Silica-immobilized NHC-CuI complex: An efficient and reusable catalyst for A3-coupling (aldehyde-alkyne-amine) under solventless reaction conditions

Article abstract of DOI:10.1002/ejoc.200800006

A novel silica-immobilized NHC-Cu^I complex was developed and used as a highly efficient catalyst in the three-component coupling reactions of aldehydes, alkynes and amines (A³-coupling). The reactions were applicable to aromatic and aliphatic aldehydes, alkynes and amines, and generated the corresponding propargylamines in good yields only in the presence of SiO₂-NHC-Cu^I (2 mol-%) at room temp. under solvent-free reaction conditions. Moreover, the catalyst was quantitatively recovered from the reaction mixture by a simple filtration and reused for ten cycles with almost consistent activity. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800006

FULL PAPER
DOI: 10.1002/ejoc.200800006
Silica-Immobilized NHC–CuI Complex: An Efficient and Reusable Catalyst for
A3-Coupling (Aldehyde–Alkyne–Amine) under Solventless Reaction Conditions
Min Wang,[a] Pinhua Li,[a] and Lei Wang*[a,b]
Keywords: Silica-immobilization / N-Heterocyclic carbenes / Copper / Coupling reactions / Heterogeneous catalysis / Sol-
ventless reactions
A novel silica-immobilized NHC–CuI complex was devel-
oped and used as a highly efficient catalyst in the three-com-
ponent coupling reactions of aldehydes, alkynes and amines
(A3-coupling). The reactions were applicable to aromatic and
aliphatic aldehydes, alkynes and amines, and generated the
corresponding propargylamines in good yields only in the
presence of SiO2–NHC–CuI (2 mol-%) at room temp. under
solvent-free reaction conditions. Moreover, the catalyst was
quantitatively recovered from the reaction mixture by a sim-
ple filtration and reused for ten cycles with almost consistent
activity.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
HAP) and layered double hydroxide supported gold (LDH–
AuCl4) reported by Likhar et al.,[15,16] and heteropolyacid-
supported silver (Ag–HPA) obtained by Reddy et al.[17]
were successfully used to catalyze A3-coupling reactions un-
der heterogeneous reaction conditions with reusability of
catalysts. Most recently, Kidwai et al.[18] have reported gold
and copper nanoparticles as reusable catalysts for the A3-
coupling reactions. However, almost all of these A3-coup-
ling reactions protocols were carried out under heating re-
action conditions.
N-Heterocyclic carbenes (NHCs) are widely used as li-
gands in inorganic and organometallic chemistry since
Arduengo and co-workers isolated the first stable N-hetero-
cyclic carbene in 1991.[19] NHCs were first considered as
simple phosphane mimics in organometallic chemistry.[20]
However, increasing experimental data clearly show that
NHC–metal catalysts can surpass their phosphane-based
counterparts in both activity and scope.[21] NHCs are
stronger σ-donors and weaker π-acceptors, causing the
properties of NHC–metal complexes to be notably different
than those of a corresponding phosphane complex. Because
of their specific coordination chemistry, NHCs both stabi-
lize and activate metal centers in quite different key cata-
lytic steps of organic syntheses, for example, C–C, C–H, C–
O, and C–N bond formation.[22] To avoid catalyst leaching,
polymer-, PEG- or silica-supported NHC–metal complexes
were synthesized and applied successfully in organic reac-
tions.[23] However, there has been no report on supported
NHC–CuI complexes.
Introduction
One of the most challenging tasks in organic synthesis is
the efficient preparation of complex molecules starting from
easily available raw materials. Especially attractive are one-
pot multi-component coupling reactions (MCRs), which in-
troduce several elements of diversity into a molecule in a
single step.[1] Three-component coupling of aldehydes, al-
kynes, and amines (A3-coupling) is one of the best examples
of such a process and has received much more attention in
recent years.[2] The resultant propargylamines obtained
from A3-coupling reactions are frequent skeletons[3] and
synthetically versatile key intermediates[4] for the prepara-
tion of many nitrogen-containing biologically active com-
pounds such as β-lactams, oxotremorine analogues, confor-
mationally restricted peptides, isosteres, natural products,
and therapeutic drug molecules.[3b,5] There are several
transition-metal catalysts, which are able to carry out these
multi-component A3-coupling reactions. These include AgI
salts,[6] AuI/AuIII salts,[2,7] AuIII–salen complexes,[8] CuI
[11]
salts,[9] Ir complexes,[10] Hg2Cl2
and Cu/Ru dimetallic
systems[12] under homogeneous reaction conditions. But all
of these systems suffer from the loss of the precious or
hazardous catalysts at the end of the reaction. In order to
achieve the recyclability of the transition-metal catalysts,
AuI, AgI and CuI in ionic liquids developed by Li et al.[13]
and Park et al.,[14] hydroxyapatite-supported copper (Cu–
[a] Department of Chemistry, Huaibei Coal Teachers College,
Huaibei, Anhui 235000, P. R. China
The increasing environmental consciousness of the chem-
ical community has led to the search for more efficient and
environmentally friendly methods for chemical syntheses.[24]
The development of heterogeneous catalysts for the synthe-
sis of fine chemicals has become a major area of research
Fax: +86-561-3090-518
E-mail: leiwang@hbcnc.edu.cn
[b] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. China
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M. Wang, P. Li, L. Wang
FULL PAPER
Scheme 1.
recently, as the potential advantages of these materials (sim-
plified recovery and reusability, the potential for incorpora-
tion in continuous reactors and microreactors) over homo-
Results and Discussion
The SiO2–NHC–CuI catalyst was readily prepared in a
geneous systems can have a major impact on the environ- three-step procedure (Scheme 1). Activated silica was
mental performance of a synthesis.[25] As a part of our on- treated with trichloro[4-(chloromethyl)phenyl]silane in dry
going interest in the synthesis of propargylamines with A3- toluene at 120 °C under an inert gas for 24 h to afford the
coupling reactions, we herein report an efficient SiO2– benzyl chloride functionalized silica. The obtained func-
NHC–CuI heterogeneous catalyst without any additives for tionalized silica material was then treated with N-methyl-
the three-component coupling of aldehydes, alkynes, and imidazole in toluene at 80 °C for 24 h to generate the corre-
amines (A3-reactions) to synthesize propargylamines at sponding silica-supported ionic liquid. The silica-supported
room temp. under solvent-free conditions. This method ionic liquid was then treated with freshly prepared CuI in
provides a wide range of substrate applicability and can be the presence of NaOtBu in dry THF at room temp. under
applied to aromatic and aliphatic aldehydes, amines and al- an inert gas for 6 h. The SiO2–NHC–CuI catalyst was ob-
kynes. In most cases, nearly quantitative yields were ob- tained as a gray-green powder, and the copper content of
tained. To the best of our knowledge, this is the first catalyst the catalyst was found to be 0.86 mmolg–1.
example with N-heterocyclic carbene as ligand for A3-coup-
ling reactions (Scheme 1).
Our initial investigation focused on the effect of solvents
on the A3-coupling reactions. In general, A3-coupling reac-
Table 1. Effect of solvent on the A3-coupling reaction using SiO2–NHC–CuI as catalyst.[a]
Entry
Solvent
Yield [%][b]
1
2
3
toluene
CH3CN
THF
82
90
84
4
5
6
7
H2O
24
30
94
62
CH3CH2OH
CH2Cl2
DMSO
DMF
8
52
9
acetone
neat
neat
95
10
11
12
95
95[c]
neat
93[d]
[a] Reaction conditions: paraformaldehyde (1.0 mmol), piperidine (1.1 mmol), phenylacetylene (1.2 mmol), SiO2–NHC–CuI (2 mol-%),
solvent (0.5 mL), nitrogen, room temp., 24 h. [b] Isolated yields. [c] 70 °C for 4 h. [d] Using NHC–CuI (2 mol-%) instead of SiO2–NHC–
CuI (2 mol-%) as catalyst.
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Silica-Immobilized NHC–CuI
tions were carried out in toluene,[2,26] CH3CN,[15,18a,27] Table 2. A3 (aldehyde/amine/alkyne) coupling reaction catalyzed by
SiO2–NHC–CuI.[a]
THF,[16,18b] H2O[6,7,9a,28] and other solvents. Here, different
solvents were employed in the A3-coupling of paraformal-
dehyde, phenylacetylene, and piperidine by using SiO2–
NHC–CuI as catalyst at room temp., and the results are
summarized in Table 1. From Table 1, it is evident that ace-
tone and CH2Cl2 are suitable reaction media for the A3-
coupling reaction (Table 1, Entries 6 and 9), whereas tolu-
ene, CH3CN, and THF afforded lower yields (Table 1, En-
tries 1, 2, and 3). Moderate yields were obtained when the
reactions were performed in DMSO and DMF (Table 1,
Entries 7 and 8). Poor results were observed when the reac-
tions were carried out in H2O and CH3CH2OH (Table 1,
Entries 4 and 5). Surprisingly, 95% of the desired product
was isolated under solvent-free reaction conditions at room
temp. for 24 h (Table 1, Entry 10). We also investigated the
reaction by using NHC–CuI (2 mol-%) instead of SiO2–
NHC–CuI (2 mol-%) as catalyst, and the result indicated
that both of them are effective in the reaction (Table 1, En-
try 12). To avoid the use of volatile solvents and to reduce
the environmental pollution, all the three-component cou-
pling reactions were performed under solvent-free reaction
conditions.
During the course of our further optimization of the con-
ditions, when using 2 mol-% of SiO2–NHC–CuI, the reac-
tions were generally completed in 4 h when performed at
70 °C (Table 1, Entry 11). The reaction time, as expected,
was inversely proportional to the temperature. Room tem-
perature was found to be optimal. Thus, the optimized reac-
tion conditions for this A3-coupling reaction are SiO2–
NHC–CuI (2 mol-%) in the absence of a solvent at room
temp. for 24 h.
To examine the scope of this three-component coupling
reaction, we extended our studies to different combinations
of aldehydes, amines, and alkynes. The results are listed in
Table 2. At the beginning of the determination of the amine
substrate scope, phenylacetylene was used as a model sub-
strate, and various amines with different aldehydes were ex-
amined (Table 2, Entries 1–7). The results indicated that cy-
clic, heterocyclic and acyclic secondary aliphatic amines gave
excellent yields of products at room temp. in the combination
of phenylacetylene/paraformaldehyde/amines under standard
reaction conditions (Table 2, Entries 1–5), whereas primary
[a] Reaction conditions: aldehyde (1.0 mmol), amine (1.1 mmol),
alkyne (1.2 mmol), SiO2–NHC–CuI (2 mol-%), nitrogen, room
temp., 24 h. [b] Isolated yield. [c] 70 °C for 4 h.
Subsequently, a variety of alkynes were also examined
aliphatic amines generated the corresponding secondary pro- for the A3-coupling by using paraformaldehyde/N,N-diben-
pargylamines in moderate yield (Table 2, Entry 6). Aromatic zylamine/alkynes (Table 2, Entries 17–20). As can be seen
primary amines, such as aniline, also reacted with benzalde- from Table 2, reactivity of both aliphatic and aromatic al-
hyde and phenylacetylene to give the corresponding products kynes was observed, in which the aromatic alkynes were
in good yields (Table 2, Entry 7).
often much more reactive than the aliphatic alkynes. Aro-
In order to expand the scope of aldehyde substrates, a matic alkynes, such as phenylacetylene and (p-methyl-
combination of phenylacetylene/piperidine/aldehydes was phenyl)acetylene, were able to undergo the three-compo-
chosen, and various aldehydes were examined. Aliphatic al- nent-coupling smoothly and generated the corresponding
dehydes, cyclic or acyclic, displayed high reactivity under products in excellent yields (Table 2, Entries 3 and 17). For-
the reaction conditions (Table 2, Entries 8–10). Aromatic tunately, the reactions involving aliphatic alkynes also gave
aldehydes with both electron-donating and electron-with- both higher conversions and isolated yields, leading to the
drawing functionalities afforded the corresponding propar- corresponding propargylamines in higherr yields (Table 2,
gylamines in good to excellent yields, and the reaction of Entries 18–20).
arenecarbaldehydes was also tolerant of ortho substitution
(Table 2, Entries 11–16).
For any heterogeneous catalyst, it is important to know
its ease of separation and possible reusability. The recycl-
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M. Wang, P. Li, L. Wang
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Table 3. Successive runs by using recovered SiO2–NHC–CuI catalyst.[a]
Cycle
Yield [%][b]
Cycle
Yield [%][b]
1
2
3
4
5
95
94
93
92
91
6
7
8
9
10
93
92
90
89
88
[a] Reaction conditions: paraformaldehyde (1.0 mmol), piperidine (1.1 mmol), phenylacetylene (1.2 mmol), SiO2–NHC–CuI catalyst
(2 mol-%), nitrogen, room temp., 24 h. [b] Isolated yield.
ability of the SiO2–NHC–CuI catalyst was also investigated.
After carrying out the reaction, the catalyst was separated
by simple filtration and washed with acetone (2 mL). After
The chemicals were purchased from commercial suppliers (Aldrich,
USA and Shanghai Chemical Company, China) and were used
without purification prior to use.
being air-dried, it can be reused directly without further
purification. The recovered catalyst was used in the next
run, and almost consistent activity was observed for ten
consecutive cycles (Table 3, Entries 1–10). Possible copper
leaching in SiO2–NHC–CuI was also determined. Induc-
tively coupled plasma (ICP) analyses of the clear filtrates
obtained by filtration after the reaction indicated that the
Cu content was Ͻ0.1 ppm.
Preparation of Benzyl Chloride Functionalized Silica: Into a 100-
mL round-bottom flask were introduced successively anhydrous
toluene (30 mL), activated silica (5.0 g), and trichloro[4-(chlo-
romethyl)phenyl]silane (2.0 g). The solution was refluxed at 120 °C
under an inert gas for 24 h. The solution was filtered, and the solid
was washed subsequently with toluene, dichloromethane, and
methanol, and dried under reduced pressure at 80 °C for 10 h to
yield 5.81 g of product. The loading of the modified silica was
readily quantified by CHN microanalysis and found to be
1.12 mmolg–1 based on the C content. The surface area and pore
volume of the modified silica were found to be 433 m2 g–1 and
0.53 cm3 g–1, respectively.
Conclusions
We have successfully developed a novel, practical and en-
vironmentally friendly method for the synthesis of propar-
gylamines through a three-component coupling of alde-
hydes, amines and alkynes by using SiO2–NHC–CuI as cat-
alyst (2 mol-%) at room temp. under solventless reaction
conditions. The reactions generated the corresponding pro-
pargylamines in high yields and were applicable to aromatic
and aliphatic aldehydes, alkynes, and amines. In addition,
this methodology offers the competitiveness of recyclability
of the catalyst without significant loss of catalytic activity,
and the catalyst could be readily recovered and reused for
ten cycles, thus making this procedure environmentally
more acceptable, whilst no catalyst leaching was observed.
Further investigation on the application of this kind of
supported catalysts in asymmetric catalysis is still underway
in our laboratory.
Preparation of Silica-Supported Ionic Liquid: Under nitrogen, N-
methylimidazole (0.41 g, 5.0 mmol) and benzyl chloride function-
alized silica (2.0 g) were mixed in toluene (15 mL) in a round-bot-
tom flask. The reaction was carried out at 80 °C for 24 h. Then the
solution was filtered, and the solid was washed with chloroform,
methanol and ethyl acetate, and dried under vacuum at 60 °C to
yield 2.08 g of a pale powder. The loading of the silica-supported
ionic liquid was quantified by CHN microanalysis and found to be
0.96 mmolg–1 based on the N content. The surface area and pore
volume of the silica-supported ionic liquid were found to be
308 m2 g–1 and 0.43 cm3 g–1, respectively. 29Si NMR (solid): δ =
–79.4 (br., SiC), –111.5 (br., SiO2) ppm.
Preparation of SiO2–NHC–CuI Catalyst: In an oven-dried Schlenk
flask, freshly prepared CuI (0.190 g, 1.0 mmol), NaOtBu (0.096 g,
1.0 mmol), silica-supported ionic liquid (1.0 g) and THF (5 mL)
were added. The resulting suspension was stirred at room temp.
under an inert gas for 6 h. Then the solution was filtered, and the
solid was washed with water (3 mL), methanol (3 mL), acetone
(3 mLϫ2), and dried under vacuum at 60 °C for 12 h. The SiO2–
NHC–CuI catalyst was obtained as a gray-green powder (1.14 g).
The copper content of the catalyst was found to be 0.86 mmolg–1
based on ICP analysis. The surface area and pore volume of the
SiO2–NHC–CuI were found to be 275 m2 g–1 and 0.38 cm3 g–1,
respectively. 29Si NMR (solid): δ = –78.7 (br., SiC), –111.5 (br.,
SiO2) ppm.
Experimental Section
General: All 1H and 13C NMR spectra were recorded with a Bruker
300 MHz FT-NMR spectrometer. Chemical shifts are given as δ
value with reference to tetramethylsilane (TMS) as the internal
standard. 29Si NMR (solid) spectra were obtained with a Bruker
400 MHz FT-NMR spectrometer. The C, H, and N analyses were
performed with a Vario El III elementar. The Cu content was deter-
mined with a Jarrell-Ash 1100 ICP analysis. Specific surface areas
and pore volumes of the samples were determined in a Micro-
meritics ASAP-2000 automated nitrogen physisorption apparatus
and calculated according to the BET method. Products were puri-
fied by flash column chromatography on 230–400 mesh silica gel.
Typical Procedure for A3-Coupling Catalyzed by SiO2–NHC–CuI:
Under nitrogen, SiO2–NHC–CuI catalyst (23.3 mg, CuI content
0.02 mmol), phenylacetylene (120 mg, 1.2 mmol), paraformalde-
hyde (30 mg, 1.0 mmol) and piperidine (94 mg, 1.1 mmol) were
added in a 10-mL of Schlenk flask. The mixture was stirred at
room temp. for 24 h. After the reaction was completed, diethyl
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Silica-Immobilized NHC–CuI
ether (3 mLϫ2) was added, and the slurry was stirred, then filtered
using a sintered-glass funnel. The residue was washed with diethyl
ether to ensure removal of the product from the surface of the
catalyst. The combined organic phases were dried with Na2SO4,
filtered, concentrated, and the residue was purified by flash
chromatography on silica gel (eluant: hexane/ethyl acetate, 3:1,
N-[1-(1-Cyclohexyl-3-phenyl-2-propynyl)]piperidine:[34] 1H NMR
(300 MHz, CDCl3): δ = 7.44–7.40 (m, 2 H, ArH), 7.30–7.25 (m, 3
H, ArH), 3.12 (d, J = 9.9 Hz, 1 H, CϵCCH), 2.66–2.58 (m, 2 H,
NCH2), 2.44–2.34 (m, 2 H, NCH2), 2.14–1.98 (m, 2 H, CH2), 1.80–
1.70 (m, 2 H, CH2), 1.70–1.36 (m, 8 H, CH2), 1.34–0.89 (m, 5 H,
CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 131.9, 128.4, 127.7,
v/v) to give the corresponding A3-coupling product N-[1-(3-phen- 123.8, 87.9, 86.3, 64.7, 39.7, 31.4, 30.5, 27.0, 26.4, 26.1, 24.8 ppm.
ylprop-2-ynyl)]piperidine as a colorless oil (190 mg, 95% yield).
N-[4-(3-Phenyl-1-propyl-2-propynyl)]piperidine:[35]
(300 MHz, CDCl3): δ = 7.44–7.42 (m, 2 H, ArH), 7.28–7.26 (m, 3
H, ArH), 3.51–3.47 (m, 1 H, CϵCCH), 2.72–2.65 (m, 2 H, NCH2),
1H
NMR
N-[1-(3-Phenylprop-2-ynyl)]piperidine:[29] 1H NMR (300 MHz,
CDCl3): δ = 7.43–7.40 (m, 2 H, ArH), 7.27–7.24 (m, 3 H, ArH),
3.45 (s, 2 H, CϵCCH2), 2.54 (br. s, 2ϫ2 H, NCH2), 1.65–1.58 (m, 2.50–2.48 (m, 2 H, NCH2), 1.72–1.53 (m, 6 H, NCH2CH2), 1.46–
2ϫ2 H, NCH2CH2), 1.45–1.42 (m, 2 H, NCH2CH2CH2) ppm. 13
NMR (75 MHz, CDCl3): δ = 131.4, 127.9, 127.7, 123.1, 84.8, 84.7,
53.2, 48.2, 25.7, 23.7 ppm.
C
1.41 (m, 4 H, CH3CH2), 0.96 (t, J = 7.2 Hz, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 131.7, 128.2, 127.8, 123.7, 88.2, 85.7,
58.3, 35.7,29.8, 26.9, 24.7, 20.2, 14.0 ppm.
N-[1-(3-Phenylprop-2-ynyl)]morpholine:[30] 1H NMR (300 MHz,
CDCl3): δ = 7.45–7.41 (m, 2 H, ArH), 7.29–7.27 (m, 3 H, ArH),
3.76–3.73 (t, J = 4.8 Hz, 2ϫ2 H, OCH2),3.48 (s, 2 H, CϵCCH2),
2.63–2.60 (t, J = 4.8 Hz, 2ϫ2 H, NCH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 131.6, 128.2, 128.1, 123.0, 85.5, 84.1, 66.8, 52.4,
48.0 ppm.
N-(1,3-Diphenyl-2-propynyl)piperidine:[36] 1H NMR (300 MHz,
CDCl3): δ = 7.65–7.63 (m, 2 H, ArH), 7.53–7.50 (m, 2 H, ArH),
7.38–7.28 (m, 6 H, ArH), 4.82 (s, 1 H, CϵCCH), 2.61–2.56 (m,
2ϫ2 H, NCH2), 1.63–1.56 (m, 4 H, NCH2CH2), 1.48–1.42 (m, 2
H, NCH2CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 138.8,
132.0, 128.7, 128.4, 128.2, 127. 6, 123.6, 87.9, 86.3, 62.6, 59.8, 26.4,
24.7 ppm.
N,N-Dibenzyl-3-phenylprop-2-ynylamine:[31] 1H NMR (300 MHz,
CDCl3): δ = 7.49–7.46 (m, 2 H, ArH), 7.42–7.40 (m, 4 H, ArH),
7.31–7.17 (m, 9 H, ArH), 3.73 (s, 2ϫ2 H, PhCH2), 3.44 (s, 2 H,
CϵCCH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 138.8, 131.7,
129.0, 128.2, 127.8, 127.0, 123.4, 85.8, 84.4, 57.7, 42.1 ppm.
N-[1-(4-Methylphenyl)-3-phenyl-2-propynyl]piperidine:[36] 1H NMR
(300 MHz, CDCl3): δ = 7.52–7.48 (m, 4 H, ArH), 7.32–7.27 (m, 3
H, ArH), 7.10 (d, J = 8.1 Hz, 2 H, ArH), 4.75 (s, 1 H, CϵCCH),
2.57–2.53 (m, 2ϫ2 H, NCH2), 2.33 (s, 3 H), 1.62–1.51 (m, 2ϫ2 H,
NCH2CH2), 1.45–1.40 (m, 2 H, NCH2CH2CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 137.2, 135.8, 132.1, 129.0, 128.8, 128.5,
128.2, 123.7, 87.9, 86.7, 62.4, 51.0, 26.4, 24.8, 21.4 ppm.
N,N-Dicyclohexyl-3-phenylprop-2-ynylamine:[32]
1H
NMR
(300 MHz, CDCl3): δ = 7.39–7.37 (m, 2 H, ArH), 7.27–7.25 (m, 3
H, ArH), 3.69 (s, 2 H, CϵCCH2), 2.85–2.78 (m, 2ϫ1 H, NCH),
1.92–1.88 (m, 2ϫ2 H, NCHCH2), 1.80–1.76 (m, 2ϫ2 H,
N-[1-(4-Methoxyphenyl)-3-phenyl-2-propynyl]piperidine:[36]
1H
NCHCH2), 1.43–1.06 (m, 2ϫ6 H, NCHCH2CH2CH2CH2) ppm. NMR (300 MHz, CDCl3): δ = 7.55–7.48 (m, 4 H, ArH), 7.30–7.26
13C NMR (75 MHz, CDCl3): δ = 131.5, 128.2, 127.6, 124.0, 89.7, (m, 3 H, ArH), 6.90–6.85 (m, 2 H, ArH), 4.73 (s, 1 H, CϵCCH),
83.3, 57.6, 35.8, 31.4, 29.8, 27.0, 26.4 ppm.
3.74 (s, 3 H, OCH3), 2.56–2.53 (m, 2ϫ2 H, NCH2), 1.62–1.53 (m,
2ϫ2 H, NCH2CH2), 1.45–1.39 (m, 2 H, NCH2CH2CH2) ppm. 13
NMR (75 MHz, CDCl3): δ = 159.0, 131.8, 130.0, 129.1, 128.0,
C
N,N-Diisopropyl-3-phenylprop-2-ynylamine:[31]
1H
NMR
(300 MHz, CDCl3): δ = 7.41–7.38 (m, 2 H, ArH), 7.28–7.26 (m, 3
H, ArH), 3.66 (s, 2 H, CϵCCH2), 3.27 (sept, J = 7.2 Hz, 2ϫ1 H,
NCH), 1.16 (d, J = 6.6 Hz, 4ϫ3 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 131.2, 128.0, 127.4, 123.6, 88.9, 83.4, 48.6,
34.8, 20.6 ppm.
127.8, 123.1, 112.9, 87.9, 86.7, 61.8, 55.2, 50.4, 26.4, 24.5 ppm.
N-[1-(4-Chlorophenyl)-3-phenyl-2-propynyl]piperidine:[36] 1H NMR
(300 MHz, CDCl3): δ = 7.56 (d, J = 8.7 Hz, 2 H, ArH), 7.50–7.47
(m, 2 H, ArH), 7.32–7.27 (m, 5 H, ArH), 4.73 (s, 1 H, CϵCCH),
2.54–2.50 (m, 2ϫ2 H, NCH2), 1.59–1.53 (m, 2ϫ2 H, NCH2CH2),
1.43–1.39 (m, 2 H, NCH2CH2CH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 137.4, 133.4, 132.0, 130.1, 128.5, 128.3, 123.3, 88.4,
85.6, 62.0, 61.8, 50.8, 26.4, 24.5 ppm.
N-Cyclohexyl-3-phenylprop-2-ynylamine: 1H NMR (300 MHz,
CDCl3): δ = 7.44–7.41 (m, 2 H, ArH), 7.28–7.25 (m, 3 H, ArH),
3.46 (s, 2 H, CϵCCH2), 2.82–2.79 (m, 1 H, NCH), 2.56–2.52 (m,
2ϫ2 H, NCH2), 1.65–1.62 (m, 2ϫ2 H, NCH2CH2), 1.45–1.43 (m,
2 H, NCH2CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 131.6,
128.1, 127.8, 123.2, 85.0, 84.9, 53.3, 48.4, 25.8, 23.8 ppm. C15H19N
(213.32): calcd. C 84.46, H 8.98, N 6.57; found C 84.28, H 9.05, N
6.67.
N-[1-(3-Chlorophenyl)-3-phenyl-2-propynyl]piperidine:[36] 1H NMR
(300 MHz, CDCl3): δ = 7.69–7.65 (m, 1 H, ArH), 7.61–7.55 (m, 3
H, ArH), 7.40–7.34 (m, 3 H, ArH), 7.32–7.29 (m, 2 H, ArH), 4.73
(s, 1 H, CϵCCH), 2.68–2.58 (m, 2ϫ2 H, NCH2), 1.72–1.59 (m,
2ϫ2 H, NCH2CH2), 1.57–1.48 (m, 2 H, NCH2CH2CH2) ppm. 13
C
N-(1,3-Diphenyl-2-propynyl)aniline:[9d] 1H NMR (300 MHz,
CDCl3): δ = 7.70–7.65 (m, 2 H, ArH), 7.45–7.20 (m, 10 H, ArH),
6.85–6.79 (m, 3 H, ArH), 5.50 (s, 1 H, CϵCCH), 4.32 (s, 1 H, NH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 146.9, 139.9, 132.2, 129.5,
129.1, 128.6, 128.5, 128.2, 127.6, 123.1, 118.9, 114.5, 88.8, 85.4,
50.9 ppm.
NMR (75 MHz, CDCl3): δ = 140.9, 134.7, 132.1, 129.6, 128.7,
128.5, 128.2, 127.7, 126.3, 123.4, 88.6, 85.5, 62.1, 50.9, 26.4,
24.7 ppm.
N-[1-(2-Chlorophenyl)-3-phenyl-2-propynyl]piperidine:[37] 1H NMR
(300 MHz, CDCl3): δ = 7.84 (d, J = 7.5 Hz, 1 H, ArH), 7.59–7.56
(m, 2 H, ArH), 7.47–7.26 (m, 6 H, ArH), 5.19 (s, 1 H, CϵCCH),
2.71–2.68 (m, 2ϫ2 H, NCH2), 1.70–1.62 (m, 2ϫ2 H, NCH2CH2),
1.51–1.48 (m, 2 H, NCH2CH2CH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 136.5, 134.8, 131.9, 130.7, 129.9, 128.9, 128.4, 128.2,
126.3, 123.3, 87.8, 85.9, 59.4, 50.9, 26.3, 24.6 ppm.
N-[4-(1-Isopropyl-3-phenyl-2-propynyl)]piperidine:[33] 1H NMR
(300 MHz, CDCl3): δ = 7.44–7.40 (m, 2 H, ArH), 7.32–7.27 (m, 3
H, ArH), 2.99 (d, J = 9.9 Hz, 1 H, CϵCCH), 2.68–2.64 (m, 2 H,
NCH2), 2.44–2.40 (m,
CH3CHCH3), 1.64–1.43 (m, 6 H, NCH2CH2CH2CH2), 1.12 (d, J
6.6 Hz, H, CH3CHCH3), 1.03 (d, 6.6 Hz, H,
2 H, NCH2), 1.96–1.88 (m, 1 H,
=
3
J
=
3
N,N-Dibenzyl[3-(p-tolyl)prop-2-ynyl]amine:[29] 1H NMR (300 MHz,
CH3CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 131.9, 128.4, CDCl3): δ = 7.43–7.18 (m, 12 H, ArH), 7.10 (d, J = 7.8 Hz, 2 H,
127.8, 123.9, 87.9, 85.7, 65.7, 50.6, 30.6, 26.2, 24.7, 20.7, 19.9 ppm.
ArH), 3.72 (s, 2ϫ2 H, PhCH2), 3.46 (s, 2 H, CϵCCH2), 2.30 (s, 3
Eur. J. Org. Chem. 2008, 2255–2261
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2259

M. Wang, P. Li, L. Wang
FULL PAPER
H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 139.0, 138.0,
131.7, 129.1, 128.2, 127.0, 120.3, 86.1, 83.6, 57.7, 42.0, 21.5 ppm.
[8]
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N,N-Dibenzyl(undec-2-ynyl)amine:[29] 1H NMR (300 MHz, CDCl3):
δ = 7.41–7.21 (m, 10 H, ArH), 3.66 (s, 2ϫ2 H, PhCH2), 3.24 (s, 2
H, CϵCCH), 2.24 (t, J = 6.6 Hz, 2 H, CH2CϵCCH2N), 1.55–1.30
(m, 12 H, CH2CH2CH2CH2CH2CH2), 0.90 (t, J = 6.9 Hz, 3 H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 139.0, 128.7, 128.0,
126.9, 85.6, 74.4, 57.5, 41.5, 31.8, 29.3, 29.1, 28.9, 22.7, 18.7,
14.0 ppm.
[10]
N,N-Dibenzyl(non-2-ynyl)amine:[29] 1H NMR (300 MHz, CDCl3): δ
= 7.39–7.17 (m, 10 H, ArH), 3.64 (s, 2ϫ2 H, PhCH2), 3.26 (s, 2
H, CϵCCH2), 2.21 (t, J = 6.6 Hz, 2 H, CH2CϵCCH2N), 1.61–
1.34 (m, 8 H, CH2CH2CH2CH2), 0.92 (t, J = 6.6 Hz, 3 H, CH3)
ppm. 13C NMR (75 MHz, CDCl3): δ = 139.0, 129.1, 128.4, 126.8,
85.7, 74.4, 57.6, 41.4, 31.4, 29.1, 28.6, 22.6, 18.7, 14.2 ppm.
[11]
[12]
[13]
[14]
[15]
Ethyl 4-(Dibenzylamino)but-2-ynoate: Oil. 1H NMR (300 MHz,
CDCl3): δ = 7.84 (d, J = 12.9 Hz, 1 H, CϵCCH), 7.38–7.30 (m, 6
H, ArH), 7.20–7.18 (m, 4 H, ArH), 4.84 (d, J = 13.2 Hz, 1 H,
CϵCCH), 4.30 (s, 2ϫ2 H, PhCH2), 4.17 (q, J = 7.2 Hz, 2 H,
CH3CH2O), 1.28 (t, J = 7.2 Hz, 3 H, CH3CH2O) ppm. 13C NMR
(75 MHz, CDCl3): δ = 169.7, 152.6, 135.9, 128.7, 127.7, 127.4, 85.8,
58.9, 26.7, 14.6 ppm. C20H21NO2 (307.39): calcd. C 78.15, H 6.89,
N 4.56; found C 78.28, H 6.75, N 4.79. HRMS: calcd. for
C20H21NO2 307.1572; found 307.1567.
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Received: January 2, 2008
Published Online: March 11, 2008
Eur. J. Org. Chem. 2008, 2255–2261
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2261