hz, 4H), 4.48 (m, 4H), 5.24-5.48 (m, 4H),
6.10 (m, 2H), 7.43 (d, J ) 2.9 Hz, 2H), 7.48 (d, J ) 2.9 Hz, 2H).
13C NMR (63 MHz, CDCl3): δ 28.3, 31.3, 62.1, 71.0, 73.8, 77.5,
117.4, 118.4, 124.7, 129.7, 133.6, 139.7, 147.9, 151.3. C36H52O5Br2
(724.6): calcd C 59.67, H 7.23; found C 59.42, H 7.30. MS (DCI/
NH3): m/z ) 742 [M + NH4+]+.
3,3′-[Oxybis(2,1-ethanediyloxy-2,2-propanediyl)]bis[5-(1,1-
dimethylethyl)-2-(vinyloxy)benzaldehyde] (5). To a well-stirred
solution of 4 (1.6 g, 2.2 mmol) in anhydrous ether (5 mL) at -90
°C was added dropwise a mixture of TMEDA (330 mg, 2.9 mmol)
and n-BuLi (1.6 M, 4 mL, 6.4 mmol) in anhydrous ether (5 mL) at
-90 °C under nitrogen. The yellow solution was stirred at -90 °C
for 1 h. Then a solution of anhydrous DMF (1.8 mL, 22.4 mmol)
in diethyl ether (2 mL) was added at -90 °C under nitrogen. The
mixture was allowed to warm to room temperature and stirred for
an other hour. Water (5 mL) was slowly added to the solution at 5
°C. The mixture was extracted with CH2Cl2 (3 × 100 mL) and the
combined organic layers were washed with water (2 × 100 mL)
and dried over MgSO4. The solvent was removed and the crude
product was purified by column chromatography using hexane/
ethyl acetate (96/4) as the eluent to give a pale yellow oil (530
mg, 40%). 1H NMR (CDCl3): δ 1.29 ppm (s, 18H), 1.65 (s, 12H),
3.45 (t, J ) 5.6 Hz, 4H), 3.68 (t, J ) 5.6 Hz, 4H), 4.46 (m, 4H),
5.30-5.40 (m, 4H), 6.05 (m, 1H), 7.75 (d, J ) 2.8 Hz, 2H) 7.83
(d, J ) 2.8 Hz, 2H) 10.28 (s, 2H). 13C NMR (63 MHz, CDCl3): δ
28.1, 31.3, 34.66, 62.1, 70.8, 71.0, 78.9, 117.7, 125.0, 129.7, 131.9,
132.8, 139.2, 142.4, 149.2, 190.6. C38H54O7 (622.85): calcd (+
H2O) C 71.62, H 8.80; found C 71.56, H 9.21. MS (ES) m/z )
645 [ M + Na+].
MnIII-Salen Complex 8. Two equivalents of sodium hydroxide
(18.8 mg, 0.47 mmol) in EtOH (10 mL) were added slowly to a
suspension of 6 (107.8 mg, 0.24 mmol) and (S)-2,3-diaminopro-
pionic acid hydrogen chloride (33.1 mg, 0.24 mmol) in EtOH (50
mL). After stirring for 2 h under nitrogen, Mn(OAc)2‚4H2O (58.0
mg, 0.24 mmol) in EtOH (10 mL) was added to the mixture. After
stirring overnight, air was bubbled through the solution for 4 h.
The solvent was evaporated and the residue was dissolved in 50
mL of CH2Cl2. The organic layer was washed with 2 × 50 mL of
H2O and dried over Na2SO4. After evaporation of the solvent and
drying under vacuum, 89 mg (57%) of complex 8 was obtained as
a dark brown microcrystalline solid. C35H47N2O7Mn (662.7): calcd
(+ CH2Cl2 + MeOH) C 57.00, H 6.85, N 3.59, Mn 7.05; found C
57.34, H 7.03, N 3.63, Mn 6.61. MS (ES): m/z ) 663.4 [M +
H+]+, 685.4 [M +Na+]+, 701.3 [M + K+]+. IR (KBr, cm-1): 1619
(CdN). UV-vis (CH3OH): λ (ꢀ) ) 278 nm (16430 L mol-1 cm-1),
290(15700), 324(11420), 352 (8200), 420 (5130). [R]20D ) -0.0460
(589 nm, 0.050 g/dm-3 in CH3OH, 10 cm path).
3,14-Bis[3-bromo-5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)-
phenyl]-3,14-dimethyl-4,7,10,13-tetraoxahexadecane (9). Com-
pound 9 was prepared as described for 4 starting from NaH (0.22
g, 5.5 mmol, 60% dispersion in oil) in THF (5 mL), 3 (1.2 g, 3.7
mmol) in THF (5 mL), and triethylene glycol ditosylate (0.924 g,
2.0 mmol) in DMF (5 mL).The crude product was purified by
column chromatography using hexane/ethyl acetate (9/1) as the
1
eluent to obtain a colorless oil (0.85 g, 55%). H NMR (CDCl3):
δ 1.27 ppm (s, 18H), 1.62 (s, 12H), 3.43 (t, J ) 5.4 Hz, 4H), 3.64
(t, J ) 5.4 Hz, 4H), 3.65 (s, 4H) 4.46 (m, 2H), 5.45 (m, 4H), 5.30-
5.40 (m, 4H), 6.05 (m, 2H), 7.75 (d, J ) 2.8 Hz, 2H) 7.83 (d, J )
2.8 Hz, 1H). 13C NMR (63 MHz, CDCl3): δ 28.3, 31.3, 34.7, 62.1,
70.7, 70.9, 73.8, 77.4, 117.3, 118.3, 124.7, 129.7, 133.6, 139.8,
147.8, 151.3. C38H56O6Br2 (768.7): calcd C 59.38, H 7.34; found
C 59.51, H 7.52. MS (DCI/NH3) m/z ) 786 [M + NH4+]+.
3,3′-(1,1,12,12-Tetramethyl-2,5,8,11-tetraoxadodecane-1,12-
diyl)bis[5-(1,1-dimethylethyl)-2-hydroxybenzaldehyde] (10). Com-
pound 10 was prepared as described for 5 starting from 9 (0.7 g,
0.93 mmol), TMEDA (140 mg, 1.22 mmol), and n-BuLi (1.6 M,
1.5 mL, 2.4 mmol) in Et2O (3 mL) and DMF (0.8 mL, 10.3 mmol)
at -90 °C. The crude product was purified by column chroma-
tography using hexane/ethyl acetate (9/1) as the eluent to give a
pale yellow oil (230 mg) which was an inseparable mixture of
deprotected and allyl protected compounds. This mixture (230 mg)
was dissolved in MeOH (5 mL) and deprotected as described for
compound 6 starting from Pd(PPh3)4 (16 mg, 0.014 mmol) and
K2CO3 (230 mg, 1.66 mmol). The crude product was purified by
column chromatography using pentane/ethyl acetate (9/1) as the
3,3′-[Oxybis(2,1-ethanediyloxy-2,2-propanediyl)]bis[5-(1,1-
dimethylethyl)-2-hydroxy-benzaldehyde] (6). To a solution of 5
(120 mg 0.193 mmol) in MeOH (3 mL) was added catalytic
amounts of Pd(PPh3)4 (11.1 mg, 0.0098 mmol) under nitrogen. The
slightly yellow solution was stirred for 5 min, and K2CO3 (160
mg, 1.16 mmol) was added. The reaction was completed within 2
h (monitored by TLC). The reaction mixture was concentrated in
a vacuum and the residue was treated with water (20 mL). The
aqueous solution was extracted with CH2Cl2 (3 × 20 mL) and dried
over Na2SO4. The organic layer was concentrated in a vacuum and
purified by column chromatography using CH2Cl2 as the eluent to
1
give a pale yellow oil (90 mg, 86%). H NMR (CDCl3): δ 1.29
1454 J. Org. Chem., Vol. 71, No. 4, 2006

Macrocyclic Catalysts for Asymmetric Epoxidation
eluent to give a pale yellow oil (160 mg, 30%). 1H NMR (CDCl3):
δ 1.30 ppm (s, 18H), 1.63 (s, 12H), 3.51 (t, J ) 4.8 Hz, 4H), 3.70
(t, J ) 4.8 Hz, 4H), 3,72 (s, 4H), 7.49 (d, J ) 2.3 Hz, 2H), 7.65
(d, J ) 2.3 Hz, 2H), 10.09 (s, 2H), 10.61 (s, 2H). 13C NMR (63
MHz, CDCl3): δ 26.6, 31.3, 34.1, 62.1, 70.7, 77.9, 121.6, 127.0,
131.8, 132.3, 142.1, 157.5, 194.7. C34H50O8 (586): calcd (+ 0.4
CH2Cl2) C 66.56, H 8.25; found C 66.98, H 7.81. MS (DCI/NH3)
m/z ) 604 [M + NH4+]+.
NMR (CDCl3): δ 1.26 ppm (s, 18H), 1.70 (s, 12H), 4.40 (s, 4H),
4.81 (s, 1H), 6.83 (s, 2H), 6.93 (s, 1H), 7.49 (d, J ) 2.7 Hz, 2H),
7.73 (d, J ) 2.7 Hz, 2H) 10.01 (s, 2H), 11.01 (s, 2H). 13C NMR
(63 MHz, CDCl3): δ 26.8, 31.3, 34.2, 64.7, 78.3, 113.3, 118.1,
121.2, 128.0, 132.1, 132.4, 140.7, 142.2, 156.1, 157.5, 195.6.
C36H46O7 (590.76): calcd (+ 0.7 CH2Cl2) C 67.79, H 7.35; found
C 67.90, H 7.26. MS (DCI/NH3) m/z ) 608 [ M + NH4+]+.
MnIII-Salen Complex 16. Complex 16 was synthesized as
described above for complex 7, starting from 15 (130 mg, 0.22
mmol) in 50 mL of EtOH, (1S,2S)-(+)-1,2-diaminocyclohexane (25
mg, 0.22 mmol), and Mn(OAc)2‚4H2O (53.9 mg, 0.22 mmol).
Yield: 120 mg, 73% as a dark brown microcrystalline solid.
C42H54N2O5ClMn (757.3): calcd (+ 0.6 CH2Cl2) C 63.38, H 6.77,
N 3.47, Mn 6.81, Cl 4.39; found C 63.01, H 6.7, N 3.35, Mn 6.89,
Cl 4.77. MS (ES): m/z ) 721.8 [M - Cl-]+. IR (KBr, cm-1):
1615 (CdN). UV-vis (CH3OH): λ (ꢀ) ) 278 nm (14663 L mol-1
cm-1), 320 (8333), 358 (5292), 412 (3805). [R]20D ) 0.0275 (589
nm, 0.052 g/dm-3 in CH3OH, 10 cm path).
MnIII-Salen Complex 11. Complex 11 was synthesized as
described above for complex 7, starting from 9 (88.0 mg, 0.15
mmol) in 50 mL of EtOH, (1S,2S)-(+)-1,2-diaminocyclohexane
(17.1 mg, 0.15 mmol), and Mn(OAc)2‚4H2O (36.8 mg, 0.15 mmol).
Yield: 90 mg, 80% as a dark brown microcrystalline solid.
C40H58N2O6ClMn (753.3): calcd (+ 0.4 CH2Cl2) C 63.78, H 7.76,
N 3.72, Mn 6.98, Cl 4.51; found C 63.55, H 7.56, N 3.65, Mn
6.61, Cl 4.78. MS (ES): m/z ) 717.5 [M - Cl-]+. IR (KBr, cm-1):
1615 (CdN). UV-vis (CH3OH): λ (ꢀ) ) 290 nm (19031 L mol-1
cm-1), 318 (13379), 356 (8469), 412 (6124). [R]20D ) 0.0482 (589
nm, 0.108 g/dm-3 in CH3OH, 10 cm path).
[3-Bromo-5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)phenyl]-
[bis(4-flurophenyl)]methanol (17). Compound 17 was prepared
as described for 3 starting from 2 (2.00 g, 5.75 mmol) in Et2O (8
mL), n-BuLi (1.6 M, 4.31 mL, 6.89 mmol), and 4,4′-difluoro-
benzophenone (2.51 g, 11.5 mmol) in anhydrous ether (30 mL) at
-78 °C. The solvent was removed, the crude product was dissolved
in 20 mL of CH2Cl2, hexane (60 mL) was added, and the flask
was placed at -20 °C overnight. The supernatant was collected by
filtration and the solvent was removed to give a pale yellow solid
MnIII-Salen Complex 12. The complex 12 was synthesized as
described above, starting from 10 (47 mg, 0.08 mmol) in 20 mL
of EtOH, (1R,2R)-(-)-1,2-diphenylethylenediamine (17 mg, 0.08
mmol), and Mn(OAc)2‚4H2O (19.6 mg, 0.08 mmol). Yield: 63 mg,
67% as a dark brown powder. C48H60N2O6ClMn (851.4): calcd C
67.72, H 7.10, N 3.29, Mn 6.46, Cl 4.16; found C 67.96, H 7.29,
N 2.94, Mn 6.21, Cl 4.67. MS (ES): m/z ) 815.5 [M - Cl-]+. IR
(KBr, cm-1): 1612 (CdN). UV-vis (CH3OH): λ (ꢀ) ) 274 nm
(16440 L mol-1 cm-1), 290 (14126), 326 (10210), 356 (6625) 424
1
(2.51 g, 90%). H NMR (CDCl3): δ 1.11 ppm (s, 9H), 3.8 (m,
(4352). [R]20 ) -0.0237 (589 nm, 0.038 g/dm-3 in CH3OH, 10
2H), 5.02-5.14 (m, 2H), 5.64-5.73 (m, 2H), 5.71 (s, 1H), 6.49
(d, J ) 2.5 Hz, 1H), 7.02 (m, 4H), 7.24 (m, 4H), 7.48 (d, J ) 2.5
Hz, 1H). 13C NMR (63 MHz, CDCl3): δ 31.0, 34.4, 73.7, 81.8,
114.5, 114.9, 117.4, 118.7, 127.0, 129.6, 129.7, 130.4, 132.3, 141.8,
151.4, 160.2, 164.1. C26H25O2Br1F2 (487): calcd C 64.07, H 5.17;
found C 64.24, H 4.71. MS (ES): m/z ) 510 [M + Na+]+.
1,1′-(Oxybis{2,1-ethanediyloxy[bis(4-fluorophenyl)-
methanediyl]})bis[3-bromo-5-(1,1-dimethylethyl)-2-(2-propen-
1-yloxy)benzene] (18). Compound 18 was prepared as described
for 4 starting from NaH (0.24 g, 6.2 mmol, 60% dispersion in oil)
in THF (6 mL), 17 (2.0 g, 4.1 mmol) in THF (8 mL), and diethylene
glycol ditosylate (0.85 g, 2.05 mmol) in DMF (8 mL).The crude
product was purified by column chromatography using hexane/
ethyl acetate (95/5) as the eluent to obtained a pale yellow solid
D
cm path).
1,1′-[[5-(Ethenyloxy)benzene-1,3-diyl]bis(methanediyloxy-2,2-
propanediyl)]bis[3-bromo-5-(1,1-dimethylethyl)-2-(2-propen-1-
yloxy)benzene] (13). Compound 13 was prepared as described for
4 starting from NaH (0.60 g, 15.0 mmol, 60% dispersion in oil) in
THF (5 mL) and 3 (2.8 g, 8.54 mmol) in THF (5 mL). 5-Allyloxy-
1,3-benzenedimethyl ditosylate (2.0 g, 3.98 mmol) in DMF (5 mL)
was added in one portion and the mixture was stirred for 48 h. The
crude product was purified by column chromatography using
hexane/ethyl acetate (95/5) as the eluent to obtained a colorless oil
1
(1.45 g, 42%). H NMR (CDCl3): δ 1.22 ppm (s, 18H), 1.70 (s,
12H), 4.31 (s, 4H), 4.48 (m, 4H), 4.52 (m, 2H), 5.23-5.47 (m,
6H), 6.08 (m, 3H), 6.86 (s, 2H), 6.89 (s, 1H), 7.45 (d, J ) 2.3 Hz,
2H) 7.52 (d, J ) 2.3 Hz, 1H). 13C NMR (63 MHz, CDCl3): δ
28.3, 31.2, 34.2, 64.5, 73.7, 77.4, 112.3, 117.2, 118.8, 118.9, 124.3,
129.8, 133.2, 133.3, 139.9, 141.1, 151.3, 158.8. C43H56O5Br2
(812.7): calcd C 63.55, H 6.95; found C 63.21, H 6.83. MS (DCI/
NH3) m/z ) 830 [M + NH4+]+.
1
(0.643 g, 30%). H NMR (CDCl3): δ 1.24 ppm (s, 18H), 3.10 (t,
J ) 4.9 Hz, 4H), 3.70 (t, J ) 4.9 Hz, 4H), 3.92 (m, 4H), 4.88-
4.99 (m, 4 H), 5.47-5.62 (m, 2H), 6.92 (m, 8H), 7.42 (m, 8H),
7.50 (d, J ) 2.5 Hz, 2H), 7.70 (d, J ) 2.5 Hz, 2H). 13C NMR (63
MHz, CDCl3): δ 31.2, 34.6, 63.4, 70.8, 72.29, 84.9, 114.4, 114.7,
116.7, 118.1, 126.2, 129.7, 129.9, 130.8, 133.3, 137.8, 138.9, 147.3,
159.7, 163.6. C56H56O5Br2F4 (1044.87): calcd (+ 0.4 CH2Cl2) C
62.79, H 5.31; found C 62.98, H 5.30. MS (ES): m/z ) 1068 [M
+ Na+]+.
3,3′-[[5-(Ethenyloxy)benzene-1,3-diyl]bis(methanediyloxy-
2,2-propanediyl)]bis[5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)-
benzaldehyde] (14). Compound 14 was prepared as described for
5 starting from 13 (0.32 g, 0.39 mmol), TMEDA (330 mg, 2.9
mmol), and n-BuLi (1.6 M, 0.75 mL, 1.2 mmol) in ether (5 mL)
and DMF (0.25 mL, 3.25 mmol) at -90 °C. After workup, the
solvent was removed to give a pale yellow oil (280 mg, 98%). 1H
NMR (CDCl3): δ 1.29 ppm (s, 18H), 1.74 (s, 12H), 4.35 (s, 4H),
4.44 (m, 4H), 4.53 (m, 2H), 5.23-5.48 (m, 6H), 6.05 (m, 3H), 6
0.87 (s, 2H), 6.91 (s, 1H) 7.77 (d, J ) 2.4 Hz, 2H) 7.86 (d, J ) 2.4
Hz, 2H), 10.29 (s, 2 H). 13C NMR (63 MHz, CDCl3): δ 28.4, 31.3,
34.7, 64.7, 68.8, 79.0, 112.3, 117.5, 117.7, 118.2, 125.2, 129.8,
131.8, 132.7, 133.3, 138.9, 140.7, 147.0, 190.7. C45H58O7 (711):
calcd (+ 0.4 CH2Cl2) C 73.23, H 7.96; found C 73.25, H 7.88.MS
(DCI/NH3) m/z ) 728 [ M + NH4+]+.
3,3′-(Oxybis{2,1-ethanediyloxy[bis(4-fluorophenyl)-
methanediyl]})bis[5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)-
benzaldehyde] (19). Compound 19 was prepared as described for
5 starting from 18 (0.410 g, 0.39 mmol), TMEDA (0.1 mL), and
n-BuLi (1.6 M, 1.0 mL, 1.2 mmol) in Et2O (2.5 mL), and DMF
(0.5 mL, 3.2 mmol) in Et2O (2 mL). The crude product was
dissolved in ethyl acetate/hexane (30 mL/30 mL) and the flask was
placed at -20 °C overnight. The solid was collected and dried in
a vacuum (338 mg, 92%). 1H NMR (CDCl3): δ 1.28 ppm (s, 18H),
3.13 (t, J ) 5.1 Hz, 4H), 3.71 (t, J ) 5.1 Hz, 4H), 3.89 (d, J ) 5.2
Hz, 4H), 4.92-5.04 (m, 4H), 5.49 (m, 2H), 6.94 (m, 8H), 7.44 (m,
8H), 7.81 (d, J ) 2.9 Hz, 2H), 8.08 (d, J ) 2.9 Hz, 2H) 10.12 (s,
2H). 13C NMR (63 MHz, CDCl3): δ 31.2, 34.7, 63.3, 70.8, 77.2,
84.2, 114.5, 114.8, 117.1, 125.7, 129.8, 130.0, 132.5, 132.9, 137.0,
138.5, 158.2, 159.8, 163.7, 190.3. C58H58O7F4 (942): calcd (+ 0.2
CH2Cl2) C 72.81, H 6.13; found C 72.90, H 5.88. MS (ES) m/z )
965.5 [M + Na+]+, 981 [M + K+]+, 997.5 [M + MeOH + Na+]+,
1013.5 [M + MeOH + K+]+.
3,3′-[(5-Hydroxybenzene-1,3-diyl)bis(methanediyloxy-2,2-pro-
panediyl)]bis[5-(1,1-dimethylethyl)-2-hydroxybenzaldehyde] (15).
Compound 15 was prepared as described for 6 starting from 14
(280 mg, 0.385 mmol) in MeOH (6 mL), Pd (PPH3)4 (20.0 mg,
0.019 mmol), and K2CO3 (360 mg, 2.61 mmol). The crude product
was purified by column chromatography using hexane/ethyl acetate
1
(9/1) as the eluent to give a pale yellow oil (145 mg, 64%). H
J. Org. Chem, Vol. 71, No. 4, 2006 1455

Martinez et al.
3,3′-(Oxybis{2,1-ethanediyloxy[bis(4-fluorophenyl)-
methanediyl]})bis[5-(1,1-dimethylethyl)-2-hydroxybenzalde-
hyde] (20). Compound 20 was prepared as described for 6 starting
from 19 (220 mg 0.234 mmol) in MeOH (5 mL), Pd(PPH3)4 (12.5
mg, 0.011 mmol), and K2CO3 (200 mg, 1.45 mmol). The crude
product was purified by column chromatography using hexane/
ethyl acetate (95/5) as the eluent to give a white solid (160 mg,
pound 24 was prepared as described for 5 starting from 23 (1.0 g,
1.28 mmol), TMEDA (0.88 mL) and n-BuLi (1.6 M, 3.2 mL, 5.12
mmol) in Et2O (3 mL) and DMF (0.99 mL, 12.8 mmol) in Et2O (3
mL). The reaction was realized at -90 °C. The crude product was
dissolved in ethyl acetate/hexane (30 mL/30 mL) and the flask was
placed at -20 °C overnight. After filtration and drying, the crude
product was directly used for the deprotection of the phenol
1
1
80%). H NMR (CDCl3): δ 1.27 ppm (s, 18H), 3.16 (t, J ) 4.9
function. H NMR (CDCl3): δ 0.62 ppm (t, 12H), 1.30 (s, 18 H),
Hz, 4H), 3.71 (t, J ) 4.9 Hz, 4H), 6.98 (m, 8H), 7.43 (m, 10H),
8.12 (d, J ) 2.4 Hz, 2H,), 9.86 (s, 2H), 11.15 (s, 2H). 13C NMR
(63 MHz, CDCl3): δ 31.2, 34.3, 63.2, 70.8, 84.5, 114.2, 114.6,
120.8, 129.2, 130.5, 130.6, 131.2, 133.1, 137.2, 156.7, 159.9, 163.9,
196.2. C52H50O7F4 (863): calcd (+ 0.7 CH2Cl2). C 68.62, H 5.62;
found C 68.77, H 5.41. MS (DCI/NH3) m/z ) 880 [M + NH4+]+.
MnIII-Salen Complex 21. Complex 21 was obtained as described
above for complex 7, from 20 (82 mg, 0.10 mmol) in 40 mL of
EtOH, (1S,2S)-(+)-1,2-diaminocyclohexane (11.8 mg, 0.10 mmol),
and Mn(OAc)2‚4H2O (25.6 mg, 0.10 mmol). Yield: 85 mg, 83%
as a dark brown microcrystalline solid. C58H58N2O5F4ClMn
(1029.5): calcd (+ 0.2 CH2Cl2) C 66.8, H 5.63, N 2.68, Mn 5.26,
Cl 3.40; found C 66.55, H 5.86, N 2.42, Mn 5.18, Cl 3.84. MS
(ES): m/z ) 993.75 [M - Cl-]+. IR (KBr, cm-1): 1615 (CdN).
UV-vis (CH3OH): λ (ꢀ) ) 276 nm (19463 L mol-1 cm-1), 330
1.90-2.10 (m, 8H), 3.45 (t, J ) 5.5 Hz, 4H), 3.74 (t, J ) 5.5 Hz,
3
4
4H), 3.76 (s, 4H), 4.41 (dd, J ) 3.7 Hz, J ) 1.5 Hz, 4H), 5.29
3
4
3
3
(dd, J ) 9.1 Hz, J ) 1.2 Hz, 2H), 5.49 (dd, J ) 9.1 Hz, J )
1.2 Hz, 2H), 5.99-6.12 (m, 2H), 7.73 (d, J ) 2.9 Hz, 2 H) 7.96
(d, J ) 2.9 Hz, 2H) 10.26 (s, 2H).
3,3′-[Oxybis(2,1-ethanediyloxy-3,3-pentanediyl)]bis[5-(1,1-
dimethylethyl)-2-hydroxybenzalde] (25). Compound 25 was
prepared as described for 6 starting from 24 (530 mg 0.781 mmol)
in MeOH (15 mL), Pd(PPH3)4 (45.0 mg, 0.391 mmol), and K2CO3
(647.4 mg, 4.68 mmol). The crude product was purified by column
chromatography using hexane/ethyl acetate (96/4) as the eluent to
give a white solid (707 mg, 80%). 1H NMR (CDCl3): δ 0.68 ppm
(t, 12H), 1.29 ppm (s, 18H), 1.88-2.15 (m, 8H), 3.54 (t, J ) 5.1
Hz, 4H), 3.84 (t, J ) 4.7 Hz, 4H), 7.50 (d, J ) 2.5 Hz), 2H), 7.67
(d, J ) 2.5 Hz, 2H), 10.11 (s, 2H), 10.81 (s, 2H). 13C NMR (63
MHz, CDCl3): δ 7.7, 27.0, 31.2, 34.1, 60.3, 70.9, 83.5, 121.3, 126.4,
129.4, 133.7, 141.4, 157.5, 194.7. C36H54O7 (598.8): calcd C 72.22,
H 9.09; found C 71.93, H 9.37. SM (ES) m/z (%) ) 621.8 [ M +
Na+]+, 637.8 [ M + K+]+.
(9743), 420 (4417). [R]20 ) 0.0072 (589 nm, 0.056 g/dm-3 in
D
CH3OH, 10 cm path).
3-[3-Bromo-5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)phenyl]-
3-pentanol (22). To a solution of 2 (32.51 g, 93.4 mmol) in
anhydrous diethyl ether (82 mL) under nitrogen at -78 °C was
added dropwise n-BuLi (1.6 M, 72 mL, 0.0112 mol). After stirring
for 1 h at -78 °C, 3-pentanone (beforehand dried over molecular
sieves 4Å, 12.83 mL, 121.4 mmol) in anhydrous Et2O (10 mL)
was added dropwise at -78 °C. The reaction mixture was stirred
for 1 h and then allowed to warm to room temperature. H2O (15
mL) was added to the solution at 5 °C. The mixture was extracted
with ether (3 × 100 mL), and the combined organic layers were
washed with H2O (2 × 100 mL) and dried over Na2SO4. The solvent
was removed and the crude product was purified by column
chromatography using hexane/ethyl acetate (98/2) as the eluent to
give a colorless oil (15.17 g, 45%). 1H NMR (CDCl3): δ 0.79 ppm
(t, 6H), 1.27 (s, 9H), 1.73-1.97 (m, 4H), 4.22 (s, 1H), 4.57 (d, J
MnIII-Salen Complex 26. Complex 26 was synthesized as
described above for complex 7, starting from 25 (80 mg, 0.0134
mmol) in 80 mL of EtOH, (1S,2S)-(+)-1,2-diaminocyclohexane
(15.3 mg, 0.0134 mmol), and Mn(OAc)2‚4H2O (32.8 mg, 0.0134
mmol). Yield: 87 mg, 85% as a dark brown microcrystalline solid.
C42H62N2O5ClMn (765.4): calcd (+ 1 EtOH +1 H2O) C 63.72, H
8.51, N 3.38, Mn 6.62, Cl 4.27; found C 63.69, H 8.59, N 3.44,
Mn 6.80, Cl 4.39. MS (ES): m/z ) 730.4 [M - Cl-]+, 788.4 [M
+ Na+]+. IR (KBr, cm-1): 1613 (CdN). UV-vis (CH3OH): λ
(ꢀ) ) 220 nm (40370 L mol-1 cm-1), 244 (37400), 293 (14650),
327 (9500), 357 (6440), 409 (4010). [R]20 ) 0.0250 (589 nm,
D
0.044 g/dm-3 in CH3OH, 10 cm path).
3,14-Bis[3-bromo-5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)-
phenyl]-3,14-diethyl-4,7,10,13-tetraoxahexadecane (27). Com-
pound 27 was prepared as described for 4 starting from NaH (4.23
g, 105.6 mmol, 60% dispersion in oil, washed with 2 × 25 mL of
pentane) in THF (35 mL) and 22 (8.53 g, 24.0 mmol) in THF (35
mL), and triethylene glycol ditosylate (5.5 g, 12.0 mmol) in DMF
(20 mL) was added in one portion. The reaction was monitored by
TLC and after 24 h, a subsequent portion of triethylene glycol
ditosylate (4.4 g, 9.6 mmol) in DMF (15 mL) was added and stirred
for 24 h. After workup, the crude product was purified by column
chromatography using hexane/ethyl acetate (9/1) as the eluent to
give a colorless oil (4.86 g, 49%). 1H NMR (CDCl3): δ 0.61 ppm
(t, 12H), 1.26 (s, 18H), 1.88-2.07 (m, 8H), 3.42 (t, J ) 5.4 Hz,
4H), 3.71 (t, J ) 5.4 Hz, 4H), 3.73 (s, 4H), 4.49 (d, J ) 5.3 Hz,
3
4
) 5.5 Hz, 2H), 5.44 (dd, J ) 17 Hz, J ) 1.6 Hz, 2H), 5.51 (d,
3J ) 17 Hz, 4J ) 1.6 Hz, 2H), 6.12 (m, 1H), 7.16 (d, J ) 2.0 Hz,
1H),7.43 (d, J ) 2.0 Hz, 1H). 13C NMR (63 MHz, CDCl3): δ 8.2,
31.2, 34.4, 34.9, 74.7, 79.3, 117.5, 118.3, 125.0, 129.2, 132.9, 138.5,
147.9, 151.3. C18H27O2Br1 (354): calcd C 60.85, H 7.66; found C
60.86, H 7.60. SM (EI): m/z (%) ) 354 [M].
1,1′-[Oxybis(2,1-ethanediyloxy-3,3-pentanediyl)]bis[3-bromo-
5-(1,1-dimethylethyl)-2-(2-propen-1-yloxy)benzene] (23). Com-
pound 23 was prepared as described for 4 starting from NaH (6.37
g, 159.3 mmol, 60% dispersion in oil, washed with 2 × 20 mL of
pentane) in THF (50 mL) and 22 (12.85 g, 36.2 mmol) in THF (50
mL), and diethylene glycol ditosylate (7.50 g, 18.1 mmol) in DMF
(26 mL) was added in one portion. The reaction was monitored by
TLC and after 15 h, a subsequent portion of diethylene glycol
ditosylate (2.7 g, 6.51 mmol) in DMF (5 mL) was added and stirred
for 33 h. After workup, the crude product was dissolved in MeOH
(250 mL) and the flask was placed at -20 °C overnight. The white
solid was collected and dried in a vacuum (4.47 g, 32%). 1H NMR
(CDCl3): δ 0.64 ppm (t, 12H), 1.27 (s, 18H), 2.00 (q, J ) 7.3 Hz,
8H), 3.44 (t, J ) 5.2 Hz, 4H), 3.83 (t, J ) 5.2 Hz, 4H), 4.50 (d, J
) 5.3 Hz, 4H), 5.28 (dd, 3J ) 10 Hz, 4J ) 1.0 Hz, 2H), 5.44 (dd,
3
4
3
4H), 5.27 (dd, J ) 16 Hz, J ) 1.4 Hz, 2H), 5.43 (dd, J ) 16
4
Hz, J ) 1.4 Hz, 2H), 6.04-6.19 (m, 2H), 7.41 (d, J ) 2.5 Hz,
2H), 7.59 (d, J ) 2.5 Hz, 2H). 13C NMR (63 MHz, CDCl3): δ 8.0,
27.5, 31.3, 34.5, 60.3, 71.0, 71.1, 73.4, 82.0, 117.3, 117.4, 126.7,
129.3, 133.6, 137.6, 147.2, 150.6. C42H64O6Br2 (824.8): calcd C
61.16, H 7.81; found C 61.26, H 7.46. SM (EI): m/z (%) ) 824
[M].
3,3′-(1,1,12,12-Tetraethyl-2,5,8,11-tetraoxadodecane-1,12-diyl)-
bis[5-(1,1-dimethylethyl)-2-(2-propenyloxy)benzaldehyde] (28).
Compound 28 was prepared as described for 5 starting from 27
(2.25 g, 2.73 mmol) in Et2O (155 mL), TMEDA (1.9 mL, 12.5
mmol) and n-BuLi (1.6 M, 6.9 mL, 11.0 mmol) in Et2O (6.5 mL),
and DMF (2.12 mL, 27.3 mmol) in Et2O (6.5 mL). The reaction
was realized at -90 °C. After workup and drying, the crude product
(colorless oil) was was directly used for the deprotection of the
phenol function. 1H NMR (CDCl3): δ 0.62 ppm (t, 12H), 1.30 (s,
4
3J ) 17 Hz, J ) 1.5 Hz, 2H), 6.05-6.21 (m, 2H), 7.43 (d, J )
2.4 Hz, 2H), 7.66 (d, J ) 2.4 Hz, 2H). 13C NMR (63 MHz,
CDCl3): δ 8.0, 27.5, 31.3, 34.5, 60.4, 71.3, 73.4, 81.9, 117.3, 117.4,
126.7, 129.7, 133.6, 137.6, 147.2, 150.6. C40H60O5Br2 (778.3): calcd
C 61.54, H 7.75; found C 61.80, H 7.79. SM (FAB, MNBA): m/z
(%) ) 803 [M + Na+]+.
3,3′-[Oxybis(2,1-ethanediyloxy-3,3-pentanediyl)]bis[5-(1,1-
dimethylethyl)-2-(2-propen-1-yloxy)benzaldehyde] (24). Com-
1456 J. Org. Chem., Vol. 71, No. 4, 2006

Macrocyclic Catalysts for Asymmetric Epoxidation
18H), 1.90-2.10 (m, 8H), 3.45 (t, J ) 5.5 Hz, 4H), 3.74 (t, J )
Catalytic Epoxidation Procedures. With NaOCl as Oxidant.
A typical reaction mixture contained substrate (16 µL of 2,2′-
dimethylchromene, 0.1 mmol) and internal standart (23.6 mg of
1,4-dibromobenzene, 0.1 mmol) in 0.5 mL of CH2Cl2, 5 µmol of
the appropriate catalyst (0.5 mL of a 10 mM CH2Cl2 stock solution;
catalyst/substrate ratio ) 5%), and 4-phenylpyridine-N-oxide (4.3
mg, 25 µmol). After stirring at 0 °C for 10 min, 0.2 mmol NaOCl
(0.4 mL of a 0.5 M solution in 0.16 mL of a 0.05 M aqueous
Na2HPO4 solution, 2 equiv of oxidant with respect to the substrate)
was added. After vigorous stirring for 2 h, the reaction was diluted
with water (2 mL) and CH2Cl2 (2 mL). The layers were separated,
the organic phase dried over Na2SO4, concentrated to ≈1 mL and
analyzed by gas chromatography.
With Hydrogen Peroxide as Oxidant. The reaction mixture
was prepared according to the procedure described above. After
stirring at 0 °C for 10 min, 35% aqueous H2O2 (30 µL, 0.34 mmol,
3.4 equiv of oxidant with respect to the substrate) was added in
four portions during 40 min. After stirring for 2 h, the reaction
mixture was diluted with water (2 mL) and CH2Cl2 (2 mL). The
filtrate was worked up as previously described and analyzed by
chiral GC as described above.
3
4
5.5 Hz, 4H), 3.76 (s, 4H), 4.41 (dd, J ) 3.7 Hz, J ) 1.5 Hz),
5.29 (dd, 3J ) 9.1 Hz, 4J ) 1.2 Hz, 2H), 5.49 (dd, 3J ) 9.1 Hz, 3J
) 1.2 Hz, 2H), 5.99-6.12 (m, 2H), 7.73 (d, J ) 2.9 Hz, 2H) 7.96
(d, J ) 2.9 Hz, 2H) 10.26 (s, 2H).
3,3′-(1,1,12,12-Tetraethyl-2,5,8,11-tetraoxadodecane-1,12-diyl)-
bis[5-(1,1-dimethylethyl)-2-hydroxybenzaldehyde] (29). Com-
pound 29 was prepared as described for 6 starting from 28 (1.98 g
2.74 mmol) in MeOH (56 mL), Pd(PPH3)4 (158.2 mg, 0.137 mmol),
and K2CO3 (2.27 g, 16.44 mmol). The crude product was purified
by column chromatography using hexane/ethyl acetate (9/1) as the
1
eluent to give a colorless oil (1.43 g, 81%). H NMR (CDCl3): δ
0.64 ppm (t, 12H), 1.28 ppm (s, 18H), 1.88-2.12 (m, 8H), 3.50 (t,
J ) 4.9 Hz, 4H), 3.75 (t, J ) 4.9 Hz, 4H), 3.75 (s, 4H), 7.49 (d,
J ) 2.4 Hz, 2H), 7.66 (d, J ) 2.4 Hz, 2H), 10.10 (s, 2H), 10.80 (s,
2H). 13C NMR (63 MHz, CDCl3): δ 7.7, 26.9, 31.2, 34.1, 60.2,
70.6, 71.0, 83.4, 121.3, 126.4, 129.5, 133.7, 141.5, 157.5, 194.7.
C38H58O8 (642.9): calcd C 71.00, H 9.09; found C 70.79, H 9.28.
SM (ES) m/z (%) ) 665.85 [ M + Na+]+, 681.65 [ M + K+]+.
MnIII-Salen Complex 30. Complex 30 was synthesized as
described above for complex 7, starting from 29 (200 mg, 0.311
mmol) in 50 mL of EtOH, (S)-(-)-1,1′-binaphthyl-2,2′-diamine
(88.5 mg, 0.311 mmol) and Mn(OAc)2‚4H2O (114.5 mg, 0.467
mmol). The resulting solution was refluxed for 10 h. Yield: 120
mg, 40% as a dark brown microcrystalline solid. C58H68N2O6ClMn
(979.6): calcd C 71.12, H 7.00, N 2.86, Mn 5.61, Cl 3.62; found
C 71.13, H 7.01, N 3.11, Mn 5.82, Cl 3.70. SM (ES): m/z ) 975.85
[MnIIISalenCl + H+]+, 989.85 [MnIIISalen(EtOH) - Cl-]+. IR
(KBr, cm-1): 1610(CdN). UV-vis (CH2Cl2): λ (ꢀ) ) 233 nm
(89400 L mol-1 cm-1), 282 (49300), 327 (24400), 388 (15400).
Acknowledgment. We are grateful to the CNRS for financial
support.
1
Supporting Information Available: Copies of H NMR and
proton-decoupled 13C NMR spectra for compounds 6, 10, 15, 20,
and 25. This material is available free of charge via the Internet at
http://pubs.acs.org.
[R]20 ) 0.0588 (589 nm, 0.080 g/dm-3 in CH3OH, 10 cm path).
JO052113C
D
J. Org. Chem, Vol. 71, No. 4, 2006 1457