Regioselective preparation of 2-phenylethylamines from 1-phenyl-2-alkyl- alkynes by hydroamination/reduction sequences

Article abstract of DOI:10.1055/s-2004-834863

Ind₂TiMe₂ is a highly active and general catalyst for the intermolecular hydroamination of alkynes. Particularly impressive is that Ind₂TiMe₂ makes it possible to perform hydroamination reactions of unsymmetrically substituted 1-phenyl-2-alkylalkynes with primary aryl-, tert-alkyl-, sec-alkyl-, and n-alkylamines in a highly regioselective fashion. Since the initially formed imines can easily be reduced with zinc-modified NaBH₃CN, 2-phenylethylamines are accessible in reliable one-pot procedures from 1-phenyl-2-alkylalkynes and primary amines on a 10 mmol scale.

Full text of DOI:10.1055/s-2004-834863

1200
PRACTICAL SYNTHETIC PROCEDURES
Regioselective Preparation of 2-Phenylethylamines from 1-Phenyl-2-alkyl-
alkynes by Hydroamination/Reduction Sequences
R
egioselective Pre
n
parationof
2
d
-Phenylethy
r
Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270,
69120 Heidelberg, Germany
Fax +49(6221)544205; E-mail: sven.doye@urz.uni-heidelberg.de
PSP
Received 27 July 2004; revised 24 August 2004
No46
Abstract: Ind2TiMe2 is a highly active and general catalyst for the intermolecular hydroamination of alkynes. Particularly impressive is
that Ind2TiMe2 makes it possible to perform hydroamination reactions of unsymmetrically substituted 1-phenyl-2-alkylalkynes with prima-
ry aryl-, tert-alkyl-, sec-alkyl-, and n-alkylamines in a highly regioselective fashion. Since the initially formed imines can easily be reduced
with zinc-modified NaBH3CN, 2-phenylethylamines are accessible in reliable one-pot procedures from 1-phenyl-2-alkylalkynes and pri-
mary amines on a 10 mmol scale.
Key words: alkynes, aminations, amines, catalysis, titanium
NHR
1) 5 mol% Ind2TiMe2
toluene, 105 °C
MeO
R-NH2
+
+
Procedure 1
NHR
2) NaBH3CN, ZnCl2
MeOH, 25 °C, 20 h
MeO
MeO
selectivities > 95:5
NHn-Pr
1) 5 mol% Ind2TiMe2
toluene, 130 °C, 24 h
+
n-PrNH2
+
Procedure 2
NHn-Pr
2) NaBH3CN, ZnCl2
MeOH, 25 °C, 20 h
R
R
R
selectivities > 95:5
Scheme 1
Introduction
Based on our initial finding that Cp2TiMe2 is a suitable
catalyst for the inter- and intramolecular hydroamination
During the last five years, the development of catalytic of alkynes,4 many other active Ti-catalysts have been
procedures for the hydroamination of alkynes has attract- identified by us5 and others.6–13 However, just recently we
ed much attention.1 With regard to scope and limitations, presented Ind2TiMe2 (Ind = indenyl) as the first general
the use of titanium complexes as hydroamination catalysts catalyst for the intermolecular addition of primary amines
has proven as the most important synthetic method among to alkynes that can be used for all possible substrate com-
the various procedures.2 Combined with a subsequent re- binations. With this catalyst, primary aryl-, tert-alkyl-,
duction of the initially formed imines, the Ti-catalyzed sec-alkyl-, and n-alkylamines can be reacted with internal
hydroamination must be seen as a new and powerful syn- and terminal alkynes. Particularly impressive was the
thetic tool for the conversion of alkynes and primary finding that Ind2TiMe2 makes it possible for the first time
amines into secondary amines. This interpretation is most to perform hydroaminations of 1-phenylpropyne with
impressively illustrated by the fact that corresponding hy- sterically less demanding n-hexylamine and benzylamine
droamination/reduction sequences have already been used in
a
highly anti-Markovnikov-selective fashion14
for highly flexible synthetic approaches towards the syn- (Scheme 1).
thesis of biologically interesting compounds (e.g. 2-aryl-
The catalyst Ind2TiMe2 can be synthesized in one-step
ethylamines, indolines, indolizidines, pyrrolizidines).3
from Ind2TiCl2 and methyllithium (Equation 1).15 The
complex is a stable crystalline yellow compound that can
be conveniently handled in air for short periods of time.
However, storage of Ind2TiMe2 under an atmosphere of
argon or nitrogen in the refrigerator is recommended. In
contrast, Ind2TiMe2 undergoes rapid decomposition in so-
SYNTHESIS 2005, No. 7, pp 1200–1204
x
x
.
x
x
.2
0
0
4
Advanced online publication: 21.10.2004
DOI: 10.1055/s-2004-834863; Art ID: Z15004SS
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Regioselective Preparation of 2-Phenylethylamines
1201
lution (Et2O, toluene) at room temperature. Therefore, by heating the reaction mixture to 105 °C under TLC-con-
prolonged handling of Ind2TiMe2 in solution should be trol (usually for 3–24 h). Subsequently, the reductions are
avoided. As a result, the preparation of Ind2TiMe2 should performed by addition of a mixture of NaBH3CN and
be performed at temperatures between –20 °C and –15 °C. ZnCl2 in MeOH (Procedure 1).5a,18 It is worth mentioning
Ind2TiMe2 is also commercially available from MCAT.16 that these reduction conditions are the result of compre-
hensive optimization studies. Although, other reduction
protocols have been used as well, in our opinion, reduc-
tions employing NaBH3CN and ZnCl2 secure optimal re-
sults of the hydroamination/reduction sequences.
3 equiv MeLi
Ind2TiCl2
Ind2TiMe2 93%
Et2O, –15 °C, 2 h
As can be seen from Table 1, the yields of the desired 2-
phenylethylamines possessing a methoxy group at the
benzene ring are usually good to excellent. While hy-
droamination reactions employing arylamines (entries 1–
3) usually need reaction times of approximately 24 hours
to reach 100% conversion, alkylamines react significantly
faster (3–5 h, entries 4–6). All hydroamination reactions
occur with very good to excellent regioselectivities,
whereby formation of the desired anti-Markovnikov re-
gioisomer is favored. In this context it is worth to mention
that the regioselectivity of hydroamination reactions of 2-
alkyl-1-phenylalkynes is generally influenced by the na-
ture of the alkyl substituent of the alkyne and the bulki-
ness of the primary amine. Increasing regioselectivity is
observed with increasing size of the amine and decreasing
size of the alkyl substituent of the alkyne.14 After subse-
quent reduction, it is possible to separate the major regio-
isomer from the minor isomer by flash chromatography.
To achieve a complete separation of the regioisomers it is
usually necessary to perform two subsequent chromatog-
raphies. However, even after one chromatography the iso-
lated yield of the major regioisomer is typically
acceptable (Table 1).
Equation 1
Since it is well established that the biological activity of
2-phenylethylamines is strongly influenced by the pres-
ence of a small alkyl substituent at the nitrogen atom and
the presence of alkoxy groups at the benzene ring,17 we
additionally developed reliable one-pot procedures for the
flexible synthesis of corresponding 2-phenylethylamines
from 1-phenyl-2-alkylalkynes. These procedures are
characterized by an efficient combination of an anti-
Markovnikov-selective Ind2TiMe2-catalyzed hydroami-
nation of 1-phenyl-2-alkylalkynes and a subsequent re-
duction of the initially formed imines.
Scope and Limitations
Equation 2 and Table 1 show some representative exam-
ples of one-pot hydroamination/reduction sequences of
unsymmetrically substituted 1-(4-methoxyphenyl)pro-
pyne (1) and primary amines 2–7 employing 5 mol%
Ind2TiMe2 as hydroamination catalyst on a 10 mmol
scale. Usually, the initial hydroamination reactions are
performed 1) by mixing all components together, and 2)
While Procedure 1 can be used for high-yielding regiose-
lective hydroamination/reduction sequences of aryl-, tert-
1) 5 mol% Ind2TiMe2
toluene, 105 °C
NHR
10 mmol scale
R-NH2
MeO
+
+
2) NaBH3CN, ZnCl2
MeOH, 25 °C, 20 h
NHR
MeO
MeO
1
2–7
8a–13a
8b–13b
Equation 2
Table 1 Reaction of 1-(4-Methoxyphenyl)propyne (1) with Amines 2–7
Entry
Amine
R
Time (h)
Yield (a + b) (%)
97 (8a/b)
Yield (a) (%)
87a (8a)
Ratio a/b
>98:2
>98:2
98:2
1
2
3
4
5
6
2
3
4
5
6
7
Ph
24
24
24
5
4-MeC6H4
4-ClC6H4
t-Bu
90 (9a/b)
71a (9a)
98 (10a/b)
70 (11a/b)
90 (12a/b)
75 (13a/b)
95a (10a)
70 (11a)
>98:2
95:5
cyclopentyl
i-Pr
3
68a (12a)
66a (13a)
4
98:2
a Obtained after one chromatography. A complete separation of the regioisomers can be achieved by two subsequent chromatographies.
Synthesis 2005, No. 7, 1200–1204 © Thieme Stuttgart · New York

1202
A. Heutling et al.
PRACTICAL SYNTHETIC PROCEDURES
alkyl-, and sec-alkylamines, high boiling sterically less experimental part are limited to reactions of aryl-, tert-
demanding n-alkyl- and benzylamines such as n-hexyl- alkyl, and sec-alkylamines as well as n-propylamine (19).
amine and benzylamine need to be added slowly to the re- Procedures for transformations of sterically less demand-
action mixture. In these cases, the speed of the amine ing n-alkyl- and benzylamines can be found elsewhere.14
addition needs to be optimized for each reaction.14 There-
Table 2 Reaction of Alkynes 14–18 with n-Propylamine (19)
fore, this publication does not contain a general procedure
for reactions of these substrates. Procedures for transfor-
Entry
Alkyne
R
Yield (a + b) Yield a
Ratio
a/b
mations of sterically less demanding high-boiling n-alkyl-
(%)
(%)
and benzylamines can be found elsewhere.14
1
2
3
4
5
14
15
16
17
18
H
80 (20a/b)
71a (20a)
63a (21a)
63a (22a)
73a (23a)
72a (24a)
96:4
96:4
95:5
95:5
96:4
However, to verify our recent finding that n-propylamine
(19) represents the only sterically less demanding amine
that does not need to be added slowly to the reaction mix-
ture during the hydroamination reactions,14 we developed
a general procedure for a regioselective hydroamination/
reduction sequence for 1-phenyl-2-alkylalkynes employ-
ing 19 on a 10 mmol scale. Equation 3 and Table 2 im-
pressively show that Ind2TiMe2-catalyzed additions of n-
propylamine (19) to unsymetrically substituted 1-phenyl-
2-alkylalkynes possessing a sterically less demanding
alkyl substituent strongly favor the formation of the anti-
Markovnikov regioisomers. However, to get the best re-
sults on a 10 mmol scale these hydroamination reactions
employing n-propylamine (19) need to be performed at
130 °C (Procedure 2). After subsequent reduction with
NaBH3CN/ZnCl2, biologically interesting 2-phenylethyl-
amine derivatives possessing an n-propyl substituent at
the nitrogen atom are obtainable with good yields and
very good regioselectivities. Usually, it is possible to sep-
arate the major regioisomer from the minor isomer by
flash chromatography (see above). Unfortunately, the
same procedure does not give satisfactory results for
ortho-substituted (MeO, Cl) 1-phenyl-2-alkylalkynes. In
these cases, the hydroamination reactions reach only a
30% conversion within 24 hours. However, hydroamina-
tion reactions of corresponding substrates under harsher
conditions (140 °C, 48 h, 10 mol% Ind2TiMe2) combined
with reductions gave the corresponding amine products in
55–72% yield.
4-MeO 84 (21a/b)
4-Cl 82 (22a/b)
3-MeO 83 (23a/b)
3-Cl 82 (24a/b)
a Obtained after one chromatography. A complete separation of the
regioisomers can be achieved by two subsequent chromatographies.
All reactions were performed under argon in flame dried Duran
glassware (e.g. Schlenk tubes equipped with Teflon stopcocks).
Toluene was distilled from molten sodium under argon. MeOH was
dried with molecular sieves (3 Å). Alkynes and amines were dis-
tilled and stored over molecular sieves (4 Å). All other reagents
were purchased from commercial sources and were used without
1
further purification. All amine products were characterized by H
NMR, 13C NMR, IR, and mass spectroscopy. Additional character-
ization data were obtained by CHN elemental analysis. All 1H NMR
spectra are reported in d units ppm downfield from tetramethyl-
silane internal standard. The 13C NMR spectra are reported in d
units ppm relative to the central line of the triplet for CDCl3 at 77.0
ppm or the triplet for C6D6 at 128.5 ppm. Characterization data are
only given for representative examples. PE = light petroleum ether
(bp 40–60 °C).
15
Ind2TiMe2
To a mixture of Ind2TiCl2 (1.00 g, 2.87 mmol) and Et2O (30 mL)
was added dropwise a 1.6 M solution of MeLi in Et2O (5.4 mL, 8.61
mmol) over a period of 5 min at –15 °C. After stirring the mixture
for 2 h at –15 °C, the resulting orange solution was carefully poured
onto a mixture of H2O and ice (30 mL). The organic layer was sep-
arated and dried (Na2SO4). After concentration under vacuum,
Ind2TiMe2 (0.82 g, 93%) was obtained as a yellow crystalline com-
pound. Note: Prolonged handling of Ind2TiMe2 in solution should
be avoided.
1H NMR (400 MHz, C6D6): d = –0.48 (s, 6 H), 5.38 (t, J = 3.3 Hz,
2 H), 5.79 (d, J = 3.3 Hz, 4 H), 6.94 (dd, J = 6.5, 3.0 Hz, 4 H), 7.20
(dd, J = 6.5, 3.0 Hz, 4 H).
13C NMR (100.6 MHz, APT, C6D6): d = 51.4 (CH3), 105.3 (CH),
117.6 (CH), 125.5 (CH), 125.6 (C), 125.7 (CH).
In summary, 2-phenylethylamines are easily accessible in
good to excellent yields from 1-phenyl-2-alkylalkynes
and primary amines by hydroamination/reduction se-
quences employing Ind2TiMe2 as highly active and gener-
al hydroamination catalyst and zinc-modified NaBH3CN
as reducing agent. Particularly important is the fact that
with Ind2TiMe2 as the hydroamination catalyst, all possi-
ble substrate combinations of alkynes and primary amines
can be used. However, the Procedures 1 and 2 given in the
NHn-Pr
1) 5 mol% Ind2TiMe2
toluene, 130 °C, 24 h
+
10 mmol scale
n-PrNH2
+
NHn-Pr
2) NaBH3CN, ZnCl2
MeOH, 25 °C, 20 h
R
R
R
20a–24a
20b–24b
14–18
19
Equation 3
Synthesis 2005, No. 7, 1200–1204 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Regioselective Preparation of 2-Phenylethylamines
1203
Procedure 1
Amine 11a
Hydroamination/Reduction Sequence on a 10 mmol Scale Em-
ploying 1-(4-Methoxyphenyl)propyne (Table 1)
Procedure 1 was used to synthesize amine 11a from 1-(4-methoxy-
phenyl)propyne (1) and tert-butylamine (5). The reaction time of
the hydroamination step was 5 h. Since only a single regioisomer
was detected by gas chromatography, purification of the crude
product was performed by Kugelrohr distillation under vacuum.
Amine 11a (1.56 g, 70%) was obtained as a colorless oil.
A 100 mL Schlenk tube equipped with a Teflon stopcock and a
magnetic stirring bar was charged with 1-(4-methoxyphenyl)pro-
pyne (1; 1.46 g, 10.0 mmol), the appropriate amine (11.0 mmol),
Ind2TiMe2 (308 mg, 0.5 mmol, 5.0 mol%), and toluene (2.0 mL).
The sealed Schlenk tube containing the reaction mixture was heated
to 105 °C (TLC control). Then, the mixture was cooled to r.t. and a
mixture of NaBH3CN (1.26 g, 20.0 mmol) and ZnCl2 (1.36 g, 10.0
mmol) in MeOH (20 mL) was added. After this had been stirred at
25 °C for 20 h, CH2Cl2 (50 mL) and aq sat. Na2CO3 solution (20
mL) were added. The resulting mixture was filtered and the solid
residue was washed with CH2Cl2 (50 mL). After extraction, the or-
ganic layer was separated. The aqueous layer was extracted with
CH2Cl2 (6 × 50 mL) and the combined organic layers were dried
(Na2SO4). After concentration under vacuum, the crude mixture of
regioisomers was analyzed by GC (Table 1) and purified by flash
chromatography (SiO2) or Kugelrohr distillation.
IR (neat): 2960, 1612, 1512, 1464, 1364, 1300, 1247, 1176, 1139,
1039, 816 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.01 (s, 9 H), 1.05 (d, J = 6.3 Hz,
3 H), 2.51 (dd, J = 13.2, 7.4 Hz, 1 H), 2.60 (dd, J = 13.2, 7.0 Hz, 1
H), 2.92 (sext, J = 6.6 Hz, 1 H), 3.78 (s, 3 H), 6.82 (br d, J = 8.5 Hz,
2 H), 7.09 (br d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, DEPT, CDCl3): d = 23.8 (CH3), 29.9 (CH3),
45.4 (CH2), 49.2 (CH), 50.8 (C), 55.8 (CH3), 113.6 (CH), 130.1
(CH), 132.1 (C), 157.9 (C).
MS (25 °C): m/z (%) = 222 (9), 206 (1), 149 (10), 121 (12), 100
(100), 91 (2).
Anal. Calcd for C14H23NO: C, 75.97; H, 10.47; N, 6.33. Found: C,
75.99; H, 10.51; N, 6.22.
Procedure 2
Hydroamination/Reduction Sequence on a 10 mmol Scale Em-
ploying n-Propylamine (Table 2)
Amine 21a
A 100 mL Schlenk tube equipped with a Teflon stopcock and a
magnetic stirring bar was charged with the alkyne (10.0 mmol), n-
propylamine (19; 650 mg, 11.0 mmol), Ind2TiMe2 (308 mg, 0.5
mmol, 5.0 mol%), and toluene (2.0 mL). The sealed Schlenk tube
containing the reaction mixture was heated to 130 °C for 24 h (due
to the small amount of volatile material in the 100 mL Schlenk tube,
no special precautions were necessary for the reactions run at
130 °C). Then, the mixture was cooled to r.t. and a mixture of
NaBH3CN (1.26 g, 20.0 mmol) and ZnCl2 (1.36 g, 10.0 mmol) in
MeOH (20 mL) was added. After this had been stirred at 25 °C for
20 h, CH2Cl2 (50 mL) and aq sat. Na2CO3 solution (50 mL) were
added. The resulting mixture was filtered and the solid residue was
washed with CH2Cl2 (20 mL). After extraction, the organic layer
was separated and the aqueous layer was extracted with CH2Cl2
(6 × 50 mL). The combined organic layers were dried (Na2SO4).
After concentration under vacuum, the crude mixture of regioiso-
mers was analyzed by GC (Table 2) and purified by flash chroma-
tography (SiO2).
Procedure 2 was used to synthesize amine 21a from 1-(4-methoxy-
phenyl)pentyne (15) and n-propylamine (19). After purification of
the crude mixture of regioisomers by flash chromatography (SiO2,
PE–EtOAc, 1:1) amine 21a (1.48 g, 63%) and a mixture of regio-
isomers 21a and 21b (0.49 g, 21%) were obtained.
IR (neat): 2956, 2931, 2872, 1612, 1512, 1465, 1300, 1247, 1177,
1127, 1039, 833, 807 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.84 (t, J = 7.4 Hz, 3 H), 0.91 (t,
J = 7.4 Hz, 3 H), 1.21 (br s, 1 H), 1.33–1.48 (m, 6 H), 2.44–2.71 (m,
5 H), 3.79 (s, 3 H), 6.83 (br d, J = 8.8 Hz, 2 H), 7.10 (br d, J = 8.8
Hz, 2 H).
13C NMR (75 MHz, DEPT, CDCl3): d = 11.7 (CH3), 14.3 (CH3),
19.0 (CH2), 23.4 (CH2), 36.2 (CH2), 39.8 (CH2), 49.1 (CH2), 55.1
(CH3), 59.0 (CH), 113.7 (CH), 130.1 (CH), 131.8 (C), 157.9 (C).
MS (25 °C): m/z (%) = 236 (5), 192 (2), 121 (8), 114 (100), 72 (6).
Anal. Calcd for C15H25NO: C, 76.55; H, 10.71; N, 5.95. Found: C,
76.24; H, 10.80; N, 5.94.
Amine 8a
Procedure 1 was used to synthesize amine 8a from 1-(4-methoxy-
phenyl)propyne (1) and aniline (2). The reaction time of the hy-
droamination step was 24 h. After purification of the crude mixture
of regioisomers by flash chromatography (SiO2, PE–EtOAc, 10:1),
amine 8a (2.11 g, 87%) and a mixture of regioisomers 8a and 8b
(0.24 g, 10%) were obtained.
Amine 22a
Procedure 2 was used to synthesize amine 22a from 1-(4-chlorophe-
nyl)pentyne (16) and n-propylamine (19). After purification of the
crude mixture of regioisomers by flash chromatography (SiO2, PE–
EtOAc, 1:1) amine 22a (1.51 g, 63%) and a mixture of regioisomers
22a and 22b (0.46 g, 19%) were obtained.
IR (neat): 3399, 2962, 2929, 2834, 1601, 1505, 1455, 1318, 1247,
1178, 1153, 1034, 813, 750, 694 cm–1.
IR (neat): 2957, 2930, 2872, 1492, 1465, 1407, 1378, 1129, 1092,
1016, 832, 801 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.83–0.92 (m, 6 H), 1.03 (br s, 1
H), 1.31–1.48 (m, 6 H), 2.45–2.59 (m, 2 H), 2.61–2.73 (m, 3 H),
7.11 (br d, J = 8.5 Hz, 2 H), 7.25 (br d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, DEPT, CDCl3): d = 11.7 (CH3), 14.2 (CH3),
18.9 (CH2), 23.4 (CH2), 36.1 (CH2), 40.1 (CH2), 49.1 (CH2), 58.8
(CH), 128.3 (CH), 130.5 (CH), 131.7 (C), 138.3 (C).
1H NMR (300 MHz, CDCl3): d = 1.10 (d, J = 6.3 Hz, 3 H), 2.62 (dd,
J = 13.6, 7.4 Hz, 1 H), 2.83 (dd, J = 13.6, 4.8 Hz, 1 H), 3.45 (br s, 1
H), 3.64–3.72 (m, 1 H), 3.74 (s, 3 H), 6.58 (d, J = 7.7 Hz, 2 H), 6.67
(t, J = 7.4 Hz, 1 H), 6.81 (br d, J = 8.5 Hz, 2 H), 7.07 (br d, J = 8.5
Hz, 2 H), 7.16 (t, J = 7.7 Hz, 2 H).
13C NMR (75 MHz, DEPT, CDCl3): d = 20.0 (CH3), 41.2 (CH2),
49.3 (CH), 55.1 (CH3), 113.3 (CH), 113.7 (CH), 117.0 (CH), 129.3
(CH), 130.3 (CH), 130.4 (C), 147.2 (C), 158.1 (C).
MS (25 °C): m/z (%) = 240 (5), 196 (3), 125 (8), 114 (100), 72 (6).
MS (25 °C): m/z (%) = 241 (6), 121 (13), 120 (100), 91 (2), 77 (6).
Anal. Calcd for C14H22ClN: C, 70.13; H, 9.25, N, 5.84; Cl, 14.79.
Found: C, 70.01; H, 9.34; N, 6.05; Cl, 14.87.
Anal. Calcd for C16H19NO: C, 79.63; H, 7.94; N, 5.80. Found: C,
79.36; H, 8.06; N, 5.85.
Synthesis 2005, No. 7, 1200–1204 © Thieme Stuttgart · New York

1204
A. Heutling et al.
PRACTICAL SYNTHETIC PROCEDURES
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Acknowledgment
Generous support by Professor E. Winterfeldt is most gratefully
acknowledged. We further thank the Deutsche Forschungsgemein-
schaft, the Fonds der Chemischen Industrie, and the Dr. Otto Röhm
Gedächtnisstiftung, Darmstadt for financial support of our research.
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