Titanium cis-1,2-diaminocyclohexane (cis-DACH) salalen catalysts for the asymmetric epoxidation of terminal non-conjugated olefins with hydrogen peroxide

Article abstract of DOI:10.1002/chem.201404639

Chiral Ti salalen complexes catalyze the asymmetric epoxidation of terminal non-conjugated olefins with hydrogen peroxide. Modular ligands based on cis-1,2-diaminocyclohexane (cis-DACH) were developed, giving high yields and enantiomeric excesses (ee, up to 96%) at catalyst loadings as low as 0.1-0.5mol%, and even under solvent-free conditions.

Full text of DOI:10.1002/chem.201404639

DOI: 10.1002/chem.201404639
Full Paper
&
Synthetic Methods
Titanium cis-1,2-Diaminocyclohexane (cis-DACH) Salalen Catalysts
for the Asymmetric Epoxidation of Terminal Non-Conjugated
Olefins with Hydrogen Peroxide
Qifang Wang,[a] Jçrg-M. Neudçrfl,[a, b] and Albrecht Berkessel*[a]
Abstract: Chiral Ti salalen complexes catalyze the asymmet-
ric epoxidation of terminal non-conjugated olefins with hy-
drogen peroxide. Modular ligands based on cis-1,2-diamino-
cyclohexane (cis-DACH) were developed, giving high yields
and enantiomeric excesses (ee, up to 96%) at catalyst load-
ings as low as 0.1–0.5mol%, and even under solvent-free
conditions.
Introduction
Method development for the catalytic synthesis of enantiomer-
ically pure epoxides continues to be one of the most exciting
fields of asymmetric catalysis. In 2005–2007, Katsuki and co-
workers reported that the bis-m-oxo titanium–trans-1,2-diami-
no-cyclohexane (DACH)-salalen catalyst 1 effected the highly
enantioselective epoxidation of various conjugated and non-
conjugated olefins with aqueous H2O2 (Figure 1).[1] Later on,
they disclosed that titanium–salan[2] catalysts are similarly
active and enantioselective, albeit for conjugated olefins only.
Aiming at a simplification of sal-
Figure 1. Katsuki’s Ti–salalen catalyst 1 and our simplified “in situ” Ti-salalen
catalyst 2.
alen catalyst 1, while retaining
activity and enantioselectivity,
we developed a short synthetic
route to trans-DACH-salalen
complexes 2.[3] Titanium cata-
lysts, such as 2, which can be
prepared in situ in a quite user-
friendly manner from ligand pre-
Scheme 1. Modular synthesis of cis-DACH-salalen ligands 5.
cursors and a titanium source,
are particularly well suited for
the highly efficient asymmetric epoxidation of conjugated ole-
fins. Unfortunately, the epoxide yields for non-conjugated ole-
fins were notoriously low.
we have reported a practical synthesis of cis-DACH-salalen li-
gands 5,[4] which is summarized briefly in Scheme 1. Enzymatic
desymmetrization of cis-DACH gave enantiopure monoalloc-
protected cis-DACH (3).[5] Reductive alkylation with a salicylic
aldehyde 4 introduces the “reduced half” of the salalen ligand.
The “non-reduced half” is attached by alloc deprotection and
condensation with a second salicylic aldehyde 4. Note that Boc
protection of 3, followed by alloc deprotection, provides
access to the enantiomeric salalen ligands ent-5.[4,5]
The corresponding Ti complexes showed quite high yields
and enantioselectivities in the epoxidation of non-conjugated
olefins with hydrogen peroxide as terminal oxidant. For exam-
ple, after in situ complexation of the cis-DACH-salalen ligand 6
(Figure 2) and Ti(OiPr)4 at room temperature, the epoxides of
1-octene and vinyl cyclohexane were obtained in 88% yield
with 94% ee, and 90% yield with 90% ee, respectively. As an
Our next step in catalyst development was the exchange of
the trans-DACH 1,2-diamine backbone for cis-DACH. Recently,
[a] Dr. Q. Wang, Dr. J.-M. Neudçrfl, Prof. Dr. A. Berkessel
University of Cologne, Department of Chemistry
Organic Chemistry, Greinstrasse 4, 50939 Cologne (Germany)
Fax: (+49)221-470-5102
E-mail: berkessel@uni-koeln.de
[b] Dr. J.-M. Neudçrfl
X-Ray crystallography
Supporting information for this article is available on the WWW under
1
http://dx.doi.org/10.1002/chem.201404639. It contains H and 13C NMR
spectra of the salalen ligands 8–21, HPLC and GC methods and chromato-
grams, and X-Ray crystallographic data.
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Figure 2. cis-DACH-salalen ligands 6 and 7.
outstanding feature, the cis-DACH-salalen ligand 6 gave 89%
isolated epoxide yield for vinyl cyclohexane at a catalyst load-
ing as low as 2 mol%.[4] For the cis-DACH-salalen ligand 7
(Figure 2), carrying phenyl substituents ortho to the phenolic
hydroxyl groups, the enantioselectivities of 1-octene and vinyl
cyclohexane epoxidation in 1,2-dichloroethane were slightly in-
ferior to the results of the cis-DACH-salalen ligand 6, but with
even higher yields.
The only drawback associated with the epoxidation of termi-
nal non-conjugated olefins with the Ti complexes of cis-DACH-
salalen ligands, such as 6, is the relatively long reaction time:
typically around 100 h. To solve this problem, we decided to
engage on ligand variation/optimization, encompassing both
“symmetric” substitution patterns (as in 6 and 7) and “non-
symmetric” ones, that is, ligands derived from two different sal-
icylic aldehydes. Additionally, we were interested in combining
the chiral binaphthyl salicylic aldehyde substructure, originally
used by Katsuki and co-workers (as in 1, Figure 1), with our cis-
DACH motif (as in 5, Scheme 1; or 6 and 7 in Figure 2). Herein,
we report the results of this approach. High epoxide yields and
enantiopurities were ultimately achieved at significantly short-
ened reaction times, at low catalyst loading, and even under
solvent-free epoxidation conditions.
Figure 3. cis-DACH salalen ligands 8–21.
Table 1), already after 72 h. For the cis-DACH-salalen ligands
10–13, carrying binaphthyl groups on both sides, poor activity
(12–36% epoxide yields after 100 h, entries 5–12, Table 1) was
observed, albeit at respectable enantioselectivities. Of this type
of ligand, the diastereomer 12 with homochiral binaphthyl
units (both sides aR) gave the highest ee (94%) for both olefins
(entries 9 and 10, Table 1). Interestingly, the trans-DACH iso-
mers of this type of ligand (10–13) are the ones originally dis-
covered by Katsuki and co-workers.[1]
With the “hybrid” ligand 14 (phenyl substitution on the
amine side, and a (aR)-binaphthyl substitution on the imine
side), the epoxidation of 1-octene (22) and vinyl cyclohexane
(23) was achieved in 87% yield/85% ee after 50 h, and 44%
yield/89% ee after 100 h, respectively (entries 13 and 14,
Table 1). Exchange of the phenyl substituent for cyclohexyl
(ligand 16) gave lower yields and enantioselectivities (en-
tries 17 and 18, Table 1). The diastereomeric ligands 15/17 with
a phenyl/cyclohexyl substituent on the amine side, and (aS)-bi-
naphthyl substitution on the imine side gave very low epoxide
yields (3–8%) and moderate enantioselectivities (66–89%, en-
tries 15, 16, and 19, 20, Table 1).
Results and Discussion
Ligand variations
The set of new salalen ligands synthesized and evaluated (8–
21) is depicted in Figure 3 (see the Experimental Section for
the details of their synthesis).
Catalyst screening
In contrast, binaphthyl substitution on the amine side, to-
gether with phenyl/cyclohexyl substitution on the imine side
(ligands 18–21) gave good epoxide yields and enantioselectivi-
ties (entries 21–28, Table 1). In this subset, the (aR)-binaphthyl/
phenyl ligand 19 showed best catalytic activity: the epoxida-
tion of 1-octene (22) and vinyl cyclohexane (23) gave, after
only 30 h, 87 and 82% yield (entries 23 and 24, Table 1). Com-
pared with the related ligand 12, the enantioselectivities were
somewhat lower (89 vs. 94% ee for 1-octene, 80 vs. 94% ee for
vinyl cyclohexane, entries 9 and 10 vs. 23 and 24, Table 1). Fi-
nally, the epoxidation of 1-octene (22) by using the ligand 21
with (aR)-binaphthyl substitution on the amine side, and a cy-
clohexyl substituent on the imine side, gave the best enantio-
1-Octene (22) and vinyl cyclohexane (23) were used as repre-
sentative non-conjugated terminal olefins, together with aque-
ous H2O2 as the oxidant to assess the ligand/catalyst efficiency.
The results are summarized in Table 1. We first examined the
“unsymmetrical” ligand 8 with a monophenyl substitution on
the amine side and a monocyclohexyl substitution on the
imine portion. For 1-octene (22) and vinyl cyclohexane (23),
the epoxides were obtained, after 100 h, in 33% yield with
86% ee (entry 1, Table 1) and 36% yield with 82% ee (entry 2,
Table 1), respectively. At identical catalyst loading (10 mol-%),
the “inverse” ligand 9 gave significantly better yields (85–86%)
and good enantioselectivities (82–91%, entries 3 and 4,
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ration of the substrate scope. The results are sum-
marized in Table 2. 1-Hexene (24), another terminal
non-conjugated olefin, was epoxidized in 82% yield
with 82% ee after 50 h with ligand 19, and in 83%
yield with 89% ee after 100 h with ligand 21 (en-
tries 1 and 2, Table 2). In the case of olefin 25, the
presence of the hydroxyl group did not significantly
affect the epoxidation (19: 61% yield/87% ee after
18 h; 21: 81% yield/91% ee after 40 h; entries 3 and
4, Table 2). A decrease of the epoxide concentration
with time indicated that in the case of ligand 19, the
product is not stable under the reaction conditions
(entry 3, Table 2). The benzoate 26 gave the epoxide
in 94% yield and with 85% ee after 30 h with ligand
19, and in 85% yield with 89% ee after 40 h with
ligand 21 (entries 5 and 6, Table 2). The benzyl ether
27 was epoxidized in 62% yield with 84% ee after
45 h with ligand 19, and in 88% yield with 89% ee
after 60 h with ligand 21 (entries 7 and 8, Table 2).
Table 2 additionally reflects the following features
of the cis-DACH-salalen epoxidation catalysts: 1) cis-
2-hexene (28) and trans-2-octene (29) were stereo-
specifically epoxidized to the corresponding cis-epox-
ide in 77–78% yield with 71–74% ee (entries 9,10),
and to trans-epoxide in 67–81% yield, but with poor
enantioselectivity (17–22%, entries 11 and 12); 2) the
trisubstituted olefins 30 and 31 were not efficiently
epoxidized by our catalytic system (entries 13–16).
Table 1. Positional scanning of the “left” and “right” halves of salalen ligands.
Entry[a] cis-Salalen
R
a* R’
a’* Olefin t [h] Yield[b] [%] ee[b] [%]
1
2
3
4
5
6
7
8
8
8
9
9
Ph
Ph
c-hexyl
c-hexyl
–
–
–
–
–
–
–
–
Ph
Ph
Ph
Ph
c-hexyl
c-hexyl
c-hexyl
c-hexyl
–
–
–
–
–
–
–
–
–
–
–
–
(S)
(S)
(S)
(S)
(R)
(R)
(R)
(R)
–
–
–
–
–
–
–
–
c-hexyl
c-hexyl
Ph
Ph
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
22
23
22
23
100 33
100 36
72 85
72 86
100 11
86
82
91
82
85
82
63
70
94
94
90
83
85
89
77
66
79
83
89
84
82
68
89
80
92
87
94
89
10
10
11
11
12
12
13
13
14
14
15
15
16
16
17
17
18
18
19
19
20
20
21
21
(S) 22
(S) 23
(R) 22
(R) 23
(R) 22
(R) 23
(S) 22
(S) 23
(R) 22
(R) 23
(S) 22
(S) 23
(R) 22
(R) 23
(S) 22
(S) 23
–
–
–
–
–
–
–
–
100
6
100 36
100 12
100 35
100 22
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
100
100
8
5
50 87
100 44
100
100
7
3
100 69
100 26
–
–
–
100
100
8
4
(S) Ph
(S) Ph
(R) Ph
(R) Ph
(S) c-hexyl
(S) c-hexyl
(R) c-hexyl
(R) c-hexyl
22
23
22
23
22
23
22
23
100 84
100 85
30 87
30 82
72 87
72 90
50 80
50 90
Effect of substrate concentration on epoxidation
efficiency
[a] Reactions were performed at room temperature with a molar ratio of substrate/
ligand/Ti(OiPr)4/30% H2O2 (aq.)=1:0.1:0.1:1.5, [substrate]=0.2 molLꢁ1; [b] Determined
by chiral GC.
We further examined the efficiency of the ligands 19
and 21 for the epoxidation of 1-octene (22) under
different reaction conditions (Table 3). We observed
that the epoxide yield significantly increased with
selectivity (94% ee, entry 27, Table 1) of the whole subset, and
80% epoxide yield after 50 h reaction time. The ligand 21 ef-
fected the epoxidation of vinyl cyclohexane (23) in 90% yield
after 50 h, with 89% ee (entry 28, Table 1).
substrate concentration. For example, upon using 1 mol% of
ligand 21/Ti(OiPr)4 at an olefin concentration of 0.2 molLꢁ1,
only 16% epoxide yield resulted after 100 h reaction time, with
92% ee (entry 1, Table 3). However, at an olefin concentration
of 2 molLꢁ1, an epoxide yield of 84% was obtained, with 95%
ee, under otherwise identical conditions (entry 2, Table 3). Most
remarkably, the epoxidation of 1-octene (22) could be per-
formed even under solvent-free conditions (i.e., neat olefin):
after 100 h, and in the presence of as little as 0.5 mol% of the
ligand 21/Ti(OiPr)4, the product epoxide was obtained in 72%
yield and with 96% ee (entry 3, Table 3).
Data from Table 1 show that the strongest “mismatch effect”
on catalytic activity occurs in the cases of the ligands 10, 13,
15, and 17 with a (aS)-binaphthyl substituent on the imine
side. Very low epoxide yields (ꢀ11%, entries 5, 6, 11, 12, 15,
16, 19, and 20, Table 1) were obtained. No such “mismatch
effect” was observed when the (aS)-binaphthyl substituent is
attached to the amine side, as was evidenced by the cis-DACH-
salalen ligands 18 and 20 (entries 21, 22 and 25, 26, Table 1).
Overall, ligand 21 emerged from this study as the optimal one.
Ligand 19 proved to be the best in terms of epoxidation rate,
but the enantioselectivity values were slightly inferior to those
obtained with ligand 21.
The related ligand 19 exhibited a different performance pro-
file. Under identical solvent-free conditions, 1-octene epoxide
was obtained only in 6% yield (entry 4, Table 3). On the other
hand, the epoxidation of 1-octene (22) was achieved in 78%
yield with 92% ee (entry 5, Table 3) after 100 h, at a catalyst
loading as low as 0.1 mol%, and on a gram scale, by using
a small amount of 1,2-dichloroethane as solvent. Addition of
diglyme (11 mol%) improved the epoxide yield further from 78
to 89%, with 92% ee (entry 5 vs. 6, Table 3). After chromato-
graphic purification, the epoxide was isolated in 82% yield
Substrate scope
Of the ligands examined, both 19 (highest catalytic activity)
and 21 (highest enantioselectivity) were chosen for the explo-
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with 92% ee, as shown in entry 6, Table 3 (in paren-
theses). To the best of our knowledge, this is the
lowest catalyst loading reported to date in Ti-cata-
lyzed asymmetric epoxidation, giving good epoxide
yield, and high enantioselectivity.
Table 2. Asymmetric epoxidation of non-conjugated olefins catalyzed by Ti com-
plexes of the cis-DACH-salalen ligands 19 and 21.
X-Ray characterization of the Ti complexes
The Ti complex 32, derived from the cis-DACH-salalen
ligand 12, was crystallized and characterized by X-ray
diffraction (Figure 4). Note that ligand 12 gave high
ee (94%), but is of low catalytic activity (Table 1, en-
tries 9 and 10). Similar to the complex derived from
the cis-DACH-salalen ligand 7,[4] a doubly m-oxo-
bridged dimer 32 was formed. The ligands 12 are
both coordinated to the Ti centers in a cis-b-mode
with D chirality at the Ti atoms. The complex 32
Entry[a]
cis-Salalen
a*
R’
Olefin
t [h]
Yield[b] [%]
ee[b] [%]
adopts
a homochiral (aR,1R,2S,D; aR,1R,2S,D)-anti
1
2
3
4
5
6
7
8
19
21
19
21
19
21
19
21
19
21
19
21
19
21
19
21
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
Ph
c-hexyl
Ph
c-hexyl
Ph
c-hexyl
Ph
c-hexyl
Ph
c-hexyl
Ph
c-hexyl
Ph
c-hexyl
Ph
24
24
25
25
26
26
27
27
28
28
29
29
30
30
31
31
50
100
18
40
30
50
45
60
24
82
83
61[c]
81
94
85
62
88
77
78
81
67
trace[c]
trace[c]
24[c]
10[c]
82
89
87
91
85
89
84
89
74
71
17
22
–
configuration. Note that in the case of Katsuki’s trans-
DACH-derived complex 1, the dimer was found to
adopt the same homochiral (aR,1S,2S,D; aR,1S,2S,D)-
anti configuration.[1]
We could also isolate and characterize (X-ray) the
Ti complex 33 (Figure 4), derived from the cis-DACH-
salalen ligand 18. The latter ligand gave quite satis-
factory catalytic activity, but lower enantioselectivity
than 12 (Table 1, entries 21 and 22). Note that the bi-
naphthyl moiety present in 33/18 has the opposite
sense of chirality (aS) compared with the ones pres-
ent in 32/12 (aR). Nevertheless, complex 33 is again
formed as a homochiral anti-dimer, with D-chirality at
both Ti centers, the latter being coordinated by the
ligand 18 in cis-b-mode. Therefore, it appears that
the configuration of the DACH moiety, in particular
that of the carbon atom neighboring the amine ni-
trogen atom, ultimately dictates the configuration at
the titanium atom.
9
10
11
12
13
14
15
16
40
40
100
100
100
100
100
–
66
82
c-hexyl
[a] Reactions were performed at room temperature with a molar ratio of substrate/
ligand/Ti(OiPr)4/30% H2O2 (aq.)=1:0.1:0.1:1.5, [substrate]=0.2 molLꢁ1; [b] Determined
by chiral GC. [c] Epoxide was not stable under the reaction conditions.
Table 3. Asymmetric epoxidation of 1-octene (22) catalyzed by Ti complexes of the li-
gands 19 and 21.
Conclusion
We have synthesized a series of new cis-DACH-de-
rived salalen ligands and evaluated them in the tita-
nium-catalyzed asymmetric epoxidation of non-con-
jugated terminal olefins with aqueous hydrogen per-
oxide. The modular synthesis allowed the reduced
and non-reduced halves of the ligand to be varied in-
dependently. This empirical study identified the sala-
lens 19 and 21 as the ligands that optimally combine
high activity and enantioselectivity. Most remarkably,
the epoxidation can be performed under solvent-free
conditions, by using as little as 0.5 mol% catalyst
loading. By using 1,2-dichloroethane as a solvent, the
catalyst loading could be further reduced to even
0.1 mol%. To date, the mechanism of this Ti-salalen-
catalyzed olefin epoxidation with hydrogen peroxide
remains largely unexplored. Consequently, the mech-
anistic features underlying for example, the matched/
Entry[a] cis-Salalen
R
Catalyst
Conc. of
Yield[b] [%] ee[b] [%]
loading [mol%] olefin [molLꢁ1
]
1
2
3
4
5
6[c]
21
21
21
19
19
19
c-hexyl
c-hexyl
c-hexyl 0.5
Ph
Ph
Ph
1
1
0.2
2
neat
neat
20
16
92
84
95
72
96
0.5
0.1
0.1
6
78
89 (82[d]
n.d.
92
92 (92[d]
20
)
)
[a] Reactions were performed at room temperature with 30% H2O2 (aq., 1.5 equiv).
[b] Determined by chiral GC. [c] Addition of 11 mol% of diglyme. [d] Yield and ee of
isolated product, after column chromatography, are shown in parentheses.
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Materials
Commercial reagents were purchased from Sigma Aldrich, Fluka, or
Acros, and used as received. The preparation of allyl (1R,2S)-2-ami-
nocyclohexyl-carbamate 3 was carried out according to a protocol
previously described by us.[5] 2-Hydroxybiphenyl-3-carbaldehyde,[4,7]
3-cyclohexyl-2-hydroxybenzaldehyde,[4] and (S)- or (R)-2-hydroxy-2’-
phenyl-1,1’-binaphthyl-3-carbaldehyde[8] were synthesized follow-
ing literature procedures.
General procedure for the asymmetric epoxidation of olefins
using in situ-prepared Ti-salalen complexes
The salalen ligand (10 mmol, 0.10 equiv) was added to a solution of
Ti(OiPr)4 (2.8 mg, 3.0 mL, 10 mmol, 0.10 equiv) in dry CH2Cl2 (500 mL).
The mixture was stirred for 1 h at RT under argon. All volatiles
were then evaporated at RT at 10ꢁ2 mbar. The olefin (0.10 mmol,
1.00 equiv), C2H4Cl2 (500 mL), 30% aqueous hydrogen peroxide
(15.3 mL, 0.15 mmol, 1.50 equiv), and internal standard were added,
and the reaction mixture was stirred at RT. If necessary, additional
portions of hydrogen peroxide were added (peroxide test by using
KI/starch). An aliquot (50 mL) was withdrawn and diluted with
CH2Cl2 (2 mL), and filtered through MgSO4. The epoxide yield and
the ratio of enantiomers were analyzed by GC based on calibra-
tions versus internal standard.
Asymmetric epoxidation of 1-octene on preparative scale
The salalen ligand 19 (6.5 mg, 10 mmol, 0.001 equiv) was added to
a solution of Ti(OiPr)4 (2.8 mg, 3.0 mL, 10 mmol, 0.001 equiv) in dry
CH2Cl2 (500 mL). The mixture was stirred for 1 h at RT under argon.
All volatiles were then evaporated at RT and at 10ꢁ2 mbar. 1-
Octene (1.122 g, 1.57 mL, 10 mmol, 1.00 equiv), 30% aqueous hy-
drogen peroxide (1.5 mL, 15 mmol, 1.50 equiv), diglyme (156 mL,
1.1 mmol, 0.11 equiv), and C2H4Cl2 (0.5 mL) were added, and the re-
action mixture was stirred at RT for 100 h. If necessary, additional
portions of hydrogen peroxide were added (peroxide test by using
KI/starch). The organic phase was collected carefully by using a pip-
ette. The aqueous phase was extracted with n-pentane (3ꢂ1 mL).
The combined organic phases were dried over MgSO4. The solvent
was evaporated, and the crude product was purified by column
chromatography, giving the pure product as a colorless liquid
Figure 4. X-ray crystal structures of bis-m-oxo-titanium complexes 32 and 33
derived from the cis-DACH-salalen ligands 12 and 18, respectively.
mismatched effects observed, cannot be addressed in a reliable
manner at the current stage. Further studies in our laboratory
aim at the elucidation of the mechanistic details of this Ti-sala-
len-catalyzed epoxidation of terminal olefin.
Experimental Section
1
(1.046 g, 82%, 92% ee). H NMR (300 MHz, CDCl3): d=2.95-2.89 (m,
General
1H), 2.76 (t, J=4.5 Hz, 1H), 2.49-2.46 (m, 1H), 1.58-1.31 (m, 10H),
0.90 ppm (t, J=6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=52.5,
47.2, 32.6, 31.8, 29.2, 26.0, 22.6, 14.1 ppm; IR (ATR): v˜ =3044 (vw),
2957 (m), 2926 (s), 2857 (m), 1481 (w), 1460 (w), 1410 (w), 1379
(w), 1258 (w), 1194 (vw), 1130 (w), 1074 (vw), 991 (vw), 918 (m),
887 (w), 833 (s), 783 (w), 758 (w), 737 (w), 725 cmꢁ1 (w); GCMS:
tR =6.63 min, m/z=128 [M+], 81, 71, 55 (HP-5 MS 5% phenyl
methyl siloxane; 30 mꢂ250 mmꢂ0.25 mm nominal; 508C !2508C
!2808C isothermal, 10 min, ramp=208Cminꢁ1).
NMR (1H and 13C NMR) spectra were recorded on a Bruker AV300 or
Bruker DPX300 instruments. Chemical shifts for protons and
carbon atoms are reported in parts per million (ppm) downfield
from tetramethylsilane and are referenced to residual proton and
carbon resonances of the solvent. IR spectra were recorded on
a Shimadzu IRAffinity-1 spectrometer with attenuated total reflec-
tance (ATR) technique. Data are reported as: wave number of ab-
sorption (cmꢁ1), intensity of absorption (s=strong, m=medium,
w=weak). GC analyses were performed with an Agilent Technolo-
gies 6890N Network GC System and Agilent HP 6890 Series GC
system by using N2 as carrier gas. HRMS data (Du=0.002 u) and
MS (ESI) analyses were recorded on a Finnigan MAT 900S instru-
ment. Elemental analyses were performed with an Elementar vario
EL elemental analyzer. A Nonius Kappa CCD diffractometer with
Denzo as measurement and analysis program package was used
for X-ray analyses. The structures were solved by using the pro-
gram SHELXS97, and the refinements were done using the pro-
gram SHELXL97.[9] The melting points were measured in open glass
capillaries by using a Bꢁchi 535 apparatus, and the presented
values are uncorrected.
Modular synthesis of cis-DACH-salalen ligands
Allyl (1R,2S)-2-aminocyclohexylcarbamate 3 (516 mg, 2.60 mmol,
1.00 equiv) was dissolved in a mixture of methanol and ethanol
(20 mL, 1:1). Aldehyde (2.60 mmol, 1.00 equiv) was added, and the
reaction mixture was stirred for 18 h at RT. NaBH4 (3.9 mmol,
1.50 equiv) was then added in small portion at 08C, and the reac-
tion mixture was stirred for 3 h at RT. The reaction was quenched
by adding water (15 mL), and the mixture was extracted with
EtOAc (3ꢂ25 mL). The combined organic layers were washed with
brine and dried over Na2SO4. After filtration, the solvent was
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evaporated under reduced pressure, and the crude product was
purified by column chromatography on silica, giving the reductive
alkylation product in 93–99% yield.
128.7, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.7, 127.4, 127.3,
127.0, 126.7, 126.6, 126.5, 126.3, 126.2, 126.0, 125.7, 125.6, 125.1,
125.0, 124.1, 123.3, 122.9, 120.2, 120.1, 119.7, 67.5, 56.1, 49.2, 32.8,
27.8, 24.9, 20.4 ppm; IR (ATR): v˜ =3053 (w), 2930 (w), 2857 (w),
1628 (m), 1508 (w), 1493 (w), 1458 (w), 1439 (m), 1397 (w), 1342
(w), 1321 (w), 1288 (w), 1252 (w), 1217 (w), 1184 (w), 1148 (w), 1113
(w), 1088 (w), 1072 (w), 1045 (w), 1028 (w), 983 (w), 941 (m), 920
(w), 893 (w), 858 (w), 820 (m), 791 (w), 760 (s), 746 (s), 698 (s),
667 cmꢁ1 (w); HRMS (ESI): exact mass calcd for C60H48N2O2: m/z=
829.37886 ([M+H]+), 851.36080 ([M+Na]+), found: m/z=
829.37932 ([M+H]+), 851.36084 ([M+Na]+); elemental analysis
calcd (%) for C60H48N2O2 (829.04): C 86.93, H 5.84, N 3.38; found: C
86.56, H 5.92, N 3.20.
cis-DACH-salalen 11: 90%, m.p. 175–1778C; 1H NMR (300 MHz,
CDCl3): d=12.81 (s, 1H, OH), 11.44 (br, 1H, OH), 8.58 (s, 1H), 8.09-
8.05 (m, 2H), 8.00 (d, J=8.1 Hz, 2H), 7.78-7.67 (m, 5H), 7.52-7.30
(m, 8H), 7.27-6.95 (m, 15H), 4.18 (s, 2H), 3.71 (s, 1H), 2.67 (s, 1H),
1.83–1.33 ppm (m, 9H); 13C NMR (75 MHz, CDCl3): d=165.5, 154.5,
154.1, 142.3, 142.2, 140.7, 140.2, 135.6, 134.1, 133.6, 133.0, 132.8,
131.9, 131.1, 128.7, 128.3, 128.3, 128.1, 128.0, 127.6, 127.4, 127.2,
127.1, 127.0, 126.6, 126.6, 126.5, 126.2, 126.2, 126.0, 125.7, 125.6,
125.1, 125.0, 124.2, 123.3, 122.8, 120.2, 120.1, 119.6, 67.7, 56.4, 49.4,
33.5, 27.6, 25.1, 20.2 ppm; IR (ATR): v˜ =3051 (w), 2932 (w), 2859
(w), 1628 (m), 1508 (w), 1495 (w), 1460 (w), 1439 (m), 1387 (w),
1346 (w), 1314 (w), 1288 (w), 1254 (w), 1217 (w), 1186 (w), 1148
(w), 1117 (w), 1088 (w), 1072 (w), 1047 (w), 1030 (w), 982 (w), 974
(w), 941 (m), 893 (w), 858 (w), 820 (m), 812 (m), 789 (w), 762 (s),
752 (s), 698 (s), 667 cmꢁ1 (w); HRMS (ESI): exact mass calcd for
C60H48N2O2: m/z=829.37886 ([M+H]+), 851.36080 ([M+Na]+),
found: m/z=829.37931 ([M+H]+), 851.36088 ([M+Na]+); elemen-
tal analysis calcd (%) for C60H48N2O2 (829.04): C 86.93, H 5.84, N
3.38; found: C 86.43, H 5.94, N 3.44.
cis-DACH-salalen 12: 87%, m.p. 177–1798C; 1H NMR (300 MHz,
CDCl3): d=12.82 (s, 1H, OH), 11.57 (br, 1H, OH), 8.54 (s, 1H), 8.09
(d, J=8.4 Hz, 2H), 8.01 (d, J=8.1 Hz, 2H), 7.81-7.71 (m, 5H), 7.53-
7.29 (m, 10H), 7.26-7.03 (m, 13H), 4.19 (q, J=14.1 Hz, 2H), 3.38 (s,
1H), 2.53 (d, J=7.5 Hz, 1H), 2.01-1.97 (m, 1H), 1.84-1.26 ppm (m,
8H); 13C NMR (75 MHz, CDCl3): d=165.4, 154.5, 154.0, 142.5, 142.2,
140.6, 139.9, 135.6, 134.4, 133.6, 133.1, 133.0, 132.8, 131.9, 131.2,
128.9, 128.7, 128.3, 128.2, 128.1, 127.8, 127.6, 127.5, 127.2, 127.1,
126.9, 126.7, 126.6, 126.4, 126.3, 126.3, 126.1, 125.7, 125.7, 125.0,
124.2, 123.2, 122.8, 120.2, 120.0, 119.5, 69.0, 55.9, 49.2, 33.5, 26.8,
24.9, 20.4 ppm; IR (ATR): v˜ =3055 (w), 2930 (w), 2857 (w), 1628 (m),
1508 (w), 1495 (w), 1458 (w), 1439 (m), 1387 (w), 1352 (w), 1342
(w), 1321 (w), 1288 (w), 1252 (w), 1217 (w), 1184 (w), 1148 (w), 1113
(w), 1088 (w), 1072 (w), 1047 (w), 1028 (w), 982 (w), 941 (m), 894
(w), 856 (w), 821 (m), 791 (w), 760 (s), 748 (s), 698 (s), 669 cmꢁ1 (w);
HRMS (ESI): exact mass calcd for C60H48N2O2: m/z=829.37886 ([M+
H]+), 851.36080 ([M+Na]+), found: m/z=829.37863 ([M+H]+),
851.36027 ([M+Na]+); elemental analysis calcd (%) for C60H48N2O2
(829.04): C 86.93, H 5.84, N 3.38; found: C 86.58, H 5.92, N 3.49.
cis-DACH-salalen 13: 93%, m.p. 177–1798C; 1H NMR (300 MHz,
CDCl3): d=12.85 (s, 1H, OH), 11.44 (br, 1H, OH), 8.46 (s, 1H), 8.10–
7.99 (m, 4H), 7.83–7.69 (m, 5H), 7.58–7.42 (m, 4H), 7.36–7.30 (m,
5H), 7.27–7.01 (m, 11H), 6.89 (t, J=7.5 Hz, 2H), 6.72 (t, J=7.5 Hz,
1H), 4.21 (q, J=13.8 Hz, 2H), 3.32 (s, 1H), 2.54 (s, 1H), 2.08–2.05
(m, 1H), 1.82–1.26 ppm (m, 8H); 13C NMR (75 MHz, CDCl3): d=
165.1, 154.3, 153.9, 142.5, 142.4, 140.6, 140.0, 135.8, 134.3, 133.7,
133.1, 133.0, 132.8, 131.8, 131.3, 128.9, 128.8, 128.4, 128.3, 128.2,
128.1, 128.1, 127.8, 127.7, 127.5, 127.3, 126.9, 126.9, 126.7, 126.6,
126.4, 126.4, 126.3, 126.1, 126.0, 125.7, 125.7, 125.1, 125.0, 124.2,
123.2, 122.9, 120.1, 120.0, 119.7, 69.2, 55.8, 49.4, 33.0, 27.0, 24.9,
20.4 ppm; IR (ATR): v˜ =3053 (w), 2930 (w), 2855 (w), 1628 (m), 1508
Palladium acetate (22.3 mg, 0.10 mmol, 0.05 equiv), triphenylphos-
phine (68 mg, 0.30 mmol, 0.15 equiv) and 1,3-dimethyl barbituric
acid (932 mg, 5.97 mmol, 3.00 equiv) were dissolved in anhydrous
CH2Cl2 (10 mL) under argon atmosphere. To this solution was
added slowly a solution of the reductive alkylation product
(1.99 mmol, 1.00 equiv) in anhydrous CH2Cl2 (10 mL). The reaction
mixture was stirred for 24 h at RT under argon. The solution was
washed with 2m sodium hydroxide solution (25 mL). The phases
were separated, and the aqueous phase was extracted with CH2Cl2
(3ꢂ15 mL). The combined organic phases were washed with brine
and dried over Na2SO4. After filtration, the solvent was evaporated
under reduced pressure, and the crude product was purified by
column chromatography on silica giving the deprotection product
in 52–86% yield. This deprotection product (1.00 equiv) was dis-
solved in EtOH. Aldehyde (1.00 equiv) was added to this solution.
The resulting mixture was stirred for 18 h at RT. The salalen ligand
was obtained as a yellow precipitate, which was filtered off and
dried under high vacuum at 608C.
cis-DACH-salalen 8: quant., m.p. 83–848C; 1H NMR (300 MHz,
CDCl3): d=13.54 (s, 1H, OH), 8.46 (s, 1H), 7.58 (d, J=7.5 Hz, 2H),
7.41 (t, J=7.5 Hz, 2H), 7.33-7.24 (m, 3H), 7.14-7.11 (m, 1H), 6.97 (d,
J=6.3 Hz, 1H), 6.90-6.81 (m, 2H), 4.04 (q, J=14.1 Hz, 2H), 3.69 (s,
1H), 3.08-3.00 (m, 1H), 2.86–2.80 (m, 1H), 2.02–1.24 ppm (m, 19H;
one of the two OH protons was not detected); 13C NMR (75 MHz,
CDCl3): d=165.9, 158.4, 155.5, 138.5, 135.6, 130.0, 129.8, 129.4,
129.2, 129.1, 128.1, 127.8, 126.8, 122.6, 119.0, 118.6, 118.2, 67.7,
56.9, 49.3, 36.3, 33.2, 33.1, 27.6, 27.0, 26.4, 24.9, 20.7 ppm; IR (ATR):
v˜ =2924 (m), 2851 (w), 1624 (m), 1591(w), 1499 (w), 1460 (m), 1445
(m), 1429 (m), 1366 (w), 1327 (w), 1298 (w), 1258 (m), 1244 (w),
1219 (w), 1198 (w), 1134 (w), 1103 (w), 1088 (w), 1072 (w), 1051 (w),
1028 (w), 980 (w), 955 (w), 916 (w), 887 (w), 860 (w), 827 (m), 791
(w), 752 (s), 698 (s), 675 cmꢁ1 (w); HRMS (ESI): exact mass calcd for
C32H38N2O2: m/z=483.30061 ([M+H]+); found: m/z=483.29995
([M+H]+); elemental analysis calcd (%) for C32H38N2O2 (482.66): C
79.63, H 7.94, N 5.80; found: C 79.35, H 7.93, N 5.72.
cis-DACH-salalen 9: quant., m.p. 84–858C; 1H NMR (300 MHz,
CDCl3): d=13.81 (s, 1H, OH), 8.55 (s, 1H), 7.63 (d, J=7.5 Hz, 2H),
7.47–7.30 (m, 5H), 7.09 (dd, J=7.5 Hz, 1.2 Hz, 1H), 6.99 (t, J=
7.5 Hz, 1H), 6.81–6.79 (m, 1H), 6.73 (t, J=7.5 Hz, 1H), 3.96 (q, J=
13.8 Hz, 2H), 3.73 (d, J=1.8 Hz, 1H), 2.97–2.89 (m, 1H), 2.83-2.77
(m, 1H), 1.98–1.22 ppm (m, 19H; one of the two OH protons was
not detected); 13C NMR (75 MHz, CDCl3): d=165.6, 158.4, 155.6,
137.7, 135.0, 133.6, 131.1, 129.9, 129.4, 128.2, 127.3, 125.9, 125.8,
121.6, 119.0, 118.8, 118.7, 67.8, 57.0, 49.4, 36.6, 33.2, 27.6, 27.1, 26.5,
24.9, 20.6 ppm; IR (ATR): v˜ =2924 (m), 2851 (w), 1624 (m), 1497 (w),
1450 (m), 1433 (m), 1368 (w), 1290 (w), 1281 (w), 1240 (m), 1207
(w), 1177 (w), 1136 (w), 1099 (w), 1072 (m), 1057 (w), 1030 (w), 980
(w), 897 (w), 856 (w), 833 (m), 797 (w), 781 (w), 756 (s), 746 (s), 698
(s), 675 cmꢁ1 (w); HRMS (ESI): exact mass calcd for C32H38N2O2: m/
z=483.30061 ([M+H]+), 505.28255 ([M+Na]+), found: m/z=
483.30035 ([M+H]+), 505.2825 ([M+Na]+); elemental analysis
calcd. (%) for C32H38N2O2 (482.66): C 79.63, H 7.94, N 5.80; found: C
79.33, H 7.95, N 5.71.
cis-DACH-salalen 10: 93%, m.p. 176–1788C; 1H NMR (300 MHz,
CDCl3): d=12.86 (s, 1H, OH), 11.40 (br, 1H, OH), 8.55 (s, 1H), 8.08
(d, J=8.4 Hz, 2H), 8.01 (d, J=8.1 Hz, 2H), 7.79–7.67 (m, 5H), 7.53–
7.30 (m, 10H), 7.26–7.07 (m, 8H), 6.92–6.76 (m, 5H), 4.15 (s, 2H),
3.66 (s, 1H), 2.63 (s, 1H), 1.81–1.32 ppm (m, 9H); 13C NMR (75 MHz,
CDCl3): d=165.1, 154.4, 154.2, 142.4, 142.3, 140.7, 140.2, 135.8,
134.1, 133.6, 133.1, 133.1, 133.0, 132.8, 131.8, 131.2, 128.9, 128.8,
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(w), 1495 (w), 1458 (w), 1439 (m), 1389 (w), 1323 (w), 1288 (w),
1254 (w), 1215 (w), 1184 (w), 1148 (w), 1113 (w), 1090 (w), 1072 (w),
1028 (w), 982 (w), 941 (m), 893 (w), 858 (w), 822 (m), 791 (w), 762
(s), 746 (s), 698 (s), 665 cmꢁ1 (w); HRMS (ESI): exact mass calcd for
C60H48N2O2: m/z=829.37886 ([M+H]+), 851.36080 ([M+Na]+),
found: m/z=829.37864 ([M+H]+), 851.36034 ([M+Na]+); elemen-
tal analysis calcd (%) for C60H48N2O2 (829.04): C 86.93, H 5.84, N
3.38; found: C 86.43, H 5.93, N 3.33.
(m), 762 (m), 746 (s), 698 (m), 665 cmꢁ1 (w); HRMS (ESI): exact mass
calcd for C46H46N2O2: m/z=659.36321 ([M+H]+), found: m/z=
659.36321 ([M+H]+); elemental analysis calcd (%) for C46H46N2O2
(658.87): C 83.85, H 7.04, N 4.25; found: C 83.40, H 7.11, N 4.24.
cis-DACH-salalen 17: 75%, m.p. 131–1328C; 1H NMR (300 MHz,
CDCl3): d=12.80 (s, 1H, OH), 11.22 (br, 1H, OH), 8.58 (s, 1H), 8.03
(d, J=8.7 Hz, 1H), 7.96 (d, J=8.1 Hz, 1H), 7.85-7.79 (m, 2H), 7.66
(d, J=8.4 Hz, 1H), 7.46 (t, J=6.9 Hz, 1H), 7.41–7.38 (m, 1H), 7.31–
7.08 (m, 7H), 6.87–6.69 (m, 5H), 3.93 (q, J=13.8 Hz, 2H), 3.67 (s,
1H), 3.00–2.93 (m, 1H), 2.76–2.73 (m, 1H), 1.89–1.22 ppm (m, 19H);
13C NMR (75 MHz, CDCl3): d=165.1, 155.6, 154.4, 142.2, 140.7,
135.8, 135.0, 133.5, 133.0, 132.8, 131.2, 128.8, 128.4, 128.3, 128.2,
128.1, 126.9, 126.7, 126.4, 126.2, 126.0, 125.8, 125.7, 125.2, 123.3,
121.7, 120.2, 120.0, 118.8, 67.9, 56.9, 49.4, 36.6, 33.3, 33.2, 32.8,
27.8, 27.1, 26.5, 24.8, 20.5 ppm; IR (ATR): v˜ =3053 (vw), 2924 (w),
2851 (w), 1630 (m), 1593 (w), 1508 (w), 1495 (w), 1449 (m), 1400
(w), 1387 (w), 1346 (w), 1327 (w), 1290 (w), 1260 (w), 1240 (w),
1207 (w), 1184 (w), 1140 (w), 1119 (w), 1082 (w), 1072 (w), 1028 (w),
984 (w), 941 (w), 920 (w), 889 (w), 860 (w), 822 (m), 793 (w), 762
(m), 746 (s), 700 (m), 665 cmꢁ1 (w); HRMS (ESI): exact mass calcd
for C46H46N2O2: m/z=659.36321 ([M+H]+), found: m/z=659.36306
([M+H]+); elemental analysis calcd (%) for C46H46N2O2 (658.87): C
83.85, H 7.04, N 4.25; found: C 83.64, H 7.07, N 4.24.
cis-DACH-salalen 18: 76%, m.p. 141–1428C; 1H NMR (300 MHz,
CDCl3): d=13.85 (s, 1H, OH), 11.42 (br, 1H, OH), 8.52 (s, 1H), 8.05
(d, J=8.1 Hz, 1H), 8.00 (d, J=8.1 Hz, 1H), 7.71-7.67 (m, 4H), 7.53–
7.30 (m, 9H), 7.25–6.95 (m, 9H), 4.19 (s, 2H), 3.73 (s, 1H), 2.67 (s,
1H), 1.94–1.35 ppm (m, 9H); 13C NMR (75 MHz, CDCl3): d=165.7,
158.4, 154.1, 142.3, 140.2, 137.7, 134.1, 133.7, 133.1, 133.0, 131.9,
131.2, 129.9, 129.4, 128.7, 128.3, 128.3, 128.1, 128.0, 127.6, 127.4,
127.3, 127.2, 126.6, 126.3, 126.2, 126.0, 125.6, 125.0, 124.0, 122.8,
119.6, 118.9, 67.4, 56.3, 49.3, 33.4, 27.7, 25.2, 20.4 ppm; IR (ATR): v˜ =
3053 (w), 2930 (w), 2857 (w), 1624 (m), 1508 (w), 1493 (w), 1433
(m), 1379 (w), 1354 (w), 1341 (w), 1319 (w), 1287 (w), 1252 (w),
1184 (w), 1138 (w), 1111 (w), 1101 (w), 1070 (w), 1028 (w), 982 (w),
978 (w), 939 (w), 893 (w), 880 (w), 854 (w), 822 (m), 799 (w), 758 (s),
748 (s), 725 (w), 698 (s), 675 cmꢁ1 (w); HRMS (ESI): exact mass calcd
for C46H40N2O2: m/z=653.31626 ([M+H]+), 675.29820 ([M+Na]+),
found: m/z=653.31583 ([M+H]+), 675.29769 ([M+Na]+); elemen-
tal analysis calcd (%) for C46H40N2O2 (652.82): C 84.63, H 6.18, N
4.29; found: C 84.46, H 6.17, N 4.22.
cis-DACH-salalen 19: 54%, m.p. 142–1438C; 1H NMR (300 MHz,
CDCl3): d=13.85 (s, 1H, OH), 11.48 (br, 1H, OH), 8.44 (s, 1H), 8.07
(d, J=8.7 Hz, 1H), 7.99 (d, J=8.1 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H),
7.66 (d, J=7.2 Hz, 2H), 7.54–7.35 (m, 10H), 7.27–6.97 (m, 8H), 4.20
(q, J=14.1 Hz, 2H), 3.38 (s, 1H), 2.52 (s, 1H), 2.07–2.03 (m, 1H),
1.90–1.27 ppm (m, 8H); 13C NMR (75 MHz, CDCl3): d=165.6, 158.4,
154.0, 142.5, 139.9, 137.7, 134.4, 133.6, 133.1, 133.0, 131.9, 131.2,
129.9, 129.4, 128.9, 128.3, 128.3, 128.1), 127.8, 127.7, 127.5, 127.2,
126.7, 126.3, 126.3, 126.1, 125.7, 125.0, 124.2, 122.9, 119.5, 118.9,
68.7, 55.7, 49.2, 33.4, 26.9, 25.0, 20.6 ppm; IR (ATR): v˜ =3051 (w),
2930 (w), 2857 (w), 1624 (m), 1508 (w), 1493 (w), 1431 (m), 1354
(w), 1341 (w), 1321 (w), 1288 (w), 1254 (w), 1184 (w), 1138 (w), 1111
(w), 1070 (w), 1028 (w), 978 (w), 939 (w), 893 (w), 854 (w), 822 (m),
798 (w), 758 (s), 748 (s), 725 (w), 698 (s), 664 cmꢁ1 (w); HRMS (ESI):
exact mass calcd for C46H40N2O2: m/z=653.31626 ([M+H]+),
675.29820 ([M+Na]+), found: m/z=653.31602 ([M+H]+),
675.29801 ([M+Na]+); elemental analysis calcd (%) for C46H40N2O2
(652.82): C 84.63, H 6.18, N 4.29; found: C 84.62, H 6.36, N 4.18.
1
cis-DACH-salalen 14: 82%, m.p. 1328C; H NMR (300 MHz, CDCl3):
d=12.76 (s, 1H, OH), 11.55 (br, 1H, OH), 8.58 (s, 1H), 8.01 (d, J=
8.7 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 7.79 (s, 1H), 7.76–7.73 (m, 1H),
7.64 (d, J=8.4 Hz, 1H), 7.55 (d, J=6.9 Hz, 2H), 7.43 (t, J=6.9 Hz,
1H), 7.35–7.20 (m, 10H), 7.07–6.94 (m, 5H), 6.82 (t, J=7.5 Hz, 1H),
4.02 (q, J=13.8 Hz, 2H), 3.70 (d, J=2.4 Hz, 1H), 2.82–2.78 (m, 1H),
1.88–1.30 ppm (m, 9H); 13C NMR (75 MHz, CDCl3): d=165.5, 155.6,
154.6, 142.2, 140.6, 138.5, 135.6, 133.6, 133.0, 132.8, 131.2, 130.0,
129.4, 129.2, 128.7, 128.3, 128.1, 128.0, 127.8, 127.1, 127.0, 126.8,
126.7, 126.5, 126.3, 125.7, 125.1, 123.2, 122.7, 120.3, 120.1, 119.0,
68.1, 57.3, 49.5, 33.2, 27.4, 24.8, 20.4 ppm; IR (ATR): v˜ =3051 (vw),
2930 (w), 2857 (w), 1630 (m), 1593 (w), 1497 (w), 1460 (m), 1429
(m), 1387 (w), 1346 (w), 1290 (w), 1260 (w), 1248 (w), 1234 (w),
1184 (w), 1142 (w), 1119 (w), 1088 (w), 1072 (w), 1028 (w), 984 (w),
961 (w), 941 (w), 920 (w), 897 (w), 864 (w), 853 (w), 824 (m), 791
(w), 756 (s), 698 (s), 667 cmꢁ1 (w); HRMS (ESI): exact mass calcd for
C46H40N2O2: m/z=653.31626 ([M+H]+), 675.29820 ([M+Na]+),
found: m/z=653.31599 ([M+H]+), 675.29815 ([M+Na]+); elemen-
tal analysis calcd. (%) for C46H40N2O2 (652.82): C 84.63, H 6.18, N
4.29; found: C 84.37, H 6.33, N 4.34.
cis-DACH-salalen 15: 85%, m.p. 131–1328C; 1H NMR (300 MHz,
CDCl3): d=12.77 (s, 1H, OH), 11.52 (br, 1H, OH), 8.55 (s, 1H), 8.02
(d, J=8.4 Hz, 1H), 7.96 (d, J=7.8 Hz, 1H), 7.82–7.78 (m, 2H), 7.65
(d, J=8.4 Hz, 1H), 7.58 (d, J=7.2 Hz, 2H), 7.46 (t, J=6.9 Hz, 1H),
7.41–7.25 (m, 8H), 7.15-7.12 (m, 1H), 7.08 (d, J=7.2 Hz, 2H, 6.98 (d,
J=6.3 Hz, 1H), 6.89–6.80 (m, 3H), 6.71 (t, J=7.2 Hz, 1H), 4.00 (q,
J=13.8 Hz, 2H), 3.66 (d, J=2.4 Hz, 1H), 2.79–2.76 (m, 1H), 1.94–
1.26 ppm (m, 9H); 13C NMR (75 MHz, CDCl3): d=165.2, 155.6, 154.4,
142.3, 140.7, 138.5, 135.8, 133.6, 133.0, 132.8, 131.2, 130.1, 129.4,
129.2, 128.8, 128.4, 128.3, 128.3, 128.2, 128.1, 127.8, 126.9, 126.8,
126.7, 126.4, 126.1, 125.7, 125.2, 123.3, 122.6, 120.2, 120.0, 119.1,
67.9, 56.9, 49.5, 32.8, 27.6, 24.7, 20.5 ppm; IR (ATR): v˜ =3051 (vw),
2930 (w), 2857 (w), 1628 (m), 1593 (w), 1499 (w), 1460 (m), 1429
(m), 1406 (w), 1387 (w), 1346 (w), 1290 (w), 1260 (w), 1248 (w),
1233 (w), 1184 (w), 1142 (w), 1119 (w), 1088 (w), 1072 (w), 1045 (w),
1028 (w), 984 (w), 961 (w), 941 (w), 920 (w), 891 (w), 862 (w), 851
(w), 822 (m), 793 (w), 756 (s), 698 (s), 665 cmꢁ1 (w); HRMS (ESI):
exact mass calcd for C46H40N2O2: m/z=653.31626 ([M+H]+),
675.29820 ([M+Na]+), found: m/z=653.31602 ([M+H]+),
675.29830 ([M+Na]+); elemental analysis calcd (%) for C46H40N2O2
(652.82): C 84.63, H 6.18, N 4.29; found: C 84.27, H 6.21, N 4.38.
cis-DACH-salalen 16: 67%, m.p. 133–1348C; 1H NMR (300 MHz,
CDCl3): d=12.79 (s, 1H, OH), 11.33 (br, 1H, OH), 8.61 (s, 1H), 8.02
(d, J=8.4 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 7.83–7.74 (m, 2H), 7.65
(d, J=8.1 Hz, 1H), 7.48–7.38 (m, 2H), 7.32–6.98 (m, 10H), 6.81-6.70
(m, 2H), 3.95 (q, J=13.5 Hz, 2H), 3.72 (s, 1H), 2.91–2.78 (m, 2H),
1.89–1.22 ppm (m, 19H); 13C NMR (75 MHz, CDCl3): d=165.4, 155.6,
154.6, 142.2, 140.6, 135.5, 135.0, 133.5, 133.0, 132.8, 131.2, 128.8,
128.7, 128.3, 128.2, 127.1, 127.0, 126.8, 126.5, 126.3, 125.9, 125.8,
125.1, 123.2, 121.8, 120.3, 120.1, 118.7, 68.2, 57.4, 49.5, 36.7, 33.2,
33.1, 27.6, 27.1, 27.0, 26.5, 24.9, 20.4 ppm; IR (ATR): v˜ =3051 (vw),
2924 (w), 2851 (w), 1630 (m), 1593 (w), 1508 (w), 1495 (w), 1449
(m), 1400 (w), 1387 (w), 1346 (w), 1325 (w), 1290 (w), 1258 (w),
1240 (w), 1221 (w), 1209 (w), 1184 (w), 1140 (w), 1119 (w), 1082 (w),
1072 (w), 1028 (w), 984 (w), 941 (w), 920 (w), 895 (w), 858 (w), 822
cis-DACH-salalen 20: 82%, m.p. 140–1418C; 1H NMR (300 MHz,
CDCl3): d=13.60 (s, 1H, OH), 11.42 (br, 1H, OH), 8.47 (s, 1H), 8.05
(d, J=8.4 Hz, 1H), 7.99 (d, J=7.8 Hz, 1H), 7.68 (d, J=8.1 Hz, 2H),
7.53-7.31 (m, 5H), 7.24–6.88 (m, 10H), 4.19 (s, 2H), 3.71 (s, 1H),
Chem. Eur. J. 2015, 21, 247 – 254
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
3.14–3.07 (m, 1H), 2.67 (d, J=13.2 Hz, 1H), 1.92–1.30 ppm (m,
19H); 13C NMR (75 MHz, CDCl3): d=165.9, 158.4, 154.2, 142.4,
140.2, 135.6, 134.1, 133.1, 133.0, 131.9, 129.9, 129.2, 128.7, 128.3,
128.1, 128.0, 127.6, 127.6, 127.4, 127.2, 126.6, 126.3, 126.2, 126.0,
125.6, 125.0, 124.2, 122.8, 119.6, 118.7, 118.2, 67.2, 56.3, 49.3, 36.3,
33.4, 33.2, 27.9, 27.1, 26.5, 25.2, 20.5 ppm; IR (ATR): v˜ =3051 (w),
2924 (w), 2851 (w), 1624 (m), 1508 (w), 1493 (w), 1439 (m), 1354
(w), 1341 (w), 1321 (w), 1300 (w), 1254 (m), 1219 (w), 1198 (w),
1180 (w), 1136 (w), 1113 (w), 1085 (w), 1051 (w), 1028 (w), 982 (w),
941 (w), 914 (w), 889 (w), 858 (w), 839 (w), 820 (m), 789 (w), 748 (s),
723 (w), 698 (s), 675 cmꢁ1 (w); HRMS (ESI): exact mass calcd for
C46H46N2O2: m/z=659.36321 ([M+H]+), 681.34515 ([M+Na]+),
found: m/z=659.36270 ([M+H]+), 681.34466 ([M+Na]+); elemen-
tal analysis calcd (%) for C46H46N2O2 (658.87): C 83.85, H 7.04, N
4.25; found: C 83.56, H 7.09, N 4.10.
cis-DACH-salalen 21: 79%, m.p. 141–1428C; 1H NMR (300 MHz,
CDCl3): d=13.61 (s, 1H, OH), 11.502 (br, 1H, OH), 8.38 (s, 1H), 8.06
(d, J=8.7 Hz, 1H), 7.98 (d, J=8.1 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H),
7.54 (s, 1H), 7.48 (t, J=7.2 Hz, 1H), 7.37–7.29 (m, 3H), 7.27-7.05 (m,
9H), 6.89 (t, J=7.8 Hz, 1H), 4.20 (q, J=14.1 Hz, 2H), 3.37 (s, 1H),
3.13–3.06 (m, 1H), 2.53 (d, J=9.3 Hz, 1H), 2.09–2.04 (m, 1H), 1.96–
1.29 ppm (m, 18H); 13C NMR (75 MHz, CDCl3): d=165.8, 158.4,
154.0, 142.5, 140.0, 135.6, 134.4, 133.1, 133.0, 131.9, 129.8, 129.3,
128.9, 128.3, 128.1, 128.1, 127.7, 127.7, 127.4, 127.2, 126.7, 126.3,
126.3, 126.1, 125.6, 125.0, 124.2, 122.8, 119.5, 118.7, 118.1, 68.6,
55.8, 49.1, 36.3, 33.4, 33.2, 33.1, 27.1, 26.5, 25.0, 20.7 ppm; IR (ATR):
v˜ =3055 (w), 2924 (w), 2851 (w), 1624 (m), 1558 (w), 1541 (w), 1508
(w), 1493 (w), 1439 (m), 1354 (w), 1341 (w), 1321 (w), 1300 (w),
1256 (m), 1219 (w), 1180 (w), 1138 (w), 1111 (w), 1086 (w), 1028 (w),
1018 (w), 982 (w), 941 (w), 912 (w), 889 (w), 858 (w), 839 (w), 820
(m), 791 (w), 748 (s), 723 (w), 698 cmꢁ1 (s); HRMS (ESI): exact mass
calcd for C46H46N2O2: m/z=659.36321 ([M+H]+), 681.34515 ([M+
Na]+), found: m/z=659.36298 ([M+H]+), 681.34710 ([M+Na]+);
elemental analysis calcd (%) for C46H46N2O2 (658.87): C 83.85, H
7.04, N 4.25; found: C 83.46, H 7.13, N 4.20.
ble Chemical Synthesis (SusChemSys)” is co-financed by the
European Regional Development Fund (ERDF) and the State of
North Rhine-Westphalia, Germany, under the Operational Pro-
gramme “Regional Competitiveness and Employment” (2007–
2013).
Keywords: asymmetric synthesis · epoxidation · hydrogen
peroxide · terminal olefins · titanium
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Associated content
CCDC-997480 (33) and CCDC-997481 (32·6CH2Cl2) contain the sup-
plementary crystallographic data for this paper. These 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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Acknowledgements
Financial support by the Fonds der Chemischen Industrie and
SusChemSys is gratefully acknowledged. The project “Sustaina-
Received: July 29, 2014
Published online on November 5, 2014
Chem. Eur. J. 2015, 21, 247 – 254
www.chemeurj.org
254
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim