Microwave-assisted catalytic intermolecular hydroamination of alkynes

Article abstract of DOI:10.1002/1099-0690(200112)2001:23<4411::aid-ejoc4411>3.0.co;2-n

Irradiation of reaction mixtures containing an alkyne, an amine, and a catalytic amount of Cp₂TiMe₂ in toluene with microwaves at a frequency of 2.45 GHz and a power output of 180-300 W results in fast reactions to give the corresponding hydroamination products. The initially formed imines can easily be reduced to secondary amines by use of H₂/Pd, LiAlH₄, or NaCNBH₃/p-TsOH. The microwave-assisted hydroamination reactions go to completion within one tenth (or less) of the time required for reactions run conventionally in an oil bath at 105 °C. By using the microwave technology, it is possible to achieve turnover frequencies TOF > 10 h^-1. Furthermore, when Cp₂TiMe₂ is used as the catalyst, hydroamination products of terminal alkynes can be isolated in reasonable yields for the first time. The addition of amines to terminal alkynes gives access to both the Markovnikov and the anti-Markovnikov products. Observed regioselectivities are different for terminal aryl- and alkylalkynes.

Full text of DOI:10.1002/1099-0690(200112)2001:23<4411::aid-ejoc4411>3.0.co;2-n

FULL PAPER
Microwave-Assisted Catalytic Intermolecular Hydroamination of Alkynes
Igor Bytschkov[a] and Sven Doye*[a]
Keywords: Alkynes / Aminations / Homogeneous catalysis / Microwave irradiation / Titanium
Irradiation of reaction mixtures containing an alkyne, an
amine, and a catalytic amount of Cp2TiMe2 in toluene with
an oil bath at 105 °C. By using the microwave technology, it
is possible to achieve turnover frequencies TOF Ͼ 10 h−1
.
microwaves at a frequency of 2.45 GHz and a power output Furthermore, when Cp2TiMe2 is used as the catalyst, hydro-
of 180−300 W results in fast reactions to give the correspond- amination products of terminal alkynes can be isolated in
ing hydroamination products. The initially formed imines can reasonable yields for the first time. The addition of amines to
easily be reduced to secondary amines by use of H2/Pd, terminal alkynes gives access to both the Markovnikov and
LiAlH4, or NaCNBH3/p-TsOH. The microwave-assisted hy- the anti-Markovnikov products. Observed regioselectivities
droamination reactions go to completion within one tenth (or
less) of the time required for reactions run conventionally in
are different for terminal aryl- and alkylalkynes.
Introduction
dramatically shortened under conditions that employed mi-
crowave heating instead of conventional heating.[6] In an
initial experiment, a typical reaction mixture containing 1.0
equiv. of diphenylacetylene (1), 1.0 equiv. of aniline (2a),
and 3.0 mol % of Cp2TiMe2 in toluene was irradiated at
a frequency of 2.45 GHz using a Prolabo Synthewave 402
microwave reactor with a power output of 300 W for 3 h.
After that time, TLC analysis showed that the starting mat-
erials had been completely consumed.[7] In a control experi-
ment, no conversion was observed in the absence of
Cp2TiMe2. Subsequent hydrogenation of the initially
formed imine 3a with H2 and 5 mol % of Pd/C gave access
to amine 4a in 93% yield (Scheme 1).
Nitrogen-containing molecules are among the most im-
portant classes of chemical substances. They play outstand-
ing roles as biologically active compounds and as industrial
chemicals. In the past, these facts lay behind the develop-
ment of a large number of methods for the synthesis of
amines, imines, and enamines. Among these methods, the
direct addition of ammonia or amines to alkenes and al-
kynes Ϫ the so-called hydroamination of alkenes and al-
kynes Ϫ represents the most attractive approach, because
the desired higher substituted nitrogen-containing products
are formed in a single reaction step from inexpensive start-
ing materials without production of waste. At present, how-
ever, no general hydroamination procedure for a wide vari-
ety of substrates is known.[1Ϫ3]
We have recently shown that dimethyltitanocene,
Cp2TiMe2,[4] represents an excellent catalyst for intermol-
ecular hydroamination of alkynes.[5] The procedure de-
veloped with this catalyst enables primary arylamines, as
well as primary tert- and sec-alkylamines, to be coupled
with several disubstituted alkynes in good to moderate
yields, although primary n-alkylamines and terminal al-
kynes can only be coupled in poor yields. Unfortunately,
elevated temperatures (100Ϫ120 °C) and long reaction
times (up to 72 h) are usually required for the reaction to
proceed.
Scheme 1. Microwave-assisted hydroamination of diphenylacetyl-
ene (1) with aniline (2a) and subsequent reduction of the initially
formed imine 3a
In comparison, a control experiment performed in an oil
bath at 105 °C showed that a reaction time of 30 h was
necessary to obtain 100% conversion for the same reaction.
This observation shows that application of microwave heat-
ing can reduce the required reaction time by a factor of 10.
The corresponding turnover frequency for this first example
is at least 10 hϪ1, which is high for a catalytic intermolecu-
lar hydroamination process. With this initial result in mind,
we conjectured that the reaction times for the dimethyltitan-
ocene-catalyzed hydroamination of alkynes might generally
Results and Discussion
During a study directed toward optimizing and generaliz-
ing our recently developed hydroamination methodology
for alkynes, we discovered that the reaction times could be
[a]
Institut für Organische Chemie der Universität Hannover
Schneiderberg 1B, 30167 Hannover, Germany
Fax: (internat.) ϩ 49-(0)511/762-3011
E-mail: sven.doye@oci.uni-hannover.de
Eur. J. Org. Chem. 2001, 4411Ϫ4418
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1223Ϫ4411 $ 17.50ϩ.50/0
4411

I. Bytschkov, S. Doye
FULL PAPER
be minimized by use of microwave irradiation. We further
assumed that short reaction times might increase the yield
of reactions when terminal alkynes were employed, because
side reactions (such as aldol-type reaction of initially
formed imines), would have only a short time to occur.
In order to investigate the scope and limitations of the
new procedure, we first examined reactions of diphenylacet-
ylene (1) with a wide variety of amines under microwave
irradiation conditions. Scheme 2 and Table 1 summarize the
obtained results. Unless otherwise noted, the reactions were
carried out with microwave irradiation at a frequency of
2.45 GHz at a power output of 300 W for 3 h, with a cata-
lyst loading of 3.0 mol % of Cp2TiMe2. The solvent was
always toluene and the reaction mixtures usually contained
alkyne and amine in a 1:1 ratio. Reduction of the initially
formed imine was typically performed with 1 atm of H2,
and 5.0 mol % of Pd/C as the catalyst.
Table 1. Microwave-assisted hydroamination of diphenylacetylene
(1) with various amines and subsequent reduction
Scheme 2. Microwave-assisted hydroamination of diphenylacetyl-
ene (1) with various amines and subsequent reduction
As can be seen from Table 1, arylamines (Entries 1Ϫ3),
as well as tert- and sec-alkylamines (Entries 4Ϫ7), can suc-
cessfully be induced to react with diphenylacetylene (1) un-
der microwave conditions. All hydroamination reactions
(Entries 1Ϫ7) went to completion within 3 h. After reduc-
tion of the initially formed imines, the corresponding sec-
ondary amines 4aϪg could be isolated in good yields. How-
ever, the imine formed from 1 and the sterically demanding
2,6-dimethylaniline (2b) (Entry 2) could not successfully be
hydrogenated. Only reduction using the strongly nucleo-
philic reducing agent LiAlH4 gave access to the desired
product 4b, in 82% yield. Particularly interesting is the reac-
tion between 1 and the enantiomerically pure amine (S)-1-
[a]
[b]
Reduction: LiAlH4, THF, 65 °C, 6 h. Ϫ
Microwave irradi-
ation: 285 W, 2 h. Ϫ [c] Amine/alkyne, 3:1. Ϫ [d] Amine/alkyne, 2:1.
[e]
[f]
Ϫ
Reduction: NaCNBH3, p-TsOH, 25 °C, THF, 4 h. Ϫ Two
diastereomers with 87.2% and 86.6% ee were obtained. Ϫ [g] Micro-
wave irradiation: 300 W, 6 h.
phenylethylamine (2f) (ee ϭ 99%) (Entry 6). After reduction droamination reactions. The results are summarized in
with NaCNBH3/p-TsOH, two diastereomers of the re- Scheme 3 and Table 2. We found that, in the presence of 3.0
sulting product 4f were obtained in a 5:2 ratio. GC analysis mol % of Cp2TiMe2, the employed alkynes smoothly re-
performed by König et al. showed that the ee values for the acted with various amines (2a, 2f, 2i, 2j) within 3 h. After
two diastereomers of 4f were only 87%. In an additional subsequent reduction, the corresponding secondary amines
hydroamination experiment between 1 and 2f, the amine 2f were obtained in good to moderate yields. As observed be-
could be reisolated after hydrolysis (SiO2) of the initially fore,[5] the unsymmetrically substituted alkyl(aryl)alkynes 6
formed imine. GC analysis of reisolated 2f showed that the and 7 gave access to the anti-Markovnikov products exclus-
ee value had decreased to 86%. It is therefore clear that the ively (Entries 3Ϫ5). Furthermore, Table 2 shows that the
hydroamination step occurs with partial racemization at the amine 4-methoxyaniline (2j), which reacted with 6 in reas-
α-carbon atom of the employed amine. Unfortunately, the onable yield (Entry 4), is a particularly interesting substrate.
usage of benzylamine 2h (Entry 8), which was a poor sub- Since the CϪN bond in 4-methoxyaniline derivatives can
strate in our initial studies,[5a] gave access only to very small easily be cleaved under oxidative conditions by ceric ammo-
amounts (2% yield) of the desired product 4h.
nium nitrate (CAN),[8] 2j can be viewed as an ammonia
In addition, we investigated the behavior of the dialkylal- equivalent. Again, partial racemization was observed dur-
kyne 3-hexyne (5) and the alkyl(aryl)alkynes 1-phenylpro- ing the hydroamination/reduction sequence with the enanti-
pyne (6) and 1-phenylbutyne (7) in microwave-assisted hy- omerically pure substrate 2f (Entry 5).
4412
Eur. J. Org. Chem. 2001, 4411Ϫ4418

Microwave-Assisted Catalytic Intermolecular Hydroamination of Alkynes
FULL PAPER
product exclusively. We had previously speculated that fast
aldol-type side reactions of the initially formed aldimines,
which are more reactive than the usually obtained ketim-
ines, may be responsible for these problems. We therefore
conjectured that the short reaction times of the microwave
irradiation technique should be suitable to expand the
scope of Cp2TiMe2-catalyzed intermolecular hydroamin-
ation of alkynes to terminal alkynes.
Scheme 3. Microwave-assisted hydroamination of dialkylalkynes
and alkyl(aryl)alkynes with various amines and subsequent reduc-
tion
We first found out that, under microwave conditions,
Cp2TiMe2-catalyzed reactions between phenylacetylene (11)
and amines are relatively fast. Even if the microwave irradi-
ation was carried out at a power output of only 180 W,
reactions between phenylacetylene (11) and amines such as
2a, 2f, and 2i went to completion within 2 h (3.0 mol %
of catalyst). The initially formed imines were reduced with
NaCNBH3/p-TsOH to yield the corresponding secondary
amines. Surprisingly, mixtures of the two regioisomers 12
and 13 were isolated from these reactions in various ratios
(Scheme 4, Table 3). Separation of the obtained isomers was
only possible for 12f and 13f (Entry 2). However, 12a/13a
Table 2. Microwave-assisted hydroamination of dialkylalkynes and
alkyl(aryl)alkynes with various amines and subsequent reduction
1
and 12i/13i could be identified from the H NMR spectra
of the isolated mixtures.
Scheme 4. Microwave-assisted hydroamination of phenylacetylene
(11) with various amines and subsequent reduction
Table 3. Microwave-assisted hydroamination of phenylacetylene
(11) with various amines and subsequent reduction
[a]
[b]
Microwave irradiation: 255 W, 3 h. Ϫ
Microwave irradiation:
210 W, 3 h. Ϫ [c] Reduction: NaCNBH3, p-TsOH, 25 °C, THF, 4 h.
[d]
Ϫ
The ee values of the two obtained diastereomers have not
been determined. Ϫ [e] Microwave irradiation: 210 W, 2 h. Ϫ [f] Two
diastereomers with 86.4% and 79.6% ee were obtained.
With these promising results in mind, we finally focused
on the intermolecular hydroamination of terminal alkynes.
As reported before, terminal alkynes are usually poor sub-
strates for the Cp2TiMe2-catalyzed intermolecular hydro-
amination of alkynes. Prior to this publication, we had only
been able to isolate hydroamination products from reac-
tions between phenylacetylene (11) and either 1-naphthyla-
mine[5a] or α-aminodiphenylmethane,[5b] in 23% and 41%
yields. In both cases we had isolated the anti-Markovnikov
[a]
The ee values of 12f and the two obtained diastereomers of 13f
have not been determined. Ϫ [b] Microwave irradiation: 210 W, 2 h.
Eur. J. Org. Chem. 2001, 4411Ϫ4418
4413

I. Bytschkov, S. Doye
FULL PAPER
The obtained yields (12 ϩ 13) for reactions between
There has previously been much speculation regarding
phenylacetylene (11) and either aniline (2a) or 4-methylanil- the reasons for the observed rate enhancements of organic
ine (2i) were 67% and 87%, respectively (Entries 1 and 3). reactions performed under microwave irradiation condi-
Formation of the anti-Markovnikov product (12a, 12i) was tions.[6] One simple and reasonable explanation is that reac-
favored in both reactions. However, if the alkylamine 2f was tion mixtures under microwave conditions are just heated
employed, the yield dropped to 34% and the selectivity was to higher temperatures than in conventionally heated reac-
reversed (Entry 2). In this case, the Markovnikov product tions. Because we were not able to determine the temper-
13f became the major amination product. Furthermore, a ature inside the reaction mixtures during microwave irradi-
large quantity of nonpolar side products, which could not ation, we are unable to rule out this explanation. As a con-
be separated further, was isolated. The structures of these trol experiment, we performed a comparable reaction be-
products has not yet been determined, but data from MS tween diphenylacetylene (1) and aniline (2a) in the presence
analysis suggest that di- or trimerization products of of 3.0 mol % of Cp2TiMe2 in toluene at 190 °C in an oil
phenylacetylene (11) are present in the obtained mixture.
bath. This experiment showed that the reaction at 190 °C
Inspired by these results, we investigated further reactions also reached 100% conversion within 3 h. This result un-
between the unactivated alkyne 1-dodecyne (14) and the ar- doubtedly shows that the rates observed for reactions per-
ylamines 2a and 2i. The hydroamination reactions were car- formed under microwave irradiation conditions are com-
ried out at a power output of 180 or 210 W for 2 h in the parable to those observed at 190 °C. However, from a prac-
presence of 3.0 mol % of Cp2TiMe2, the initially formed tical point of view the microwave heating technique is a
imines being reduced with NaCNBH3/p-TsOH. The desired viable option for performing Cp2TiMe2-catalyzed hydroam-
secondary amines were isolated as mixtures of regioisomers, ination reactions conveniently and safely in a short time.
in 49% and 80% yields (Scheme 5, Table 4). Again, the re-
gioisomers could not be separated. Determination of the
Conclusion
structures of the isomers was carried out by GC/MS and
1H NMR analysis. Surprisingly, the Markovnikov products
16a and 16i were the major products, in contrast to the
behavior of phenylacetylene (11). At present, it is not clear
what factors are responsible for this switch in regioselectiv-
ity. Attempts to hydroaminate silylated alkynes have not yet
been successful.
In summary, we have shown that reaction times for the
dimethyltitanocene-catalyzed intermolecular hydroamin-
ation of alkynes can be significantly shortened by per-
forming the experiments in a microwave reactor. The micro-
wave-assisted reactions go to completion within one tenth
(or less) of the time required for reactions run convention-
ally in an oil bath at 105 °C. With the microwave technique,
it was possible to achieve turnover frequencies TOF Ͼ 10
h
Ϫ1. Furthermore, hydroamination products of terminal al-
kynes could be isolated in reasonable yields for the first time
when Cp2TiMe2 was used as the catalyst. Surprisingly, we
found that addition of amines to terminal alkynes gave ac-
cess to both the Markovnikov- and the anti-Markovnikov
products. The observed regioselectivities were different for
terminal aryl- and alkylalkynes.
Scheme 5. Microwave-assisted hydroamination of 1-dodecyne (14)
with various amines and subsequent reduction
Experimental Section
Table 4. Microwave-assisted hydroamination of 1-dodecyne (14)
with various amines and subsequent reduction
General Remarks: All reactions were performed under argon in
flame-dried Duran glassware (Schlenk tubes equipped with Teflon
stopcocks). Toluene was distilled from molten sodium under argon.
Dimethyltitanocene was synthesized according to ref.[4a] Unless
otherwise noted, all reagents were purchased from commercial
sources and were used without further purification. Microwave ir-
radiation was carried out at a frequency of 2.45 GHz, using a Pro-
labo Synthewave 402 microwave reactor with a maximum power
output of 300 W (power is controllable between 0 and 100%).
Yields refer to isolated yields of 95% or higher purity, as deter-
mined by GC, 1H NMR, and elemental analysis for new com-
1
pounds. All products were characterized by H NMR, 13C NMR,
and infrared (IR) spectroscopy, and mass spectrometry (MS). New
compounds were further characterized by CHN elemental analysis.
Unless otherwise noted, NMR spectra were recorded in CDCl3
with a Bruker Avance 400 MHz spectrometer. All 1H NMR spectra
are reported in δ units ppm downfield from tetramethylsilane in-
[a]
Microwave irradiation: 210 W, 2 h.
4414
Eur. J. Org. Chem. 2001, 4411Ϫ4418

Microwave-Assisted Catalytic Intermolecular Hydroamination of Alkynes
FULL PAPER
ternal standard. All 13C NMR spectra are reported in δ units ppm
relative to the central line of the triplet for CDCl3 at δ ϭ 77.0.
Infrared spectra were recorded with a Bruker Vector 22 spectro-
(100.6 MHz, DEPT, CDCl3): δ ϭ 45.0 (CH2), 59.5 (CH), 113.9
(CH), 117.8 (CH), 126.5 (CH), 126.7 (CH), 127.1 (CH), 128.5
(CH), 128.5 (CH), 129.0 (CH), 129.2 (CH), 137.6 (C), 143.1 (C),
meter, using an attenuated total reflection (ATR) method. Mass 146.9 (C); IR: ν˜ ϭ 3422, 3085, 3063, 2999, 2926, 2855, 1673, 1601,
spectra were recorded with a Finnigan MAT 312 or a VG Autospec 1504, 1453, 1428, 1355, 1317, 1263, 1178, 993, 912, 872, 829 cmϪ1
(EI) with an ionization potential of 70 eV. Elemental analyses were
carried out with an Elementar Vario EL machine. Gas chromato-
;
MS (70 °C): m/z (%) ϭ 274 (1) [Mϩ ϩ 1], 196 (5), 182 (79), 120
(16), 105 (100), 91 (45), 77 (36), 65 (6); C20H19N (273.4): calcd. C
graphy analyses were performed with a HewlettϪPackard HP 6890 87.87, H 7.00, N 5.12; found C 87.84, H 7.17, N 4.93.
series gas chromatograph. GC/MS analyses were performed with a
Shimadzu GC-17A gas chromatograph equipped with a Shimadzu
QP-5000 mass spectrometer. The ee values for compounds 4f and
10f were determined by gas-chromatographic separation with
modified cyclodextrins in Professor W. A. König’s group. PE: light
petroleum ether, b.p. 40Ϫ60 °C.
Amine 4b: General procedures A and C were used to convert di-
phenylacetylene (1) and 2,6-dimethylaniline (2b) into the title prod-
uct. Purification by flash chromatography (PE/EtOAc, 12:1) af-
forded 4b (594 mg, 82%) as a yellow oil. 1H NMR (400 MHz,
CDCl3): δ ϭ 2.05 (s, 6 H), 3.12 (dd, J ϭ 12.0, 8.0 Hz, 1 H), 3.24
(dd, J ϭ 12.0, 8.0 Hz, 1 H), 4.39 (t, J ϭ 8.0 Hz, 1 H), 6.74 (t, J ϭ
7.4 Hz, 1 H), 6.88 (d, J ϭ 7.4 Hz, 2 H), 7.01Ϫ7.23 (m, 10 H); 13C
NMR (100.6 MHz, DEPT, CDCl3): δ ϭ 18.9 (CH3), 43.4 (CH2),
63.3 (CH), 121.5 (CH), 126.1 (CH), 126.8 (CH), 127.1 (CH), 128.1
(CH), 128.3 (CH), 128.8 (CH), 129.2 (C), 129.4 (CH), 138.7 (C),
Hydroamination. ؊ General Procedure A: The amine (2.4 mmol),
the alkyne (2.4 mmol), toluene (1.0 mL), and a solution of
Cp2TiMe2 (0.126 mL, 0.57 mol/L in toluene, 0.072 mmol, 3.0
mol %) were placed in a Schlenk tube. The Schlenk tube was then
sealed with a Teflon stopcock and transferred to the microwave
reactor. The mixture was irradiated at 100% power output (300 W)
for 3 h. After cooling to room temperature, the volatile components
were removed under vacuum.
˜
143.3 (C), 144.4 (C); IR: ν ϭ 3401, 3061, 3027, 2945, 2855, 1595,
1494, 1474, 1453, 1257, 1216, 1098, 1029, 915, 763, 740, 698 cmϪ1
;
MS (25 °C): m/z (%) ϭ 300 (14) [Mϩ Ϫ 1], 208 (100), 105 (31), 91
(21), 77 (10); C22H23N (301.4): calcd. C 87.66, H 7.69, N 4.65;
found C 87.36, H 7.60, N 4.51.
Reduction. ؊ General Procedure B (H2, Pd/C): Pd/C (255 mg, 5%
Pd, 0.12 mmol Pd, 5.0 mol %) was stirred in THF (3.0 mL) at 25
°C under 1 atm of H2 for 30 min. A solution of the crude hydroam-
ination product in THF (3.0 mL) was then added. The resulting
mixture was stirred under 1 atm H2 at 25 °C for 72 h. Filtration,
concentration, and purification by flash chromatography on silica
gel afforded the analytically pure product.
Amine 4c: General procedures A and B were used to convert di-
phenylacetylene (1) and 1-naphthylamine (2c) into the title product.
The microwave irradiation was carried out at a power output of
95% (285 W) for 2 h. Purification by flash chromatography (PE/
EtOAc, 18:1) afforded 4c (450 mg, 58%) as a colorless solid. 1H
NMR (400 MHz, CDCl3): δ ϭ 3.15 (dd, J ϭ 13.9, 5.5 Hz, 1 H),
3.28 (dd, J ϭ 13.9, 8.3 Hz, 1 H), 4.75 (dd, J ϭ 8.3, 5.5 Hz, 1 H),
4.85 (br. s, 1 H), 6.34 (d, J ϭ 6.4 Hz, 1 H), 7.10Ϫ7.33 (m, 10 H),
7.35Ϫ7.44 (m, 4 H), 7.71Ϫ7.77 (m, 2 H); 13C NMR (100.6 MHz,
DEPT, CDCl3): δ ϭ 45.3 (CH2), 59.2 (CH), 106.5 (CH), 117.5
(CH), 119.7 (CH), 123.6 (CH), 124.7 (CH), 125.6 (CH), 126.4
(CH), 126.9 (CH), 127.1 (CH), 128.6 (CH), 128.7 (CH), 128.7
(CH), 129.2 (CH), 134.1 (C), 137.6 (C), 142.0 (C), 143.0 (C); IR:
Reduction. ؊ General Procedure C (LiAlH4): A solution of the
crude hydroamination product in THF (2.0 mL) was added to a
suspension of LiAlH4 (182 mg, 4.8 mmol) in THF (5.0 mL) at
room temperature. The mixture was then heated to 65 °C for 6 h.
After cooling to room temperature, the mixture was slowly poured
into ice-cold water (20 mL). CH2Cl2 (20 mL) and 2  KOH
(3.0 mL) were added and the resulting mixture was stirred for
30 min. The organic layer was separated and the water layer was
extracted with CH2Cl2 (3 ϫ). The combined organic layers were
dried with MgSO4 and concentrated under vacuum. Purification
by flash chromatography on silica gel afforded the analytically
pure product.
˜
ν ϭ 3427, 3064, 2999, 2925, 2854, 1581, 1525, 1495, 1479, 1454,
1408, 1345, 1279, 1253, 1115, 899, 844 cmϪ1; MS (70 °C): m/z
(%) ϭ 323 (2) [Mϩ], 232 (8), 196 (3), 182 (25), 128 (3), 105 (19), 91
(100), 77 (5), 65 (10); C24H21N (323.4): calcd. C 89.13, H 6.54, N
4.33; found C 88.94, H 6.52, N 4.12.
Amine 4d: General procedures A and B were used to convert di-
phenylacetylene (1) and tert-butylamine (2d) into the title product.
Because of the low boiling point of tert-butylamine, an excess of
amine (7.2 mmol) was used in the hydroamination step. Purification
by flash chromatography (PE/EtOAc, 10:1) afforded 4d (438 mg,
72%) as a bright yellow oil. 1H NMR (400 MHz, CDCl3): δ ϭ 0.84
(s, 9 H), 2.72 (dd, J ϭ 12.0, 9.0 Hz, 1 H), 2.92 (dd, J ϭ 12.0, 5.6 Hz,
1 H), 3.98 (dd, J ϭ 9.0, 5.6 Hz, 1 H), 7.12 (d, J ϭ 7.0 Hz, 2 H),
7.15Ϫ7.30 (m, 6 H), 7.38 (d, J ϭ 7.4 Hz, 2 H); 13C NMR
(100.6 MHz, DEPT, CDCl3): δ ϭ 29.8 (CH3), 47.1 (CH2), 51.2 (C),
59.3 (CH), 126.3 (CH), 126.4 (CH), 127.1 (CH), 128.1 (CH), 128.3
Reduction. ؊ General Procedure D (NaCNBH3): The crude hydro-
amination product was dissolved in THF (2.0 mL). NaCNBH3
(302 mg, 4.8 mmol) and p-toluenesulfonic acid monohydrate
(46 mg, 0.24 mmol) were added and the mixture was stirred at
room temperature. After 4 h, diethyl ether (5.0 mL) and 2  HCl
(5.0 mL) were added. The mixture was stirred for 1 h at room tem-
perature. The organic layer was separated and saturated NaHCO3
solution was added to the water layer until pH ϭ 7 was reached.
The water layer was extracted with diethyl ether (2 ϫ). The com-
bined organic layers were dried with MgSO4 and concentrated un-
der vacuum. Purification by flash chromatography on silica gel af-
forded the analytically pure product.
˜
(CH), 129.3 (CH), 139.2 (C), 147.4 (C); IR: ν ϭ 3085, 3064, 2999,
2963, 2861, 1601, 1494, 1454, 1390, 1365, 1251, 1230, 1096, 1069,
1029, 910, 570, 555, 520 cmϪ1; MS (25 °C): m/z (%) ϭ 238 (1) [Mϩ
Ϫ CH3], 181 (11), 162 (72), 106 (100), 91 (9), 77 (6); purity by GC:
Ͼ 99%. 4d has already been described in ref.[9]
Amine 4a: General procedures A and B were used to convert di-
phenylacetylene (1) and aniline (2a) into the title product. Purifica-
tion by flash chromatography (PE/EtOAc, 15:1) afforded 4a
(610 mg, 93%) as a bright yellow oil. 1H NMR (400 MHz, CDCl3):
δ ϭ 1.60 (br. s, 1 H), 3.03 (dd, J ϭ 13.9, 8.1 Hz, 1 H), 3.14 (dd, Amine 4e: General procedures A and B were used to convert di-
J ϭ 13.9, 5.8 Hz, 1 H), 4.57 (dd, J ϭ 8.2, 5.8 Hz, 1 H), 6.47 (d, phenylacetylene (1) and cyclohexylamine (2e) into the title product.
J ϭ 8.0 Hz, 2 H), 6.63 (t, J ϭ 7.4 Hz, 1 H), 7.04 (t, J ϭ 7.5 Hz, 2 Purification by flash chromatography (PE/EtOAc, 12:1) afforded
1
H), 7.11 (d, J ϭ 6.8 Hz, 2 H), 7.15Ϫ7.35 (m, 8 H); 13C NMR
4e (521 mg, 78%) as a colorless oil. H NMR (400 MHz, CDCl3):
Eur. J. Org. Chem. 2001, 4411Ϫ4418
4415

I. Bytschkov, S. Doye
FULL PAPER
δ ϭ 0.72Ϫ0.89 (m, 1 H), 0.95Ϫ1.16 (m, 4 H), 1.20Ϫ1.75 (m, 5 H), Amine 8a: General procedures A and B were used to convert 3-
1.85 (br. d, J ϭ 12.4 Hz, 1 H), 2.21 (m, 1 H), 2.84 (dd, J ϭ 13.4, hexyne (5) and aniline (2a) into the title product. Because of the
8.0 Hz, 1 H), 2.91 (dd, J ϭ 13.4, 6.0 Hz, 1 H), 4.05 (dd, J ϭ 6.1,
low boiling point of 3-hexyne, an excess of alkyne (4.8 mmol) was
8.0 Hz, 1 H), 7.10 (d, J ϭ 6.9 Hz, 2 H), 7.13Ϫ7.35 (m, 8 H); 13C used in the hydroamination step. For procedure A, only 0.5 mL
NMR (100.6 MHz, DEPT, CDCl3): δ ϭ 24.7 (CH2), 25.1 (CH2), toluene was used. The microwave irradiation was carried out at a
26.0 (CH2), 32.6 (CH2), 34.7 (CH2), 45.6 (CH2), 53.4 (CH), 61.1 power output of 85% (255 W) for 3 h. Purification by flash chroma-
(CH), 126.2 (CH), 126.8 (CH), 127.2 (CH), 128.2 (CH), 128.2 tography (PE/EtOAc, 15:1) afforded 8a (230 mg, 54%) as a bright
˜
yellow oil.
1H NMR (400 MHz, CDCl3): δ ϭ 0.91 (t, J ϭ 7.2 Hz,
(CH), 129.2 (CH), 139.0 (C), 144.5 (C); IR: ν ϭ 3322, 3084, 3064,
2999, 2932, 2854, 1602, 1494, 1453, 1346, 1261, 1144, 1071, 1029, 3 H), 0.91 (t, J ϭ 7.4 Hz, 3 H), 1.30Ϫ1.65 (m, 6 H), 3.29 (quint,
913, 891, 627, 569, 533 cmϪ1; MS (60 °C): m/z (%) ϭ 278 (1) [Mϩ J ϭ 5.8 Hz, 1 H), 3.35Ϫ3.75 (br. s, 1 H), 6.56 (d, J ϭ 7.8 Hz, 2 H),
Ϫ 1], 188 (100), 165 (5), 106 (66), 91 (19), 77 (6); C20H25N (279.4): 6.64 (t, J ϭ 7.3 Hz, 1 H), 7.14 (dd, J ϭ 8.4, 7.4 Hz, 2 H); 13C NMR
calcd. C 85.97, H 9.02, N 5.01; found C 85.73, H 9.09, N 4.93.
(100.6 MHz, DEPT, CDCl3): δ ϭ 10.0 (CH3), 14.2 (CH3), 19.1
(CH2), 27.2 (CH2), 36.6 (CH2), 53.9 (CH), 112.9 (CH), 116.5 (CH),
Amine 4f: General procedures A and D were used to convert di-
phenylacetylene (1) and (S)-1-phenylethylamine (2f) into the title
product. An excess of amine (4.8 mmol) was used in the hydroam-
ination step. Purification by flash chromatography (PE/EtOAc, 3:1)
afforded 4f (562 mg, 78%) as a bright yellow oil. The two obtained
diastereomers (ratio 5:2; ee: 87.2% and 86.6%) could not be separ-
ated by flash chromatography. The 1H and 13C NMR spectroscopic
˜
129.2 (CH), 148.0 (C); IR: ν ϭ 3399, 3052, 3018, 2958, 2930, 2872,
1601, 1504, 1461, 1429, 1379, 1319, 1274, 1179, 1153, 1076, 1032,
992, 893, 865, 745, 691 cmϪ1; MS (25 °C): m/z (%) ϭ 177 (31) [Mϩ],
148 (90), 134 (100), 118 (10), 106 (15), 91 (3), 77 (8), 65 (3); Purity
by GC 97.4%. Compound 8a has already been described in ref.[11]
Amine 8i: General procedures A and D were used to convert 3-
data refer to the major diastereomer. The other characterization hexyne (5) and 4-methylaniline (2i) into the title product. Because
data refer to the diastereomeric mixture. 1H NMR (400 MHz,
of the low boiling point of 3-hexyne, an excess of alkyne (4.8 mmol)
CDCl3): δ ϭ 1.18 (d, J ϭ 6.8 Hz, 3 H), 1.74 (br. s, 1 H), 2.78 (dd, was used in the hydroamination step. For procedure A, only 0.5 mL
J ϭ 13.6, 9.3 Hz, 1 H), 2.87 (dd, J ϭ 13.6, 5.1 Hz, 1 H), 3.45 (q, toluene was used. The microwave irradiation was carried out at a
J ϭ 6.8 Hz, 1 H), 3.55 (dd, J ϭ 9.3, 5.1 Hz, 1 H), 6.77Ϫ6.84 (m, 2
power output of 70% (210 W) for 3 h. Purification by flash chroma-
H), 7.01Ϫ7.06 (m, 2 H), 7.13Ϫ7.34 (m, 11 H); 13C NMR tography (PE/EtOAc, 15:1) afforded 8i (271 mg, 59%) as a bright
1
(100.6 MHz, DEPT, CDCl3): δ ϭ 24.8 (CH3), 45.3 (CH2), 54.8 yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 0.90 (t, J ϭ 7.0 Hz,
(CH), 61.0 (CH), 126.3 (CH), 126.3 (CH), 126.6 (CH), 126.9 (CH), 3 H), 0.91 (t, J ϭ 7.4 Hz, 3 H), 1.20Ϫ1.65 (m, 6 H), 2.23 (s, 3 H),
127.3 (CH), 128.2 (CH), 128.2 (CH), 128.3 (CH), 129.3 (CH), 138.7 3.25 (quint, J ϭ 5.8 Hz, 1 H), 6.51 (d, J ϭ 8.2 Hz, 2 H), 6.96 (d,
(C), 144.1 (C), 145.3 (C); IR: ν ϭ 3319, 3082, 3061, 3026, 2960, J ϭ 8.2 Hz, 2 H); 13C NMR (100.6 MHz, DEPT, CDCl3): δ ϭ 9.9
˜
2922, 2850, 1602, 1493, 1466, 1453, 1369, 1201, 1131, 1110, 1070, (CH3), 14.2 (CH3), 19.2 (CH3), 20.3 (CH2), 27.2 (CH2), 36.6 (CH2),
1028, 910, 758, 698 cmϪ1; MS (25 °C): m/z (%) ϭ 210 (94) [Mϩ
Ϫ
54.3 (CH), 113.3 (CH), 125.9 (C), 129.7 (CH), 145.7 (C); IR: ν˜ ϭ
C7H7], 181 (8), 105 (100), 91 (16), 77 (21); C22H23N (301.4): calcd. 3401, 3015, 2958, 2927, 2871, 1618, 1518, 1460, 1405, 1379, 1318,
C 87.66, H 7.69, N 4.64; found C 87.27, H 7.72, N 4.56.
1300, 1271, 1181, 1152, 1119, 804 cmϪ1; MS (25 °C): m/z (%) ϭ
191 (36) [Mϩ], 162 (94), 148 (100), 134 (5), 120 (9), 106 (9), 91 (7),
77 (3), 65 (3); purity by GC: 96.1%. 8i has already been described
in ref.[11]
Amine 4g: General procedures A and B were used to convert di-
phenylacetylene (1) and 2-aminopentane (2g) into the title product.
Purification by flash chromatography (PE/EtOAc, 10:1) afforded
4g (432 mg, 67%) as a bright yellow oil. The two obtained diastereo- Amine 9f: General procedures A and B were used to convert 1-
mers (ratio 10:1) could not be separated by flash chromatography. phenylpropyne (6) and (S)-1-phenylethylamine (2f) into the title
1
The H and 13C NMR spectroscopic data refer to the major dia-
product. For procedure A, only 0.5 mL toluene was used. Purifica-
stereomer. The other characterization data refer to the diastereo- tion by flash chromatography (PE/EtOAc, 10:1) afforded 9f
meric mixture. 1H NMR (400 MHz, CDCl3): δ ϭ 0.78 (t, J ϭ 7.0 Hz, (401 mg, 70%) as a colorless oil. The two obtained diastereomers
3 H), 0.86 (d, J ϭ 6.1 Hz, 3 H), 1.10Ϫ1.34 (m, 4 H), 2.37 (m, 1 (ratio 7:1) could not be separated by flash chromatography. The 1H
H), 2.90 (m, 2 H), 4.00 (t, J ϭ 7.0 Hz, 1 H), 7.07 (d, J ϭ 6.9 Hz,
and 13C NMR spectroscopic data refer to the major diastereomer.
2 H), 7.13Ϫ7.33 (m, 8 H) ppm; 13C NMR (100.6 MHz, DEPT, The other characterization data refer to the diastereomeric mixture.
CDCl3): δ ϭ 14.1 (CH3), 19.2 (CH2), 19.6 (CH3), 40.5 (CH2), 45.6 1H NMR (400 MHz, CDCl3): δ ϭ 0.91 (d, J ϭ 6.4 Hz, 3 H), 1.30
(CH2), 49.4 (CH), 61.4 (CH), 126.2 (CH), 126.8 (CH), 127.3 (CH), (d, J ϭ 6.7 Hz, 3 H), 1.86 (br. s, 1 H), 2.49 (dd J ϭ 13.0, 7.5 Hz,
128.1 (CH), 128.2 (CH), 129.2 (CH), 139.0 (C), 144.0 (C) ppm; IR: 1 H), 2.76 (m, 1 H), 2.88 (dd, J ϭ 13.0, 5.0 Hz, 1 H), 3.93 (q, J ϭ
˜
ν ϭ 3062, 3026, 2956, 2925, 2870, 1602, 1494, 1453, 1372, 1157,
6.7 Hz, 1 H), 7.07 (d, J ϭ 6.9 Hz, 2 H), 7.15Ϫ7.40 (m, 8 H); 13C
1069, 1028, 912, 757, 697 cmϪ1; MS (25 °C): m/z (%) ϭ 266 (16) NMR (100.6 MHz, DEPT, CDCl3): δ ϭ 21.0 (CH3), 24.4 (CH3),
[Mϩ Ϫ 1], 252 (19), 224 (100), 202 (10); C19H25N (267.4): calcd. C
85.34, H 9.42, N 5.23; found C 84.86, H 9.34, N 4.70.
42.5 (CH2), 51.9 (CH), 55.3 (CH), 125.9 (CH), 126.5 (CH), 126.8
(CH), 128.2 (CH), 128.4 (CH), 129.3 (CH), 139.5 (C), 145.7 (C);
IR: ν˜ ϭ 3061, 3025, 2961, 2923, 2865, 1602, 1493, 1452, 1370, 1272,
1200, 1127, 1086, 1029, 965, 909, 848, 761, 744, 699 cmϪ1; MS (25
°C): m/z (%) ϭ 224 (2) [Mϩ Ϫ CH3], 210 (5), 148 (57), 105 (100),
91 (15), 77 (9), 65 (3); purity by GC: 95.8%. Compound 9f has
already been described in reference.[12]
Amine 4h: General procedures A and B were used to convert di-
phenylacetylene (1) and benzylamine (2h) into the title product.
The microwave irradiation was carried out at a power output of
100% (300 W) for 6 h. Purification by flash chromatography (PE/
EtOAc, 10:1) afforded 4h (14 mg, 2%) as a colorless solid. Because
of the small amount of isolated product, identification of 4h was
Amine 9j: General procedures A and D were used to convert 1-
phenylpropyne (6) and 4-methoxyaniline (2j) into the title product.
1
carried out only by its H NMR spectrum. Compound 4h has al-
ready been described in reference.[10] 1H NMR (400 MHz, CDCl3): The scale of the reaction was only 0.8 mmol. The microwave irradi-
δ ϭ 2.92 (s, 1 H), 2.97 (m, 2 H), 3.47 (d, J ϭ 13.5 Hz, 1 H), 3.67 ation was carried out at a power output of 70% (210 W) for 2 h.
(d, J ϭ 13.5 Hz, 1 H), 3.89 (t, J ϭ 7.0 Hz, 1 H), 7.05Ϫ7.40 (m, Purification by flash chromatography (PE/EtOAc, 10:1) afforded 9j
15 H).
(131 mg, 68%) as a bright yellow oil. 1H NMR (400 MHz, CDCl3):
4416
Eur. J. Org. Chem. 2001, 4411Ϫ4418

Microwave-Assisted Catalytic Intermolecular Hydroamination of Alkynes
FULL PAPER
δ ϭ 1.13 (d, J ϭ 6.3 Hz, 3 H), 2.67 (dd, J ϭ 13.3, 7.4 Hz, 1 H), output of 60% (180 W) for 2 h. Purification by flash chromato-
2.94 (dd, J ϭ 13.3, 4.6 Hz, 1 H), 3.20 (br. s, 1 H), 3.68 (m, 1 H), graphy (PE/EtOAc, 2:1) afforded 12f (54 mg, 10%) as a colorless
3.75 (s, 3 H), 6.62 (d, J ϭ 8.8 Hz, 2 H), 6.79 (d, J ϭ 8.8 Hz, 2 H), oil and the regioisomer 13f (130 mg, 24%) as a bright yellow oil.
7.10Ϫ7.35 (m, 5 H); 13C NMR (100.6 MHz, DEPT, CDCl3): δ ϭ The two diastereomers of 13f (ratio 3:1) could not be separated by
20.1 (CH3), 42.2 (CH2), 50.7 (CH), 55.8 (CH3), 115.0 (CH), 115.3 flash chromatography. The characterization data for 13f refer to
1
(CH), 126.2 (CH), 128.3 (CH), 129.5 (CH), 138.6 (C), 141.0 (C), the mixture of diastereomers. Compound 12f: H NMR (400 MHz,
152.2 (C); IR: ν˜ ϭ 3391, 3026, 2928, 2831, 1508, 1453, 1407, 1375, CDCl3): δ ϭ 1.36 (d, J ϭ 6.5 Hz, 3 H), 2.65Ϫ2.90 (m, 4 H), 3.80
1281, 1231, 1178, 1149, 1109, 1092, 1035, 817, 796, 743, 699 cmϪ1
;
(q, J ϭ 6.5 Hz, 1 H), 7.10Ϫ7.40 (m, 10 H); 13C NMR (100.6 MHz,
MS (25 °C): m/z (%) ϭ 241 (17) [Mϩ], 212 (3), 191 (3), 150 (100), DEPT, CDCl3): δ ϭ 21.3 (CH3), 33.5 (CH2), 47.7 (CH2), 58.7 (CH),
135 (3), 122 (2), 107 (5), 91 (6), 77 (2); C16H19NO (241.3): calcd.
C 79.63, H 7.94, N 5.80; found C 79.60, H 8.09, N 5.72.
126.7 (CH), 127.2 (CH), 128.6 (CH), 128.6 (CH), 129.1 (CH), 137.5
˜
(C), 138.9 (C); IR: ν ϭ 2983, 2818, 1733, 1646, 1551, 1496, 1455,
1374, 1243, 1118, 1044, 918, 863, 762, 699 cmϪ1; MS (120 °C): m/
z (%) ϭ 225 (4) [Mϩ], 210 (60), 134 (40), 120 (10), 105 (100), 91
(8), 77 (15), 65 (2); purity by GC: 95.1%. Compound 12f has al-
ready been described in reference.[10] Compound 13f: 1H NMR
(400 MHz, CDCl3): δ ϭ 1.31 and 1.35 (d, J ϭ 6.5 Hz, 12 H), 3.52
and 3.77 (q, J ϭ 6.5 Hz, 4 H), 7.10Ϫ7.40 (m, 20 H); 13C NMR
(100.6 MHz, DEPT, CDCl3): δ ϭ 24.0 (CH3), 25.7 (CH3), 55.8
(CH), 56.2 (CH), 126.6 (CH), 126.7 (CH), 126.8 (CH), 126.9 (CH),
Amine 10f: General procedures A and D were used to convert 1-
phenylbutyne (7) and (S)-1-phenylethylamine (2f) into the title
product. For procedure A, only 0.5 mL of toluene was used. Puri-
fication by flash chromatography (PE/EtOAc, 10:1) afforded 10f
(356 mg, 59%) as a colorless oil. The two obtained diastereomers
(ratio 5:3; ee: 79.6% and 86.4%) could not be separated by flash
chromatography. For further purification the obtained amine was
converted into the hydrochloride salt. It was therefore dissolved in
MeOH (2.0 mL), and HCl (5.0 mL, 1.0 mol/L in Et2O) was added
at room temperature. The mixture was stirred for 20 h at room
temperature. Filtration afforded 10f·HCl (376 mg, 54%) as a color-
less solid. The characterization data refer to the diastereomeric
˜
128.4 (CH), 145.3 (C, br); IR: ν ϭ 3061, 3025, 2961, 2924, 2862,
1601, 1582, 1492, 1450, 1368, 1202, 1124, 1070, 1023, 910, 760, 697
cmϪ1; MS (25 °C): m/z (%) ϭ 225 (4) [Mϩ], 210 (88), 148 (3), 120
(10), 105 (100), 91 (4), 77 (15), 65 (1); purity by GC: 99.0%. Com-
pound 13f has already been described in ref.[15]
1
mixture of amine hydrochloride salts. H NMR (400 MHz, D2O):
δ ϭ 0.88 (t, J ϭ 7.2 Hz, 3 H), 0.99 (t, J ϭ 7.2 Hz, 3 H), 1.42Ϫ1.92
(m, 10 H), 2.77Ϫ3.37 (m, 6 H), 4.42Ϫ4.62 (m, 2 H), 7.02Ϫ7.62 m
(20 H); 13C NMR (100.6 MHz, DEPT, D2O): δ ϭ 10.7 (CH3), 11.2
(CH3), 21.8 (CH3), 22.0 (CH3), 25.2 (CH2), 26.1 (CH2), 37.8 (CH2),
39.0 (CH2), 59.3 (CH), 59.6 (CH), 61.5 (CH), 61.7 (CH), 129.4
(CH), 130.2 (CH), 130.3 (CH), 130.3 (CH), 131.9 (CH), 131.9
(CH), 132.0 (CH), 132.1 (CH), 132.3 (CH), 132.4 (CH), 132.5
(CH), 132.6 (CH), 138.5 (C), 138.6 (C), 138.6 (C), 139.2 (C); IR:
Amines 12i/13i: General procedures A and D were used to convert
phenylacetylene (11) and 4-methylaniline (2i) into the title products.
The scale of the reaction was only 1.8 mmol. For procedure A, only
0.5 mL toluene was used. The microwave irradiation was carried
out at a power output of 70% (210 W) for 2 h. Purification by flash
chromatography (PE/EtOAc, 10:1) afforded a mixture of the re-
gioisomers 12i and 13i (331 mg, 87%) in a ratio 12i/13i ϭ 4:1 as a
bright yellow oil. The two obtained isomers could not be separated
by flash chromatography. The 1H and 13C NMR spectroscopic data
refer to the major isomer 12i. The other characterization data refer
to the mixture of isomers. The minor isomer 13i was identified by
˜
ν ϭ 2973, 2748, 2706, 2667, 2467, 1582, 1497, 1455, 1382, 1313,
1280, 1213, 1157, 1077, 1032, 968, 924, 765, 742, 699 cmϪ1; MS
(25 °C): m/z (%) ϭ 224 (2), 162 (93), 120 (9), 105 (100), 92 (14), 79
(6), 77 (7); purity by GC (amine): Ͼ 99%. Compound 10f has al-
ready been described in ref.[12]
1
its H NMR signals at δ ϭ 1.47 (d, J ϭ 6.8 Hz, 3 H) and 4.43 (q,
1
J ϭ 6.8 Hz, 1 H). H NMR (400 MHz, CDCl3): δ ϭ 2.23 (s, 3 H),
2.87 (t, J ϭ 7.0 Hz, 2 H), 3.35 (t, J ϭ 7.0 Hz, 2 H), 3.60 (br. s, 1
H), 6.53 (d, J ϭ 8.3 Hz, 2 H), 6.99 (d, J ϭ 8.3 Hz, 2 H), 7.10Ϫ7.40
(m, 5 H); 13C NMR (100.6 MHz, DEPT, CDCl3): δ ϭ 20.5 (CH3),
35.5 (CH2), 45.4 (CH2), 113.2 (CH), 126.3 (CH), 126.7 (C), 128.5
Amines 12a/13a: General procedures A and D were used to convert
phenylacetylene (11) and aniline (2a) into the title products. The
scale of the reaction was only 1.8 mmol. For procedure A, only
0.5 mL of toluene was used. The microwave irradiation was carried
out at a power output of 60% (180 W) for 2 h. Purification by flash
chromatography (PE/EtOAc, 8:1) afforded a mixture of the re-
gioisomers 12a and 13a (239 mg, 67%) in a ratio 12a/13a ϭ 3:1 as
a bright yellow oil. The two obtained isomers could not be separ-
ated by flash chromatography. The 1H and 13C NMR spectroscopic
data refer to the major isomer 12a. The other characterization data
refer to the mixture of isomers. The minor isomer 13a was identi-
˜
(CH), 128.7 (CH), 129.7 (CH), 139.3 (C), 145.6 (C); IR: ν ϭ 3402,
3024, 2917, 2862, 1616, 1517, 1493, 1452, 1317, 1300, 1254, 1182,
1125, 1077, 1029, 965, 911, 806, 748, 697 cmϪ1; MS (25 °C): m/z
(%) ϭ 211 (53) [Mϩ], 196 (30), 149 (7), 134 (21), 120 (100), 105
(16), 91 (15), 77 (7), 65 (5); purity by GC (12i ϩ 13i): 95.5%. 12i
and 13i have already been described.[16,17]
Amines 15a/16a: General procedures A and D were used to convert
1-dodecyne (14) and aniline (2a) into the title products. For proced-
ure A only 0.5 mL of toluene was used. The microwave irradiation
was carried out at a power output of 60% (180 W) for 2 h. Purifica-
tion by flash chromatography (PE/EtOAc, 10:1) afforded a mixture
of the regioisomers 15a and 16a (306 mg, 49%) in a ratio 15a/16a ϭ
1:7 as a bright yellow oil. The two obtained isomers could not be
separated by flash chromatography. The 1H and 13C NMR spectro-
scopic data refer to the major isomer 16a. The other characteriza-
tion data refer to the mixture of isomers. The minor isomer 15a was
identified by GC/MS analysis. 1H NMR (400 MHz, CDCl3): δ ϭ
0.87 (t, J ϭ 6.7 Hz, 3 H), 1.17 (d, J ϭ 6.3 Hz, 3 H), 1.20Ϫ1.64 (m,
18 H), 3.38Ϫ3.48 (m, 1 H), 3.70 (br. s, 1 H), 6.59 (d, J ϭ 7.8 Hz, 2
1
fied by its H NMR signals at δ ϭ 1.48 (d, J ϭ 6.8 Hz, 3 H) and
1
4.45 (q, J ϭ 6.8 Hz, 1 H). H NMR (400 MHz, CDCl3): δ ϭ 2.88
(t, J ϭ 7.1 Hz, 2 H), 3.36 (t, J ϭ 7.1 Hz, 2 H), 3.75 (br. s, 1 H),
6.50Ϫ7.40 (m, 10 H); 13C NMR (100.6 MHz, DEPT, CDCl3): δ ϭ
35.4 (CH2), 45.0 (CH2), 113.0 (CH), 117.5 (CH), 126.4 (CH), 128.5
˜
(CH), 128.7 (CH), 129.2 (CH), 139.2 (C), 147.9 (C); IR: ν ϭ 3407,
3052, 3024, 2922, 1599, 1504, 1452, 1430, 1371, 1316, 1257, 1179,
1154, 1114, 1073, 1029, 991, 869, 745, 690 cmϪ1; MS (25 °C): m/z
(%) ϭ 197 (45) [Mϩ], 182 (25), 120 (4), 106 (100), 93 (12), 91 (7),
76 (16), 65 (1); purity by GC (12a ϩ 13a): Ͼ 99%. 12a and 13a
have already been described.[13,14]
Amines 12f/13f: General procedures A and D were used to convert
phenylacetylene (11) and (S)-1-phenylethylamine (2f) into the title H), 6.67 (t, J ϭ 7.3 Hz, 1 H), 7.16 (br. t, J ϭ 7.6 Hz, 2 H); 13C
products. The microwave irradiation was carried out at a power
NMR (100.6 MHz, DEPT, CDCl3): δ ϭ 14.1 (CH3), 20.6 (CH3),
Eur. J. Org. Chem. 2001, 4411Ϫ4418
4417

I. Bytschkov, S. Doye
FULL PAPER
[2k]
205Ϫ209;
M. R. Bürgstein, H. Berberich, P. W. Roesky,
22.7 (CH2), 26.1 (CH2), 29.3 (CH2), 29.6 (CH2), 29.7 (CH2), 31.9
(CH2), 37.1 (CH2), 44.1 (CH2), 48.8 (CH), 113.4 (CH), 117.1 (CH),
129.2 (CH),147.3 (C); IR: ν ϭ 3403, 2955, 2922, 2852, 1601, 1503,
1464, 1427, 1376, 1317, 1255, 1178, 1153, 1075, 1031, 993, 865, 745,
721, 690 cmϪ1; MS (25 °C): m/z (%) ϭ 261 (100) [Mϩ], 246 (40),
121 (40), 106 (30), 91 (3), 77 (9), 65 (2); purity by GC (15a ϩ 16a):
98.6%. Compounds 15a and 16a have already been described.[18,19]
[2l]
Organometallics 1998, 17, 1452Ϫ1454;
hedron Lett. 1998, 39, 5961Ϫ5962;
T. E. Müller, Tetra-
[2m]
T. E. Müller, M. Gros-
˜
che, E. Herdtweck, A.-K. Pleier, E. Walter, Y.-K. Yan, Organo-
metallics 2000, 19, 170Ϫ183; [2n] S. Burling, L. D. Fields, B. A.
[2o]
Messerle, Organometallics 2000, 19, 87Ϫ90;
Y. K. Kim, T.
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Amines 15i/16i: General procedures A and D were used to convert
1-dodecyne (14) and 4-methylaniline (2i) into the title products. For
procedure A, only 0.5 mL of toluene was used. The microwave
irradiation was carried out at a power output of 70% (210 W) for
2 h. Purification by flash chromatography (PE/EtOAc, 15:1) af-
forded a mixture of the regioisomers 15i and 16i (527 mg, 80%) in
a ratio 15i/16i ϭ 2:5 as a bright yellow oil. The two obtained iso-
mers could not be separated by flash chromatography. The 1H and
13C NMR spectroscopic data refer to the major isomer 16i. The
other characterization data refer to the mixture of isomers. The
minor isomer 15i was identified by GC/MS analysis. 1H NMR
(400 MHz, CDCl3): δ ϭ 0.88 (t, J ϭ 6.7 Hz, 3 H), 1.15 (d, J ϭ
6.3 Hz, 3 H), 1.20Ϫ1.64 (m, 18 H), 2.23 (s, 3 H), 3.35Ϫ3.45 (m, 1
H), 6.54 (d, J ϭ 8.1 Hz, 2 H), 6.97 (d, J ϭ 8.1 Hz, 2 H); 13C NMR
(100.6 MHz, DEPT, CDCl3): δ ϭ 14.1 (CH3), 18.4 (CH2), 20.3
(CH3), 20.6 (CH3), 22.7 (CH2), 26.1 (CH2), 27.2 (CH2), 29.3 (CH2),
29.6 (CH2), 29.7 (CH2), 31.9 (CH2), 37.1 (CH2), 49.1 (CH), 113.7
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Acknowledgments
Generous support by Professor E. Winterfeldt is most gratefully
acknowledged. We thank Professor W. A. König for the determina-
tion of the ee values of compounds 4f and 10f. We further thank
the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen
Industrie, and the Bayer AG for their financial support of our re-
search.
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