An (Aminopyrimidinato)titanium catalyst for the hydroamination of alkynes and alkenes

Article abstract of DOI:10.1002/ejoc.201301004

A new (aminopyrimidinato)titanium complex has been synthesised from inexpensive and easily accessible 2-(tert-butylamino)pyrimidine and [Ti(NMe ₂)₄] and used as a catalyst for the intermolecular hydroamination of alkynes as well as the cyclization of aminoalkenes. The hydroamination reactions of 1-phenylpropyne and terminal arylalkynes deliver the corresponding anti-Markovnikov addition products with excellent yields and regioselectivities. A new (aminopyrimidinato)titanium complex has been synthesised from inexpensive 2-(tert-butylamino)pyrimidine and [Ti(NMe ₂)₄] and used as a catalyst for the intermolecular hydroamination of alkynes as well as the cyclization of aminoalkenes. The complex represents the first example of a catalyst for the hydroamination of alkynes that contains an aminoheteroaromatic ancillary ligand.

Full text of DOI:10.1002/ejoc.201301004

FULL PAPER
DOI: 10.1002/ejoc.201301004
An (Aminopyrimidinato)titanium Catalyst for the Hydroamination of Alkynes
and Alkenes
Christian Brahms,[a] Patrik Tholen,[a] Wolfgang Saak,[a] and Sven Doye*[a]
Keywords: Synthetic methods / Hydroamination / Nitrogen heterocycles / Alkenes / Alkynes / Amines / Titanium
A new (aminopyrimidinato)titanium complex has been syn-
thesised from inexpensive and easily accessible 2-(tert-but-
ylamino)pyrimidine and [Ti(NMe2)4] and used as a catalyst
for the intermolecular hydroamination of alkynes as well as
the cyclization of aminoalkenes. The hydroamination reac-
tions of 1-phenylpropyne and terminal arylalkynes deliver
the corresponding anti-Markovnikov addition products with
excellent yields and regioselectivities.
titanium catalysts for the intramolecular hydroamination of
primary aminoalkenes.[7]
Introduction
The direct addition of N–H across carbon–carbon mul-
tiple bonds represents a very promising synthetic approach
towards waste-free production of various nitrogen-contain-
ing molecules. As a consequence, the so-called hydro-
amination of unactivated alkenes and alkynes has been ex-
tensively investigated in recent years[1] and it turned out
that group 4 metal complexes are among the most promis-
ing catalysts for these highly desirable synthetic transforma-
tions.[2] Interestingly, a number of these group 4 metal com-
plexes are also able to catalyze a closely related reaction,
the so-called hydroaminoalkylation of alkenes, which in-
volves the addition of the α-C–H bond of an amine across
a C–C double bond.[3,4] During a recent study directed
towards optimization of the latter transformation, we found
that (2-aminopyridinato)titanium complexes,[5] generated in
situ from [Ti(NMe2)4] and 2-(methylamino)pyridine, are
particularly efficient catalysts for the regioselective hydro-
aminoalkylation of styrenes.[4g] Inspired by this finding and
by the surprising fact that, to the best of our knowledge,
corresponding catalysts have never been used for alkyne
hydroamination before, we decided to investigate the poten-
tial use of (aminopyridinato)titanium complexes as well as
titanium complexes with other N,N-chelating ligands as
hydroamination catalysts. In this context, it must be noted
that in 2005 and 2007, Eisen et al. described the unusual
hydroamination of methylenecyclopropanes in the presence
of a titanium catalyst that contained two 2-[(diphenylphos-
phanyl)amino]pyridinato ancillary ligands[6] and, very re-
cently, during the course of our sudy, Schafer and Kempe
et al. presented the first examples of (2-aminopyridinato)-
Results and Discussion
Initial hydroamination reactions of alkynes that were
performed in the presence of the above mentioned (2-
aminopyridinato)titanium catalysts generated in situ from
[Ti(NMe2)4] and one or two equivalents of 2-(methyl-
amino)pyridine gave only disappointing results. However,
based on the well-established fact that sterically hindered
and electrophilic titanium complexes usually represent
highly active hydroamination catalysts,[2] we chose 2-(tert-
butylamino)pyrimidine (1; Scheme 1) as a promising alter-
native ligand precursor because it consists of a sterically
demanding tert-butylamino group in combination with a
more electron-deficient pyrimidine ring. Aminopyrimidine
1 is easily accessible in one step from commercially available
and inexpensive 2-chloropyrimidine and tert-butylamine by
nucleophilic aromatic substitution.[8] Treatment of
[Ti(NMe2)4] with two equivalents of ligand precursor 1 at
room temperature in diethyl ether resulted in the clean for-
mation of aminopyrimidinato complex 2 in excellent yield
(Scheme 1). The obtained solid material could be recrys-
tallized from hexanes to give red crystals that were suitable
for X-ray crystallographic analysis (Figure 1).[9] The solid-
state structure surprisingly reveals a highly unsymmetrical
and strongly distorted octahedral geometry around the tita-
nium centre. However, initial hydroamination reactions of
1-phenylpropyne (3) with p-toluidine (4) revealed that com-
plex 2 is a competent catalyst for the intermolecular hydro-
amination of alkynes (Table 1). In the presence of 5 mol-%
2, the reaction goes to completion within 24 h at 80 °C and,
after subsequent reduction (NaBH3CN/ZnCl2), the product
5a could be isolated in 97% yield (Table 1, entry 3). Particu-
larly important is the fact that no formation of the Markov-
nikov regioisomer 5b could be observed by GC analysis.
[a] Institut für Chemie, Universität Oldenburg,
Carl-von-Ossietzky-Str. 9–11, 26111 Oldenburg, Germany
E-mail: doye@uni-oldenburg.de
http://www.chemie.uni-oldenburg.de/oc/doye
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301004.
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C. Brahms, P. Tholen, W. Saak, S. Doye
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This finding is in sharp contrast to a comparable control gioisomer. Although ortho,ortho-dimethyl-substituted sub-
experiment performed with [Ti(NMe2)4] as the hydro- strates 2,6-dimethylaniline and 2,4,6-trimethylaniline clearly
amination catalyst,[10] which resulted in the formation of a represent good substrates for the two-step process, the pres-
93:7 mixture of regioisomers 5a and 5b (91% yield).
ence of one large ortho-bromo substituent on the aniline
system leads to a significantly reduced rate of the hydro-
amination reaction (Table 2, entry 5). In this case, the reac-
tion time of the hydroamination step had to be extended to
48 h to obtain the corresponding product 9a in a moderate
yield of only 59%. Interestingly, the ortho-bromo derivative
also results in a slightly reduced regioselectivity (97:3) of
the hydroamination reaction. On the other hand, various
alkylamines (Table 2, entries 6–10) undergo the hydro-
amination/reduction sequence with much better yields (Ն
85%). However, as observed before,[11] the regioselectivity
of the hydroamination significantly decreases with decreas-
ing steric bulk of the amine substrate. As a result, the use
of sterically less demanding n-octylamine or benzylamine
led to regioselectivities of only 9:1 (Table 2, entries 6 and
7). Regarding these two substrates, it is also worth men-
tioning that the hydroamination does not require slow ad-
dition of the amine to the reaction mixture, which was es-
sential for the corresponding [Ind2TiMe2]-catalysed (Ind =
η5-indenyl) hydroamination reactions.[11b] Among the steri-
cally more demanding alkylamines, isobutylamine, cyclo-
pentylamine and benzhydrylamine, the latter substrate
clearly gave the most promising result (Table 2, entry 10)
because the obtained product 14a (90% yield) represents an
N-protected amphetamine, which can easily be deprotected
Scheme 1. Synthesis of bis[2-(tert-butylamino)pyrimidine]bis(di-
methylamino)titanium (2).[8]
Table 1. Hydroamination of 1-phenylpropyne (3) with p-toluidine
(4) catalysed by complex 2 and subsequent reduction.
Figure 1. X-ray crystal structure of complex 2.[9] Selected bond
lengths [Å] and angles [°]: Ti1–N1 2.1875(9), Ti1–N2 2.2055(9),
Ti1–N4 2.2548(8), Ti1–N5 2.0686(9), Ti1–N7 1.9234(8), Ti1–N8
1.9233(8), N1–Ti1–N2 60.79(3), N4–Ti1–N5 61.60(3), C1–N1–Ti1
94.08(6), C1–N2–Ti1 95.10(6), C9–N4–Ti1 90.11(6), C9–N5–Ti1
98.93(6).
Although the reaction sequence of 1-phenylpropyne (3)
with p-toluidine (4) also gives satisfactory results with a
lower catalyst loading (3 mol-%; Table 1, entry 9) or a re-
duced reaction time (12 h) of the hydroamination step
(Table 1, entry 7), we performed additional hydroamin-
ation/reduction sequences with alkyne 3 and a variety of
primary amines under the conditions detailed in Table 1,
entry 3 (5 mol-% 2, 80 °C, 24 h). The corresponding results
shown in Table 2 (entries 1–10) clearly show that the amino-
pyrimidinato complex 2 is a very good catalyst for highly
regioselective addition of many aryl- and alkylamines to 1-
phenylpropyne (3). When methyl- or methoxy-substituted
anilines were used as amine substrates (Table 2, entries 1–4)
for the hydroamination/reduction sequence, the correspond-
ing biologically interesting 2-phenylethylamine derivatives
could be isolated in excellent yields (Ն 89%). In all cases,
the regioselectivity of amine addition to 1-phenylpropyne
Entry
Catalyst 2
T
[°C]
t
[h]
Yield
[%][a]
Ratio
[mol-%]
5a/5b[b]
1
2
3
4
5
6
7
8
9
10
5
5
5
5
5
5
5
5
3
1
105
90
80
70
60
80
80
80
80
80
24
24
24
24
24
18
12
6
97
97
97
54
10
95
90
70
90
20
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
97:3
24
24
[a] Reaction conditions: (1) alkyne
3 (2.40 mmol), amine 4
(2.64 mmol), catalyst 2, toluene (1 mL); (2) NaBH3CN
(4.80 mmol), ZnCl2 (2.40 mmol), MeOH (10 mL), 25 °C, 20 h,
yields refer to isolated compounds. [b] The ratio of 5a/5b was deter-
(3) was Ն 99:1 in favour of the anti-Markovnikov re- mined by GC analysis prior to flash chromatography.
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A Catalyst for Hydroamination of Alkynes and Alkenes
Table 2. Hydroamination/reduction reaction sequences with alkynes and primary amines performed with catalyst 2.
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Table 2. (continued).
[a] Reaction conditions: (1) alkyne (2.40 mmol), amine (2.64 mmol), catalyst 2 (0.12 mmol, 5 mol-%), toluene (1 mL), 50–120 °C, 24 h;
(2) NaBH3CN (4.80 mmol), ZnCl2 (2.40 mmol), MeOH (10 mL), 25 °C, 20 h, yields refer to isolated compounds (a + b). [b] The ratio of
a/b was determined by GC analysis prior to flash chromatography. [c] The reaction time was 48 h.
under reductive conditions.[12] The very good regioselectiv-
To complete the investigation of the behaviour of various
ity of the hydroamination (99:1) clearly proves that benz- alkynes, we also used aminopyrimidinato catalyst 2 for
hydrylamine is a much better ammonia equivalent for the hydroamination/reduction sequences of less reactive dialk-
hydroamination of alkynes than benzylamine, which only yl- or diaryl-substituted internal alkynes (Table 2, entries
gave a modest regioselectivity (90:10; Table 2, entry 6). In 18–20). Whereas the hydroamination of 2-butyne already
this context, it should be noted that product 8a (Table 2, takes place at 80 °C with a reasonable rate (Table 2, en-
entry 4) also contains a protecting group on the nitrogen try 18), high-yielding transformations of the sterically more
atom. The well-established p-methoxyphenyl group can eas- demanding alkynes 4-octyne and diphenylacetylene re-
ily be cleaved under oxidative conditions.[13] Probably as a
result of the sterically very demanding aminopyrimidinato
ligands of catalyst 2 so far, no successful reaction could be
achieved with tert-butylamine.
Table 3. Intramolecular hydroamination of aminoalkenes catalysed
by complex 2.[a]
To gain a preliminary impression of the behaviour of ad-
ditional alkynes, we then focused on the corresponding
transformations of terminal aryl- and alkylalkynes with p-
toluidine (4; Table 2, entries 11–17). First, it must be men-
tioned that electron-neutral and electron-poor arylalkynes
undergo facile hydroamination even at 50 °C with excellent
regioselectivities of Ն 98:2 in favour of the anti-Markovni-
kov addition products (Table 2, entries 11–13).[14] Although
hydroamination of the electron-rich arylalkyne 4-methoxy-
phenylacetylene was slow at 50 °C, a good yield of the
hydroamination/reduction sequence could be achieved
when the hydroamination was performed at 80 °C. How-
ever, in this case a significantly reduced regioselectivity of
only 88:12 was observed (Table 2, entry 14). Interestingly
and in good agreement with reported results with other tita-
nium catalysts,[11b] the regioselectivity of the hydroamin-
ation was reversed when alkylalkynes were used as sub-
strates (Table 2, entries 15–17). In these cases, the Marovni-
kov addition products are formed preferentially, with mod-
est to good selectivities. However, even in these cases the
combined yields of both regioisomers obtained from the
hydroamination/reduction sequences were good.
Entry
n
R1
T [°C]
R2
Yield [%][b]
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
2
2
2
2
3
Ph (25)
95
H (26)
45
96
99
64
76
83
–
75
87
37
–
Ph (25)
105
120
120
140
160
160
140
160
160
H (26)
Ph (25)
H (26)
–(CH2)5– (27)
–(CH2)5– (27)
–(CH2)5– (27)
Me (29)
pTs (28)
pTs (28)
pTs (28)
pTs (30)
H (32)
Ph (31)
Ph (31)
–(CH2)5– (33)
Me (35)
Ph (37)
9
H (32)
pTs (34)
10
11
12
105–160 pTs (36)
105–200 H (38)
–
[a] Reaction conditions: (1) aminoalkene (2.00 mmol), catalyst 2
(0.10 mmol, 5 mol-%), toluene (1 mL), 95–200 °C, 24 h; if appli-
cable (2) p-toluenesulfonyl chloride (3.00 mmol), NaOH (1 m,
6 mL), CH2Cl2 (20 mL), 25 °C, 18 h. [b] Isolated yield.
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A Catalyst for Hydroamination of Alkynes and Alkenes
mined by gas chromatography prior to flash chromatography. For
thin-layer chromatography, silica on aluminium foil with fluores-
cent indicator 254 nm from Fluka was used. The substances were
detected with UV light and/or iodine. For flash chromatography,
silica gel from Fluka (particle size 0.037–0.063 mm) was used. Prior
to use, hexanes, ethyl acetate and tert-butylmethyl ether (MTBE)
were distilled for flash chromatography. All products that have al-
ready been reported in the literature were characterized by 1H
NMR, 13C NMR and 19F NMR spectroscopic analysis if appli-
cable and identified by comparison with the literature data. New
quired elevated temperatures (Table 2, entries 19 and 20).
However, even in these cases, the products of the hydro-
amination/reduction sequences were obtained in good to
very good yields.
Finally, we found that aminopyrimidinato complex 2 was
also able to catalyze the intramolecular hydroamination of
selected gem-disubstituted aminoalkenes (Table 3). A selec-
tion of corresponding pyrrolidines (26, 28) and piperidine
(32, 34) derivatives could be isolated in good to very good
yields from reaction mixtures that had been stirred for 24 h products were additionally characterized by infrared (IR) spec-
troscopy and mass spectrometry (MS and HRMS). NMR spectra
were recorded with Bruker Avance DRX 500 MHz or Bruker
Avance III 500 MHz spectrometers. All 1H NMR spectra are re-
ported in δ units (ppm) relative to the signal of CDCl3 (δ =
7.26 ppm), or the signal of ferrocene (δ = 4.00 ppm), or the signal
of the methyl group of [D8]toluene (δ = 2.08 ppm). All 13C NMR
spectra are reported in δ units (ppm) relative to the central line of
the triplet for CDCl3 (δ = 77.16 ppm) or to the methyl group of
[D8]toluene (δ = 20.43 ppm). 19F NMR spectra are reported in δ
units (ppm) relative to the signal of CFCl3 (δ = 0.00 ppm). Mass
spectra were recorded with a Finnigan MAT 95 spectrometer (EI)
or a Waters Q-TOF Premier spectrometer (ESI). Infrared spectra
were recorded with a Bruker Tensor 27 spectrometer equipped with
a MKII Golden Single Reflection Diamond using an attenuated
total reflection (ATR) method. GC analyses were performed with
a Shimadzu GC-2010 plus gas chromatograph equipped with a
flame-ionization detector. Melting points were determined in a
capillary with a Schropp-Gerätetechnik melting point MPM-H2
apparatus.
at elevated temperatures in the presence of 5 mol-% catalyst
2. This finding, in combination with the results described
for the hydroamination of alkynes, strongly underlines the
impression that titanium complexes with aminopyridinato
ligands[7] or other N,N-chelating ligands represent a very
promising new class of hydroamination catalysts.
Conclusions
Our studies have shown that an (aminopyrimidinato)tita-
nium complex can be used as an efficient catalyst for the
intermolecular hydroamination of alkynes as well as the cy-
clization of selected gem-disubstituted aminoalkenes. Par-
ticularly important is the fact that corresponding reactions
of 1-phenylpropyne and terminal arylalkynes deliver the
corresponding anti-Markovnikov hydroamination products
with excellent yields and regioselectivities. This finding, in
combination with the good results obtained with the two
ammonia equivalents benzhydrylamine and p-methoxyanil-
ine, will offer a number of synthetic possibilities for future
applications of the process. The new hydroamination cata-
lyst is easily accessible from inexpensive and readily avail-
able starting materials {2-(tert-butylamino)pyrimidine and
[Ti(NMe2)4]} and represents the first example of a catalyst
for the hydroamination of alkynes that contains an amino-
heteroaromatic ancillary ligand. Further studies dealing
with early-transition-metal hydroamination catalysts ob-
tainable from many other easily accessible aminoheteroaro-
matics will be reported in due course.
Bis[2-(tert-butylamino)pyrimidine]bis(dimethylamino)titanium (2):
[Ti(NMe2)4] (0.673 g, 3.0 mmol) was slowly added to a solution of
2-(tert-butylamino)pyrimidine (1; 0.907 g, 6.0 mmol) in Et2O
(5 mL) at 25 °C. The reaction mixture was stirred for 4 h and then
the solvent was removed under vacuum. The resulting solid was
recrystallized from hexanes to give red crystals of complex 2
(1.178 g, 2.70 mmol, 90%). 1H NMR (500 MHz, [D8]toluene,
25 °C): δ = 7.89 (dd, J = 4.4, 2.9 Hz, 2 H, Ar-H), 7.43 (br. s, 2 H,
Ar-H), 5.54 (t, J = 4.7 Hz, 2 H, Ar-H), 3.22 (s, 12 H, N-CH3), 1.59
(s, 18 H, CH3) ppm. 13C NMR (125 MHz, [D8]toluene, 25 °C): δ =
166.1 (C), 159.1 (CH), 151.3 (CH), 104.7 (CH), 55.1 (C), 48.5
(CH3), 30.2 (CH3) ppm. MS (ESI, CH2Cl2 + MeOH): m/z (%) =
436 (100) [M]+.
Intermolecular Hydroamination of Alkynes. General Procedure A:
An oven-dried Schlenk tube equipped with a Teflon stopcock and
a magnetic stirring bar was transferred into a nitrogen-filled
glovebox and charged with catalyst 2 (52 mg, 0.12 mmol, 5 mol-%),
alkyne (2.40 mmol), amine (2.64 mmol) and toluene (1 mL). The
tube was sealed and the resulting mixture was heated to 50–120 °C
(Table 2) for 24 h, then the mixture was cooled to room tempera-
ture, and a mixture of NaBH3CN (302 mg, 4.80 mmol) and anhy-
drous ZnCl2 (327 mg, 2.40 mmol) in anhydrous methanol (10 mL)
was added. The mixture was stirred at 25 °C for 20 h, then CH2Cl2
(40 mL) and saturated aqueous Na2CO3 solution (50 mL) were
added. After extraction, the organic layer was separated and the
aqueous layer was extracted with CH2Cl2 (5ϫ20 mL). The com-
bined organic layers were dried with MgSO4 and, after concentra-
tion under vacuum, the residue was purified by flash chromatog-
raphy (SiO2) to give the amine products.
Experimental Section
General: All reactions were performed under an inert atmosphere
of nitrogen in oven-dried Schlenk tubes (Duran glassware, 100 mL,
ø = 30 mm) equipped with Teflon stopcocks and magnetic stirring
bars (15ϫ4.5 mm). Complex [Ti(NMe2)4], tert-butylamine, 2-
chloropyrimidine and toluene (toluene extra dry with molecular
sieves) were purchased from Acros Organics. 2-(tert-Butylamino)-
pyrimidine (1) was synthesised according to a literature pro-
cedure.[8] Prior to use, all alkynes, amines and aminoalkenes were
purified by Kugelrohr distillation and degassed. Alkynes, amines,
aminoalkenes,
bis[2-(tert-butylamino)pyrimidine]bis(dimethyl-
amino)titanium (2) and toluene were stored in a nitrogen-filled
glovebox (M. Braun, Unilab). All other reagents were purchased
from commercial sources and were used without further purifica-
tion. Unless otherwise noted, yields refer to isolated yields of pure
compounds as gauged by thin-layer chromatography (TLC), 1H
and 13C NMR spectroscopy. The ratio of regioisomers was deter-
Intramolecular Hydroamination of Alkenes. General Procedure B:
An oven-dried Schlenk tube equipped with a Teflon stopcock and
a magnetic stirring bar was transferred into a nitrogen-filled
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C. Brahms, P. Tholen, W. Saak, S. Doye
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glovebox and charged with catalyst 2 (44 mg, 0.10 mmol, 5 mol-%),
aminoalkene (2.00 mmol) and toluene (1 mL). The tube was sealed
and the resulting mixture was heated to 95–200 °C (Table 3) for
24 h, then the mixture was cooled to room temperature and hydro-
lysed with wet CH2Cl2 (20 mL). After concentration under
vacuum, the residue was purified by flash chromatography (SiO2)
to give the amine product.
CDCl3, 25 °C): δ = 142.2 (C), 139.6 (C), 130.8 (C), 129.6 (CH),
129.5 (C), 129.5 (CH), 128.3 (CH), 126.1 (CH), 54.4 (CH), 44.5
(CH2), 20.8 (CH3), 20.7 (CH3), 19.0 (CH3) ppm. MS (EI, 70 eV):
m/z (%) = 253 (1) [M]+, 162 (100) [C11H16N]+, 91 (19) [C7H7]+.
HRMS (EI, 70 eV): calcd. for C18H23N 253.1825; found 253.1826.
IR (ATR): ν = 661, 698, 738, 761, 855, 920, 987, 1030, 1099, 1128,
˜
1221, 1259, 1343, 1373, 1439, 1454, 1473, 1495, 1594, 2857, 2923,
2962, 3027, 3382 cm–1.
Intramolecular Hydroamination of Alkenes and Subsequent Forma-
tion of a p-Toluenesulfonamide. General Procedure C: An oven-dried
Schlenk tube equipped with a Teflon stopcock and a magnetic stir-
ring bar was transferred into a nitrogen-filled glovebox and charged
4-Methoxy-N-(1-methyl-2-phenylethyl)aniline (8a):[15] General pro-
cedure A (80 °C) was used to synthesise the title compound from
1-phenylpropyne and p-methoxyaniline. Purification by flash
chromatography (SiO2; hexanes/EtOAc, 10:1) gave product 8a
(556 mg, 2.30 mmol, 96%) as a colourless oil. Rf = 0.23 (hexanes/
with catalyst
2 (44 mg, 0.10 mmol, 5 mol-%), aminoalkene
(2.00 mmol) and toluene (1 mL). The tube was sealed and the re-
sulting mixture was heated to 120–160 °C (Table 3) for 24 h, then
the mixture was cooled to room temperature and hydrolysed with
wet CH2Cl2 (20 mL). The obtained mixture was transferred into a
50 mL round-bottom flask and p-toluenesulfonyl chloride (572 mg,
3.00 mmol) and aqueous sodium hydroxide (1 m, 6 mL) were
added. The resulting two-phase mixture was stirred at 25 °C for
18 h, then the organic layer was separated and dried with MgSO4.
After concentration under vacuum, the residue was purified by
flash chromatography (SiO2) to give the p-toluenesulfonamide
product.
1
EtOAc, 10:1). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.35 (t, J
= 7.4 Hz, 2 H, Ar-H), 7.27 (t, J = 7.4 Hz, 1 H, Ar-H), 7.24 (d, J
= 7.0 Hz, 2 H, Ar-H), 6.86 (d, J = 8.9 Hz, 2 H, Ar-H), 6.67 (d, J
= 8.9 Hz, 2 H, Ar-H), 3.80 (s, 3 H, O-CH3), 3.77–3.70 (m, 1 H,
CH), 3.27 (br. s, 1 H, N-H), 2.99 (dd, J = 13.4, 4.8 Hz, 1 H, CH2),
2.72 (dd, J = 13.4, 7.4 Hz, 1 H, CH2), 1.19 (d, J = 6.4 Hz, 3 H,
CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 152.1
(C), 141.4 (C), 138.7 (C), 129.6 (CH), 128.4 (CH), 126.3 (CH),
115.1 (CH), 55.8 (CH3), 50.5 (CH), 42.4 (CH2), 20.3 (CH3) ppm.
2-Bromo-N-(1-methyl-2-phenylethyl)aniline (9a): General procedure
A (80 °C) was used to synthesise the title compound from 1-phenyl-
propyne and o-bromoaniline. The reaction time of the hydroamin-
ation was 48 h. Purification by flash chromatography (SiO2; hex-
anes/MTBE, 200:1) gave product 9a (410 mg, 1.41 mmol, 59%) as
a colourless oil. Rf = 0.17 (hexanes/MTBE, 200:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.47 (d, J = 7.9 Hz, 1 H, Ar-H),
7.35 (t, J = 7.5 Hz, 2 H, Ar-H), 7.31–7.19 (m, 4 H, Ar-H), 6.75 (d,
J = 8.1 Hz, 1 H, Ar-H), 6.60 (t, J = 7.6 Hz, 1 H, Ar-H), 4.36 (br. s,
1 H, N-H), 3.87–3.79 (m, 1 H, CH), 2.99 (dd, J = 13.5, 5.0 Hz, 1
H, CH2), 2.79 (dd, J = 13.5, 7.2 Hz, 1 H, CH2), 1.24 (d, J = 6.5 Hz,
3 H, CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ =
144.0 (C), 138.2 (C), 132.7 (CH), 129.6 (CH), 128.6 (CH), 128.5
(CH), 126.5 (CH), 117.6 (CH), 112.0 (CH), 110.2 (C), 49.7 (CH),
42.3 (CH2), 20.2 (CH3) ppm. MS (EI, 70 eV): m/z (%) = 291 (1)
[M, 81Br]+, 289 (2) [M, 79Br]+, 200 (80) [C8H9BrN, 81Br]+, 198 (100)
[C8H9BrN, 79Br]+, 91 (43) [C7H7]+. HRMS (ESI, +): calcd. for
4-Methyl-N-(1-methyl-2-phenylethyl)aniline (5a):[11a] General pro-
cedure A (80 °C) was used to synthesise the title compound from
1-phenylpropyne and p-toluidine. Purification by flash chromatog-
raphy (SiO2; hexanes/EtOAc, 20:1) gave product 5a (525 mg,
2.33 mmol, 97%) as a colourless oil. Rf = 0.23 (hexanes/EtOAc,
20:1). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.42 (t, J = 7.3 Hz,
2 H, Ar-H), 7.34 (t, J = 7.4 Hz, 1 H, Ar-H), 7.31 (d, J = 7.0 Hz, 2
H, Ar-H), 7.14 (d, J = 8.3 Hz, 2 H, Ar-H), 6.69 (d, J = 8.4 Hz, 2
H, Ar-H), 3.92–3.77 (m, 1 H, CH), 3.46 (br. s, 1 H, N-H), 3.06 (dd,
J = 13.4, 4.7 Hz, 1 H, CH2), 2.80 (dd, J = 13.4, 7.4 Hz, 1 H, CH2),
2.39 (s, 3 H, CH3), 1.26 (d, J = 6.4 Hz, 3 H, CH3) ppm. 13C NMR
(125 MHz, DEPT, CDCl3, 25 °C): δ = 145.0 (C), 138.7 (C), 129.9
(CH), 129.6 (CH), 128.4 (CH), 126.4 (C), 126.3 (CH), 113.7 (CH),
49.7 (CH), 42.3 (CH2), 20.5 (CH3), 20.3 (CH3) ppm.
2,6-Dimethyl-N-(1-methyl-2-phenylethyl)aniline (6a):[11b] General
procedure A (80 °C) was used to synthesise the title compound
from 1-phenylpropyne and 2,6-dimethylaniline. Purification by
flash chromatography (SiO2; hexanes/EtOAc, 20:1) gave product 6a
(510 mg, 2.14 mmol, 89%) as a colourless oil. Rf = 0.28 (hexanes/
C H N79BrK 328.0103; found 328.0105. IR (ATR): ν = 638, 668,
˜
15 16
699, 737, 793, 833, 923, 966, 1017, 1046, 1091, 1113, 1151, 1161,
1201, 1217, 1245, 1282, 1319, 1377, 1427, 1453, 1497, 1506, 1594,
2926, 2966, 3026, 3062, 3402 cm–1.
1-Phenyl-2-benzylaminopropane (10a)[11a] and 1-Phenyl-1-benzyl-
aminopropane (10b):[11a] General procedure A (80 °C) was used to
synthesise the title compounds from 1-phenylpropyne and benzyl-
amine. Purification by flash chromatography (SiO2; hexanes/
EtOAc/Et3N, 100:20:1) gave products 10a (416 mg, 1.85 mmol,
77%) and 10b (49 mg, 0.22 mmol, 9%) as colourless oils.
Compound 10a: Rf = 0.16 (hexanes/EtOAc/Et3N, 100:20:1). 1H
NMR (500 MHz, CDCl3, 25 °C): δ = 7.33–7.28 (m, 4 H, Ar-H),
7.27–7.21 (m, 4 H, Ar-H), 7.19 (d, J = 7.1 Hz, 2 H, Ar-H), 3.88
(d, J = 13.3 Hz, 1 H, N-CH2), 3.77 (d, J = 13.3 Hz, 1 H, N-CH2),
3.01–2.94 (m, 1 H, CH), 2.81 (dd, J = 13.4, 7.0 Hz, 1 H, CH2),
2.67 (dd, J = 13.4, 6.5 Hz, 1 H, CH2), 1.66 (br. s, 1 H, N-H), 1.13
(d, J = 6.3 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, DEPT,
CDCl3, 25 °C): δ = 140.5 (C), 139.5 (C), 129.4 (CH), 128.4 (CH),
128.1 (CH), 126.9 (CH), 126.2 (CH), 53.8 (CH), 51.4 (CH2), 43.6
(CH2), 20.3 (CH3) ppm.
1
EtOAc, 20:1). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.35 (t, J
= 7.4 Hz, 2 H, Ar-H), 7.27 (t, J = 7.4 Hz, 1 H, Ar-H), 7.24 (d, J
= 7.0 Hz, 2 H, Ar-H), 7.06 (d, J = 7.5 Hz, 2 H, Ar-H), 6.88 (t, J
= 7.5 Hz, 1 H, Ar-H), 3.62–3.54 (m, 1 H, CH), 3.01 (dd, J = 13.0,
4.8 Hz, 1 H, CH2), 2.98 (br. s, 1 H, N-H), 2.63 (dd, J = 13.0, 8.5 Hz,
1 H, CH2), 2.31 (s, 6 H, CH3), 1.12 (d, J = 6.4 Hz, 3 H, CH3) ppm.
13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 144.8 (C), 139.5
(C), 129.5 (CH), 129.3 (C), 129.0 (CH), 128.4 (CH), 126.2 (CH),
121.5 (CH), 54.2 (CH), 44.5 (CH2), 20.9 (CH3), 19.2 (CH3) ppm.
2,4,6-Trimethyl-N-(1-methyl-2-phenylethyl)aniline (7a): General
procedure A (80 °C) was used to synthesise the title compound
from 1-phenylpropyne and 2,4,6-trimethylaniline. Purification by
flash chromatography (SiO2; hexanes/EtOAc, 20:1) gave product 7a
(563 mg, 2.22 mmol, 93%) as a colourless oil. Rf = 0.25 (hexanes/
1
EtOAc, 20:1). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.39 (t, J
= 7.3 Hz, 2 H, Ar-H), 7.31 (t, J = 7.3 Hz, 1 H, Ar-H), 7.28 (d, J
= 7.1 Hz, 2 H, Ar-H), 6.93 (s, 2 H, Ar-H), 3.59–3.51 (m, 1 H, CH),
3.06 (dd, J = 13.0, 4.8 Hz, 1 H, CH2), 2.93 (br. s, 1 H, N-H), 2.65 Compound 10b: Rf = 0.34 (hexanes/EtOAc/Et3N, 100:20:1). 1H
(dd, J = 13.0, 8.5 Hz, 1 H, CH2), 2.35 (s, 3 H, CH3), 2.32 (s, 6 H,
NMR (500 MHz, CDCl3, 25 °C): δ = 7.32–7.11 (m, 10 H, Ar-H),
CH3), 1.16 (d, J = 6.4 Hz, CH3) ppm. 13C NMR (125 MHz, DEPT, 3.59 (d, J = 13.2 Hz, 1 H, N-CH2), 3.50–3.43 (m, 1 H, CH), 3.47
7588
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 7583–7592

A Catalyst for Hydroamination of Alkynes and Alkenes
(d, J = 13.4 Hz, 1 H, N-CH2), 1.77–1.66 (m, 1 H, CH2), 1.65–1.55
propyne and cyclopentylamine. Purification by flash chromatog-
(m, 1 H, CH2), 1.19 (s, 1 H, N-H), 0.72 (t, J = 7.4 Hz, 3 H, raphy (SiO2; hexanes/EtOAc/Et3N, 12:4:1) gave product 13a
CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 143.7
(456 mg, 2.23 mmol, 93%) as a colourless oil. Rf = 0.42 (hexanes/
(C), 140.4 (C), 128.5 (CH), 128.4 (CH), 127.6 (CH), 127.2 (CH), EtOAc/Et3N, 12:4:1). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.31
127.0 (CH), 64.3 (CH), 51.5 (CH2), 31.0 (CH2), 10.9 (CH3) ppm.
(t, J = 7.3 Hz, 2 H, Ar-H), 7.25–7.18 (m, 3 H, Ar-H), 3.26–3.19
(m, 1 H, N-CH), 3.03–2.96 (m, 1 H, N-CH), 2.78 (dd, J = 13.3,
6.8 Hz, 1 H, CH2), 2.62 (dd, J = 13.3, 6.8 Hz, 1 H, CH2), 1.96–
1.88 (m, 1 H, cyclopentyl-H), 1.87–1.80 (m, 1 H, cyclopentyl-H),
1.69–1.47 (m, 4 H, cyclopentyl-H), 1.32–1.23 (m, 1 H, cyclopentyl-
H), 1.22–1.12 (m, 1 H, cyclopentyl-H), 1.09 (d, J = 6.3 Hz, 3 H,
CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 139.7
(C), 129.3 (CH), 128.4 (CH), 126.2 (CH), 57.0 (CH), 53.0 (CH),
43.9 (CH2), 33.9 (CH2), 33.0 (CH2), 23.8 (CH2), 23.8 (CH2), 20.6
(CH3) ppm.
N-(1-Phenylpropan-2-yl)octane-1-amine (11a) and N-(1-Phenyl-
propan-1-yl)octane-1-amine (11b): General procedure A (80 °C) was
used to synthesise the title compounds from 1-phenylpropyne and
n-octylamine. Purification by flash chromatography (SiO2; hexanes/
MTBE/Et3N, 20:5:1) gave products 11a (500 mg, 2.02 mmol, 84%)
and 11b (50 mg, 0.20 mmol, 8%) as colourless oils.
Compound 11a: Rf = 0.26 (hexanes/MTBE/Et3N, 20:5:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.33 (t, J = 7.4 Hz, 2 H, Ar-H),
7.25–7.21 (m, 3 H, Ar-H), 2.97–2.89 (m, 1 H, CH), 2.78 (dd, J =
13.3, 7.0 Hz, 1 H, CH2), 2.74–2.68 (m, 1 H, N-CH2), 2.65 (dd, J =
13.3, 6.5 Hz, 1 H, CH2), 2.60–2.53 (m, 1 H, N-CH2), 1.54–1.40 (m,
2 H, CH2), 1.38–1.24 (m, 10 H, CH2), 1.10 (d, J = 6.3 Hz, 3 H,
CH3), 0.93 (t, J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz,
DEPT, CDCl3, 25 °C): δ = 139.6 (C), 129.3 (CH), 128.4 (CH), 126.1
(CH), 54.7 (CH), 47.4 (CH2), 43.7 (CH2), 31.9 (CH2), 30.3 (CH2),
29.5 (CH2), 29.3 (CH2), 27.4 (CH2), 22.7 (CH2), 20.3 (CH3), 14.2
(CH3) ppm. MS (EI, 70 eV): m/z (%) = 247 (1) [M]+, 156 (100)
[C10H22N]+, 91 (19) [C7H7]+. HRMS (ESI, +): calcd. for C17H30N
2-Benzhydrylamino-1-phenylpropane (14a): General procedure A
(80 °C) was used to synthesise the title compound from 1-phenyl-
propyne and benzhydrylamine. Purification by flash chromatog-
raphy (SiO2; hexanes/EtOAc, 40:1) gave product 14a (649 mg,
2.23 mmol, 93%) as a colourless oil. Rf = 0.13 (hexanes/EtOAc,
40:1). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.46 (d, J = 7.5 Hz,
2 H, Ar-H), 7.41–7.26 (m, 11 H, Ar-H), 7.22 (d, J = 7.1 Hz, 2 H,
Ar-H), 5.09 (s, 1 H, CH), 3.00–2.93 (m, 1 H, CH), 2.91 (dd, J =
13.0, 6.7 Hz, 1 H, CH2), 2.75 (dd, J = 13.0, 6.2 Hz, 1 H, CH2),
1.80 (br. s, 1 H, N-H), 1.20 (d, J = 6.2 Hz, 3 H, CH3) ppm. 13C
NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 144.7 (C), 144.0 (C),
139.6 (C), 129.5 (CH), 128.5 (CH), 128.4 (CH), 128.3 (CH), 127.4
(CH), 127.4 (CH), 126.9 (CH), 126.9 (CH), 126.1 (CH), 64.2 (CH),
51.8 (CH), 43.9 (CH2), 20.6 (CH3) ppm. MS (EI, 70 eV): m/z (%)
= 301 (1) [M]+, 210 (19) [C15H16N]+, 167 (100) [C13H12]+, 91 (10)
[C7H7]+. HRMS (ESI, +): calcd. for C22H24N 302.1909; found
248.2378; found 248.2376. IR (ATR): ν = 599, 625, 635, 698, 741,
˜
845, 909, 1031, 1085, 1130, 1342, 1373, 1454, 1495, 1603, 2853,
2923, 2957, 3027 cm–1.
Compound 11b: Rf = 0.33 (hexanes/MTBE/Et3N, 20:5:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.38–7.21 (m, 5 H, Ar-H), 3.49 (dd,
J = 8.0, 5.7 Hz, 1 H, CH), 2.49–2.37 (m, 2 H, N-CH2), 1.83–1.74
(m, 1 H, CH2), 1.70–1.60 (m, 1 H, CH2), 1.51–1.38 (m, 2 H, CH2),
1.32–1.18 (m, 10 H, CH2), 0.87 (t, J = 6.9 Hz, 3 H, CH3), 0.80 (t,
J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3,
25 °C): δ = 144.2 (C), 128.4 (CH), 127.5 (CH), 127.0 (CH), 65.4
(CH), 48.0 (CH2), 32.0 (CH2), 31.0 (CH2), 30.3 (CH2), 29.6 (CH2),
29.4 (CH2), 27.5 (CH2), 22.8 (CH2), 14.2 (CH3), 10.9 (CH3) ppm.
MS (EI, 70 eV): m/z (%) = 247 (1) [M]+, 218 (100) [C15H24N]+, 91
(48) [C7H7]+. HRMS (ESI, +): calcd. for C17H30N 248.2378; found
302.1905. IR (ATR): ν = 600, 621, 639, 695, 743, 832, 913, 1028,
˜
1060, 1075, 1089, 1139, 1180, 1278, 1344, 1373, 1451, 1492, 1599,
1624, 1661, 2845, 2925, 2961, 3025, 3060 cm–1.
4-Methyl-N-(2-phenylethyl)aniline (15a):[15] General procedure A
(50 °C) was used to synthesise the title compound from phenyl-
acetylene and p-toluidine. Purification by flash chromatography
(SiO2; hexanes/EtOAc, 40:1) gave product 15a (440 mg, 2.09 mmol,
87%) as a colourless oil. Rf = 0.10 (hexanes/EtOAc, 40:1). 1H
NMR (500 MHz, CDCl3, 25 °C): δ = 7.43 (t, J = 7.4 Hz, 2 H, Ar-
H), 7.38–7.31 (m, 3 H, Ar-H), 7.12 (d, J = 8.3 Hz, 2 H, Ar-H),
6.66 (d, J = 8.4 Hz, 2 H, Ar-H), 3.59 (br. s, 1 H, N-H), 3.49 (t, J
= 7.1 Hz, 2 H, N-CH2), 3.01 (t, J = 7.1 Hz, 2 H, CH2), 2.38 (s, 3
H, CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ =
145.8 (C), 139.5 (C), 129.8 (CH), 128.9 (CH), 128.6 (CH), 126.7
(C), 126.4 (CH), 113.3 (CH), 45.5 (CH2), 35.6 (CH2), 20.5
(CH3) ppm.
4-Methyl-N-[2-(4-methylphenyl)ethyl]aniline (16a):[16] General pro-
cedure A (50 °C) was used to synthesise the title compound from
p-methylphenylacetylene and p-toluidine. Purification by flash
chromatography (SiO2; hexanes/EtOAc, 40:1) gave product 16a
(427 mg, 1.89 mmol, 79%) as a colourless solid. The obtained solid
material could be recrystallized from ethanol to give colourless
crystals that were suitable for X-ray crystallographic analysis.[17] Rf
= 0.21 (hexanes/EtOAc, 40:1). 1H NMR (500 MHz, CDCl3, 25 °C):
δ = 7.22–7.12 (m, 4 H, Ar-H), 7.05 (d, J = 8.0 Hz, 2 H, Ar-H),
6.59 (d, J = 8.4 Hz, 2 H, Ar-H), 3.52 (br. s, 1 H, N-H), 3.40 (t, J
= 7.1 Hz, 2 H, N-CH2), 2.91 (t, J = 7.1 Hz, 2 H, CH2), 2.39 (s, 3
H, CH3), 2.31 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, DEPT,
CDCl3, 25 °C): δ = 145.9 (C), 136.4 (C), 135.9 (C), 129.8 (CH),
129.3 (CH), 128.7 (CH), 126.7 (C), 113.3 (CH), 45.6 (CH2), 35.1
(CH2), 21.1 (CH3), 20.5 (CH3) ppm.
248.2373. IR (ATR): ν = 601, 701, 754, 839, 901, 922, 1030, 1126,
˜
1200, 1303, 1360, 1380, 1456, 1494, 1604, 1734, 2806, 2855, 2926,
2959, 3029, 3064, 3085 cm–1.
2-Isobutylamino-1-phenylpropane (12a): General procedure
A
(80 °C) was used to synthesise the title compound from 1-phenyl-
propyne and isobutylamine. Purification by flash chromatography
(SiO2; hexanes/EtOAc/Et3N, 30:1:1) gave product 12a (412 mg,
2.15 mmol, 90%) as a colourless oil. Rf = 0.23 (hexanes/EtOAc/
1
Et3N, 30:1:1). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.28 (t, J
= 7.4 Hz, 2 H, Ar-H), 7.22–7.16 (m, 3 H, Ar-H), 2.90–2.82 (m, 1
H, N-CH), 2.73 (dd, J = 13.3, 7.0 Hz, 1 H, N-CH2), 2.61 (dd, J =
13.3, 6.5 Hz, 1 H, N-CH2), 2.47 (dd, J = 11.4, 6.8 Hz, 1 H, CH2),
2.35 (dd, J = 11.4, 6.8 Hz, 1 H, CH2), 1.73–1.62 (m, 1 H, CH),
1.44 (br. s, 1 H, N-H), 1.05 (d, J = 6.3 Hz, 3 H, CH3), 0.83 (d, J =
6.7 Hz, 3 H, CH3), 0.82 (d, J = 6.7 Hz, 3 H, CH3) ppm. 13C NMR
(125 MHz, DEPT, CDCl3, 25 °C): δ = 139.7 (C), 139.3 (CH), 128.4
(CH), 126.2 (CH), 55.5 (CH2), 54.7 (CH), 43.7 (CH2), 28.4 (CH),
20.8 (CH3), 20.7 (CH3), 20.4 (CH3) ppm. MS (EI, 70 eV): m/z (%)
= 191 (1) [M]+, 100 (100) [C6H14N]+, 91 (36) [C7H7]+. HRMS (ESI,
+): calcd. for C H N 192.1752; found 192.1750. IR (ATR): ν =
˜
13 22
600, 700, 743, 826, 912, 964, 1032, 1091, 1126, 1214, 1246, 1292,
1345, 1373, 1456, 1471, 1497, 1604, 1739, 2812, 2871, 2928, 2957,
3029, 3065, 3086 cm–1.
2-Cyclopentylamino-1-phenylpropane (13a):[11b] General procedure
4-Methyl-N-{2-[4-(trifluoromethyl)phenyl]ethyl}aniline (17a): Gene-
A (80 °C) was used to synthesise the title compound from 1-phenyl-
ral procedure A (50 °C) was used to synthesise the title compound
Eur. J. Org. Chem. 2013, 7583–7592
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7589

C. Brahms, P. Tholen, W. Saak, S. Doye
FULL PAPER
from p-trifluoromethylphenylacetylene and p-toluidine. Purifica-
tion by flash chromatography (SiO2; hexanes/EtOAc, 40:1) gave
product 17a (583 mg, 2.09 mmol, 87%) as a yellow oil. Rf = 0.06
(hexanes/EtOAc, 40:1). 1H NMR (500 MHz, CDCl3, 25 °C): δ =
7.64 (d, J = 8.1 Hz, 2 H, Ar-H), 7.38 (d, J = 8.0 Hz, 2 H, Ar-H),
7.09 (d, J = 8.3 Hz, 2 H, Ar-H), 6.63 (d, J = 8.3 Hz, 2 H, Ar-H),
3.54 (br. s, 1 H, N-H), 3.47 (t, J = 7.0 Hz, 2 H, N-CH2), 3.01 (t, J
= 7.0 Hz, 2 H, CH2), 2.33 (s, 3 H, CH3) ppm. 13C NMR (125 MHz,
DEPT, CDCl3, 25 °C): δ = 145.5 (C), 143.8 (C), 130.0 (CH), 129.2
(8) [C7H7]+. HRMS (ESI, +): calcd. for C15H24N 218.1909; found
218.1906. IR (ATR): ν = 704, 805, 888, 1123, 1149, 1182, 1251,
˜
1301, 1317, 1405, 1447, 1479, 1519, 1583, 1618, 2849, 2919, 3017,
3401 cm–1.
Compound 19b: Rf = 0.25 (hexanes/MTBE, 30:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 6.98 (d, J = 8.2 Hz, 2 H, Ar-H),
6.53 (d, J = 8.2 Hz, 2 H, Ar-H), 3.33–3.27 (m, 1 H, CH), 2.25 (s,
3 H, CH3), 1.88–1.64 (m, 5 H, cyclohexyl-H), 1.51–1.41 (m, 1 H,
cyclohexyl-H), 1.35–0.97 (m, 5 H, cyclohexyl-H), 1.12 (d, J =
6.5 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3,
25 °C): δ = 145.6 (C), 129.9 (CH), 126.1 (C), 113.6 (CH), 53.8
(CH), 43.1 (CH), 30.0 (CH2), 28.5 (CH2), 26.8 (CH2), 26.7 (CH2),
26.5 (CH2), 20.5 (CH3), 17.5 (CH3) ppm. MS (EI, 70 eV): m/z (%)
= 217 (5) [M]+, 134 (100) [C9H12N]+, 91 (5) [C7H7]+. HRMS (ESI,
2
3
(CH), 128.9 (q, JC,F = 32.4 Hz, C), 127.1 (C), 125.6 (q, JC,F
=
1
3.7 Hz, CH), 124.4 (q, JC,F = 271.8 Hz, CF3), 113.4 (CH), 45.2
(CH2), 35.5 (CH2), 20.5 (CH3) ppm. 19F NMR (470 MHz, CDCl3,
25 °C): δ = –62.3 ppm. MS (EI, 70 eV): m/z (%) = 279 (12) [M]+,
159 (5) [C8H6F3]+, 120 (100) [C8H10N]+, 91 (12) [C7H7]+. HRMS
(ESI, +): calcd. for C16H17NF3 280.1313; found 280.1310. IR
+): calcd. for C H N 218.1909; found 218.1903. IR (ATR): ν =
˜
15 24
(ATR): ν = 596, 616, 707, 735, 809, 842, 955, 1020, 1068, 1111,
˜
703, 804, 841, 890, 954, 993, 1008, 1042, 1063, 1078, 1121, 1142,
1159, 1182, 1250, 1298, 1316, 1373, 1404, 1448, 1483, 1517, 1582,
1618, 2851, 2921, 2963, 3016, 3408 cm–1.
1163, 1260, 1323, 1419, 1482, 1521, 1586, 1618, 2868, 2924, 3022,
3405 cm–1.
N-[2-(4-Methoxyphenyl)ethyl]-4-methylaniline (18a) and N-[1-(4-
Methoxyphenyl)ethyl]-4-methylaniline (18b):[18] General procedure
A (80 °C) was used to synthesise the title compounds from p-meth-
oxyphenylacetylene and p-toluidine. Purification by flash
chromatography (SiO2; hexanes/EtOAc, 20:1) gave products 18a
(460 mg, 1.80 mmol, 75%) and 18b (61 mg, 0.24 mmol, 10%) as
colourless oils.
Compound 18a: Rf = 0.07 (hexanes/EtOAc, 20:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.18 (d, J = 8.5 Hz, 2 H, Ar-H),
7.05 (d, J = 8.1 Hz, 2 H, Ar-H), 6.91 (d, J = 8.6 Hz, 2 H, Ar-H),
6.60 (d, J = 8.3 Hz, 2 H, Ar-H), 3.84 (s, 3 H, O-CH3), 3.52 (br. s,
1 H, N-H), 3.38 (t, J = 7.0 Hz, 2 H, N-CH2), 2.89 (t, J = 7.0 Hz,
2 H, CH2), 2.30 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, DEPT,
CDCl3, 25 °C): δ = 158.3 (C), 145.7 (C), 131.4 (C), 129.9 (CH),
129.8 (CH), 126.9 (C), 114.1 (CH), 113.4 (CH), 55.3 (CH3), 45.8
(CH2), 34.6 (CH2), 20.5 (CH3) ppm. MS (EI, 70 eV): m/z (%) = 241
(6) [M]+, 121 (17) [C8H9O]+, 120 (100) [C8H10N]+, 91 (15) [C7H7]
+, 77 (5) [C6H5]+. HRMS (ESI, +): calcd. for C16H20NO 242.1545;
4-Methyl-N-(1-methylheptyl)aniline (20b):[11b] General procedure A
(80 °C) was used to synthesise the title compound from 1-octyne
and p-toluidine. Purification by flash chromatography (SiO2; hex-
anes/MTBE, 200:1) gave products 20a (36 mg, 0.16 mmol, 7%) and
20b (411 mg, 1.87 mmol, 78%) as colourless oils.
Compound 20b: Rf = 0.07 (hexanes/MTBE, 200:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 6.88 (d, J = 8.3 Hz, 2 H, Ar-H),
6.42 (d, J = 8.4 Hz, 2 H, Ar-H), 3.36–3.28 (m, 1 H, CH), 3.19 (br. s,
1 H, N-H), 2.14 (s, 3 H, CH3), 1.55–1.42 (m, 1 H, CH2), 1.37–1.14
(m, 9 H, CH2), 1.06 (d, J = 6.3 Hz, 3 H, CH3), 0.80 (t, J = 6.9 Hz,
3 H, CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ =
145.5 (C), 129.9 (CH), 126.1 (C), 113.5 (CH), 49.0 (CH), 37.3
(CH2), 32.0 (CH2), 29.5 (CH2), 26.3 (CH2), 22.8 (CH2), 20.9 (CH3),
20.5 (CH3), 14.2 (CH3) ppm.
4-Methyl-N-(3-phenylpropyl)aniline (21a):[19] General procedure A
(80 °C) was used to synthesise the title compound from 3-phenyl-
propyne and p-toluidine. Purification by flash chromatography
(SiO2; hexanes/EtOAc, 20:1) gave products 21a (97 mg, 0.43 mmol,
18%) and 5a (378 mg, 1.68 mmol, 70%) as colourless oils.
Compound 21a: Rf = 0.13 (hexanes/EtOAc, 40:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.34–7.27 (m, 2 H, Ar-H), 7.24–7.16
(m, 3 H, Ar-H), 7.00 (d, J = 8.2 Hz, 2 H, Ar-H), 6.57 (d, J =
8.3 Hz, 2 H, Ar-H), 3.15 (t, J = 7.1 Hz, 2 H, N-CH2), 2.74 (t, J =
7.6 Hz, 2 H, CH2), 2.25 (s, 3 H, CH3), 1.97 (pent, J = 7.3 Hz, 2 H,
CH2), 1.28 (br. s, 1 H, N-H) ppm. 13C NMR (125 MHz, DEPT,
CDCl3, 25 °C): δ = 145.6 (C), 141.8 (C), 129.9 (CH), 128.6 (CH),
128.5 (CH), 127.3 (C), 126.1 (CH), 113.7 (CH), 44.4 (CH2), 33.5
(CH2), 31.1 (CH2), 20.5 (CH3) ppm.
found 242.1540. IR (ATR): ν = 703, 806, 1034, 1090, 1111, 1125,
˜
1177, 1242, 1300, 1318, 1441, 1463, 1477, 1510, 1583, 1613, 2834,
2859, 2917, 3001, 3398 cm–1.
Compound 18b: Rf = 0.12 (hexanes/EtOAc, 20:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.35 (d, J = 8.7 Hz, 2 H, Ar-H),
6.98 (d, J = 8.4 Hz, 2 H, Ar-H), 6.92 (d, J = 8.7 Hz, 2 H, Ar-H),
6.52 (d, J = 8.4 Hz, 2 H, Ar-H), 4.49 (q, J = 6.7 Hz, 1 H, CH),
3.83 (s, 3 H, O-CH3), 2.26 (s, 3 H, CH3), 1.54 (d, J = 6.7 Hz, 3 H,
CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 158.5
(C), 145.1 (C), 137.5 (C), 129.7 (CH), 127.0 (CH), 126.4 (C), 114.1
(CH), 113.6 (CH), 55.3 (CH3), 53.2 (CH), 25.1 (CH3), 20.5
(CH3) ppm.
4-Methyl-N-(1-methylpropyl)aniline (22):[20] General procedure A
(80 °C) was used to synthesise the title compound from 2-butyne
and p-toluidine. Purification by flash chromatography (SiO2; hex-
anes/MTBE, 30:1) gave product 22 (239 mg, 1.46 mmol, 61%) as a
N-[2-(Cyclohexyl)ethyl]-4-methylaniline (19a) and N-[1-(Cyclohex-
yl)ethyl]-4-methylaniline (19b): General procedure A (80 °C) was
used to synthesise the title compounds from cyclohexylacetylene
and p-toluidine. Purification by flash chromatography (SiO2; hex-
anes/MTBE, 30:1) gave products 19a (160 mg, 0.74 mmol, 31%)
and 19b (317 mg, 1.46 mmol, 61%) as colourless oils.
colourless oil. Rf
=
0.22 (hexanes/MTBE, 30:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.06 (d, J = 8.4 Hz, 2 H, Ar-H),
6.59 (d, J = 8.4 Hz, 2 H, Ar-H), 3.48–3.41 (m, 1 H, CH), 3.33 (br. s,
1 H, N-H), 2.32 (s, 3 H, CH3), 1.72–1.61 (m, 1 H, CH2), 1.58–1.48
(m, 1 H, CH2), 1.23 (d, J = 6.4 Hz, 3 H, CH3), 1.03 (t, J = 7.5 Hz,
3 H, CH3) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ =
145.5 (C), 129.8 (CH), 126.0 (C), 113.5 (CH), 50.2 (CH), 29.7
(CH2), 20.4 (CH3), 20.3 (CH3), 10.5 (CH3) ppm.
Compound 19a: Rf = 0.18 (hexanes/MTBE, 30:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.03 (d, J = 7.1 Hz, 2 H, Ar-H),
6.59 (d, J = 7.3 Hz, 2 H, Ar-H), 3.42 (br. s, 1 H, N-H), 3.15 (t, J
= 7.3 Hz, 2 H, N-CH2), 2.29 (s, 3 H, CH3), 1.83–0.74 (m, 13
H) ppm. 13C NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 146.4
(C), 129.8 (CH), 126.5 (C), 113.1 (CH), 42.3 (CH2), 37.3 (CH2), 4-Methyl-N-(1-propylpentyl)aniline (23):[21] General procedure A
35.7 (CH), 33.5 (CH2), 26.7 (CH2), 26.4 (CH2), 20.5 (CH3) ppm.
(120 °C) was used to synthesise the title compound from 4-octyne
and p-toluidine. Purification by flash chromatography (SiO2; hex-
MS (EI, 70 eV): m/z (%) = 217 (9) [M]+, 120 (100) [C8H10N]+, 91
7590
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 7583–7592

A Catalyst for Hydroamination of Alkynes and Alkenes
anes/MTBE, 30:1) gave product 23 (374 mg, 1.70 mmol, 71%) as a
colourless oil. Rf
(500 MHz, CDCl3, 25 °C): δ = 7.03 (d, J = 8.3 Hz, 2 H, Ar-H),
6.56 (d, J = 8.4 Hz, 2 H, Ar-H), 3.40–3.33 (m, 1 H, CH), 3.34 (br. s,
(m, 1 H, CH2), 1.70 (br. s, 1 H, N-H), 1.52–1.45 (m, 1 H, CH2),
1.06–0.96 (m, 1 H, CH2), 0.86 (d, J = 6.4 Hz, 3 H, CH3) ppm. 13C
NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 148.8 (C), 144.7 (C),
128.7 (CH), 128.3 (CH), 126.5 (CH), 125.9 (CH), 125.9 (CH), 55.8
=
0.33 (hexanes/MTBE, 30:1). 1H NMR
1 H, N-H), 2.29 (s, 3 H, CH3), 1.63–1.33 (m, 10 H, CH2), 0.98 (t, (CH2), 52.4 (CH), 45.3 (C), 35.5 (CH2), 31.4 (CH2), 22.5
J = 7.2 Hz, 3 H, CH3), 0.96 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C
NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 146.0 (C), 129.9 (CH),
125.7 (C), 113.1 (CH), 53.0 (CH), 37.4 (CH2), 34.8 (CH2), 28.2
(CH2), 23.0 (CH2), 20.4 (CH3), 19.3 (CH2), 14.4 (CH3), 14.2
(CH3) ppm.
(CH3) ppm.
N-(p-Tolylsulfonyl)-3-methyl-2-azaspiro[5,5]undecane (34): General
procedure C (160 °C) was used to synthesise the title compound
from aminoalkene 33. Purification by flash chromatography (SiO2;
hexanes/EtOAc, 20:1) gave product 34 (240 mg, 0.75 mmol, 37%)
as a colourless solid. Rf = 0.14 (hexanes/EtOAc, 20:1), m.p. 71.4–
73.2 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.69 (d, J =
8.0 Hz, 2 H, Ar-H), 7.26 (d, J = 7.8 Hz, 2 H, Ar-H), 4.24–4.17 (m,
1 H, CH), 3.57 (d, J = 12.7 Hz, 1 H, N-CH2), 2.59 (d, J = 12.7 Hz,
1 H, N-CH2), 2.41 (s, 3 H, CH3), 1.98–1.86 (m, 1 H, CH2), 1.59–
1.16 (m, 13 H, CH2), 0.94 (d, J = 6.8 Hz, 3 H, CH3) ppm. 13C
NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 142.8 (C), 138.6 (C),
129.6 (CH), 127.2 (CH), 48.5 (CH), 48.2 (CH2), 38.3 (CH2), 33.1
(C), 31.1 (CH2), 30.2 (CH2), 26.7 (CH2), 26.6 (CH2), 21.6 (CH2),
21.6 (CH3), 21.5 (CH2), 14.4 (CH3) ppm. MS (EI, 70 eV): m/z (%)
= 321 (1) [M]+, 306 (45) [C17H24NO2S]+, 212 (12), 155 (29)
[C7H7O2S]+, 91 (100) [C7H7]+. HRMS (ESI, +): calcd. for
N-(1,2-Diphenylethyl)-4-methylaniline (24):[11b] General procedure
A (120 °C) was used to synthesise the title compound from diphen-
ylacetylene and p-toluidine. Purification by flash chromatography
(SiO2; hexanes/EtOAc, 20:1) gave product 24 (655 mg, 2.28 mmol,
95%) as a colourless oil. Rf = 0.31 (hexanes/EtOAc, 20:1). 1H
NMR (500 MHz, CDCl3, 25 °C): δ = 7.45–7.29 (m, 8 H, Ar-H),
7.22 (d, J = 7.0 Hz, 2 H, Ar-H), 6.97 (d, J = 8.3 Hz, 2 H, Ar-H),
6.49 (d, J = 8.4 Hz, 2 H, Ar-H), 4.66 (dd, J = 8.3, 5.7 Hz, 1 H,
CH), 4.13 (br. s, 1 H, N-H), 3.22 (dd, J = 14.0, 5.7 Hz, 1 H, CH2),
3.10 (dd, J = 14.0, 8.3 Hz, 1 H, CH2), 2.27 (s, 3 H, CH3) ppm. 13C
NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 145.1 (C), 143.7 (C),
137.9 (C), 129.6 (CH), 129.3 (CH), 128.6 (CH), 128.6 (CH), 127.1
(CH), 126.8 (C), 126.7 (CH), 126.6 (CH), 113.9 (CH), 59.6 (CH),
45.3 (CH2), 20.4 (CH3) ppm.
C H NO NaS 344.1660; found 344.1664. IR (ATR): ν = 547,
˜
18 27
2
604, 661, 707, 750, 817, 859, 902, 918, 932, 961, 985, 1008, 1034,
1093, 1132, 1146, 1168, 1220, 1249, 1285, 1301, 1318, 1382, 1450,
1493, 1596, 2849, 2923 cm–1.
2-Methyl-4,4-diphenylpyrrolidine (26):[4a] General procedure
B
(120 °C) was used to synthesise the title compound from aminoalk-
ene 25. Purification by flash chromatography (SiO2; MTBE/7N
NH3 in MeOH, 19:1) gave product 26 (470 mg, 1.98 mmol, 99%)
as a colourless oil. Rf = 0.19 (MTBE/7N NH3 in MeOH, 19:1). 1H
NMR (500 MHz, CDCl3, 25 °C): δ = 7.18–7.04 (m, 8 H, Ar-H),
7.03–6.96 (m, 2 H, Ar-H), 3.52 (d, J = 11.4 Hz, 1 H, N-CH2), 3.32
(d, J = 11.4 Hz, 1 H, N-CH2), 3.25–3.17 (m, 1 H, CH), 2.58 (dd,
J = 12.7, 6.6 Hz, 1 H, CH2), 2.11 (br. s, 1 H, N-H), 1.88 (dd, J =
12.7, 9.1 Hz, 1 H, CH2), 1.05 (d, J = 6.4 Hz, 3 H, CH3) ppm. 13C
NMR (125 MHz, DEPT, CDCl3, 25 °C): δ = 147.8 (C), 147.0 (C),
128.3 (CH), 128.3 (CH), 127.0 (CH), 127.0 (CH), 126.0 (CH), 126.0
(CH), 57.9 (CH2), 57.3 (C), 53.1 (CH), 47.1 (CH2), 22.3
(CH3) ppm.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of the H and 13C NMR spectra of all products. X-ray
crystal structure of product 16a.
Acknowledgments
The authors thank the Deutsche Forschungsgemeinschaft (DFG)
for financial support of the research.
[1] For general reviews on the hydroamination of alkenes and alk-
ynes, see: a) T. E. Müller, M. Beller, Chem. Rev. 1998, 98, 675–
703; b) J. J. Brunet, D. Neibecker, in: Catalytic Heterofunction-
alization (Eds.: A. Togni, H. Grützmacher), Wiley-VCH,
Weinheim, Germany, 2001, p. 91–141; c) F. Pohlki, S. Doye,
Chem. Soc. Rev. 2003, 32, 104–114; d) F. Alonso, I. Beletskaya,
M. Yus, Chem. Rev. 2004, 104, 3079–3160; e) K. C. Hultzsch,
Adv. Synth. Catal. 2005, 347, 367–391; f) K. C. Hultzsch, Org.
Biomol. Chem. 2005, 3, 1819–1824; g) R. Severin, S. Doye,
Chem. Soc. Rev. 2007, 36, 1407–1420; h) J.-J. Brunet, N.-C.
Chu, M. Rodriguez-Zubiri, Eur. J. Inorg. Chem. 2007, 4711–
4722; i) T. E. Müller, K. C. Hultzsch, M. Yus, F. Foubelo, M.
Tada, Chem. Rev. 2008, 108, 3795–3892.
[2] For reviews on group 4 metal-catalysed hydroamination reac-
tions, see: a) I. Bytschkov, S. Doye, Eur. J. Org. Chem. 2003,
935–946; b) S. Doye, Synlett 2004, 1653–1672; c) A. V. Lee,
L. L. Schafer, Eur. J. Inorg. Chem. 2007, 2243–2255.
[3] For a review on the hydroaminoalkylation of alkenes, see: P. W.
Roesky, Angew. Chem. 2009, 121, 4988–4991; Angew. Chem.
Int. Ed. 2009, 48, 4892–4894.
N-(p-Tolylsulfonyl)-3-methyl-2-azaspiro[4,5]decane (28):[22] General
procedure C (160 °C) was used to synthesise the title compound
from aminoalkene 27. Purification by flash chromatography (SiO2;
hexanes/EtOAc, 15:1) gave product 28 (511 mg, 1.66 mmol, 83%)
as a colourless solid. Rf = 0.20 (hexanes/EtOAc, 15:1). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.67 (d, J = 8.2 Hz, 2 H, Ar-H),
7.25 (d, J = 8.2 Hz, 2 H, Ar-H), 4.23–4.14 (m, 1 H, CH), 3.56 (d,
J = 12.7 Hz, 1 H, N-CH2), 2.57 (d, J = 12.8 Hz, 1 H, N-CH2), 2.39
(s, 3 H, CH3), 1.97–1.85 (m, 1 H, CH2), 1.57–1.12 (m, 11 H, CH2),
0.91 (d, J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, DEPT,
CDCl3, 25 °C): δ = 142.8 (C), 138.4 (C), 129.5 (CH), 127.1 (CH),
48.5 (CH), 48.0 (CH2), 38.2 (CH2), 33.0 (C), 30.9 (CH2), 26.6
(CH2), 26.5 (CH2), 21.6 (CH3), 21.5 (CH2), 21.4 (CH2), 14.3
(CH3) ppm.
2-Methyl-5,5-diphenylpiperidine (32):[23] General procedure
B
[4] a) C. Müller, W. Saak, S. Doye, Eur. J. Org. Chem. 2008, 2731–
2739; b) R. Kubiak, I. Prochnow, S. Doye, Angew. Chem. 2009,
121, 1173–1176; Angew. Chem. Int. Ed. 2009, 48, 1153–1156;
c) I. Prochnow, R. Kubiak, O. N. Frey, R. Beckhaus, S. Doye,
ChemCatChem 2009, 1, 162–172; d) R. Kubiak, I. Prochnow,
S. Doye, Angew. Chem. 2010, 122, 2683–2686; Angew. Chem.
Int. Ed. 2010, 49, 2626–2629; e) I. Prochnow, P. Zark, T. Müller,
S. Doye, Angew. Chem. 2011, 123, 6525–6529; Angew. Chem.
Int. Ed. 2011, 50, 6401–6405; f) D. Jaspers, W. Saak, S. Doye,
Synlett 2012, 2098–2102; g) J. Dörfler, S. Doye, Angew. Chem.
(160 °C) was used to synthesise the title compound from amino-
alkene 31. Purification by flash chromatography (SiO2; MTBE/7N
NH3 in MeOH, 19:1) gave product 32 (483 mg, 1.74 mmol, 87%)
as a colourless oil. Rf = 0.18 (MTBE/7N NH3 in MeOH, 19:1). 1H
NMR (500 MHz, CDCl3, 25 °C): δ = 7.26 (d, J = 8.0 Hz, 2 H, Ar-
H), 7.18 (t, J = 7.8 Hz, 2 H, Ar-H), 7.10–7.01 (m, 3 H, Ar-H), 6.99
(d, J = 7.3 Hz, 2 H, Ar-H), 6.96 (t, J = 7.2 Hz, 1 H, Ar-H), 3.76
(dd, J = 13.7, 3.1 Hz, 1 H, N-CH2), 2.97 (d, J = 13.7 Hz, 1 H, N-
CH2), 2.68–2.59 (m, 1 H, CH), 2.59–2.50 (m, 1 H, CH2), 2.10–2.01
Eur. J. Org. Chem. 2013, 7583–7592
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7591

C. Brahms, P. Tholen, W. Saak, S. Doye
FULL PAPER
2013, 125, 1851–1854; Angew. Chem. Int. Ed. 2013, 52, 1806–
1809; h) T. Preuß, W. Saak, S. Doye, Chem. Eur. J. 2013, 19,
3833–3837; i) J. A. Bexrud, P. Eisenberger, D. C. Leitch, P. R.
Payne, L. L. Schafer, J. Am. Chem. Soc. 2009, 131, 2116–2118.
[5] For reviews on metal complexes with 2-aminopyridinato li-
gands, see: a) R. Kempe, Eur. J. Inorg. Chem. 2003, 791–803;
b) R. Kempe, N. Hoss, T. Irrgang, J. Organomet. Chem. 2002,
647, 12–20; c) R. Kempe, Z. Anorg. Allg. Chem. 2010, 636,
2135–2147.
[6] a) E. Smolensky, M. Kapon, M. S. Eisen, Organometallics
2005, 24, 5495–5498; b) E. Smolensky, M. Kapon, M. S. Eisen,
Organometallics 2007, 26, 4510–4527.
[7] E. Chong, S. Qayyum, L. L. Schafer, R. Kempe, Organometal-
lics 2013, 32, 1858–1865.
[14]
For selected examples of Ti-catalysed anti-Markovnikov ad-
ditions of primary amines to terminal alkynes, see: a) Z.
Zhang, L. L. Schafer, Org. Lett. 2003, 5, 4733–4736; b) A. Til-
lack, V. Khedkar, H. Jiao, M. Beller, Eur. J. Org. Chem. 2005,
5001–5012; c) Z. Chen, L. Li, Y. Chen, B. Hu, J. Wu, X. Wang,
T. Lei, Y. Li, J. Chem. Res. 2012, 249–253; see also ref.[11b]
I. Bytschkov, S. Doye, Eur. J. Org. Chem. 2001, 4411–4418.
L. Naya, M. Larrosa, R. Rodríguez, J. Cruces, Tetrahedron
Lett. 2012, 53, 769–772.
[15]
[16]
[17]
Product
16a:
Colourless
crystals,
dimensions
0.63ϫ0.44ϫ0.12 mm3, monoclinic, space group P2(1)/c, unit
cell dimensions: a = 261882(16) Å, b = 5.6083(4) Å, c =
8.9619(6) Å,
α = 90°, β = 93.682(4)°, γ = 90°, V =
1313.53(15) Å3, Z = 4, ρ = 1.139 Mg/m3, Θmax = 29.56°, radia-
tion Mo Kα, λ = 0.71073 Å, φ and ω-scans with Bruker KAPPA
APEX-II CCD at T = 120(2) K, 36777 reflections measured,
3669 unique [Rint = 0.0423], 2977 observed [IϾ2σ(I)], inten-
sities were corrected for Lorentz and polarization effects, an
empirical absorption correction was applied using Bruker
SAINT based on the Laue symmetry of the reciprocal space,
μ = 0.066 mm–1, Tmin = 0.9601, Tmax = 0.9919, structure solved
by direct methods and refined against F2 with a Full-matrix
least-squares algorithm using the SHELXS-97 software pack-
age, 160 parameters refined, hydrogen atoms were treated using
appropriate riding models, goodness of fit 1.091 for observed
reflections, final residual values R1 = 0.0589, wR2 = 0.1560 for
observed reflections, largest diff. peak, hole 0.363 and
–0.193 eÅ–3. CCDC-953364 contains the supplementary crys-
tallographic data for 16a. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[8] N. A. Al-Awadi, O. M. E. El-Dusouqui, K. Kaul, H. H. Dib,
Int. J. Chem. Kinet. 2000, 32, 403–407.
[9] Complex 2: Red crystals, dimensions 0.43ϫ0.25ϫ0.23 mm3,
monoclinic, space group I2/a, unit cell dimensions: a =
17.0232(3) Å, b = 15.7340(3) Å, c = 17.7778(5) Å, α = 90°, β =
104.8130(10)°, γ = 90°, V = 4603.41(18) Å3, Z = 8, ρ =
1.260 Mg/m3, Θmax = 35.20°, radiation Mo Kα, λ = 0.71073 Å,
φ and ω-scans with Bruker KAPPA APEX-II CCD at T =
120(2) K, 96014 reflections measured, 10158 unique [Rint
=
0.0342], 7963 observed [IϾ2σ(I)], intensities were corrected for
Lorentz and polarization effects, an empirical absorption cor-
rection was applied using Bruker SAINT based on the Laue
symmetry of the reciprocal space, μ = 0.394 mm–1, Tmin
=
0.8484, Tmax = 0.9148, structure solved by direct methods and
refined against F2 with a Full-matrix least-squares algorithm
using the SHELXS-97 software package, 272 parameters re-
fined, hydrogen atoms were treated using appropriate riding
models, goodness of fit 1.058 for observed reflections, final re-
sidual values R1 = 0.0369, wR2 = 0.0962 for observed reflec-
tions, largest diff. peak, hole 0.680 and –0.328 eÅ–3. CCDC-
925787 contains the supplementary crystallographic data for 2.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[18]
L. C. M. Castro, J.-B. Sortais, C. Darcel, Chem. Commun.
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Received: July 5, 2013
Published Online: October 2, 2013
7592
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Eur. J. Org. Chem. 2013, 7583–7592