Practical one-pot synthesis of secondary amines by zinc-catalyzed reductive amination

Article abstract of DOI:10.1007/s10562-010-0463-4

In the present study, the zinc-catalyzed reductive amination of various aldehydes has been examined in detail. Simple zinc(II) triflate was applied as hydrosilylation catalyst for the reduction of the in situ formed imine by condensation of an aldehyde with an amine. Using a practical Lewis acid catalyst and PMHS [poly(methylhydrosiloxane)] as cheap hydride source excellent yields and a broad functional group tolerance were achieved.

Full text of DOI:10.1007/s10562-010-0463-4

Catal Lett (2011) 141:55–61
DOI 10.1007/s10562-010-0463-4
Practical One-Pot Synthesis of Secondary Amines
by Zinc-Catalyzed Reductive Amination
Stephan Enthaler
Received: 25 August 2010 / Accepted: 2 October 2010 / Published online: 21 October 2010
Ó Springer Science+Business Media, LLC 2010
Abstract In the present study, the zinc-catalyzed reduc-
tive amination of various aldehydes has been examined in
detail. Simple zinc(II) triflate was applied as hydrosilyla-
tion catalyst for the reduction of the in situ formed imine
by condensation of an aldehyde with an amine. Using a
practical Lewis acid catalyst and PMHS [poly(meth-
ylhydrosiloxane)] as cheap hydride source excellent yields
and a broad functional group tolerance were achieved.
this regard, the reduction of in situ formed imines, syn-
thesized from readily available ketones or aldehydes with
amines, offers an interesting access to higher functional-
ized amines. In more detail, this one-pot reductive ami-
nation protocol is based on two synthetic steps. First the
imine is synthesized by condensation of a carbonyl com-
pound and an amine, and in the second step the reduction is
carried out applying hydrogen or hydrogen donors as
reductant. Although hydrogenation and transfer hydroge-
nation of C=N bonds in the presence of catalytic amounts
of metal precursors are the most developed ways, catalytic
hydrosilylation is a desirable choice because of mild
reaction conditions and straightforwardness [17–19].
Indeed, during the last decades several reductive amination
protocols based on transition metals or metal free catalysts
have been reported [20–35]. A number of catalysts rely on
precious metals such as rhodium, ruthenium, and iridium.
However, difficulties can arise by catalyst deactivation/
poisoning, since stoichiometric amounts of water are
formed. Furthermore, the selectivity towards the amine
formation will be strongly influenced by the applied car-
bonyl compound, because of their easy reduction to the
corresponding alcohol. In addition, due to the high price
and the toxicity less expensive and low toxic metals are
highly requested for replacement [36]. Here the use of zinc
is probably of great interest [37–49]. Although several
research groups demonstrated the abilities of zinc catalysts
in the reduction of imines [50–53], reductive amination
protocols are scarcely reported [54–60]. In most cases
stoichiometric or sub-stoichiometric amounts of zinc
reagents or special reducing reagents were applied. Hence
it is still a challenging task to find a robust and easy to
adopt zinc-based catalyst for those reactions. Herein we
describe the efficient and selective synthesis of secondary
amines by zinc-catalyzed reductive amination.
Keywords Zinc Á Hydrosilylation Á Amination Á
Homogeneous catalysis
1
Introduction
One of the primary research objectives in modern chem-
istry is the progress of more environmental benign, effi-
cient, and selective methods to access key structures [1–4].
One aspect to realize ‘‘green chemistry’’ is the application
of catalysts since e.g., reduction of waste, energy, high
atom efficiency and selectivity have been demonstrated for
various reactions [5–8]. On the other hand the step-by-step
construction of molecular bonds can be replaced by per-
forming several steps in one-pot, because ecological and
economical rewards come up [9–12]. Undoubtedly, a
plethora of reported methodologies have been embedded
those protocols. Among the strategies, the synthesis of
amines is of vast importance, because of their key role in
bulk and fine chemicals, and pharmaceuticals [13–16]. In
S. Enthaler (&)
Department of Chemistry, Cluster of Excellence ‘‘Unifying
Concepts in Catalysis’’, Technische Universit a¨ t Berlin, Straße
des 17. Juni 135, 10623 Berlin, Germany
e-mail: stephan.enthaler@tu-berlin.de
123

5
6
S. Enthaler
2
Results and Discussion
Table 1 Investigation of reaction parameters in the reductive ami-
nation of 1
5
mol-% [Zn]
PMHS
H2N
In the first set of experiments we studied the influence of
zinc salts on the condensation reaction of benzaldehyde
with aniline. The influence of Zn-catalysts on condensation
reactions has been reported [61]. Both reagents were dis-
solved in [D ]toluene and 10 mol-% of a zinc salt [ZnF ,
O
N
N
H
+
-
H O
THF
2
1
2
3
4
a
b
Entry
Zn-source
mol%
Additive
T (°C)
Yield (%)
8
2
1
2
3
ZnF
ZnCl
ZnBr
Zn(BF
Zn(OAc)
Zn(acac)2
2
5
5
5
5
5
5
5
5
1
5
5
5
5
5
5
1
–
5
5
A
A
A
A
A
A
A
A
A
A
B
–
60
60
60
60
60
60
60
60
60
60
60
60
60
80
80
80
80
60
80
\1
4
ZnCl , ZnBr , Zn(BF ) , Zn(OTf) ] was added. Without
2
2
4 2
2
2
any zinc salt the equilibrium is almost quantitative shifted
to the imine. Same fact is true in the presence of metal
sources; here no significant negative influence on product
formation could be observed by following the reaction with
2
4
c
4
4
)
2
27
\1
2
5
2
c
6
1
H NMR measurements. Noteworthy, the condensation
7
8
Zn(OTf)
ZnO
2
21
\1
\1
21
\1
44
79
reaction is very fast therefore the influence of zinc salts on
the reaction rate could not determined by NMR methods.
After clarifying that the condensation reactions of benzal-
dehyde with aniline proceeds in the presence of zinc salts,
we extended the protocol to the reductive amination. By
addition of PMHS [poly(methylhydrosiloxane)], a cheap
and low toxic compound, we offered a hydride source to
the system. Initially, several zinc salts (5 mol-% catalyst
loading) were tested in the reductive amination (Table 1).
Molsieves were added to remove the water, which is
formed during the condensation step, and consequently to
shift the equilibrium towards the imine and minimize cat-
alyst deactivation processes. After 4 h at 60 °C in THF the
9
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
–
2
2
2
2
2
2
2
2
d
10
11
12
13
e
–
f
14
15
16
17
18
19
–
99 (92)
g
g
–
65
31
\3
33
26
–
–
Zn(BF
4
)
2
–
Zn(BF4)2
–
1
reaction was stopped. In case of zinc halogen salts only
Reactions were carried out with 0.12 mmol zinc precursor (5 mol-%),
.4 mmol benzaldehyde, 2.4 mmol aniline, 0.5 mL PMHS, 2.0 mL
small amounts of the corresponding amine 4 were detected.
-
2
-
Increasing the Lewis acidity of the zinc by BF4 and OTf
THF, 4 h at 60 °C. The yield was determined by GC (30 m Rxi-5 ms
a
column, 40–300 °C) with dodecane as internal standard. Catalyst
loading. A = molsieves, B = CyN=C=NCy. The corresponding
anion yields up to 27% were obtained. Surprisingly, if the
water scavenger is removed the yield increased to 44%.
Further improvement was observed by increasing the
reaction temperature to 80 °C. Here excellent yield
b
c
d
e
hydrate was used. Reaction was carried out in toluene. Reaction
f
g
was carried out in methanol for 24 h. Isolated yield. Reaction time:
1 h
([99%) of the amine was feasible. A sample taken after a
reaction time of 1 h showed 65% yield of the amine, while
is formed during the reaction the catalytic performance of
this should be marginal.
lowering the catalyst loading to 1 mol% led to 31% yield,
-
1
which corresponds to a turnover frequencies of 31 h
Table 1, entries 14 and 15). Decreasing the temperature to
5 °C long reaction times are required to obtain product 4.
Further on, several hydride sources were tested under
reaction conditions described in Table 2. Here, excellent
yield (95%) of N-benzyl N-phenyl amine was obtained
after 4 h by using phenylsilane. Good yield was achieved
with triethoxysilane. In case of triphenylsilane, dimethyl-
phenylsilane and triethylsilane a lower hydride transfer was
detected. However, further studies were performed with
PMHS, because of the great availability, stability, the low
(
2
Noteworthy in the absence of zinc only small amounts of
product were observed (Table 1, entry 16). Remarkable,
the protocol is highly selective since no reduction of
benzaldehyde to yield benzyl alcohol or over-alkylation
was observed. To clarify the role of the metal or traces of in
situ formed CF SO H the reaction was carried out with
2
, 3
price and safety considerations.
3
3
CF SO H as catalyst (5.0 mol-%) for the reductive ami-
3
Moreover we studied the influence of various amine-
ligands on the reaction outcome. In general, the addition of
3
nation of benzaldehyde with aniline in THF at 60 °C for
4 h. A yield of 45% of 4 was achieved, which is signifi-
cantly lower than the results obtained with Zn(OTf) (44%
2
2
2
The costs for 0.1 mol per Si–H: (EtO)
3 3
SiH: 66€; PhSiH : 72€;
after 4 h) and exhibits the influence of the metal. If TfOH
Ph
3
SiH: 74€; Me PhSiH: 61€; Et SiH: 12€; PMHS: 2€.
2
3
3
During our studies we used triethoxysilane as reducing reagent
without incident. However, Buchwald et al. reported on difficulties
when working with triethoxysilane [62].
1
The reaction was also performed in toluene as solvent, but a
decreased yield was found compared to THF.
1
23

Practical One-Pot Synthesis of Secondary Amines
57
Table 2 Influence of the hydride source on the reductive amination
selectivity ([99%) for the reduction of the C=N bond was
observed in the presence of ketones, esters, C–C double
bonds, nitro and epoxide groups, while alkinyl and sulfonyl
groups are reduced to some extend. In addition, aceto-
phenone was tested instead of benzaldehyde as carbonyl
functionality in the reductive amination. However, under
similar conditions with aniline as amine component no
product at all was observed, while increasing the temper-
ature to 100 °C in toluene as solvent and applying an
excess of the amine component a moderate yield of 60%
5
mol-% Zn(OTf)2
2
H N
O
silane
+
N
H
THF, 60 °C, 4h
1
2
4
Entry
Silane
B:A
T (°C)
Yield (%)
1
2
3
4
5
6
7
8
(EtO)
3
SiH
1:1
1:1
1:1
1:1
1:1
1:1
1:1.5
1:5
60
60
60
60
60
60
60
60
71
95
\1
28
11
44
40
43
PhSiH
3
Ph
Me
Et SiH
3
SiH
4
2
PhSiH
were observed.
1
Afterwards H NMR experiments were carried out to
3
PMHS
PMHS
PMHS
examine the reaction mechanism. First Zn(OTf)2 was
reacted with PMHS in [D ]THF to examine a potential zinc
8
hydride mechanism. Applying the triflate group as probe
1
9
only a slight shift in the F NMR spectra was observed,
80.7 ppm (Zn(OTf) , PMHS in [D ]THF) compared to
Reactions were carried out with 0.12 mmol ZnOTf
2
2
(5 mol-%),
.4 mmol benzaldehyde, 2.4 mmol aniline, 3.6 mmol silane, 1.0 mL
-
2
8
THF, 4 h at 60 °C. The yield was determined by GC (30 m Rxi-5 ms
column, 40–300 °C) with dodecane. B benzaldehyde, A = aniline
-79.1 ppm (Zn(OTf) in [D ]THF). Even after heating for
2 8
several days no zinc hydride signal could be detected in the
1
5
H NMR on the NMR time scale [49, 63, 64, 65]. As main
component of this mixture Zn(OTf) (thf) (41) was isolated
ligands has no significant positive effect on the reaction
2
4
outcome compared to unmodified Zn(OTf) , probably
2
as colourless crystals and was characterized by single-
crystal X-ray diffraction analysis (Fig. 1). The obtained
solid structure is similar to the results reported by Nefedov
and co-workers [66]. The octahedral zinc is axial coordi-
nated by the triflate groups and in the equatorial plane four
THF molecules are located. The isolated compound was
subjected to catalysis and compared with the in situ gen-
erated system, but no difference in reactivity was found.
Hence, the complex can be seen as intermediate or pre-
catalyst for the reductive amination. Next the complex was
caused by a negative influence on the Lewis acidity. Hence
simple Zn(OTf) was used for further studies. To explore
2
the scope and limitation of the presented catalyst system,
reductive aminations of a selection of carbonyl compounds
and amines were performed. As temperature 60 °C was
chosen, due to higher stability of the silanes at lower
temperature and to exclude interfering effects (e.g. reduc-
tion of sensitive functional groups). First various aldehydes
were reacted with aniline as amine source (Table 3). In
most cases the reaction time was extended towards 24 h to
ensure full conversion. Here, excellent yields were
obtained for benzaldehydes substituted with electron-
withdrawing as well as electron-donating groups (Table 3,
entries 1–8). In addition no negative effect was observed
when shielding the aldehyde by a mesityl group. Only in
case of p-methoxy benzaldehyde a decreased yield was
detected. In addition hetero aromatic aldehydes were reac-
ted with aniline under reductive conditions (Table 3, entries
1
9
dissolved in [D ]THF and the reaction was followed by
8
F
NMR (Zn(OTf) (thf) d = -79.1 ppm). After addition of
2
4
p-methoxybenzaldehyde (10 equiv.) a slight shift of
1.8 ppm was recorded probably caused by ligand exchange
or solvation effects (-80.9 ppm). Next aniline (10 equiv.)
was added to form the corresponding imine and water.
1
9
Here the F NMR signal was shifted towards -78.9 ppm
(D = 2 ppm), probably caused by coordination of the
imine and water. Aside a sample of Zn(OTf) (thf) was
2
4
9
–10). Moreover, pyridine derivatives were explored, but
reacted with a tenfold excess of water in [D ]THF and a
8
unfortunately only traces of product were observed, prob-
ably due to the coordination abilities of pyridine. Aside
alkyl based aldehydes were tested, yielding the corre-
sponding product in excellent yield (Table 3, entries
signal at -77.5 ppm was observed, which excludes the
formation of pure Zn(OTf) aqua complexes under cata-
2
lytic conditions and make a coordination of the imine to the
zinc most likely. The influence of the imine, based on
1
1–16). Next we investigated the influence of the amine
component in combination with benzaldehyde (Table 3,
entries 17–29). Here, excellent yields were obtained with
various aromatic substitution patterns, while difficulties
arose with hydroxy groups in o- or p-position, respectively.
Moreover, the chemoselectivity of the reductive ami-
nation was studied with an additional substrate, which is
sensitive towards reduction chemistry (Table 4). Excellent
4
A detailed investigation is currently in progress.
5
19
The F NMR shift for Zn(OTf)
which is also known to catalyzes reductive aminations, hence the
formation of CF SO H can be not excluded. The reaction was carried
out with CF SO H as catalyst (5.0 mol%) for the reductive amination
of benzaldehyde with aniline in THF at 60 °C for 24 h. A yield of
5% of 4 was achieved, which is significantly lower than the results
obtained with Zn(OTf)2.
2 3 3
is similar to the shift of CF SO H,
3
3
3
3
4
123

5
8
S. Enthaler
Table 3 Scope and limitations of Zn(OTf)
2
Table 3 continued
5
mol-% Zn(OTf)2
a
R2
Entry
18
Substrate
Product
Yield (%)
H
2
N
PMHS
R1
R1
+
R2
O
N
H
THF, 60 °C
Bu
t
NH2
>99 (95)
92 (86)
36
But
NH
2
2
2
2a
a
Entry
1
Substrate
Product
Yield (%)
MeO
CHO
HN
19
Me
HO
NH
2
87 (85)
5
MeO
23
Me
HO
NH
2
3a
5
a
a
But
CHO
d
2
3
HN
98 (91)
99 (91)
NH
20
2
6
But
24
25
NH
NH
6
2
4a
F
F
HN
2
1
2
F
3
C
NH
2
98 (88)
CHO
CHO
7
a
F3C
7
25a
F
F
F
F
4
HN
62 (58)
2
Br
Cl
NH2
99 (92)
97 (92)
85 (79)
71
Br
NH
26
2
6a
8a
8
Cl
Cl
NH
2
23
5
6
7
HN
>99 (92)
>99 (89)
>99 (97)
27
Cl
NH
2
7a
CHO
9
a
9
OH
NH2
OH
NH
24
Br
CHO
HN
1
0
Br
28
28a
1
0a
NH2
2
5
NH
HN
CHO
29
2
9a
1
1
11a
2a
NH2
O
2
N
O2N
H
N
8
9
HN
>99 (83)
92 (78)
26
27
97 (92)
60
3
0
3
0a
CHO
1
12
S
NH2
CHO
HN
HN
S
31
NH
1
3
3
1a
1
3a
O
1
1
1
0
O
>99 (81)
28
29
NH2
49
CHO
3
2
NH
1
5
4
1
4a
32a
CHO
HN
1
>99 (90)
99 (92)
1
NH2
3
3
H
>99
1
5a
N
3
3a
2
CHO
HN
Reactions were carried out with 0.12 mmol zinc precursor (5 mol-%),
2.4 mmol aldehyde, 2.4 mmol amine, 0.5 mL PMHS, 2.0 mL THF,
1
6
1
6a
6
MS and H NMR. The yield was determined by mass spectrometry
0 °C. Reaction time: 24 h. All products were characterized by GC–
1 a
3b
HCHO
1
1
17
N
>99
>99
1
and H NMR. In parenthesis the isolated yield is given. Aqueous
b
1
7a
c
solution stabilized with methanol. An excess of 17 was used. An
d
excess of 18 was used. Reaction time: 4 h. Similar yield was
observed after 24 h
4c
H
H
N
O
O
n
18a
18
H
N
p-anisaldehyde and aniline, on the Zn(OTf) was further-
2
O
1
5
19
31
more studied by IR investigations. Using the C=N group as
probe with varying Zn:imine ratio from 1:1 to 1:10. Beside
-1
1
9a
2
H
O
N
the frequency for the free C=N (1,625 cm ) new signal
1
6
7
20
47
-
1
-1
with a shoulder at 1,687 cm ,
0a
appears at 1,699 cm
which can probably attributed to an interaction with the
1
MeO
NH2
>99 (97)
Zn(OTf) [67, 68]. Finally, PMHS (10 equiv.) was added,
2
19
but the signal in F NMR has not changed, even after
MeO
NH
2
1
2
1a
1
23

Practical One-Pot Synthesis of Secondary Amines
59
Table 4 Zinc-catalyzed reductive amination in the presence of
reduction sensitive substrates
amounts of D O (0.0, 0.5, 1.0 1.5 equiv. with respect to the
2
6
imine) to clarify the role of water. First, a higher solubility
5
mol-% Zn(OTf)2
PMHS
of ZnOTf was observed for water containing samples (1.0
2
OMe
H2N
and 1.5 equiv.), since a homogeneous solution appeared
after addition. In case of the reaction without water addition
a heterogeneous solution was detected. Secondly, a higher
reaction rate was found for water containing experiments.
An incorporation of deuterium was only monitored for the
O
1 equiv. additive
+
N
H
THF, 60 °C, 4h
OMe
1
21
21a
a
b
Entry
Additive
Yield (%)
Yield (%)
1
9
NH-functionality. Remarkable, F NMR investigations for
all experiments showed a single signal for the coordinated
triflate group in the range of d = -77.7 to -77.8 ppm. This
result rules out the formation of Zn–H species on the NMR
O
1
83
<1
3
4
O
2
3
4
>99
>99
>99
<1
<1
<1
OMe
3
5
time scale. To study the hydride transfer Et SiD was applied
3
7
as reducing reagent. As expected a selective incorporation
O
N
O
in the methylene groups was observed.
MeO
36
Based on our findings and in accordance to catalysts
reported in the literature we assume a Lewis acid mecha-
nism (Scheme 1) [50–53]. First the condensation of the
amine with the aldehyde proceeds rapidly yielding the
imine and water. Noteworthy the equilibrium is signifi-
cantly shifted to the imine side also in the absence of the
catalyst (vide supra). Hence, the concentration of benzal-
dehyde is low and the reduction is prevented yielding in
excellent selectivities for the imine reduction. As initial step
of the catalytic cycle the zinc catalyst is interacting with the
imine nitrogen and activates the imine carbon (intermediate
A). Next, the silane reacts with the activated species. An
interaction of the hydride with the imine carbon and an
interaction of the silicon with the triflate group via a six-
membered transition state are assumed (intermediate B).
The hydride is transferred to the imine carbon while the silyl
group is coupled to the triflate group (intermediate C).
Noteworthy, the intermediate C can also react with the
silane to form a H–Zn(OTf) species, but which was not
detectable within the scope of the applied analytical meth-
ods. Subsequently the silyl group is shifted to the nitrogen
atom and the silylated amine is released and the recovered
3
7
5
6
Ph
Ph 38
94
81
9
8
O
S
3
9
O
7
>99
<1
4
0
Reactions were carried out with 0.036 mmol ZnOTf
.72 mmol benzaldehyde, 0.72 mmol 21, 0.15 mL PMHS, 1.0 mL
THF, 4 h at 60 °C. The yield was determined by GC (30 m Rxi-5 ms
2
(5 mol-%),
0
a
b
column, 40–300 °C) with dodecane. Yield of 21a. Yield of 34a–40a
Zn(OTf) is able to coordinate the next substrate molecule.
2
The silylated amine is hydrolyzed by the water formed
during the condensation reaction to yield the desired amine.
3
Conclusions
2 4
Fig. 1 Molecular structure of Zn(OTf) (thf) (41). Hydrogen atoms
In conclusion we have demonstrated the usefulness of zinc
catalysts in the reductive amination of aldehydes with
are omitted for clarity. Thermal ellipsoids are drawn at the 50%
probability level. Selected distances (pm) and angles (°): O1–Zn:
2
.075(2), O2–Zn: 2.085(2), O3–Zn: 2.089(2), O4–Zn: 2.090(2), O5–
Zn: 2.094(2), O1–Zn–O2: 177.13(9), O3–Zn–O5: 177.71(9), O4–Zn–
O6: 175.67 (10)
6
Experiments were carried out with N-[(4-methoxyphenyl)methy-
lene]benzenamine in benzene-d6 and heated to 80 °C. A decreased
reaction rate was found compared to THF. However, without addition
1
heating for several hours. In the H NMR we clearly see the
19
of water: 14%; 0.5 equiv.: 50%; 1.0 equiv.: 54%; 1.5 equiv.: 49%.
NMR investigations for all experiments showed a single signal for the
F
formation of the product.
1
In addition, H NMR investigations were performed with
triflate group in the range of d = -77.7–77.8 ppm.
7
ZnOTf , the isolated imine, PMHS and stoichiometric
2
Reaction conditions as stated in Table 3.
123

6
0
S. Enthaler
Ph
R3Si
Ph
Ph
Ph
mixture was stirred in a preheated oil bath at 60 °C for 4 h.
The mixture was cooled on an ice bath and was treated with
dodecane (10 lL) as GC standard (for GC-analysis),
methanol (1.0 mL), and aqueous sodium hydroxide solu-
tion (1.0 mL) with vigorous stirring (Caution: The reaction
mixture bubbled enthusiastically upon the addition of the
base). The reaction mixture was stirred for 60 min at 0 °C
and was then extracted with diethyl ether (29 10.0 mL).
The combined organic layers were washed with brine,
HN
Ph
H2O
N
N
O
NH2
Ph
+
-
H2O
Ph
Ph
Zn(OTf)2
O
S
F3C
SiR3
N
O
O
(TfO)2Zn
Ph
Zn
Ph
Ph
N
C
A
TfO
Ph
H
dried over anhydrous Na SO , filtered (an aliquot was
2
H-SiR3
4
O
OTf
Zn
F3C
S
Ph
Ph
removed for GC-analysis), and concentrated in vacuo. The
O
O
N
yield was monitored by GC (30 m Rxi-5 ms column,
1
R3Si
H
40–300 °C and by H NMR. The crude product was puri-
B
fied by column chromatography. The obtained analytical
data are in agreement with literature reports [26, 54, 69–
Scheme 1 Proposed catalytic cycle for the reductive amination
80].
amines to access secondary amines. Applying a commer-
4.3 X-ray structure determination
cially available catalyst [Zn(OTf) ] and PMHS as cheap
2
hydride source under non-inert conditions makes this
method straightforward. The excellent performance of the
system was exhibited in the reductive aminations of several
substrates with outstanding yields and a broad functional
group tolerance. In addition mechanistical investigations
assumed a Lewis acid based mechanism.
Crystals were each mounted on a glass capillary in per-
fluorinated oil and measured under a flow of nitrogen. The
data of 52 was collected on an Oxford Diffraction Xcalibur
˚
S Sapphire at 123 K (MoK radiation, k = 0.71073 A).
a
The structures were solved by direct methods and refined
on F2 with the SHELX-97 [81] software package. The
positions of the H atoms were calculated and considered
isotropically according to a riding model.
4
Experimental Section
Compound 41: Orthorhombic; space group P2(1)2(1)
(1); a = 8.6644(2), b = 16.1969(4), c = 18.9911(5); V =
2
4
.1 General
3
-3
˚
2
665.14(11) A ; Z = 11; q = 1.625 mg m ; m (MoK ) =
calc
a
-1
0.092 mm ; 11,224 collected reflections; 4,683 crystallo-
1
13
H and C NMR spectra were recorded with Bruker AFM
graphically independent reflections (Rint = 0.0418); 3,734
1
19
13
2
00 spectrometer ( H: 200.13 MHz; F: 188.31 MHz; C:
5.5 MHz) using the proton signals of the deuterated sol-
reflections with I[2r(l); hmax = 25.00°; R(F ) = 0.0369
o
7
(
I[2r(l)); wR(F ) = 0.0526 (all data); 335 refined
2o
vents as reference. Single crystal X-ray diffraction mea-
surements were recorded on an Oxford Diffraction
Xcalibur S Saphire spectrometer. IR spectra were recorded
either on a Nicolet Series II Magna-IR-System 750 FTR-IR
or on a Perkin Elmer Spectrum 100 FT-IR. Electron-impact
mass spectra (EI-MS) were recorded on a Finnigan
MAT95S. GC-MS measurements were carried out on a
Shimadzu GC-2010 gas chromatograph (30 m Rxi-5ms
column) linked with a Shimadzu GCMA-QP 2010 Plus
mass spectrometer.
parameters.
Acknowledgments This work was supported by the Cluster of
Excellence ‘‘Unifying Concepts in Catalysis’’ (sponsored by the
Deutsche Forschungsgemeinschaft and administered by the Techni-
sche Universit a¨ t Berlin). The authors thank Sebastian Krackl and
Peter Frenzel for technical support.
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