Ind2TiMe2-catalyzed addition of methyl- and ethylamine to alkynes

Article abstract of DOI:10.1002/ejoc.200500458

We describe a very simple hydrogenation-like experimental protocol for the addition of gaseous methyl- and ethylamine to alkynes in the presence of Ind₂TiMe₂ as the catalyst. For efficient hydroamination reactions it is sufficient to stir a mixture of the alkyne and the catalyst in toluene at temperatures between 80°C (terminal alkynes) and 105°C (internal alkynes) under a constant pressure of 1 atm of the corresponding amine. After subsequent reduction of the initially formed imines, methyl- and ethylamine derivatives are the final products of the described one-pot reaction sequences. In the case of 2-alkyl-1-phenylalkynes as starting materials, biologically interesting 2-phenylethylamine derivatives possessing a small methyl or ethyl substituent at the N atom are easily accessible by the new reaction protocol. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500458

FULL PAPER
Ind2TiMe2-Catalyzed Addition of Methyl- and Ethylamine to Alkynes
Klaudia Marcseková,[a] Bernd Wegener,[a] and Sven Doye*[a]
Keywords: Alkynes / Amines / Homogeneous catalysis / Hydroamination / Titanium
We describe a very simple hydrogenation-like experimental
protocol for the addition of gaseous methyl- and ethylamine
to alkynes in the presence of Ind2TiMe2 as the catalyst. For
efficient hydroamination reactions it is sufficient to stir a mix-
ture of the alkyne and the catalyst in toluene at temperatures
between 80 °C (terminal alkynes) and 105 °C (internal al-
kynes) under a constant pressure of 1 atm of the correspond-
ing amine. After subsequent reduction of the initially formed
imines, methyl- and ethylamine derivatives are the final pro-
ducts of the described one-pot reaction sequences. In the
case of 2-alkyl-1-phenylalkynes as starting materials, biolo-
gically interesting 2-phenylethylamine derivatives pos-
sessing a small methyl or ethyl substituent at the N atom are
easily accessible by the new reaction protocol.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
in fast reactions. After some optimization studies, which
were mainly focused on the size of the magnetic stirring
bar (optimum: 15×4.5 mm) used for the reactions, we were
delighted to see that the addition of methylamine to diphen-
ylacetylene (1) goes to completion within less than 7 h at
105 °C in the presence of 5 mol-% of Ind2TiMe2 (91% con-
version after 5 h). After subsequent reduction of the ini-
tially formed imine with NaBH3CN/ZnCl2 in methanol
(one-pot procedure), the desired methylamine derivative 2
was isolated in 92% yield (Scheme 1).
Introduction
During the last few years, Ti-catalyzed hydroaminations
of alkynes have attracted much attention.[1] While most Ti
complexes efficiently catalyze the addition of less basic aryl-
amines to alkynes, corresponding reactions employing basic
alkylamines are more challenging. Among the class of alk-
ylamines, sterically less hindered n-alkyl- and benzylamines
usually show the lowest reactivity.[2] However, from a bio-
logical point of view the generation of methylamino groups
is highly desirable since many biologically active com-
pounds possess this sub-structure. As a consequence, we in-
vestigated the addition of gaseous methylamine (and ethyl-
amine) to alkynes.[3] Subsequent reductions of the expected
N-methyl imine products should give access to the desired
methylamine derivatives.
Results and Discussion
Based on mechanistic investigations of the Ind2TiMe2-
catalyzed hydroamination of alkynes, which suggest that the
addition of sterically less hindered amines to alkynes is in-
verse first order in the concentration of the amine,[4] we
simply stirred solutions of diphenylacetylene (1) in toluene
in the presence of 5 mol-% Ind2TiMe2 (Ind = indenyl) at
105 °C in 100-mL Schlenk tubes (Ø 30 mm) under methyl-
amine (1 atm, b. p. –6 °C). For that purpose, we used a reg-
ular Schlenk vacuum line filled with methylamine (instead
of argon). We assumed that this simple hydrogenation-like
set-up of the experiments automatically results in low con-
centrations of gaseous methylamine in the liquid phase and
Scheme 1. Ind2TiMe2-catalyzed hydroamination of symmetrically
substituted internal alkynes with methyl- and ethylamine and sub-
sequent reduction.
An additional experiment, employing gaseous ethyl-
amine (b. p. 17 °C) also gave the expected product 3 in very
good yield (84%). However, corresponding reactions of the
dialkylalkyne 6-dodecyne (4) were less successful. In both
hydroamination/reduction experiments performed with
methyl- and ethylamine only trace amounts of the desired
products 5 and 6 were formed.
[a] Organisch-Chemisches Institut, Universität Heidelberg,
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49-6221-54-4205
E-mail: sven.doye@urz.uni-heidelberg.de
Eur. J. Org. Chem. 2005, 4843–4851
DOI: 10.1002/ejoc.200500458
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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K. Marcseková, B. Wegener, S. Doye
FULL PAPER
Since dialkylalkynes had turned out to be poor sub- interesting methylamino group were obtained after subse-
strates for Ind2TiMe2-catalyzed addition reactions of meth- quent reduction as the major products. Except in the case of
yl- and ethylamine, we focused on reaction sequences of ortho-substituted 23a, the products were obtained in good
unsymmetrically
substituted
2-alkyl-1-phenylalkynes yields. However, the poor yield of 23a mainly reflects the
(Table 1). Under the reaction conditions described above, decreased rate of the hydroamination of the sterically more
methylamine smoothly reacted with the alkynes 7–16. As demanding ortho-substituted alkyne substrate 13. In this
the result of the good regioselectivity generally observed for context, it is worth to mention that, in order to compare
Ind2TiMe2-catalyzed hydroamination reactions,[4,5] 2-phen- the various experiments, all hydroamination reactions were
ylethylamine derivatives 17–26a possessing a biologically stopped after 7 h. The results shown in Table 1 further
Table 1. Ind2TiMe2-catalyzed hydroamination of 2-alkyl-1-phenylalkynes with methylamine and subsequent reduction.
[a] Reaction conditions: 1) alkyne (4.0 mmol), Ind2TiMe2 (0.2 mmol, 5.0 mol-%), methylamine (1 atm), toluene, 105 °C, 7 h; 2) NaBH3CN
(8.0 mmol), ZnCl2 (4.0 mmol), MeOH, 25 °C, 20 h. [b] Determined by GC/MS analyses prior to chromatography. [c] Obtained after one
chromatography. A complete separation of the regioisomers can be achieved by two subsequent chromatographies.
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Eur. J. Org. Chem. 2005, 4843–4851

Ind2TiMe2-Catalyzed Addition of Methyl- and Ethylamine to Alkynes
FULL PAPER
Table 2. Ind2TiMe2-catalyzed hydroamination of 2-alkyl-1-phenylalkynes with ethylamine and subsequent reduction.
[a] Reaction conditions: 1) alkyne (4.0 mmol), Ind2TiMe2 (0.2 mmol, 5.0 mol-%), ethylamine (1 atm), toluene, 105 °C, 7 h; 2) NaBH3CN
(8.0 mmol), ZnCl2 (4.0 mmol), MeOH, 25 °C, 20 h. [b] Determined by GC/MS analyses prior to chromatography. [c] Obtained after one
chromatography. A complete separation of the regioisomers can be achieved by two subsequent chromatographies.
prove that chloro and methoxy substituents in the phenyl found that better yields were obtained when the hydroamin-
ring do not significantly influence the efficiency of the reac- ation reactions were performed at 80 °C (105 °C, yields
tion sequences. As observed before,[4] the regioselectivities Ͻ15%). An explanation for this result is the well known
of the hydroamination reactions decrease with increasing fact that terminal alkynes, especially arylalkynes tend to un-
size of the alkyl substituents of the 2-alkyl-1-phenylalkyne dergo oligomerization reactions at elevated temperatures in
substrates (compare entries 3 and 10).
the presence of many Ti complexes.[4,6] However, compared
Table 2 summarizes corresponding hydroamination/ to the results obtained with most of the internal alkynes,
reduction one-pot experiments employing ethylamine. the yields shown in Table 3 are only moderate. Since it is
However, with regard to yields and regioselectivities, well established that the regioselectivity of hydroaminations
the results are comparable to those obtained with methyl- of terminal alkynes decreases with decreasing size of the
amine.
amine,[4,7] it is not surprising that the additions of methyl-
Finally, we focused on additions of methyl- and ethyl- and ethylamine to alkynes 36–38 take place without any
amine to terminal alkynes (Table 3). In this case, it was regioselectivity.
Eur. J. Org. Chem. 2005, 4843–4851
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K. Marcseková, B. Wegener, S. Doye
FULL PAPER
tained by CHN elemental analysis and/or high-resolution mass
spectrometry (HRMS). NMR spectra were recorded with the fol-
lowing spectrometers: Bruker Avance ARX 250, Bruker Avance
DRX 300, Bruker AC 300, Bruker Avance DRX 400, Bruker Av-
Table 3. Ind2TiMe2-catalyzed hydroamination of terminal alkynes
with methyl- and ethylamine and subsequent reduction.
1
ance DRX 500. All H NMR spectra are reported in δ units ppm
relative to the signal for CDCl3 at δ = 7.26 ppm. All 13C NMR
spectra are reported in δ units ppm relative to the central line of
the triplet for CDCl3 at δ = 77.0 ppm. Infrared spectra were re-
corded with a Bruker Vector 22 spectrometer using an attenuated
total reflection (ATR) method. Mass spectra were recorded with a
JEOL JMS-700 or a Finnigan TSQ 700 (EI) spectrometer with an
ionization potential of 70 eV. Elemental analyses were carried out
with an Elementar Vario EL machine. GC/MS analyses were per-
formed with a Hewlett–Packard HP 5890 Series II gas chromato-
graph equipped with a Hewlett–Packard HP 5972 Series I Mass
Selective Detector. PE: light petroleum ether, b. p. 40–60 °C.
[a] Reaction conditions: 1) alkyne (4.0 mmol), Ind2TiMe2
(0.2 mmol, 5.0 mol-%), amine (1 atm), toluene, 80 °C, 7 h; 2)
NaBH3CN (8.0 mmol), ZnCl2 (4.0 mmol), MeOH, 25 °C, 20 h.
[b] Determined by GC/MS analyses prior to chromatography.
Addition of Methyl- or Ethylamine to Internal Alkynes. General Pro-
cedure A: Under Ar, the alkyne (4.0 mmol) and Ind2TiMe2 (62 mg,
0.20 mmol, 5.0 mol-%) were placed in a Schlenk tube equipped
with a Teflon stopcock and a magnetic stirring bar. The Schlenk
tube was then connected to a vacuum line operated with gaseous
methyl- or ethylamine (instead of argon or nitrogen). After evacua-
tion, the Schlenk tube was flushed with the gaseous amine (1 atm,
3 ×). Then, toluene (2.0 mL) was added and the resulting mixture
was stirred under a constant pressure of 1 atm of methyl- or ethyl-
amine at 105 °C for 7 h. The resulting dark brown solution was
cooled to room temperature and a mixture of NaBH3CN (503 mg,
8.0 mmol) and ZnCl2 (543 mg, 4.0 mmol) in methanol (20 mL) was
added. After this had been stirred at 25 °C for 16 h, CH2Cl2
(50 mL) and saturated Na2CO3 solution (20 mL) were added. The
resulting mixture was filtered and the solid residue was washed with
CH2Cl2 (50 mL). After extraction, the organic layer was separated.
The aqueous layer was extracted with CH2Cl2 (5×50 mL) and the
combined organic layers were dried with MgSO4. After concentra-
tion under vacuum, the crude mixture of regioisomers was analyzed
by GC/MS (if applicable) and purified by flash chromatography
(SiO2).
Conclusions
In summary, we have presented a very simple hydrogena-
tion-like experimental protocol for the addition of gaseous
methyl- and ethylamine to alkynes in the presence of
Ind2TiMe2 as the catalyst. For efficient hydroamination re-
actions it is sufficient to stir a mixture of the alkyne and the
catalyst in toluene at temperatures between 80 °C (terminal
alkynes) and 105 °C (internal alkynes) under a constant
pressure of 1 atm of the corresponding amine. After subse-
quent reduction of the initially formed imines, methyl- and
ethylamine derivatives are the final products of the de-
scribed one-pot reaction sequences. While the yields of the
products obtained from terminal alkynes are only moder-
ate, good results are observed when diphenyl- and 2-alkyl-
1-phenylalkynes are employed as starting materials. In the
case of 2-alkyl-1-phenylalkynes, the hydroamination reac-
tions take place with good regioselectivities (anti-Markovni-
kov). Correspondingly, biologically interesting 2-phenyle-
thylamine derivatives possessing a methyl or ethyl substitu-
ent at the N atom are easily accessible by the new reaction
protocol.
Addition of Methyl- or Ethylamine to Terminal Alkynes. General
Procedure B: Under Ar, the alkyne (4.0 mmol) and Ind2TiMe2
(62 mg, 0.20 mmol, 5.0 mol-%) were placed in a Schlenk tube
equipped with a Teflon stopcock and a magnetic stirring bar. The
Schlenk tube was then connected to a vacuum line operated with
gaseous methyl- or ethylamine (instead of argon or nitrogen). After
evacuation, the Schlenk tube was flushed with the gaseous amine
(1 atm, 3 ×). Then, toluene (2.0 mL) was added and the resulting
mixture was stirred under a constant pressure of 1 atm of methyl-
or ethylamine at 80 °C for 7 h. The resulting dark brown solution
was cooled to room temperature and a mixture of NaBH3CN
(503 mg, 8.0 mmol) and ZnCl2 (543 mg, 4.0 mmol) in methanol
(20 mL) was added. After this had been stirred at 25 °C for 16 h,
CH2Cl2 (50 mL) and saturated Na2CO3 solution (20 mL) were
added. The resulting mixture was filtered and the solid residue was
washed with CH2Cl2 (50 mL). After extraction, the organic layer
was separated. The aqueous layer was extracted with CH2Cl2
(5×50 mL) and the combined organic layers were dried with
MgSO4. After concentration under vacuum, the crude mixture of
regioisomers was analyzed by GC/MS and purified by flash
chromatography (SiO2).
Experimental Section
General Remarks: All reactions were performed in flame-dried
Schlenk tubes (Duran glassware, 100 mL, Ø 30 mm) equipped with
Teflon stopcocks and magnetic stirring bars (15×4.5 mm). Toluene
was distilled from molten sodium under argon. Ind2TiMe2 was syn-
thesized according to ref.[8] or purchased from MCAT.[9] Diphenyl-
acetylene (1) was dissolved in CH2Cl2, dried with Na2SO4, and
recovered by evaporation of the solvent. Alkynes 4, 7–16, and 36–
38 were purified by distillation. Methyl- and ethylamine were re-
ceived from BASF AG (Ludwigshafen). All other reagents were
received from commercial sources and were used without further
purification. Unless otherwise noted, yields refer to isolated yields
of pure compounds as gauged by thin-layer chromatography
Amine 2: General procedure A was used to synthesize amine 2 from
diphenylacetylene (1) and methylamine. After purification by flash
1
(TLC), H and 13C NMR spectroscopy. All products were charac-
terized by 1H NMR, 13C NMR, infrared (IR) spectroscopy, and chromatography (PE/EtOAc, 1:1), amine 2 (777 mg, 3.68 mmol,
1
mass spectrometry (MS). Additional characterization data were ob-
92%) was isolated as a colorless oil. H NMR (250 MHz, CDCl3):
4846
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Eur. J. Org. Chem. 2005, 4843–4851

Ind2TiMe2-Catalyzed Addition of Methyl- and Ethylamine to Alkynes
δ = 1.49 (br. s, 1 H), 2.21 (s, 3 H), 2.88 (dd, J = 13.2, 8.0 Hz, 1 H), purification by flash chromatography (EtOAc/MeOH, 10:1), amine
FULL PAPER
2.96 (dd, J = 13.2, 5.6 Hz, 1 H), 3.72 (dd, J = 8.3, 5.8 Hz, 1 H),
19a (489 mg, 2.36 mmol, 59%) and a mixture of regioisomers 19a
7.13–7.31 (m, 10 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ and 19b (130 mg, 0.63 mmol, 16%) were obtained as colorless oils.
1
= 34.7 (CH3), 45.2 (CH2), 66.9 (CH), 126.4 (CH), 127.1 (CH), 19a: H NMR (300 MHz, CDCl3): δ = 0.97 (t, J = 7.0 Hz, 3 H),
127.3 (CH), 128.3 (CH), 128.4 (CH), 129.3 (CH), 138.9 (C), 143.5
1.38–1.51 (m, 4 H), 2.42 (s, 3 H), 2.66–2.77 (m, 3 H), 3.85 (s, 3 H),
6.79–6.84 (m, 3 H), 7.17–7.25 (dd, J = 7.7, 7.2 Hz, 1 H) ppm. 13C
NMR (75 MHz, DEPT, CDCl3): δ = 14.9 (CH3), 19.5 (CH2), 34.3
(CH3), 36.2 (CH2), 41.0 (CH2), 55.7 (CH3), 61.1 (CH), 111.9 (CH),
(C) ppm. IR: ν = 3084, 3061, 3027, 2972, 2936, 2846, 2789, 1602,
˜
1494, 1474, 1453, 1443, 1353, 1133, 1070, 1029, 758, 700 cm–1. MS
(25 °C): m/z (%) = 212 (19) [MH+], 120 (100) [M+ – C7H7], 91 (27)
[C7H7+], 77 (8). C15H17N (211.3): calcd. C 85.26, H 8.11, N 6.63; 115.6 (CH), 122.3 (CH), 129.9 (CH), 142.0 (C), 160.2 (C) ppm. IR:
found C 85.31, H 8.12, N 6.92.
ν = 2956, 2932, 2871, 2835, 2791, 1601, 1584, 1489, 1455, 1261,
˜
1153, 1049, 778, 696 cm–1. HRMS (%) calcd. [C13H21NO+]
207.1623, found 207.1595 (2); calcd. [C10H14NO+] 164.1075, found
164.1074 (96); calcd. [C8H9O+] 121.0653, found 121.0662 (45);
calcd. [C5H12N+] 86.0970, found 86.0980 (100). C13H21NO (207.3):
calcd. C 75.31, H 10.21, N 6.76, O 7.72; found C 75.34, H 10.41,
N 6.55.
Amine 3: General procedure A was used to synthesize amine 3 from
diphenylacetylene (1) and ethylamine. After purification by flash
chromatography (PE/EtOAc, 3:1), amine 3 (757 mg, 3.36 mmol,
1
84%) was isolated as a colorless oil. H NMR (250 MHz, CDCl3):
δ = 0.95 (t, J = 7.2 Hz, 3 H), 1.36 (br. s, 1 H), 2.34–2.45 (m, 2 H),
2.87–2.93 (m, 2 H), 3.83 (t, J = 6.6 Hz, 1 H), 7.08–7.28 (m, 10 H)
ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 15.3 (CH3), 42.0
(CH2), 45.3 (CH2), 64.9 (CH), 126.3 (CH), 127.0 (CH), 127.3 (CH),
128.3 (CH), 128.4 (CH), 129.3 (CH), 139.0 (C), 144.0 (C) ppm. IR:
Amine 20a: General procedure A was used to synthesize amine 20a
from 1-(4-chlorophenyl)-1-propyne (10) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
20a (563 mg, 3.06 mmol, 77%) and a mixture of regioisomers 20a
and 20b (75 mg, 0.41 mmol, 10%) were obtained as colorless oils.
ν = 3061, 3026, 2965, 2920, 2868, 2815, 1602, 1494, 1463, 1453,
˜
1143, 1070, 1030, 790, 699 cm–1. MS (25 °C): m/z (%) = 226 (27)
[MH+], 134 (100) [M+ – C7H8], 91 (50) [C7H7+], 79 (27), 77 (21).
C16H19N (225.3): calcd. C 85.29, H 8.50, N 6.22; found C 85.00,
H 8.56, N 6.29.
1
20a: H NMR (300 MHz, CDCl3): δ = 1.04 (d, J = 6.3 Hz, 3 H),
1.39 (br. s, 1 H), 2.41 (s, 3 H), 2.55–2.61 (dd, J = 7.0, 6.3 Hz, 1 H),
2.68–2.81 (m, 2 H), 7.11 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = 8.5 Hz,
2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 19.5 (CH3),
33.9 (CH3), 42.6 (CH2), 56.2 (CH), 128.5 (CH), 130.6 (CH), 132.0
Amine 17a: General procedure A was used to synthesize amine 17a
from 1-(4-methoxyphenyl)-1-propyne (7) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
17a (573 mg, 3.20 mmol, 80%) and a mixture of regioisomers 17a
and 17b (57 mg, 0.32 mmol, 8%) were obtained as colorless oils.
(C), 137.9 (C) ppm. IR: ν = 3026, 2967, 2932, 2849, 2790, 1492,
˜
1446, 1407, 1372, 1090, 1016, 800, 666 cm–1. HRMS (%) calcd.
[C10H14N35Cl+] 183.0815, found 183.0737 (11); calcd.
[C10H13N37Cl+] 184.0707, found 184.0714 (66); calcd.
[C10H13N35Cl+] 182.0737, found 182.0714 (22); calcd.
1
17a: H NMR (300 MHz, CDCl3): δ = 1.04 (d, J = 5.9 Hz, 3 H),
1.38 (s, 1 H), 2.39 (s, 3 H), 2.53–2.77 (m, 3 H), 3.79 (s, 3 H), 6.84
(d, J = 8.4 Hz, 2 H), 7.10 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR
(75 MHz, DEPT, CDCl3): δ = 19.7 (CH3), 34.0 (CH3), 42.6 (CH2),
55.2 (CH), 56.5 (CH3), 113.8 (CH), 130.2 (CH), 131.5 (C), 158.1
[C9H11N37Cl+]
170.0551, found
170.0574 (15);
calcd.
[C9H11N35Cl+] 168.0580, found 168.0570 (45); calcd. [C7H6N37Cl+]
127.0129, found 127.0128 (32); calcd. [C7H6N35Cl+] 125.0158,
found 125.0128 (95). C10H14ClN (183.7): C 65.39, H 7.68, N 7.63;
found C 65.11, H 7.56, N 7.73.
(C) ppm. IR: ν = 3031, 2971, 2834, 2789, 1612, 1513, 1441, 1251,
˜
1178, 1037, 806, 754 cm–1. HRMS (%) calcd. [C11H17NO+]
179.1310, found 179.1300 (4); calcd. [C11H16NO+] 178.1232, found
178.1222 (6); calcd. [C10H14NO+] 164.1075, found 164.1067 (10);
Amine 21a: General procedure A was used to synthesize amine 21a
from 1-(4-chlorophenyl)-1-pentyne (11) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
21a (601 mg, 2.84 mmol, 71%) and a mixture of regioisomers 21a
and 21b (42 mg, 0.20 mmol, 5%) were obtained as colorless oils.
calcd. [C8H9O+] 121.0653, found 121.0648 (40); calcd. [C6H6
]
+
78.0470, found 78.0461 (13); calcd. [C3H8N+] 58.0657, found
+
58.0643 (100); calcd. [C3H7
] 43.0548, found 43.0557 (23).
C11H17NO (179.3): calcd. C 73.70, H 9.56, N 7.81; found C 73.21,
H 9.56, N 7.94.
1
21a: H NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 3 H),
1.15 (br. s, 1 H), 1.34–1.37 (m, 4 H), 2.37 (s, 3 H), 2.60–2.64 (m, 3
H), 7.10 (d, J = 8.1 Hz, 2 H), 7.24 (d, J = 8.4 Hz, 2 H) ppm. 13C
NMR (75 MHz, DEPT, CDCl3): δ = 14.3 (CH3), 18.9 (CH2), 33.7
(CH3), 35.5 (CH2), 39.6 (CH2), 60.5 (CH), 128.5 (CH), 130.6 (CH),
Amine 18a: General procedure A was used to synthesize amine 18a
from 1-(4-methoxyphenyl)-1-pentyne (8) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
18a (480 mg, 2.32 mmol, 58%) and a mixture of regioisomers 18a
and 18b (84 mg, 0.41 mmol, 10%) were obtained as colorless oils.
131.8 (C), 138.2 (C) ppm. IR: ν = 3026, 2957, 2931, 2871, 2791,
˜
1492, 1090, 1016, 799 cm–1. HRMS (%) calcd. [C12H18N37Cl+]
213.1098, found 213.1077 (1); calcd. [C12H17N37Cl+] 212.1020,
found 212.1024 (2); calcd. [C12H18N35Cl+] 211.1128, found
211.1174 (1); calcd. [C12H17N35Cl+] 210.1050, found 210.1026 (5);
calcd. [C9H11N37Cl+] 170.0551, found 170.0536 (39); calcd.
[C9H11N35Cl+] 168.0580, found 168.0566 (100); calcd. [C9H11N+]
133.0891, found 133.0887 (24); calcd. [C7H6N37Cl+] 127.0129,
found 127.0145 (24); calcd. [C7H6N35Cl+] 125.0158, found
125.0152 (72); calcd. [C5H12N+] 86.0970, found 86.0977 (100).
C12H18ClN (211.7): calcd. C 68.07, H 8.57, N 6.62; found C 67.78,
H 8.56, N 6.64.
1
18a: H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 6.6 Hz, 3 H),
1.36–1.40 (m, 4 H), 2.37 (s, 3 H), 2.57–2.69 (m, 3 H), 3.79 (s, 3 H),
6.82 (d, J = 8.4 Hz, 2 H), 7.08 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR
(75 MHz, DEPT, CDCl3): δ = 14.9 (CH3), 19.5 (CH2), 34.3 (CH3),
36.1 (CH2), 39.9 (CH2), 55.8 (CH3), 61.3 (CH), 114.4 (CH), 130.7
(CH), 132.3 (C), 158.6 (C) ppm. IR: ν = 3336, 2956, 2931, 2871,
˜
2789, 1612, 1513, 1465, 1352, 1301, 1248, 1038, 834 cm–1. HRMS
(%) calcd. [C13H21NO+] 207.1623, found 207.1591 (1); calcd.
[C13H20NO+] 206.1545, found 206.1521 (4); calcd. [C10H14NO+]
164.1075, found 164.1079 (33); calcd. [C9H12NO+] 150.0919, found
150.0944 (89); calcd. [C8H9O+] 121.0653, found 121.0660 (52);
calcd. [C5H12N+] 86.0970, found 86.0988 (100). C13H21NO (207.3):
calcd. C 75.31, H 10.21, N 6.76; found C 75.03, H 10.31, N 6.62.
Amine 22a: General procedure A was used to synthesize amine 22a
from 1-(3-chlorophenyl)-1-pentyne (12) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
22a (525 mg, 2.48 mmol, 62%) and a mixture of regioisomers 22a
Amine 19a: General procedure A was used to synthesize amine 19a
from 1-(3-methoxyphenyl)-1-pentyne (9) and methylamine. After
Eur. J. Org. Chem. 2005, 4843–4851
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4847

K. Marcseková, B. Wegener, S. Doye
FULL PAPER
and 22b (88 mg, 0.42 mmol, 9%) were obtained as colorless oils.
(m, 1 H), 0.37–0.46 (m, 1 H), 0.53–0.72 (m, 2 H), 1.36 (br. s, 1 H),
1
22a: H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3 H), 1.80–1.88 (dt, J = 8.8, 5.2 Hz, 1 H), 2.45 (s, 3 H), 2.75 (dd, J =
1.26–1.38 (m, 5 H), 2.38 (s, 3 H), 2.65 (m, 3 H), 7.06 (d, J = 6.6 Hz, 13.6, 8.1 Hz, 1 H), 2.91 (dd, J = 13.6, 5.2 Hz, 1 H), 7.19–7.31 (m,
1 H), 7.17–7.19 (m, 3 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): 5 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 1.7 (CH2), 4.9
δ = 14.0 (CH3), 18.6 (CH2), 33.5 (CH3), 35.3 (CH2), 39.8 (CH2),
(CH2), 15.7 (CH), 34.7 (CH3), 41.8 (CH2), 66.6 (CH), 126.1 (CH),
60.2 (CH), 126.0 (CH), 127.3 (CH), 129.1 (CH), 129.3 (CH), 133.9 128.3 (CH), 129.4 (CH), 139.5 (C) ppm. IR: ν = 3076, 3026, 3000,
˜
(C), 141.7 (C) ppm. IR: ν = 3061, 2957, 2931, 2871, 2792, 1597, 2939, 2849, 2787, 1603, 1494, 1453, 1140, 1073, 741, 699 cm–1.
˜
1572, 1476, 1352, 1208, 1082, 883, 779, 700, 684 cm–1. HRMS (%)
calcd. [C12H18N37Cl+] 213.1098, found 213.1046 (1); calcd.
HRMS (%) calcd. [C12H17N+] 175.1361, found 175.1323 (2); calcd.
[C12H16N+] 174.1283, found 174.1299 (5); calcd. [C9H12N+]
134.0907, found 134.0975 (46); calcd. [C8H10N+] 120.0813, found
120.0801 (21); calcd. [C7H7+] 91.0548, found 91.0575 (100); calcd.
[C5H10N+] 84.0813, found 84.0840 (100). 25b: 1H NMR (300 MHz,
CDCl3): δ = –0.13 to –0.05 (m, 1 H), –0.01 to 0.07 (m, 1 H), 0.27–
0.42 (m, 2 H), 0.46–0.54 (m, 1 H), 1.39–1.48 (m, 1 H), 1.61–1.69
(m, 1 H), 2.23 (s, 3 H), 3.54 (t, J = 6.6 Hz, 1 H), 7.18–7.28 (m, 5
[C12H17N37Cl+]
[C12H18N35Cl+]
212.1020,
211.1128,
found
found
212.0987
211.1063
(2);
(1);
calcd.
calcd.
[C12H17N35Cl+] 210.1050, found 210.1061 (7); calcd. [C9H11N37Cl+]
170.0551, found 170.0561 (57); calcd. [C9H11N35Cl+] 168.0580,
found 168.0580 (100); calcd. [C7H6N37Cl+] 127.0129, found
127.0124 (20); calcd. [C7H6N35Cl+] 125.0158, found 125.0143 (64);
calcd. [C5H12N+] 86.0970, found 86.0949 (100). C12H18ClN (211.7): H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 4.1 (CH2), 4.6
calcd. C 68.07, H 8.57, N 6.62; found C 67.78, H 8.55, N 6.49.
(CH2), 8.2 (CH), 34.3 (CH3), 43.0 (CH2), 66.0 (CH), 127.0 (CH),
127.3 (CH), 128.3 (CH), 143.6 (C) ppm. IR: ν = 3076, 3000, 2924,
˜
Amine 23a: General procedure A was used to synthesize amine 23a
from 1-(2-chlorophenyl)-1-pentyne (13) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
23a (228 mg, 1.08 mmol, 27%) and mixture of regioisomers 23a
and 23b (102 mg, 0.48 mmol, 12%) were obtained as colorless oils.
2850, 2789, 1602, 1475, 1136, 1017, 753, 701 cm–1. HRMS (%)
calcd. [C12H17N+] 175.1361, found 175.1360 (1); calcd. [C10H14N+]
148.1126, found 148.1138 (11); calcd. [C9H12N+] 134.0970, found
134.0964 (17); calcd. [C8H10N+] 120.0813, found 120.0815 (100);
calcd. [C6H12N+] 98.0970, found 98.0963 (14); calcd. [C7H7
]
+
1
23a: H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.0 Hz, 3 H),
91.0548, found 91.0554 (18); calcd. [C5H10N+] 84.0813, found
84.0823 (13).
1.31–1.46 (m, 5 H), 2.40 (s, 3 H), 2.76–2.90 (m, 3 H), 7.15–7.19 (m,
3 H), 7.30 (d, J = 7.0 Hz, 1 H) ppm. 13C NMR (75 MHz, DEPT,
CDCl3): δ = 14.3 (CH3), 18.9 (CH2), 33.7 (CH3), 35.8 (CH2), 38.4
(CH2), 58.9 (CH), 126.6 (CH), 127.6 (CH), 129.6 (CH), 131.6 (CH),
Amines 26a/26b: General procedure A was used to synthesize
amines 26a and 26b from 1-(3-methoxyphenyl)-2-cyclopropyle-
thyne (16) and methylamine. After purification by flash chromatog-
raphy (EtOAc/MeOH, 2:1), amine 26a (465 mg, 2.26 mmol, 57%)
and amine 26b (93 mg, 0.45 mmol, 11%) were obtained as colorless
oils. 26a: 1H NMR (300 MHz, CDCl3): δ = –0.04 to 0.04 (m, 1 H),
0.23–0.31 (m, 1 H), 0.38–0.47 (m, 1 H), 0.54–0.74 (m, 2 H), 1.53
(br. s, 1 H), 1.84 (dd, J = 8.5, 3.7 Hz, 1 H), 2.44 (s, 3 H), 2.72 (dd,
J = 13.2, 8.1 Hz, 1 H), 2.90 (dd, J = 13.6, 4.8 Hz, 1 H), 3.79 (s, 3
H), 6.74–6.80 (m, 3 H), 7.20 (dd, J = 8.8, 7.4 Hz, 1 H) ppm. 13C
NMR (75 MHz, DEPT, CDCl3): δ = 1.6 (CH2), 5.1 (CH2), 15.7
(CH), 34.6 (CH3), 42.0 (CH2), 55.1 (CH3), 66.4 (CH), 111.4 (CH),
115.1 (CH), 121.8 (CH), 129.2 (CH), 141.1 (C), 159.6 (C) ppm. IR:
134.3 (C), 137.7 (C) ppm. IR: ν = 3066, 2957, 2931, 2871, 2793,
˜
1475, 1443, 1052, 750, 682 cm–1. HRMS (%) calcd. [C12H17N37Cl+]
212.1020. found 212.0992 (4); calcd. [C12H18N35Cl+] 211.1128,
found 211.1048 (2); calcd. [C12H17N35Cl+] 210.1050, found
210.1040 (9); calcd. [C9H11N37Cl+] 170.0551, found 170.0563 (66);
calcd. [C9H11N35Cl+] 168.0580, found 168.0583 (100); calcd.
[C7H637Cl+] 127.0129, found 127.0123 (29); calcd. [C7H635Cl+]
125.0158, found 125.0146 (86); calcd. [C5H12N+] 86.0970, found
86.0990 (100). C12H18ClN (211.7): calcd. C 68.07, H 8.57, N 6.62;
found C 68.34, H 8.74, N 6.58.
Amine 24a: General procedure A was used to synthesize amine 24a
from 1-(4-methylphenyl)-1-pentyne (14) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1), amine
24a (536 mg, 2.80 mmol, 70%) and mixture of regioisomers 24a
and 24b (53 mg, 0.28 mmol, 7%) were obtained as colorless oils.
ν = 3333, 3073, 2999, 2941, 2835, 2787, 1601, 1584, 1488, 1260,
˜
1153, 1050, 697 cm–1. HRMS (%) calcd. [C13H19NO+] 205.1467,
found 205.1480 (1); calcd. [C13H18NO+] 204.1388, found 204.1397
(2); calcd. [C9H13NO+] 151.0997, found 151.0967 (62); calcd.
[C9H12NO+] 150.0919, found 150.0929 (100); calcd. [C5H10N+]
84.0813, found 84.0830 (27). C13H19NO (205.3): calcd. C 76.06, H
9.33, N 6.82; found C 75.54, H 9.42, N 6.88. 26b: 1H NMR
(300 MHz, CDCl3): δ = –0.04 to –0.02 (m, 1 H), –0.01 to 0.02 (m,
1 H), 0.06–0.45 (m, 2 H), 0.55–0.60 (m, 1 H), 1.39–1.48 (m, 1 H),
1.62–1.71 (m, 2 H), 2.29 (s, 3 H), 3.55 (t, J = 6.6 Hz, 1 H), 3.81 (s,
3 H), 6.76–6.80 (m, 1 H), 6.87–6.90 (m, 2 H), 7.21 (d, J = 7.3 Hz,
1 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 4.1 (CH2), 4.7
(CH2), 8.2 (CH), 34.6 (CH3), 43.2 (CH2), 55.2 (CH3), 66.1 (CH),
112.2 (CH), 112.7 (CH), 119.7 (CH), 129.2 (CH), 146.0 (C), 159.7
1
24a: H NMR (500 MHz, CDCl3): δ = 0.84 (t, J = 6.7 Hz, 3 H),
1.20–1.38 (m, 5 H), 2.24 (s, 3 H), 2.29 (s, 3 H), 2.45–2.70 (m, 3 H),
6.98 (d, J = 8.6 Hz, 2 H), 7.02 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR
(125 MHz, DEPT, CDCl3): δ = 14.3 (CH3), 18.8 (CH2), 20.9 (CH3),
33.7 (CH3), 35.5 (CH2), 39.8 (CH2), 60.6 (CH), 129.0 (CH), 129.1
(CH), 135.4 (C), 136.5 (C) ppm. IR: ν = 3003, 2957, 2930, 2871,
˜
2789, 1515, 1454, 1378, 1352, 1142, 1096, 823, 800 cm–1. HRMS
(%) calcd. [C13H21N+] 191.1674, found 191.1666 (1); calcd.
[C13H20N+] 190.1596, found 190.1589 (5); calcd. [C10H14N+]
148.1126, found 148.1138 (76); calcd. [C9H11N+] 133.0891, found
133.0878 (12); calcd. [C8H9+] 105.0704, found 105.0686 (46); calcd.
[C5H12N+] 86.0970, found 86.0974 (100); calcd. [C2H6N+] 44.0500,
found 44.0511 (30). C13H21N (191.3): calcd. C 81.61, H 11.06, N
7.32; found C 81.53, H 10.79, N 7.44.
(C) ppm. IR: ν = 3338, 3076, 2998, 2935, 2835, 2787, 1599, 1486,
˜
1256, 1148, 1046, 783, 701 cm–1. HRMS (%) calcd. [C13H19NO+]
205.1467, found 205.1435 (1); calcd. [C13H18NO+] 204.1388, found
204.1374 (3); calcd. [C9H13NO+] 151.0997, found 151.0961 (86);
calcd. [C9H12NO+] 150.0919, found 150.0944 (100); calcd.
[C8H9NO+] 135.0684, found 135.0659 (12); calcd. [C8H9O+]
121.0653, found 121.0650 (10); calcd. [C7H9N+] 107.0735, found
107.0738 (16).
Amines 25a/25b: General procedure A was used to synthesize
amines 25a and 25b from 1-phenyl-2-cyclopropylethyne (15) and
methylamine. After purification by flash chromatography (EtOAc/
MeOH, 2:1), amine 25a (336 mg, 1.92 mmol, 48%) and amine 25b Amine 27a: General procedure A was used to synthesize amine 27a
1
(119 mg, 0.68 mmol, 17%) were obtained as colorless oils. 25a: H
NMR (300 MHz, CDCl3): δ = –0.06 to 0.02 (m, 1 H), 0.22–0.30
from 1-(4-methoxyphenyl)-1-propyne (7) and ethylamine. After pu-
rification by flash chromatography (EtOAc/MeOH, 1:1), amine 27a
4848
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 4843–4851

Ind2TiMe2-Catalyzed Addition of Methyl- and Ethylamine to Alkynes
FULL PAPER
(595 mg, 3.08 mmol, 77%) and a mixture of regioisomers 27a and
27b (33 mg, 0.17 mmol, 4%) were obtained as colorless oils. 27a:
731, 715, 665 cm–1. HRMS (%) calcd. [C11H16N37Cl+] 199.0942,
found 199.0935 (1); calcd. [C11H15N37Cl+] 198.0864, found
1H NMR (300 MHz, CDCl3): δ = 1.01 (t, J = 6.2 Hz, 3 H), 1.04 198.0873 (5); calcd. [C11H16N35Cl+] 197.0927, found 197.0916 (2);
(d, J = 7.1 Hz, 3 H), 2.54–2.58 (q, J = 6.1 Hz, 2 H), 2.61–2.66 (dd,
J = 7.4, 7.0 Hz, 2 H), 2.81–2.89 (m, 1 H), 3.76 (s, 3 H), 6.80 (d, J
calcd. [C11H15N35Cl+] 196.0893, found 196.0873 (17); calcd.
[C10H13N37Cl+] 184.0707, found 184.0714 (14); calcd.
= 8.6 Hz, 2 H), 7.06 (d, J = 8.7 Hz, 2 H) ppm. 13C NMR (75 MHz, [C10H13N35Cl+] 182.0737, found 182.0736 (41); calcd.
DEPT, CDCl3): δ = 15.4 (CH3), 20.2 (CH3), 41.5 (CH2), 42.7 [C7H6N37Cl+] 127.0129, found 127.0119 (32); calcd. [C7H6N35Cl+]
(CH3), 54.6 (CH), 55.1 (CH3), 113.7 (CH), 130.1 (CH), 131.5 (C), 125.0158, found 125.0140 (100); calcd. [C7H7+] 91.0548, found
158.0 (C) ppm. IR: ν = 2963, 2930, 2834, 1612, 1512, 1464, 1301,
91.0561 (21); calcd. [C7H5+] 89.0391, found 89.0400 (34); calcd.
[C4H10N+] 72.0813, found 72.0816 (100); calcd. [C2H6N+] 44.0500,
˜
1247, 1177, 1125, 1037, 808 cm–1. MS (25 °C): m/z (%) = 194 (100)
[MH+], 164 (24) [M+ – C2H6], 121 (18) [M+ – C4H10N], 91 (4) found 44.0519 (77). C11H16ClN (197.7): C 66.83, H 8.16, N 7.08;
[C7H7], 72 (69) [C4H10N]. C12H19NO (193.3): calcd. C 74.57, H found C 66.57, H 8.35, N 7.30.
9.91, N 7.25; found C 74.09, H 10.08, N 7.25.
Amine 31a: General procedure A was used to synthesize amine 31a
Amine 28a: General procedure A was used to synthesize amine 28a
from 1-(4-methoxyphenyl)-1-pentyne (8) and ethylamine. After pu-
rification by flash chromatography (EtOAc/MeOH, 10:1), amine
28a (575 mg, 2.60 mmol, 65%) and a mixture of regioisomers 28a
and 28b (71 mg, 0.32 mmol, 8%) were obtained. 28a: 1H NMR
(300 MHz, CDCl3): δ = 0.90 (t, J = 6.6 Hz, 3 H), 1.03 (t, J =
7.3 Hz, 3 H), 1.36–1.39 (m, 4 H), 2.53–2.71 (m, 5 H), 3.79 (s, 3 H),
from 1-(4-chlorophenyl)-1-pentyne (11) and ethylamine. After puri-
fication by flash chromatography (EtOAc/MeOH, 2:1), amine 31a
(632 mg, 2.80 mmol, 70%) and a mixture of regioisomers 31a and
31b (34 mg, 0.15 mmol, 4%) were obtained as colorless oils. 31a:
1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 6.6 Hz, 3 H), 1.00
(t, J = 7.0 Hz, 3 H), 1.34–1.36 (m, 4 H), 2.57–2.72 (m, 5 H), 7.08
(d, J = 8.5 Hz, 2 H), 7.23 (d, J = 6.25 Hz, 2 H) ppm. 13C NMR
6.81 (d, J = 8.5 Hz, 2 H), 7.08 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 14.3 (CH3), 15.5 (CH3), 19.0 (CH2),
(75 MHz, DEPT, CDCl3): δ = 14.3 (CH3), 15.5 (CH3), 19.0 (CH2), 36.2 (CH2), 40.2 (CH2), 41.4 (CH2), 58.9 (CH), 128.4 (CH), 130.6
36.2 (CH2), 39.9 (CH2), 41.4 (CH2), 55.2 (CH3), 59.0 (CH), 113.8 (CH), 131.8 (C), 138.3 (C) ppm. IR: ν = 2958, 2930, 2876, 1865,
˜
(CH), 130.1 (CH), 131.8 (C), 157.9 (C) ppm. IR: ν = 3320, 2957,
1597, 1492, 1466, 1133, 1092, 1016, 833, 801, 745, 716, 665,
538 cm–1. HRMS (%) calcd. [C13H20N37Cl+] 227.1255, found
227.1189 (1); calcd. [C13H19N37Cl+] 226.1177, found 226.1165 (2);
calcd. [C13H20N35Cl+] 225.1284, found 225.1244 (1); calcd.
˜
2931, 2871, 2836, 1612, 1513, 1465, 1301, 1248, 1039, 834,
807 cm–1. HRMS (%) calcd. [C14H23NO+] 221.1780, found
221.1730 (2); calcd. [C14H22NO+] 220.1701, found 220.1716 (7);
calcd. [C11H16NO+] 178.1232, found 178.1222 (57); calcd.
[C13H19N35Cl+]
224.1206,
found
224.1185
(8);
calcd.
[C10H14NO+] 164.1075, found 164.1068 (40); calcd. [C8H9O+] [C10H13N37Cl+] 184.0707, found 184.0685 (41); calcd.
121.0653, found 121.0649 (100); calcd. [C6H14N+] 100.1126, found
100.1117 (100). C14H23ON (221.3): calcd. C 75.97, H 10.47, N 6.33;
found C 76.08, H 10.76, N 6.48.
[C10H13N35Cl+] 182.0737, found 182.0706 (100); calcd.
[C7H6N37Cl+] 127.0129, found 127.0155 (32); calcd. [C7H6N35Cl+]
125.0158, found 125.0153 (94); calcd. [C6H14N+] 100.1126, found
100.1129 (100). C13H20ClN (225.8): calcd. C 69.16, H 8.93, N 6.20;
found C 68.97, H 8.98, N 6.40.
Amine 29a: General procedure A was used to synthesize amine 29a
from 1-(3-methoxyphenyl)-1-pentyne (9) and ethylamine. After pu-
rification by flash chromatography (EtOAc/MeOH, 10:1), amine
29a (442 mg, 2.00 mmol, 50%) and a mixture of regioisomers 29a
Amine 32a: General procedure A was used to synthesize amine 32a
from 1-(3-chlorophenyl)-1-pentyne (12) and ethylamine. After puri-
fication by flash chromatography (EtOAc/MeOH, 2:1), amine 32a
and 29b (168 mg, 0.76 mmol, 19%) were obtained as colorless oils.
1
29a: H NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 6.9 Hz, 3 H), (611 mg, 2.71 mmol, 68%) and a mixture of regioisomers 32a and
1.03 (t, J = 7.2 Hz, 3 H), 1.34–1.42 (m, 4 H), 2.51–2.75 (m, 5 H),
3.79 (s, 3 H), 6.73 (s, 1 H), 6.73–6.78 (m, 3 H), 7.17 (dd, J = 7.6,
7.6 Hz, 1 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 14.1
32b (73 mg, 0.32 mmol, 8%) were obtained as colorless oils. 32a:
1H NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 6.6 Hz, 3 H), 1.04
(t, J = 7.2 Hz, 3 H), 1.33–1.38 (m, 4 H), 2.58–2.74 (m, 5 H), 7.04
(CH3), 15.3 (CH3), 18.8 (CH2), 36.0 (CH2), 40.7 (CH2), 41.1 (CH2), (d, J = 6.6 Hz, 1 H), 7.16–7.20 (m, 3 H) ppm. 13C NMR (75 MHz,
54.9 (CH3), 58.7 (CH), 111.1 (CH), 114.8 (CH), 121.5 (CH), 129.1
DEPT, CDCl3): δ = 14.0 (CH3), 15.3 (CH3), 18.7 (CH2), 35.9
(CH) ppm. IR: ν = 2957, 2931, 2871, 2834, 1601, 1584, 1489, 1466, (CH2), 40.4 (CH2), 41.1 (CH2), 58.6 (CH), 126.0 (CH), 127.3 (CH),
˜
1455, 1437, 1260, 1165, 1050, 778, 697 cm–1. HRMS (%) calcd. 129.1 (CH), 129.3 (CH), 133.9 (C), 141.8 (C) ppm. IR: ν = 2958,
˜
[C14H23NO+] 221.1780, found 221.1794 (2); calcd. [C11H16NO+]
178.1232, found 178.1228 (100); calcd. [C8H9O+] 121.0653, found
121.0662 (45); calcd. [C6H14N+] 100.1126, found 100.1110 (100).
C14H23NO (221.3): calcd. C 75.97, H 10.47, N 6.33; found C 75.60,
H 10.49, N 6.58.
2930, 2871, 1597, 1572, 1476, 1428, 1379, 1208, 1135, 1082, 999,
884, 780, 701, 684, 666 cm–1. HRMS (%) calcd. [C13H20N37Cl+]
227.1284, found 227.1251 (1); calcd. [C13H19N37Cl+] 226.1177,
found 226.1146 (2); calcd. [C13H20N35Cl+] 225.1284, found
225.1245 (1); calcd. [C13H19N35Cl+] 224.1206, found 224.1202 (5);
calcd. [C10H13N37Cl+] 184.0707, found 184.0706 (34); calcd.
[C10H13N35Cl+] 182.0737, found 182.0716 (100); calcd.
[C7H6N37Cl+] 127.0129, found 127.0154 (15); calcd. [C7H6N35Cl+]
125.0158, found 125.0157 (52); calcd. [C6H14N+] 100.1126, found
100.1121 (100). C13H20ClN (225.8): calcd. C 69.16, H 8.93, N 6.20;
found C 69.16, H 8.99, N 6.30.
Amine 30a: General procedure A was used to synthesize amine 30a
from 1-(4-chlorophenyl)-1-propyne (10) and ethylamine. After puri-
fication by flash chromatography (EtOAc/MeOH, 10:1), amine 30a
(569 mg, 2.88 mmol, 72%) and a mixture of regioisomers 30a and
30b (111 mg, 0.56 mmol, 14%) were obtained as colorless oils. 30a:
1H NMR (300 MHz, CDCl3): δ = 1.04–1.11 (m, 6 H), 1.50 (br. s,
1 H), 2.54–2.61 (q, J = 6.6 Hz, 2 H), 2.71–2.78 (dd, J = 13.2,
6.3 Hz, 2 H), 2.89–2.91 (m, 1 H), 7.11 (d, J = 8.1 Hz, 2 H), 7.28
(d, J = 8.1 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ
= 15.4 (CH3), 20.1 (CH3), 41.5 (CH2), 42.9 (CH2), 54.5 (CH), 128.5
Amine 33a: General procedure A was used to synthesize amine 33a
from 1-(2-chlorophenyl)-1-pentyne (13) and ethylamine. After puri-
fication by flash chromatography (EtOAc/MeOH, 10:1), amine 33a
(302 mg, 1.34 mmol, 33%) and a mixture of regioisomers 33a and
33b (103 mg, 0.46 mmol, 12%) were obtained as colorless oils. 33a:
1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.0 Hz, 3 H), 1.04
(CH), 130.6 (CH), 132.0 (C), 138.0 (C) ppm. IR: ν = 3297, 2966,
˜
2926, 2869, 2816, 1492, 1455, 1407, 1374, 1134, 1090, 1016, 835,
Eur. J. Org. Chem. 2005, 4843–4851
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4849

K. Marcseková, B. Wegener, S. Doye
FULL PAPER
(t, J = 7.0 Hz, 3 H), 1.29–1.49 (m, 4 H), 2.55–2.71 (m, 2 H), 2.76–
2.90 (m, 3 H), 7.14–7.22 (m, 3 H), 7.32 (d, J = 7.5 Hz, 1 H) ppm.
13C NMR (75 MHz, DEPT, CDCl3): δ = 14.3 (CH3), 15.6 (CH3),
1584, 1488, 1466, 1454, 1437, 11260, 1153, 1048, 1019, 783, 736,
696 cm–1. HRMS (%) calcd. [C14H21NO+] 219.1623, found
219.1544 (1); calcd. [C11H16NO+] 178.1232, found 178.1222 (25);
19.0 (CH2), 36.5 (CH2), 39.0 (CH2), 41.4 (CH2), 57.2 (CH), 126.6 calcd. [C8H9O+] 121.0653, found 121.0648 (71); calcd. [C6H12N+]
(CH), 127.5 (CH), 129.6 (CH), 131.6 (CH), 134.3 (C), 137.7 (C)
98.0970, found 98.0948 (100); calcd. [C4H10N+] 72.0813, found
72.0829 (66); calcd. [C4H8N+] 70.0657, found 70.0680 (38).
C14H21NO (219.3): C 76.67, H 9.65, N 6.39; found C 76.41, H 9.58,
N 6.59. 35b: 1H NMR (300 MHz, CDCl3): δ = –0.07 to 0.01 (m, 1
H), 0.04–0.12 (m, 1 H), 0.30–0.47 (m, 2 H), 0.51–0.60 (m, 1 H),
ppm. IR: ν = 3066, 2959, 2930, 2871, 1474, 1444, 1138, 1052, 1038,
˜
750, 682 cm–1. HRMS (%) calcd. [C13H19N37Cl+] 226.1177, found
226.1162 (2); calcd. [C13H19N35Cl+] 224.1206, found 224.1221 (5);
calcd. [C10H13N37Cl+] 184.0707, found 184.0704 (31); calcd.
[C10H13N35Cl+] 182.0737, found 182.0720 (98); calcd. [C7H637Cl+] 1.07 (t, J = 7.2 Hz, 3 H), 1.38–1.48 (m, 1 H), 1.64–1.73 (m, 1 H),
127.0129, found 127.0145 (17); calcd. [C7H635Cl+] 125.0158, found
125.0151 (50); calcd. [C6H14N+] 100.1120, found 100.1123 (100).
C13H20ClN (225.13): calcd. C 69.16, H 8.93, N 6.20; found C 69.51,
H 8.85, N 6.50.
2.49 (q, J = 7.1 Hz, 2 H), 3.67 (t, J = 6.9 Hz, 1 H), 3.80 (s, 3 H),
6.75 (d, J = 6.7 Hz, 1 H), 6.88 (s, 1 H), 6.90 (d, J = 6.8 Hz, 1 H),
7.19 (m, 1 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 4.1
(CH2), 4.6 (CH2), 8.3 (CH), 15.4 (CH3), 42.0 (CH2), 43.3 (CH2),
55.2 (CH3), 64.0 (CH), 112.1 (CH), 112.7 (CH), 119.7 (CH), 129.1
Amines 34a/34b: General procedure A was used to synthesize
amines 34a and 34b from 1-phenyl-2-cyclopropylethyne (15) and
ethylamine. After purification by flash chromatography (EtOAc/
MeOH, 2:1), amine 34a (333 mg, 1.76 mmol, 44%) and amine 34b
(CH), 146.5 (C), 159.7 (C) ppm. IR: ν = 2999, 2962, 2919, 2834,
˜
1599, 1486, 1465, 1260, 1047, 783, 701 cm–1. HRMS (%) calcd.
[C14H21NO+] 219.1623, found 219.1601 (2); calcd. [C14H20NO+]
218.1545, found 218.1559 (9); calcd. [C10H14NO+] 164.1075, found
164.1090 (100); calcd. [C10H12NO+] 162.0919, found 162.0923 (28);
calcd. [C9H10NO+] 148.0762, found 148.0790 (25); calcd. [C8H9O+]
121.0653, found 121.0631 (63); calcd. [C7H7+] 91.0548, found
91.0541 (29); calcd. [C6H5+] 77.0391, found 77.0421 (31).
1
(128 mg, 0.68 mmol, 14%) were obtained as colorless oils. 34a: H
NMR (300 MHz, CDCl3): δ = –0.08 to 0.00 (m, 1 H), 0.19–0.27
(m, 1 H), 0.36–0.45 (m, 1 H), 0.50–0.59 (m, 1 H), 0.67–0.78 (m, 1
H), 1.05 (t, J = 7.0 Hz, 3 H), 1.76 (br. s, 1 H), 1.94–2.01 (m, 1 H),
2.59 (dq, J = 11.4, 7.4 Hz, 1 H), 2.76–2.94 (m, 2 H), 7.19–7.31 (m,
5 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 2.2 (CH2), 4.8 Amines 39a/39b: General procedure B was used to synthesize
(CH2), 15.4 (CH3), 16.1 (CH), 42.0 (CH2), 65.0 (CH), 126.1 (CH), amines 39a and 39b from 4-methoxyphenylacetylene (36) and ethyl-
128.3 (CH), 129.4 (CH), 139.5 (C) ppm. IR: ν = 3076, 3063, 3026,
amine. After purification by flash chromatography (EtOAc/MeOH,
2:1), amine 39a (156 mg, 0.87 mmol, 22%) and amine 39b (150 mg,
0.84 mmol, 21%) were obtained as colorless oils. 39a: 1H NMR
(300 MHz, CDCl3): δ = 1.09 (t, J = 7.1 Hz, 3 H), 1.23 (br. s, 1 H),
˜
3000, 2967, 2922, 2869, 2848, 2805, 1603, 1494, 1453, 1141, 1031,
1019, 766, 699 cm–1. HRMS (%) calcd. [C13H19N+] 189.1517, found
189.1520 (1); calcd. [C12H16N+] 174.1283, found 174.1296 (2);
calcd. [C11H14N+] 160.1126, found 160.1094 (3); calcd. [C10H14N+] 2.66 (q, J = 7.1 Hz, 2 H), 2.75 (br. t, J = 7.1 Hz, 2 H), 2.85 (br. t,
148.1126, found 148.1133 (23); calcd. [C9H12N+] 134.0970, found
134.0957 (57); calcd. [C6H12N+] 98.0970, found 98.0988 (100);
calcd. [C7H7+] 91.0548, found 91.0540 (75). C13H19N (189.3): calcd.
C 82.48, H 10.12, N 7.40; found C 82.31, H 10.20, N 7.69. 34b: 1H
NMR (300 MHz, CDCl3): δ = –0.12 to –0.05 (m, 1 H), 0.00–0.07
(m, 1 H), 0.24–0.42 (m, 2 H), 0.45–0.55 (m, 1 H), 1.02 (t, J =
7.4 Hz, 3 H), 1.36–1.45 (m, 2 H), 1.60–1.68 (m, 1 H), 2.44 (dq, J
J = 6.5 Hz, 2 H), 3.78 (s, 3 H), 6.83 (d, J = 8.5 Hz, 2 H), 7.12 (d,
J = 8.7 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ =
15.2 (CH3), 35.5 (CH2), 44.0 (CH2), 51.2 (CH), 55.2 (CH3), 113.9
(CH), 129.6 (CH), 132.2 (C), 158.0 (C) ppm. IR: ν = 2962, 2934,
˜
2834, 1612, 1513, 1464, 1300, 1247, 1178, 1129, 1038, 822 cm–1.
HRMS (%) calcd. [C11H17NO+] 179.1310, found 179.1314 (11);
calcd. [C10H14NO+] 164.1075, found 164.1080 (14); calcd.
= 8.9, 7.4 Hz, 2 H), 3.66 (t, J = 7.0 Hz, 1 H), 7.16–7.27 (m, 5 H) [C9H11O+] 135.0810, found 135.0784 (19); [C8H10O+] 122.0732,
ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 4.1 (CH2), 4.6
found 122.0743 (90); [C7H7+] 91.0548, found 91.0563 (14); [C6H6
]
+
(CH2), 8.2 (CH), 15.4 (CH3), 42.0 (CH2), 43.4 (CH2), 64.0 (CH), 78.0470, found 78.0477 (15); [C6H5+] 77.0391, found 77.0397 (15).
126.8 (CH), 127.2 (CH), 128.2 (CH), 144.7 (C) ppm. IR: ν = 3076, C11H17NO (179.3): calcd. C 73.70, H 9.56, N 7.81; found C 73.28,
˜
1
3024, 2966, 2920, 2840, 1602, 1492, 1453, 1133, 1016, 753,
701 cm–1. HRMS (%) calcd. [C13H19N+] 189.1517, found 189.1498 = 7.1 Hz, 3 H), 1.35 (d, J = 6.6 Hz, 3 H), 2.43–2.56 (m, 2 H), 3.73
(1); calcd. [C9H13N+] 135.1048, found 135.0999 (96); calcd.
(q, J = 6.5 Hz, 1 H), 3.80 (s, 3 H), 6.86 (d, J = 8.7 Hz, 2 H), 7.23
[C9H12N+] 134.0970, found 134.0941 (100); calcd. [C7H8N+] (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ
H 9.28, N 7.88. 39b: H NMR (300 MHz, CDCl3): δ = 1.07 (t, J
106.0657, found 106.0639 (23); calcd. [C7H6N+] 104.0500, found
= 15.4 (CH3), 24.2 (CH3), 41.9 (CH2), 55.2 (CH3), 57.6 (CH), 113.7
104.0497 (19); calcd. [C7H7+] 91.0548, found 91.0549 (47); calcd. (CH), 127.5 (CH), 137.9 (C), 158.5 (C) ppm. IR: ν = 2962, 2834,
˜
[C6H7+] 79.0548, found 79.0564 (36). C13H19N (189.3): calcd. C 1611, 1512, 1464, 1301, 1244, 1177, 1037, 832, 557 cm–1. HRMS
82.48, H 10.12, N 7.40; found C 82.05, H 9.90, N 7.70.
(%) calcd. [C11H17NO+] 179.1310, found 179.1307 (4); calcd.
[C11H16NO+] 178.1232, found 178.1211 (3); calcd. [C10H14NO+]
164.1075, found 164.1069 (100); calcd. [C9H11O+] 135.0810, found
135.0793 (20). C11H17NO (179.3): calcd. C 73.70, H 9.56, N 7.81;
found C 74.11, H 9.92, N 7.33.
Amines 35a/35b: General procedure A was used to synthesize
amines 35a and 35b from 1-(3-methoxyphenyl)-2-cyclopropyle-
thyne (16) and ethylamine. After purification by flash chromatog-
raphy (EtOAc/MeOH, 10:1), amine 35a (412 mg, 1.88 mmol, 47%)
and amine 35b (88 mg, 0.40 mmol, 10%) were obtained as colorless
Amines 40a/40b: General procedure B was used to synthesize
oils. 35a: 1H NMR (300 MHz, CDCl3): δ = –0.05 to 0.03 (m, 1 H), amines 40a and 40b from 4-chlorophenylacetylene (37) and ethyl-
0.20–0.28 (m, 1 H), 0.37–0.46 (m, 1 H), 0.51–0.60 (m, 1 H), 0.66–
amine. After purification by flash chromatography (EtOAc/MeOH,
0.77 (m, 1 H), 1.04 (t, J = 7.0 Hz, 3 H), 1.40 (br. s, 1 H), 1.91–1.99 2:1), amine 40a (120 mg, 0.65 mmol, 16%) and a mixture of re-
(dd, J = 5.1 Hz, 3.6 Hz, 1 H), 2.53–2.59 (dd, J = 7.1 Hz, 4.1 Hz, 1
H), 2.70–2.86 (m, 3 H), 3.80 (s, 3 H), 6.75–6.76 (m, 3 H), 7.17–7.22
(m, 1 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 2.2 (CH2),
gioisomers 40a and 40b (191 mg, 1.04 mmol, 26%) were obtained
as colorless oils. 40a: H NMR (300 MHz, CDCl3): δ = 1.12 (t, J
= 7.1 Hz, 3 H), 2.01 (br. s, 1 H), 2.69 (q, J = 7.2 Hz, 2 H), 2.77–
1
5.1 (CH2), 15.7 (CH3), 16.4 (CH), 42.3 (CH2), 42.4 (CH2), 55.3 2.92 (m, 4 H), 7.15 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2 H)
(CH3), 65.0 (CH), 111.6 (CH), 115.3 (CH), 122.0 (CH), 129.4 (CH), ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 15.0 (CH3), 35.6
141.3 (C), 159.8 (C) ppm. IR: ν = 2999, 2961, 2937, 2834, 1601, (CH2), 43.9 (CH2), 50.72 (CH2), 128.6 (CH), 130.0 (CH), 131.9 (C),
˜
4850
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 4843–4851

Ind2TiMe2-Catalyzed Addition of Methyl- and Ethylamine to Alkynes
FULL PAPER
138.4 (C) ppm. IR: ν = 3025, 2967, 2926, 2816, 1492, 1092, 1015,
C10H15NO (165.2): calcd. C 72.69, H 9.15, N 8.48; found C 72.87,
H 9.24, N 7.62.
˜
781 cm–1. HRMS (%) calcd. [C10H14N37Cl+] 185.0785, found
185.0746 (2); calcd. [C10H13N37Cl+] 184.0707, found 184.0686 (5);
calcd. [C10H14N35Cl+] 183.0815, found 183.0767 (5); calcd.
[C10H13N35Cl+] 182.0737, found 182.0720 (15); calcd. [C8H837Cl+]
141.0285, found 141.0299 (18); calcd. [C8H835Cl+] 139.0315, found
Amines 43a/43b: General procedure B was used to synthesize
amines 43a and 43b from 1-dodecyne (38) and methylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1, 5 vol.-
% NH3), amine 43a (245 mg, 1.22 mmol, 31%) and amine 43b
139.0309 (54); calcd. [C7H637Cl+] 127.0129, found 127.0143 (23);
1
(258 mg, 1.21 mmol, 30%) were obtained as colorless oils. 43a: H
calcd. [C7H635Cl+] 125.0158, found 125.0157 (72); calcd. [C8H7
]
+
NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.3 Hz, 3 H), 1.20–1.38
(m, 18 H), 1.40–1.55 (m, 2 H), 2.01 (br. s, 1 H), 2.43 (s, 3 H), 2.56
(t, J = 7.4 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ
= 14.1 (CH3), 22.7 (CH2), 27.3 (CH2), 29.3 (CH2), 29.6 (CH2),
29.6 (CH2), 29.7 (CH2), 29.8 (CH2), 31.9 (CH2), 36.4 (CH3), 52.1
103.0548, found 103.0540 (63); calcd. [C7H7+] 91.0548, found
91.0543 (23); calcd. [C7H5+] 89.0391, found 89.0387 (46); calcd.
[C3H8N+] 58.0657, found 58.0659 (100); calcd. [CH4N+] 30.0344,
found 30.0351 (100).
(CH ) ppm. IR: ν = 2924, 2854, 2790, 1558, 1467, 1380, 1310, 1068,
˜
2
Amines 41a/41b: General procedure B was used to synthesize
amines 41a and 41b from 1-dodecyne (38) and ethylamine. After
purification by flash chromatography (EtOAc/MeOH, 2:1, 5 vol-%
NH3), amine 41a (261 mg, 1.22 mmol, 31%) and amine 41b
722 cm–1. HRMS (%) calcd. [C13H29N+] 199.2300, found 199.2292
(100); calcd. [C13H28N+] 198.2222, found 198.2208 (25); calcd.
[C12H26N+] 184.2065, found 184.2054 (15); calcd. [C8H18N+]
128.1439, found 128.1449 (8), calcd. [C6H14N+] 100.1126, found
1
(258 mg, 1.21 mmol, 30%) were obtained as colorless oils. 41a: H
1
100.1134 (17). 43b: H NMR (300 MHz, CDCl3): δ = 0.87 (t, J =
NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.3 Hz, 3 H), 1.10 (t, J
= 7.2 Hz, 3 H), 1.20–1.35 (m, 18 H), 1.40–1.55 (m, 2 H), 2.57–2.68
(m, 4 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 14.1 (CH3),
15.4 (CH3), 22.7 (CH2), 27.5 (CH2), 29.3 (CH2), 29.6 (CH2), 29.7
6.3 Hz, 3 H), 1.01 (d, J = 6.3 Hz, 3 H), 1.20–1.37 (m, 16 H), 1.38–
1.50 (m, 2 H), 2.39 (s, 3 H), 2.45–2.55 (m, 1 H) ppm. 13C NMR
(75 MHz, DEPT, CDCl3): δ = 14.1 (CH3), 19.8 (CH3), 22.7 (CH2),
26.0 (CH2), 29.3 (CH2), 29.6 (CH2), 29.6 (CH2), 29.9 (CH2), 31.9
(CH ), 30.3 (CH ), 31.9 (CH ), 44.2 (CH ), 50.0 (CH ) ppm. IR: ν
˜
2
2
2
2
2
(CH ), 33.9 (CH ), 36.9 (CH ), 55.0 (CH) ppm. IR: ν = 2958, 2925,
˜
= 2958, 2923, 2853, 2811, 1466, 1376, 1133, 722 cm–1. HRMS (%)
calcd. [C14H31N+] 213.2457, found 213.2448 (7); calcd. [C13H28N+]
198.2222, found 198.2231 (5); calcd. [C4H10N+] 72.0813, found
72.0826 (14). C14H31N (213.4): calcd. C 78.79, H 14.64, N 6.56;
found C 78.34, H 14.77, N 6.62. 41b: 1H NMR (300 MHz, CDCl3):
δ = 0.87 (t, J = 6.2 Hz, 3 H), 1.03 (d, J = 6.3 Hz, 3 H), 1.11 (t, J
= 7.2 Hz, 3 H), 1.20–1.40 (m, 18 H), 1.44 (br. s, 1 H), 2.54–2.75
(m, 3 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ = 14.1 (CH3),
15.6 (CH3), 20.4 (CH3), 22.7 (CH2), 26.1 (CH2), 29.3 (CH2), 29.6
(CH2), 29.9 (CH2), 31.9 (CH2), 37.3 (CH2), 41.5 (CH2), 53.2 (CH)
2
3
2
2854, 2786, 1575, 1465, 1374, 1341, 1155, 722 cm–1. HRMS (%)
calcd. [C13H29N+] 199.2300, found 199.2299 (6); calcd. [C13H28N+]
198.2222, found 198.2226 (13); calcd. [C12H26N+] 184.2065, found
184.2080 (75). C13H29N (199.2): calcd. C 78.31, H 14.66, N 7.03;
found C 77.99, H 15.07, N 7.12.
Acknowledgments
We thank the Deutsche Forschungsgemeinschaft, the Fonds der
Chemischen Industrie and the Dr. Otto Röhm Gedächtnisstiftung,
Darmstadt, for financial support of our research. We are grateful
to BASF AG for a gift of methyl- and ethylamine. We thank the
Bundesopiumstelle, Bonn, for approving the synthesis of amine 17a.
ppm. IR: ν = 2959, 2923, 2854, 1466, 1375, 1153, 1119, 721 cm–1.
˜
HRMS (%) calcd. [C14H31N+] 213.2457, found 213.2451 (2); calcd.
[C14H30N+] 212.2378, found 212.2389 (2), [C13H28N+] 198.2222,
found 198.2242 (19); calcd. [C4H10N+] 72.0813, found 72.0821
(100). C14H31N (213.4): calcd. C 78.79, H 14.64, N 6.56; found C
78.62, H 14.89, N 6.69.
[1] For reviews, see: a) I. Bytschkov, S. Doye, Eur. J. Org. Chem.
2003, 935–946; b) S. Doye, Synlett 2004, 1653–1672; c) A.
Odom, Dalton. Trans. 2005, 225–233.
[2] a) E. Haak, I. Bytschkov, S. Doye, Angew. Chem. 1999, 111,
3584–3586; Angew. Chem. Int. Ed. 1999, 38, 3389–3391; b) A.
Heutling, S. Doye, J. Org. Chem. 2002, 67, 1961–1964.
[3] For U- and Th-catalyzed additions of methyl- and ethylamine
to alkynes, see: T. Straub, A. Haskel, T. G. Neyroud, M. Ka-
pon, M. Botoshansky, M. S. Eisen, Organometallics 2001, 20,
5017–5035, and references cited therein.
Amines 42a/42b: General procedure B was used to synthesize
amines 42a and 42b from 4-methoxyphenylacetylene (36) and me-
thylamine. After purification by flash chromatography (EtOAc/
MeOH, 2:1, 5 vol.-% NH3), amine 42a (130 mg, 0.77 mmol, 20%)
and amine 42b (127 mg, 0.77 mmol, 19%) were obtained as color-
1
less oils. 42a: H NMR (250 MHz, CDCl3): δ = 1.52 (br. s, 1 H),
2.43 (s, 3 H), 2.70–2.83 (m, 4 H), 3.78 (s, 3 H), 6.84 (d, J = 8.6 Hz,
2 H), 7.12 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT,
CDCl3): δ = 35.0 (CH2), 36.1 (CH3), 53.2 (CH2), 55.2 (CH3), 113.9
[4] A. Heutling, F. Pohlki, S. Doye, Chem. Eur. J. 2004, 10, 3059–
3071.
(CH), 129.6 (CH), 131.9 (C), 158.0 (C) ppm. IR: ν = 3313, 2934,
˜
[5] For an explanation of the regioselectivity observed in group-
IV metal catalyzed hydroaminations of alkynes, see: A. M. Bar-
anger, P. J. Walsh, R. G. Bergman, J. Am. Chem. Soc. 1993,
115, 2753–2763.
2835, 2456, 2793, 1607, 1511, 1458, 1295, 1247, 1176, 1036,
821 cm–1. HRMS (%) calcd. [C10H15NO+] 165.1154, found
165.1131 (3); calcd. [C9H10O+] 134.0732, found 134.0745 (100);
calcd. [C8H10O+] 122.0732, found 122.0723 (40); calcd. [C8H9O+]
[6] Y. Shi, J. T. Ciszewski, A. L. Odom, Organometallics 2001, 20,
1
121.0653, found 121.0657 (72). 42b: H NMR (300 MHz, CDCl3):
3967–3969.
[7] a) A. Tillack, I. Garcia Castro, C. G. Hartung, M. Beller, An-
gew. Chem. 2002, 114, 2646–2648; Angew. Chem. Int. Ed. 2002,
41, 2541–2543; b) A. Tillack, H. Jiao, I. Garcia Castro, C. G.
Hartung, M. Beller, Chem. Eur. J. 2004, 10, 2409–2420; c) A.
Tillack, V. Khedkar, M. Beller, Tetrahedron Lett. 2004, 45,
8875–8878.
δ = 1.35 (d, J = 6.6 Hz, 3 H), 2.29 (s, 3 H), 2.61 (br. s, 1 H), 3.62
(q, J = 6.6 Hz, 1 H), 3.79 (s, 3 H), 6.87 (d, J = 8.7 Hz, 2 H), 7.23
(d, J = 8.6 Hz, 2 H) ppm. 13C NMR (75 MHz, DEPT, CDCl3): δ
= 23.4 (CH3), 34.0 (CH3), 55.1 (CH3), 59.4 (CH), 113.7 (CH), 127.6
(CH), 136.7 (C), 158.6 (C) ppm. IR: ν = 3330, 2957, 2835, 2788,
˜
1611, 1512, 1463, 1246, 1178, 1036, 832 cm–1. HRMS (%) calcd.
[C10H15NO+] 165.1154, found 165.1143 (6); calcd. [C10H14NO+]
164.1075, found 164.1077 (9); calcd. [C9H12NO+] 150.0919, found
150.0924 (100); calcd. [C9H11O+] 135.0810, found 135.0784 (23).
[8] A. Heutling, R. Severin, S. Doye, Synthesis 2005, 1200–1204.
[9] www.mcat.de.
Received: June 22, 2005
Published Online: September 27, 2005
Eur. J. Org. Chem. 2005, 4843–4851
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4851