Zinc(II)-Catalyzed Synthesis of Propargylamines by Coupling Aldimines and Ketimines with Alkynes

Article abstract of DOI:10.1002/ejoc.201701567

A Zn^II-catalyzed reaction between imines, which were derived from unactivated aldehydes or ketones and primary amines or α-amino acid esters, and terminal alkynes has led to the rapid and efficient formation of tri- and tetrasubstituted propargylamines (from aldimines and ketimines, respectively) in good to excellent yields. No additives or extra Lewis acid reagents were required for the imine-alkyne coupling reaction.

Full text of DOI:10.1002/ejoc.201701567

A Journal of
Accepted Article
Title: Zinc(II)-catalyzed synthesis of propargyl amines by coupling of
aldimines and ketimines with alkynes
Authors: Syeda Aaliya Shehzadi, Aamer Saeed, Filip Lemière, Bert U.
W. Maes, and Kourosch Abbaspour Tehrani
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701567
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701567
Supported by

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
Zinc(II)-catalyzed synthesis of propargyl amines by coupling of
aldimines and ketimines with alkynes
Syeda Aaliya Shehzadi,[a] Aamer Saeed,[b] Filip Lemière,[c] Bert U. W. Maes,[a] and
Kourosch Abbaspour Tehrani*[a]
Dedication ((optional))
Abstract:
A
Zn(II) triflate-promoted reaction of aldimines or
circumvent this unreactivity in alkyne coupling reactions, some
approaches, eventually enantioselective, make use of more
reactive, ketiminium species by using secondary amines.[10, 12-13]
Lewis acid activation of a N-thiophosphinoyl ketimine by Cu(I)[14]
or Lewis acid activation of in situ generated imines by a
Ti(OEt)4/CuCl2 couple also have been used (Scheme 1).[13,15]
The introduction of electron withdrawing N-substituents such as
thiophosphinoyl[14] and p-toluenesulfonyl[11] groups also enhance
the reactivity of the corresponding ketimines towards catalytic
alkyne addition.
ketimines, derived from unactivated aldehydes or ketones and
primary amines or α-amino acid esters, with terminal alkynes,
leading to a rapid and efficient formation of tri- (from aldimines) and
tetra- (from ketimines) substituted propargyl amines in good to
excellent yields has been described. No additives or extra Lewis acid
reagents are required for the ketimine-alkyne coupling.
Introduction
The synthesis of tri- and tetra- substituted propargyl amines has
been widely investigated not only due to their intrinsic biological
and pharmacological activities[1-4] but also due to their utility as
chemical building blocks, in particular for the synthesis of
nitrogen containing compounds such as allylamines, pyrrolidines,
oxazoles and pyrroles.[5]
The most straightforward approach to synthesize propargyl
amines is the condensation of Alkynes, Amines and Aldehydes
(A3) under catalytic conditions.[6] Other traditional methods
involve the amination of propargylic triflates, propargylic
phosphates, propargylic esters, oxyphosphonium salts and
propargylic halides.[7] Still, convenient and more efficient
methods to construct propargylic amines by direct coupling
reactions, including acyclic aliphatic amines and alkynes, are
extremely attractive. By extension, tetra-substituted propargyl
amines can be derived from ketones, amines and alkynes under
similar conditions as developed for aldehydes. Due to the lower
reactivity of ketones (750 times less reactive then aldehydes)[8]
the three-component coupling of Ketones, Amines and Alkynes
(KA2) has still been largely underdeveloped. Some special
classes of more reactive ketones, like cyclohexanones can react
under A3-conditions and can be converted into the
corresponding tetra-substituted propargyl amine.[9-11]
Ketimines are in general less reactive towards nucleophilic
additions than aldimines owing to steric hindrance in the C-C
bond-forming step, as well due to electronic effects. In order to
[a]
S. A. Shehzadi, B. U. W. Maes, K. Abbaspour Tehrani*
Organic Synthesis, Department of Chemistry, University of
Antwerp, Groenenborgerlaan 171, B-2020, Antwerp, Belgium
E-mail: kourosch.abbaspourtehrani@uantwerpen.be
https://www.uantwerpen.be/en/rg/orsy/
Scheme 1. Previous approaches for tetra-substituted propargyl amines.
[b]
[c]
A. Saeed
An alternative approach to tetrasubstituted propargyl amines
involves Cu(OTf)2[16a,b] or Zn(II)[16c] catalysed hydroamination of
Department of Chemistry, Quaid-I-Azam University, Islamabad
45320 Pakistan
F. Lemière
Biomolecular & Analytical Mass Spectrometry and Center for
Proteomics, Department of Chemistry, University of Antwerp, B-
2020 Antwerp, Belgium
alkynes, leading to
a ketiminium species, which finally
undergoes alkynylation.[17] Recently, advances were made in
the synthesis of propargyl amines using heterogeneous
catalysts such as SiO2@Cu monodispersed Cu-nanoparticles,[18]
Supporting information for this article is given via a link at the end
of the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
5
ZnI2 (25)
100/24
100/24
100/24
50/24
PhMe
43
Cu(I)-N2S2-salen type complex covalently anchored onto MCM-
41 silica, bis[2-(phenylthio)benzylidene]-1,2-ethylenediamine
copper(I) complexes, [Cu(N2S2)]X-Y (X = CN, Cl, Br, I),[19]
mesoporous two-dimensional copper silicate catalyst (CuSBA-
15)[20] and CuFe2O4 nanoparticles.[21] The majority of these
methods are limited to aromatic aldehydes and cyclic amines.
Between this variety of metal acetylides, Cu-acetylide and Zn-
acetylide are more nucleophilic.[22] Zinc acetylides have been
found to be even more reactive then their Cu counterparts when
reacted with nitrones as already investigated by Carreira.[23]
Zinc triflate also has been applied in some special cases like for
the addition of cyclopropylacetylene to reactive cyclic
trifluoromethylated N-acyl imines.[24] Keeping in mind the lower
reactivity of ketimines as compared to aldimines there is hence
the need to increase the nucleophilicity of the attacking alkyne
nucleophile. So far, to the best of our knowledge, no example of
a Zn-catalyzed alkynylation of N-alkyl aldimines and ketimines
has been reported. Therefore, important challenges remain and
room for improvement exists. In the present study we focused
on the reaction between N-alkyl aldimines and ketimines with
alkynes in the presence of catalytic amounts of zinc salts.
6
Zn(OAc)2 (25)
In(OTf)3 (25)
In(OTf)3 (50)
Zn(OTf)2 (50)
Zn(OTf)2 (50)
Zn(OTf)2 (10)
CuBr2 (10) [c]
CuCl2 (10) [c]
CuI2 (10) [c]
PhMe
PhMe
CH2Cl2
PhMe
CH2Cl2
PhMe
PhMe
PhMe
PhMe
PhMe
NR[d]
77[ f]
64
7
8
9
100/24
50/24
96
10
11
12
13
14
15
88
100/16
100/24
100/24
100/10
100/24
96
92
88
89
72[e]
Cu(OTf)2 (10)
[a] All reactions were carried out with 0.5 mmol of imine in 2 mL of
solvent. [b] Isolated yields. [c] Under argon. [d] NR = no reaction. [e] Also
diphenyl-1,3-butadiyne was formed. [ f] 2 equiv of 2a was used.
Since In(OTf)3 in CH2Cl2 was identified previously by our group
as a good catalyst for alkyne coupling of α,α-dichloroaldimines[26]
imine 1a was also reacted with phenylacetylene and 25 mol-%
of In(OTf)3 in toluene (Table 1, entry 7). Interestingly this
electron rich aldimine gave rise to an isolated yield of 77% of the
corresponding propargyl amine. In almost all cases toluene gave
superior yields compared to CH2Cl2. By increasing the Zn(OTf)2
catalyst amount until 50 mol-% and the reaction time to 24 h at
100 °C, 96% yield of product 3aa was obtained (Table 1, entry
9). By decreasing the Zn(OTf)2 catalyst to 10 mol-% and using
toluene as solvent at 100 °C, no appreciable decrease in yield
was noticed (Table 1, entry 11). Below 10 mol-% of Zn(OTf)2 the
product yield dropped dramatically (see Table S1). By replacing
the air by argon, as required when using copper catalysts (Table
1, entries 12-15), no significant improvement in the yield of 3aa
was observed. In view of the results in Table 1 an optimum yield
of 96% of 3aa was obtained when aldimine 1a was reacted with
2a in the presence of 10 mol-% Zn(OTf)2 as catalyst and toluene
as solvent at 100 °C for 16 h in a sealed vial. These conditions
were applied for further reactions.
With these optimized conditions in hand, the scope of the
reaction was explored using a broad range of imines, prepared
by condensing aldehydes and primary amines in the presence of
anhydrous magnesium sulfate as a drying agent. The imines
derived from pivaldehyde, the enolisable isobutyraldehyde and
butyraldehyde (Scheme 2, 3ba-3da) were well tolerated under
the developed conditions. In case of benzaldimine some
undefined side reactions were observed at 100 °C, while by
lowering the temperature to 50 °C for 16 h, starting material was
still present. By increasing the reaction temperature to 70 °C for
24 h, using 1.5 equiv of phenylacetylene with 15 mol-% of
Zn(OTf)2 catalyst, the desired 1,3-diphenyl-N-propylprop-2-yn-1-
amine (3ea) was obtained in 70% yield.
,
Results and Discussion
As a starting point, the sterically hindered pivaldehyde, n-
propylamine (an aliphatic primary amine) and phenylacetylene
were reacted under one pot conditions in the presence of 10
mol-% of Zn(OTf)2 and molecular sieves in toluene. Besides
10% conversion to the desired propargyl amine 3aa, also traces
of aldimine 1a and propargylic alcohol, which has been reported
by aldehyde-alkyne coupling in the presence of stoechiometric
[25]
1
Zn(OTf)2 were observed in the H NMR. Problably the Zn salt
is acting here as a Lewis acid catalysing the imine formation,
hence rendering it unavailable for acetylide generation. Forced
by this result further studies were continued using the preformed
imine of pivaldehyde namely, 2,2-dimethyl-N-propylpropan-1-
imine (1a). The reaction of 1a with 1 equiv of phenylacetylene 2a
in the presence of 25 mol-% of Zn(OTf)2 delivered the propargyl
amine 3aa in 72% yield (Table 1, entry 1). Other zinc salts, like
ZnCl2, ZnBr2, ZnI2 and Zn(OAc)2 as catalyst all proved less active
than Zn(OTf)2 (Table 1, entries 2-6).
Table 1. Optimization of catalyst and reaction conditions for aldimine-
alkyne coupling.
Further, it was observed that a number of nitrogen substituents
on the imine, including propyl, allyl, n-pentyl, iso-amyl, benzyl
and methoxy substituted benzylamines as well as more sterically
hindered groups like iso-propyl, cyclohexyl, tert-butyl and
alkoxycarbonylmethyl all gave excellent yields of the secondary
propargyl amines 3 (Scheme 2, 3fa-3pa).
Yield of
Entry[a]
Catalyst (mol-%)
T/t (°C/h)
Solvent
3[b] (%)
1
2
3
4
Zn(OTf)2 (25)
ZnCl2 (25)
ZnCl2 (50)
ZnBr2 (25)
100/10
100/24
50/24
PhMe
PhMe
CH2Cl2
PhMe
72
78
55[f]
100/24
51
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
Scheme 2. Scope of the evaluated A3 reaction: variation of the aldehyde and
[a]
[b]
amine component.
Yield after basic work up.
Yield after column
chromatography on silica gel. [c] 15 mol-% Zn(OTf)2, 1.5 equiv phenylacetylene,
70 °C, 24 h.
Scheme 3. Scope of the evaluated A3 reaction: variation of the alkyne
component. [a] Yield after basic work up. [b] Yield after column chromatography.
While exploring the substrate scope of alkyne substituents, it
was revealed that both aryl and alkyl acetylenes could be used.
Aromatic alkynes with a variety of electron-withdrawing and
electron-donating substituents were successfully coupled with
pivaldimines (Scheme 3). A wide variety of aliphatic alkynes with
functional groups, like tertiary amines, acetal, ester, halide or
even a hetarene in the alkyne moiety were tolerated. Only the
reaction of 3- and 4-aminophenylacetylene furnished complex
mixtures, while 2-aminophenylacetylene gave propargylamine
3al in 56% yield together with 26% of an intramolecular
hydroamination-oxidation side product 3al'[27] (Scheme 3).
Encouraged by the generality of these results, we turned our
efforts towards the more challenging coupling of alkynes with
ketimines. As a preliminary experiment, butanone, butylamine
and phenylacetylene were reacted in the presence of 50 mol-%
Ti(OEt4) and 5 mol % CuCl2 in toluene at 110 °C for 24 h,
according to the recent literature.[15] Since no reaction was
observed, the catalytic system was changed to 15 mol-%
Zn(OTf)2, which besides some traces of imine and some traces
of the corresponding tertiairy propargylic alcohol[28] afforded no
product at all. When benzyl amine was reacted with butanone
and phenylacetylene in 20 mol-% Zn(OTf)2 in the presence of 4Å
MS or Ti(OiPr)4 as drying agent, we were gratified to observe
15-20% conversion to the corresponding propargylic amine.
Since imine formation is crucial in this conversion, further
optimization was focused on using the ketimines. Ketimines
were prepared from ketones and the appropriate primary amine
using either activated molecular sieves,[29] concd HCl[30] or
Ti(OiPr)4 [31] as water scavengers.
In a first attempt, N-propylcyclohexanimine (4a) was reacted
under the conditions for aldimine coupling. Interestingly, this
conversion went smoothly and furnished the corresponding
tetrasubstituted propargylamine 5aa in 90% yield (Scheme 4).
Next, the generality of this method was verified by reacting the
less reactive N-propylbutan-2-imine (4b) with 2a and 10 mol-%
of Zn(OTf)2 as a catalyst. Because of the rather low yield of
tetrasubstituted propargyl amine 5ba (51%), (Scheme 4) more
catalyst (15 mol-%) and a longer reaction time (24 h) was
applied, leading to a 90% yield of 5ba. The addition of more
Zn(OTf)2 or an extra equivalent of alkyne had no noticeable
effect on the yield. Finally, the application of 15 mol-% catalyst in
toluene at 100 °C for 24 h was selected as the standard
condition for the coupling of alkynes with ketimines (4a-o)
(Scheme 5).
Scheme 4. Cyclic and acyclic ketimine-alkyne coupling.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
The substrate scope was then explored, especially focusing on
enolizable ketones and primary acyclic amines, those classes
being the more difficult and less explored coupling partners. A
number of ketones with different chain lengths and
functionalized alkynes reacted very well under the developed
conditions to deliver propargyl amines with α-amino tertiary
carbon in good yields (Scheme 4, 5aa-5ja). Imines derived from
hetarene containing ketones like phenyl(pyridin-2-yl)-methanone
(4q)[32] and phenyl(pyridin-4-yl)methanone (4r)[32] did not react
with phenylacetylene, even not when adding 0.5 equiv of
Zn(OTf)2.
limited to cyclohexanone and acetone using 20 mol-% of CuBr
to deliver trisubstituted propargylamines in moderate to low
yield.[33] Since α-amino ester side chains are present in various
important drugs and allow to functionalize peptide chains with a
range of different functional groups,[34] several ketimines (4k-o)
derived from natural α-amino acids such as L-valine methyl ester,
L-alanine methyl ester and L-lysine methyl ester were prepared
(see SI). The reaction of these functionalized ketimines with
various alkynes in the presence of 15 mol-% of Zn(OTf)2 all
proved feasible, leading to diastereomeric mixtures of secondary
propargylic amines bearing a α-tetrasubstituted carbon center
(Scheme 5, 5ka-5oo).
Conclusions
In conclusion, a convenient and operationally simple Zn(II)-
catalyzed synthesis of secondary propargyl amines, bearing tri-
and tetrasubstituted -carbons starting from imines and alkynes
is demonstrated. A broad range of functional groups (aliphatic
and aromatic halides, amines, ester, acetal, MeO, CF3, alkyl)
were well tolerated on the alkyne moiety. Also enolizable and
sterically hindered aldimines, enolizable acyclic and cyclic
ketimines and ketimines derived from α-amino esters, which
traditionally are very difficult reaction partners, were coupled in
good to excellent yields.
Experimental Section
General experimental procedure for the aldimine-alkyne coupling
In an oven dried 10 mL vial containing 1 mL of toluene and a stirring bar,
the aldimines 1a-p (0.5 mmol), the acetylene (0.5 mmol, 1 equiv) and
Zn(OTf)2 (0.018 g, 0.05 mmol) were added successively and the vial was
sealed under air. The reaction mixture was stirred at 100ºC for 16 h.
Afterwards the reaction mixture was diluted with CH2Cl2 (10 mL) washed
and extracted with 0.5 N NaOH (10 mL). The organic phase was dried
over MgSO4 and the solvent was evaporated under reduced pressure to
get pure product. In almost all cases pure products were obtained unless
otherwise stated.
4,4-Dimethyl-1-phenyl-N-propylpent-1-yn-3-amine (3aa): 1H NMR
(400 MHz, CDCl3): δ = 7.43 - 7.40 (m, 2H, CHarom, ortho), 7.28 - 7.26 (m,
3H, CHarom, meta and CHarom, para), 3.15 (s, 1H, CH), 2.96 - 2.90 (m, 1H,
NC(H)H), 2.62 - 2.55 (m, 1H, NC(H)H), 1.59 - 1.45 (m, 2H, NCH2CH2),
1.05 (s, 9H, C(CH3)3), 0.95 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible
ppm. 13C NMR (100 MHz, CDCl3): δ = 131.6 (Carom, ortho), 128.2 (Carom,
meta), 127.7 (Carom, para), 123.8 (Carom, quat), 91.0 and 84.1 (CC), 61.1
(NCH), 50.8 (NCH2), 35.1 (C(CH3)3), 26.6 (C(CH3)3), 23.2 (CH2CH3), 11.8
(CH2CH3) ppm. HRMS (ESI) m/z calculated for [C16H23N+H]+: 230.1903;
found 230.1899.
4-Methyl-1-phenyl-N-propylpent-1-yn-3-amine (3ba): 1H NMR (400
MHz, CDCl3): δ = 7.43 – 7.41 (m, 2H, aromatic), 7.30 – 7.26 (m, 3H,
aromatic), 3.40 (d, J = 5.3 Hz, 1H, NCH), 2.91 – 2.85 (m, 1H, NC(H)H),
2.65 – 2.59 (m, 1H, NC(H)H), 1.98 - 1.90 (m, 1H, (CH3)2CH), 1.59 – 1.49
(m, 2H, NCH2CH2), 1.06 and 1.05 (2 × d, J = 6.7 Hz, 2 x 3H, CH(CH3)2),
0.95 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz,
CDCl3): δ = 131.7, 128.2, 127.8, 123.7, 90.1, 84.3, 57.1, 50.0, 32.9, 23.3,
Scheme 5. Zn(OTf)2-catalyzed reaction between ketimines and alkynes. All
reactions were carried out at 0.5 mmol scale of ketimine 4 in a sealed vial for
[a]
[b]
24 h.
Yields after basic workup.
Yields after column chromatography on
silica gel. [c] dr not determined.
Very few examples of coupling reactions of α-amino ester with
ketones and alkynes have been reported. The existing method is
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
19.9, 17.9, 11.9 ppm. HRMS (ESI) m/z calculated for [C15H21N+H]+:
29.6, 26.6, 22.7, 14.1 ppm. HRMS (ESI) m/z calculated for [C18H27N+H]+:
216.1747; found 216.1743.
258.2216; found 258.2221.
1-(4-Ethylphenyl)-4-methyl-N-propylpent-1-yn-3-amine
(3bd):
1H
N-Isopentyl-4,4-dimethyl-1-phenylpent-1-yn-3-amine (3ha): 1H NMR
(400 MHz, CDCl3): δ = 7.42 – 7.39 (m, 2H, aromatic), 7.26 – 7.25 (m, 3H,
aromatic), 3.14 (s, 1H, NCH), 3.00 (ddd, J = 11.3, 8.6, 6.2 Hz, 1H,
NC(H)H), 2.68 (ddd, J = 11.3, 8.6, 6.2 Hz, 1H, NC(H)H), 1.73 – 1.63 (m,
1H, CH(CH3)2), 1.41 – 1.36 (m, 2H, NCH2CH2), 1.05 (s, 9H, C(CH3)3),
0.92 (d, J = 6.7 Hz, 6H, CH(CH3)2), NH not visible ppm. 13C NMR (100
MHz, CDCl3): δ = 131.6, 128.2, 127.6, 123.9, 90.9, 84.2, 61.3, 47.0, 39.2,
35.1, 26.6, 26.2, 22.8, 22.6 ppm. HRMS (ESI) m/z calculated for
[C18H27N+H]+: 258.2216; found 258.2212.
NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 8.1 Hz, 2H, aromatic), 7.12 (d, J
= 8.1 Hz, 2H, aromatic), 3.39 (d, J = 5.3 Hz, 1H, NCH), 2.89 – 2.84 (m,
1H, NC(H)H)), 2.63 (q, J = 7.6 Hz, 2H CH3CH2Ph), 2.66 – 2.58 (m, 1H,
overlapped signal, NC(H)H)), 1.95 - 1.90 (m, 1H, (CH3)2CH), 1.60 – 1.48
(m, 2H, NCH2CH2), 1.22 (t, J = 7.6 Hz, 3H, CH3CH2Ph), 1.05 and 1.04 (2
× d, J = 6.7 Hz, 2 × 3H, CH(CH3)2), 0.95 (t, J = 7.4 Hz, 3H,
NCH2CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ =
144.2, 131.7, 127.8, 120.8, 89.2, 84.4, 57.1, 50.0, 32.9, 28.8, 23.2, 19.9,
17.8, 15.4, 11.9 ppm. HRMS (ESI) m/z calculated for [C17H25N+H]+:
244.2060; found 244.2055.
1
N-Benzyl-4,4-dimethyl-1-phenylpent-1-yn-3-amine (3ia): H NMR (400
MHz, CDCl3): δ = 7.45 – 7.40 (m, 4H, aromatic), 7.34 – 7.23 (m, 6H,
aromatic), 4.15 (d, J = 13.3 Hz, 1H, NC(H)H), 3.87 (d, J = 13.3 Hz, 1H
NC(H)H), 3.16 (s, 1H, NCH), 1.33 (broad s, 1H, NH), 1.06 (s, 9H,
C(CH3)3) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.6, 131.7, 128.4,
128.3, 128.3, 127.8, 126.9, 123.8, 90.4, 84.5, 60.2, 52.4, 35.1, 26.6 ppm.
HRMS (ESI) m/z calculated for [C20H23N+H]+: 278.1903; found 278.1909.
N-Allyl-1-(4-ethylphenyl)-4-methylpent-1-yn-3-amine (3cd): 1H NMR
(400 MHz, CDCl3): δ = 7.34 (d, J = 8.0 Hz, 2H, aromatic), 7.12 (d, J = 8.0
Hz, 2H, aromatic), 5.94 (ddt, J = 16.4, 10.3, 6.0 Hz, 1H, CH CH2), 5.24
(dd, J = 17.2, 1.4 Hz, 1H, CH C(H)H), 5.11 (d, J = 10.2 Hz, 1H, CH
C(H)H), 3.55 (dd, J = 13.8, 5.7 Hz, 1H, NC(H)H), 3.42 (d, J = 5.3 Hz, 1H,
NCH ), 3.33 (dd, J = 13.8, 6.4 Hz, 1H, N-C(H)H), 2.63 (q, J = 7.6 Hz, 2H,
CH2CH3), 1.96 – 1.89 (m, 1H, (CH3)2CH)), 1.22 (t, J = 7.6 Hz, 3H,
CH2CH3), 1.06 and 1.05 (2 × d, J = 6.7 Hz, 2 × 3H, (CH3)2CH), NH not
visible ppm. 13C NMR (100 MHz, CDCl3): δ = 144.2, 136.8, 131.7, 127.8,
120.8, 116.1, 88.8, 84.7, 56.4, 50.5, 33.0, 28.8, 19.9, 17.9, 15.4 ppm.
HRMS (ESI) m/z calculated for [C17H23N+H]+: 242.1903; found 242.1900.
1
4,4-Dimethyl-N-(4-methylbenzyl)-1-phenylpent-1-yn-3-amine (3ja): H
NMR (400 MHz, CDCl3): δ = 7.45 – 7.41 (m, 2H, Ph), 7.28 (m, 3H + 2H,
Ph and p-MePh), 7.12 (d, J = 7.8 Hz, 2H,), 4.10 (d, J = 13.1 Hz, 1H,
NC(H)H), 3.82 (d, J = 13.1 Hz, 1H, NC(H)H), 3.15 (s, 1H, NCH), 2.32 (s,
3H, PhCH3), 1.29 (br s, 1H, NH), 1.05 (s, 9H, C(CH3)3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 137.5, 136.4, 131.6, 128.9, 128.3, 128.2, 127.7,
123.8, 90.5, 84.5, 60.1, 52.1, 35.1, 26.6, 21.1 ppm. HRMS (ESI) m/z
calculated for [C20H23N+H]+: 292.2060; found 292.2054.
1
1-Phenyl-N-propylhex-1-yn-3-amine (3da): H NMR (400 MHz, CDCl3):
δ = 7.42 – 7.40 (m, 2H, aromatic), 7.28 – 7.26 (m, 3H, aromatic), 3.58 (dd,
J = 5.9, 7.7 Hz, 1H, NCH), 2.88 (ddd, J = 11.2, 8.3, 6.5 Hz, 1H, NC(H)H),
2.63 (ddd, J = 11.2, 8.4, 6.0 Hz, 1H, NC(H)H), 1.70 – 1.64 (m, 2H), 1.57
– 1.50 (m, 4H), 1.26 (br s, 1H, NH), 0.97 (t, J = 7.2 Hz, 3H, CH3), 0.95 (t,
J = 7.4 Hz, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 131.7, 128.2,
127.8, 123.6, 91.5, 83.5, 50.6, 49.6, 38.4, 23.3, 19.5, 13.9, 11.9 ppm.
HRMS (ESI) m/z calculated for [C15H21N+H]+: 216.1747; found 216.1750.
N-(2,4-Dimethoxybenzyl)-4,4-dimethyl-1-phenylpent-1-yn-3-amine
(3ka): 1H NMR (400 MHz, CDCl3): δ = 7.43 – 7.41 (m, 2H, aromatic),
7.26 – 7.23 (m, 4H, aromatic) 6.44 – 6.42 (m, 2H, aromatic), 4.10 (d, J =
13.4 Hz, 1H, NC(H)H), 3.78 (d, J = 13.4 Hz, 1H, NC(H)H), 3.78 and 3.77
(2 × s, 2 × 3H, 2 × OCH3), 3.15 (s, 1H, NCH), 1.64 (broad s, 1H, NH),
1.04 (s, 9H, C(CH3)3) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.0, 158.8,
131.6, 130.5, 128.2, 127.6, 124.0, 121.0, 103.8, 98.6, 90.6, 84.3, 60.3,
55.3 (2 carbon), 47.7, 35.0, 26.6 ppm. HRMS (ESI) m/z calculated for
[C22H27NO2+H]+: 338.2115; found 338.2114.
1,3-Diphenyl-N-propylprop-2-yn-1-amine (3ea): 1H NMR (400 MHz,
CDCl3): δ = 7.59 – 7.57 (m, 2H, aromatic), 7.47 – 7.44 (m, 2H, aromatic),
7.37 – 7.33 (m, 3H, aromatic), 7.29 – 7.25 (m, 3H, aromatic), 4.79 (s, 1H,
NCH), 2.80 (ddd, J = 11.2, 7.7, 7.2 Hz, 1H, NC(H)H), 2.68 (ddd, J = 11.2,
7.8, 6.5 Hz, 1H, NC(H)H), 1.58 – 1.51 (m, 2H, NCH2CH2), 0.93 (t, J = 7.4
Hz, 3H, CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 140.7,
131.7, 128.5, 128.2, 128.1, 127.7, 127.6, 123.2, 89.7, 85.3, 54.7, 49.3,
23.2, 11.9 ppm. HRMS (ESI) m/z calculated for [C18H19N+H]+: 250.1590;
found 250.1586.
N-(2,5-Dimethoxybenzyl)-4,4-dimethyl-1-phenylpent-1-yn-3-amine
(3la): 1H NMR (400 MHz, CDCl3): δ = 7.44 – 7.41 (m, 2H, Ph), 7.28 –
7.24 (m, 3H, Ph), 7.01 (d, J = 2.8 Hz, 1H, diOMePh), 6.76 (d, J = 8.8 Hz,
1H, diOMePh), 6.72 (dd J = 8.8, 2.8 Hz, 1H, diOMePh), 4.14 (d, J = 13.9
Hz, 1H, NC(H)H), 3.84 (d, J = 13.9 Hz, 1H, NC(H)H), 3.76 (s, 3H, OCH3),
3.74 (s, 3H, OCH3), 3.18 (s, 1H, NCH), 1.70 (broad s, 1H, NH), 1.06 (s,
9H, C(CH3)3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.6, 152.0, 131.6,
129.9, 128.2, 127.7, 123.9, 116.0, 112.1, 111.4, 90.4, 84.5, 60.5, 56.0,
55.6, 47.9, 35.1, 26.6 ppm. HRMS (ESI) m/z calculated for
[C22H27NO2+H]+: 338.2115; found 338.2107.
N-Allyl-4,4-dimethyl-1-phenylpent-1-yn-3-amine (3fa): 1H NMR (400
MHz, CDCl3): δ = 7.43 - 7.40 (m, 2H, aromatic), 7.28 - 7.26 (m, 3H,
aromatic), 5.93 (m, 1H, HC=CH2), 5.25 (ddd, J = 17.2, 3.3, 1.5 Hz, 1H,
HC=C(H)H ), 5.10 (ddd, J = 10.2, 3.0, 1.5 Hz, 1H, HC=C(H)H), 3.59 (ddt,
J = 14.0, 5.4, 1.5 Hz, 1H, NC(H)H), 3.31 (ddt, J = 14.0, 6.5, 1.2 Hz, 1H,
NC(H)H), 3.19 (s, 1H, NCH), 1.15 (br s, 1H, NH), 1.06 (s, 9H, C(CH3)3)
ppm. 13C NMR (100 MHz, CDCl3): δ = 137.1, 131.7, 131.6, 128.2, 127.7,
123.7, 116.0, 90.4, 84.5, 60.3, 51.1, 35.0, 26.6 ppm. HRMS (ESI) m/z
calculated for [C16H21N+H]+: 228.1747; found 228.1746.
N-(4,4-Dimethyl-1-phenylpent-1-yn-3-yl)cyclohexanamine (3ma) : 1H
NMR (400 MHz, CDCl3): δ = 7.41 - 7.39 (m, 2H, aromatic), 7.28 - 7.26 (m,
3H, aromatic), 3.23 (s, 1H, CCCH), 2.75 (tt, J = 9.8, 3.7 Hz, 1H, CH-Cy),
1.77 – 1.58 (m, 6H, Cy), 1.35 – 1.18 (m, 4H, Cy), 1.04 (s, 9H, C(CH3)3),
NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 131.6, 128.2, 127.6,
124.0, 91.6, 83.5, 57.9, 55.0, 35.0, 34.7, 32.5, 26.6, 26.3, 25.1, 24.6 ppm.
HRMS (ESI) m/z calculated for [C19H27N+H]+: 270.2216; found 270.2235.
4,4-Dimethyl-N-pentyl-1-phenylpent-1-yn-3-amine (3ga): 1H NMR
(400 MHz, CDCl3): δ = 7.42 - 7.40 (m, 2H, aromatic), 7.29 - 7.25 (m, 3H,
aromatic), 3.15 (s, 1H, NCH), 2.96 (ddd, J = 11.3, 8.2, 6.4 Hz, 1H,
NC(H)H), 2.60 (ddd, J = 11.3, 8.2, 6.0 Hz, 1H, NCHH), 1.58 – 1.44 (m,
2H, NCH2CH2), 1.35 – 1.33 (m, 4H, CH2CH2CH3), 1.05 (s, 9H, C(CH3)3),
0.90 (t, J = 7.0 Hz, 3H, CH3), NH not visible ppm. 13C NMR (100 MHz,
CDCl3): δ = 131.6, 128.2, 127.7, 123.9, 90.9, 84.1, 61.2, 48.9, 35.1, 29.8,
N-Isopropyl-4,4-dimethyl-1-phenylpent-1-yn-3-amine (3na): 1H NMR
(400 MHz, CDCl3): δ = 7.42 – 7.39 (m, 2H, aromatic), 7.28 – 7.26 (m, 3H,
aromatic), 3.19 (s, 1H, CCCH), 3.13 (septet, J = 6.20 Hz, 1H, CH(CH3)2),
1.12 (d, J = 6.3 Hz, 3H, CH(CH3)CH3), 1.04 (s, 9H, C(CH3)3), 1.01 (d, J =
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
6.1 Hz, 3H, CH(CH3)CH3), NH not visible ppm. 13C NMR (100 MHz,
CDCl3): δ = 131.6, 128.2, 127.6, 123.9, 91.3, 83.7, 58.4, 46.9, 34.9, 26.6,
24.4, 21.8 ppm. HRMS (ESI) m/z calculated for [C16H23N+H]+: 230.1903;
found 230.1904.
50.8, 35.2, 26.7, 23.2, 11.9 ppm. HRMS (ESI) m/z calculated for
[C20H25N+H]+: 280.2060; found 280.2066.
1-(2-Methoxyphenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine (3af):
1H NMR (400 MHz, CDCl3): δ = 7.37 (dd, J = 7.4 Hz, 1.5 Hz, 1H,
aromatic), 7.22 (dt, J = 8.0 Hz, 1.6 Hz, 1H, aromatic), 6.88 – 6.82 (m, 2H,
aromatic), 3.83 (s, 3H, OCH3), 3.19 (s, 1H, CCCH), 2.97 (ddd, J = 11.3,
8.1, 6.5 Hz, 1H, NC(H)H), 2.61 (ddd, J = 11.3, 8.2, 6.0 Hz, 1H, NC(H)H),
1.61 – 1.45 (m, 2H, NCH2CH2CH3), 1.07 (s, 9H, C(CH3)3), 0.95 (t, J = 7.4
Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ =
160.2, 133.3, 129.0, 120.3, 113.2, 110.8, 95.2, 80.2, 61.3, 55.7, 50.7,
35.1, 26.6, 23.2, 11.9 ppm. HRMS (ESI) m/z calculated for
[C17H25NO+H]+: 260.2009; found 260.2004.
1
N-(tert-Butyl)-4,4-dimethyl-1-phenylpent-1-yn-3-amine (3oa): H NMR
(400 MHz, CDCl3): δ = 7.38 – 7.36 (m, 2H, aromatic), 7.27 – 7.24 (m, 3H,
aromatic), 3.13 (s, 1H, CCCH), 1.16 (s, 9H, C(CH3)3), 1.02 (s, 9H,
C(CH3)3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 131.1,
128.0, 127.3, 124.0, 94.0, 83.0, 54.0, 50.7, 35.3, 29.8, 26.2 ppm. HRMS
(ESI) m/z calculated for [C17H25N+H]+: 244.2060; found 244.2071.
Ethyl (4,4-dimethyl-1-phenylpent-1-yn-3-yl)glycinate (3pa): 1H NMR
(400 MHz, CDCl3): δ = 7.34 – 7.31 (m, 2H, aromatic), 7.20 – 7.18 (m, 3H,
aromatic), 4.09 (q, J = 7.1 Hz, 2H, OCH2CH3), 3.59 (d, J = 17.2 Hz, 1H,
NCHHCO2), 3.48 (d, J = 17.2 Hz, 1H, NCHHCO2), 3.23 (s, 1H,
CH(CH3)3), 1.70 (br s, 1H, NH), 1.17 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.01
(s, 9H, CH(CH3)3) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.4 (C=O),
130.6, 127.2, 126.9, 122.4, 88.0 (CC), 84.1 (CC), 59.8, 59.6, 48.6,
34.1, 25.5, 13.2 ppm. HRMS (ESI) m/z calculated for [C17H23NO2+H]+:
274.1802; found 274.1815.
1-(3-Methoxyphenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine (3ag):
1H NMR (400 MHz, CDCl3): δ = 7.18 (t, J = 7.9 Hz, 1H, aromatic), 7.01 (d,
J = 7.6 Hz, 1H, aromatic), 6.94 (t, J = 2.3 Hz, 1H, aromatic), 6.82 (dd, J =
8.3 Hz, 2.6 Hz, 1H, aromatic), 3.77 (s, 3H, OCH3), 3.14 (s, 1H, CCCH),
2.93 (ddd, J = 11.3, 7.9, 6.6 Hz, 1H, NC(H)H), 2.58 (ddd, J = 11.3, 8.0,
6.1 Hz, 1H, NC(H)H), 1.60 – 1.45 (m, 2H, NCH2CH2CH3), 1.05 (s, 9H,
C(CH3)3), 0.95 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.4, 129.2, 124.9, 124.2, 116.7, 114.1, 90.8,
84.0, 61.1, 55.2, 50.8, 35.1, 26.6, 23.2, 11.9 ppm. HRMS (ESI) m/z
calculated for [C17H25NO+H]+: 260.2009; found 260.2002.
4,4-Dimethyl-N-propyl-1-(o-tolyl)pent-1-yn-3-amine (3ab): 1H NMR
(400 MHz, CDCl3): δ = 7.39 (d, J = 7.4 Hz, 1H, aromatic), 7.17 – 7.07 (m,
3H, aromatic), 3.19 (s, 1H, NCH), 2.95 (ddd, J = 11.3, 7.9, 6.6, 1H,
NC(H)H), 2.61 (ddd, J = 11.3, 8.0, 6.0, 1H, NC(H)H), 2.43 (s, 3H, PhCH3),
1.61 – 1.45 (m, 2H, NCH2CH2), 1.07 (s, 9H, C(CH3)3), 0.95 (t, J = 7.4 Hz,
3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 139.8,
132.0, 129.3, 127.7, 125.5, 123.7, 94.9, 83.0, 61.3, 50.8, 35.0, 26.6, 23.2,
20.9, 11.9 ppm. HRMS (ESI) m/z calculated for [C17H25N+H]+: 244.2060;
found 244.2059.
1-(4-Methoxyphenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine (3ah):
1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 8.8 Hz, 2H, aromatic), 6.81
(d, J = 8.8 Hz, 2H, aromatic), 3.77 (s, 3H, OCH3), 3.13 (s, 1H, CCCH),
2.92 (ddd, J = 11.3, 8.0, 6.5 Hz, 1H, NC(H)H), 2.57 (ddd, J = 11.3, 8.1,
6.0 Hz, 1H, NC(H)H), 1.58 – 1.46 (m, 2H, NCH2CH2CH3), 1.05 (s, 9H,
C(CH3)3), 0.94 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.2, 132.9, 116.0, 113.9, 89.3, 83.8, 61.1, 55.2,
50.8, 35.1, 26.6, 23.2, 11.9 ppm. HRMS (ESI) m/z calculated for
[C17H25NO+H]+: 260.2009; found 260.2006.
4,4-Dimethyl-N-propyl-1-(m-tolyl)pent-1-yn-3-amine (3ac): 1H NMR
(400 MHz, CDCl3): δ = 7.24 - 7.20 (m, 2H, aromatic), 7.15 (t, J = 7.5 Hz,
1H, aromatic), 7.06 (d, J = 7.6 Hz, 1H, aromatic), 3.13 (s, 1H, NCH), 2.93
(ddd, J = 11.3, 7.9, 6.6 Hz, 1H, NC(H)H), 2.58 (ddd, J = 11.3, 8.0, 6.1 Hz,
1H, NC(H)H), 2.30 (s, 3H, PhCH3), 1.60 – 1.44 (m, 2H, NCH2CH2CH3),
1.05 (s, 9H, C(CH3)3), 0.95 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible
ppm. 13C NMR (100 MHz, CDCl3): δ = 137.8, 132.2, 128.7, 128.5, 128.1,
123.7, 90.5, 84.2, 61.1, 50.8, 35.1, 26.6, 23.2, 21.2, 11.9 ppm. HRMS
(ESI) m/z calculated for [C17H25N+H]+: 244.2060; found 244.2061.
1-(4-Methoxy-2-methylphenyl)-4,4-dimethyl-N-propylpent-1-yn-3-
amine (3ai): 1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 8.5 Hz, 1H,
aromatic), 6.72 (d, J = 2.5 Hz, 1H, aromatic), 6.65 (dd, J = 8.5 Hz, J = 2.5
Hz, 1H, aromatic), 3.76 (s, 3H, OCH3), 3.17 (s, 1H, CCCH), 2.94 (ddd, J
= 11.3, 7.9, 6.6 Hz, 1H, NC(H)H), 2.60 (ddd, J = 11.4, 8.1, 6.0 Hz, 1H,
NC(H)H), 2.41 (s, 3H, PhCH3), 1.60 – 1.45 (m, 2H, NCH2CH2CH3), 1.06
(s, 9H, C(CH3)3), 0.95 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm.
13C NMR (100 MHz, CDCl3): δ = 159.1, 141.5, 133.2, 116.0, 115.0, 111.1,
93.2, 82.8, 61.3, 55.2, 50.8, 35.0, 26.6, 23.2, 21.2, 11.9 ppm. HRMS
(ESI) m/z calculated for [C18H28NO+H]+: 275.2244; found 275.2240.
1-(4-Ethylphenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine (3ad): 1H
NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 8.1 Hz, 2H, aromatic), 7.11 (d, J
= 8.1 Hz, 2H, aromatic), 3.14 (s, 1H, NCH), 2.93 (ddd, J = 11.3, 8.0, 6.6,
1H, NC(H)H), 2.61 – 2.55 (m, 1H, NC(H)H), 2.62 (q overlapping, J = 7.4
Hz, PhCH2CH3), 1.60 – 1.44 (m, 2H, NCH2CH2CH3), 1.21 (t, J = 7.6 Hz,
3H, NCH2CH2CH3), 1.05 (s, 9H, C(CH3)3), 0.94 (t, J = 7.4 Hz, 3H,
PhCH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 144.0,
131.6, 127.8, 121.1, 90.1, 84.2, 61.1, 50.8, 35.1, 28.8, 26.6, 23.2, 15.4,
11.9 ppm. HRMS (ESI) m/z calculated for [C18H27N+H]+: 258.2276; found
258.2222.
1-(6-Methoxynaphthalen-2-yl)-4,4-dimethyl-N-propylpent-1-yn-3-
1
amine (3aj): H NMR (400 MHz, CDCl3): δ = 7.84 (s, 1H, aromatic), 7.62
(t, J = 9.4 Hz, 2H, aromatic), 7.43 (dd, J = 8.4 Hz, 1.4 Hz, 1H, aromatic),
7.11 (dd, J = 8.9 Hz, 2.5 Hz, 1H, aromatic), 7.04 (d, J = 2.4 Hz, 1H,
aromatic), 3.85 (s, 3H, OCH3), 3.18 (s, 1H, CCCH), 2.97 (ddd, J = 11.3,
7.9, 6.6 Hz, 1H, NC(H)H), 2.61 (ddd, J = 11.4, 8.0, 6.1 Hz,, 1H, NC(H)H),
1.60 – 1.48 (m, 2H, NCH2CH2CH3), 1.09 (s, 9H, C(CH3)3), 0.96 (t, J = 7.4
Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ =
158.1, 133.8, 130.9, 129.3, 129.1, 128.5, 126.6, 119.2, 118.7, 105.8,
90.5, 84.5, 61.2, 55.2, 50.8, 35.1, 26.6, 23.2, 11.9 ppm. HRMS (ESI) m/z
calculated for [C21H27NO+H]+: 310.2171; found 310.2168.
4,4-Dimethyl-1-(naphthalen-1-yl)-N-propylpent-1-yn-3-amine
(3ae):
1H NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 8.3 Hz, 1H, aromatic), 7.79
(d, J = 8.0 Hz, 1H, aromatic), 7.73 (d, J = 7.3 Hz, 1H, aromatic), 7.64 (d,
J = 7.0 Hz, 1H, aromatic), 7.53 (dt, J = 7.0 Hz, 1.3 Hz, 1H, aromatic),
7.46 (dt, J = 7.3 Hz, 1.3 Hz, 1H, aromatic), 7.36 (t, J = 7.1 Hz, 1H,
aromatic), 3.30 (s, 1H, CCCH), 3.07 – 3.03 (ddd, J = 11.3, 7.9, 6.6 Hz,
1H, NC(H)H), 2.68 (ddd, J = 11.3, 8.0, 6.0 Hz, 1H, NC(H)H), 1.64 – 1.49
(m, 2H, NCH2CH2CH3), 1.14 (s, 9H, C(CH3)3), 0.97 (t, J = 7.4 Hz, 3H,
CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 133.4,
133.2, 130.3, 128.2, 128.1, 126.5, 126.2, 125.2, 121.5, 96.0, 82.2, 61.4,
4-(4,4-Dimethyl-3-(propylamino)pent-1-yn-1-yl)-N,N-dimethylaniline
1
(3ak): H NMR (400 MHz, CDCl3): δ = 7.29 (d, J = 8.9 Hz, 2H, aromatic),
6.61 (d, J = 8.9 Hz, 2H, aromatic), 3.13 (s, 1H, CCCH), 2.96 – 2.90 (m
overlap, 1H, NC(H)H), 2.93 (s overlap, 6H, N(CH3)2), 2.58 (ddd, J = 11.4,
8.2, 6.0 Hz, 1H, NC(H)H), 1.58 – 1.46 (m, 2H, NCH2CH2CH3), 1.04 (s, 9H,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
C(CH3)3), 0.94 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR
(100 MHz, CDCl3): δ = 149.8, 132.6, 112.0, 111.0, 88.2, 84.7, 61.2, 50.8,
40.3, 35.1, 26.6, 23.2, 11.9 ppm. HRMS (ESI) m/z calculated for
[C18H28N2+H]+: 273.2325; found 273.2320.
CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 160.9 (d,
1JC-F = 247.2 Hz, CF), 134.7 (d, J = 5.3 Hz), 130.7 (d, J = 8.2 Hz), 125.0
(d, J = 18.0 Hz), 119.5 (d, J = 3.8 Hz) , 115.0 (d, J = 23.0 Hz), 90.1 (d, J
= 1.2 Hz), 83.3, 61.1, 50.8, 35.1, 26.6, 23.2, 14.3 (d, J = 3.5 Hz), 11.9
ppm. HRMS (ESI) m/z calculated for [C17H24NF+H]+: 262.1966; found
262.1986.
2-(4,4-Dimethyl-3-(propylamino)pent-1-yn-1-yl)aniline (3al): 1H NMR
(400 MHz, CDCl3): δ = 7.26 (dd, J = 7.7, 1.2 Hz, 1H, aromatic), 7.09 (dt, J
= 7.7 Hz, 1.5 Hz, 1H, aromatic), 6.70 – 6.65 (m, 2H, aromatic), 4.16
(broad s, 2H, NH2), 3.21 (s, 1H, CCCH), 2.93 (ddd, J = 11.3, 8.0, 6.6 Hz,
1H, NC(H)H), 2.60 (ddd, J = 11.3, 8.0, 6.0 Hz, 1H, NC(H)H), 1.60 – 1.48
(m, 2H, NCH2CH2CH3), 1.07 (s, 9H, C(CH3)3), 0.94 (t, J = 7.4 Hz, 3H,
CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 147.6,
132.2, 129.1, 117.9, 114.2, 108.7, 96.1, 80.7, 61.4, 50.8, 35.0, 26.7, 23.1,
11.8 ppm. HRMS (ESI) m/z calculated for [C16H24N2+H]+: 245.2012;
found 245.2018.
4,4-Dimethyl-N-propyl-1-(pyridin-2-yl)pent-1-yn-3-amine (3aq): 1H
NMR (400 MHz, CDCl3): δ = 8.56 (ddd, J = 4.8, 1.6, 0.8 Hz, 1H,
aromatic), 7.61 (dt, J = 7.7 Hz, 1.8 Hz, 1H, aromatic), 7.40 (td, J = 7.8 Hz,
0.9 Hz, 1H, aromatic), 7.19 (ddd, J = 7.6, 4.9, 1.1 Hz, 1H, aromatic), 3.18
(s, 1H, CCCH), 2.96 (ddd, J = 11.4, 8.0, 6.5 Hz, 1H, NC(H)H), 2.58 (ddd,
J = 11.4, 8.1, 6.1 Hz, 1H, NC(H)H), 1.54 – 1.45 (m, 2H, NCH2CH2CH3),
1.38 (br s, 1H, NH), 1.07 (s, 9H, C(CH3)3), 0.94 (t, J = 7.4 Hz, 3H,
CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.9, 143.8, 136.0,
127.1, 122.4, 91.4, 83.9, 61.0, 50.8, 35.2, 26.6, 23.2, 11.8 ppm. HRMS
(ESI) m/z calculated for [C15H22N2+H]+: 231.1856; found 231.1852.
1
1-(1H-Indol-2-yl)-2,2-dimethyl-N-propylpropan-1-imine (3al'): H NMR
(400 MHz, CDCl3): δ = 7.96 (d, J = 9.0 Hz, 1H, CH-4), 7.66 (d, J = 8.5Hz,
1H, CH-7), 7.57 (t, J = 7.2 Hz, 1H, CH-6), 7.35 (t, J = 8.1 Hz, 1H, CH-5),
6.55 (s, 1H, CH-3), 4.82 (broad s, 1H, NH), 3.32 – 3.27 (m, 2H, NCH2),
1.85 – 1.75 (m, 2H, NCH2CH2), 1.45 (s, 9H, C(CH3)3), 1.09 (t, J = 7.4 Hz,
3H, CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.0 (C=N), 149.6
(C-2), 147.9 (C-7a), 128.6 (CH-4 and CH-6), 123.9 (CH-5), 118.8 (CH-7),
117.4 (C-3a), 95.4 (CH-3), 45.0 (NCH2), 38.0 (C(CH3)3), 30.3 (C(CH3)3),
22.4 (CH2CH3), 11.9 (CH3) ppm. HRMS (ESI) m/z calculated for
[C16H22N2+H]+: 243.1861; found 243.1862.
1-Cyclohexyl-4,4-dimethyl-N-propylpent-1-yn-3-amine (3ar): 1H NMR
(400 MHz, CDCl3): δ = 2.91 (d, J = 1.8 Hz, 1H, NCH), 2.84 (ddd, J = 11.3,
8.1, 6.6 Hz, 1H, NC(H)H), 2.50 (ddd, J = 11.3, 8.1, 6.0 Hz, 1H, NC(H)H),
2.43 – 2.39 (m, 1H, CHCH2), 1.79 – 1.67 (m, 4H, Cy ), 1.52 – 1.42 (m, 6H,
Cy), 1.44 – 1.28 (m, 2H, NCH2CH2CH3), 0.97 (s, 9H, C(CH3)3), 0.92 (t, J
= 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3):
δ = 88.2, 80.8, 60.6, 50.7, 34.8, 33.13, 33.09, 29.1, 26.5, 26.1, 24.8, 23.1,
11.9 ppm. HRMS (ESI) m/z calculated for [C16H29N+H]+: 236.2373; found
236.2370.
1-(4-Chlorophenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine (3am):
1H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 8.5 Hz, 2H, aromatic), 7.24
(d, J = 8.5 Hz, 2H, aromatic), 3.13 (s, 1H, CCCH), 2.91 (ddd, J = 11.3,
7.9, 6.6 Hz, 1H, NC(H)H), 2.57 (ddd, J = 11.3, 7.9, 6.6 Hz, 1H, NC(H)H),
1.58 – 1.44 (m, 2H, NCH2CH2CH3), 1.05 (s, 9H, C(CH3)3), 0.95 (t, J = 7.4
Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ =
133.6, 132.8, 128.5, 122.3, 92.0, 83.1, 61.1, 50.8, 35.1, 26.6, 23.2, 11.8
ppm. HRMS (ESI) m/z calculated for [C16H22NCl+H]+: 264.1514; found
264.1517.
1-(Cyclohex-1-en-1-yl)-4,4-dimethyl-N-propylpent-1-yn-3-amine
(3as): 1H NMR (400 MHz, CDCl3): δ = 6.05 – 6.03 (m, 1H ,C=CH), 3.03
(s, 1H, CCCH), 2.85 (ddd, J = 11.3, 8.0, 6.6 Hz, 1H, NC(H)H), 2.51 (ddd,
J = 11.3, 8.1, 6.0 Hz, 1H, NC(H)H), 2.13 – 2.08 (m, 4H), 1.67 – 1.42 (m,
6H), 0.99 (s, 9H, C(CH3)3), 0.92 (t, J = 7.4 Hz, 3H, CH2CH3), NH not
visible ppm. 13C NMR (100 MHz, CDCl3): δ = 133.3, 121.0, 87.9, 85.9,
61.0, 50.7, 35.0, 29.7, 26.6, 25.6, 23.2, 22.4, 21.7, 11.8 ppm. HRMS
(ESI) m/z calculated for [C16H27N+H]+: 234.2216; found 234.2210.
1-(4-Bromophenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine (3an): 1H
NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 8.5 Hz, 2H, aromatic), 7.26 (d, J
= 8.5 Hz, 2H, aromatic), 3.13 (s, 1H, CCCH), 2.91 (ddd, J = 11.3, 7.9,
6.6 Hz, 1H, NC(H)H), 2.56 (ddd, J = 11.3, 8.0, 6.1 Hz, 1H, NC(H)H), 1.59
– 1.44 (m, 2H, NCH2CH2CH3), 1.04 (s, 9H, C(CH3)3), 0.94 (t, J = 7.4 Hz,
3H, CH2CH3), NH not visible. 13C NMR (100 MHz, CDCl3): δ = 133.5,
133.1, 131.4, 121.8, 92.2, 83.1, 61.1, 50.7, 35.1, 26.6, 23.1, 11.8. HRMS
(ESI) m/z calculated for [C16H22NBr+H]+: 308.1008; found 308.1006.
2,2-Dimethyl-N-propyloct-4-yn-3-amine (3at): 1H NMR (400 MHz,
CDCl3): δ = 2.91 (t, J = 2.0 Hz, 1H, NCH), 2.85 (ddd, J = 11.3, 8.1, 6.5
Hz, 1H, NC(H)H), 2.50 (ddd, J = 11.3, 8.2, 6.0 Hz, 1H, NC(H)H), 2.18 (td,
J = 6.9, 2.0 Hz, 2H, CH2CC), 1.57 – 1.44 (m, 4H, overlapped signal),
0.99 (t, J = 7.3 Hz, 3H, CH2CH3), 0.98 (s, 9H, C(CH3)3) 0.93 (t, J = 7.4 Hz,
3H, CH2CH3), NH not visible ppm.13C NMR (100 MHz, CDCl3): δ = 83.8,
81.0, 60.7, 50.7, 34.8, 26.5, 23.1, 22.6, 20.8, 13.5, 11.8 ppm. HRMS
(ESI) m/z calculated for [C13H25N+H]+: 196.2060; found 196.2067.
4,4-Dimethyl-N-propyl-1-(4-(trifluoromethyl)phenyl)pent-1-yn-3-
amine (3ao): 1H NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 8.5 Hz, 2H,
aromatic), 7.50 (d, J = 8.5 Hz, 2H, aromatic), 3.17 (s, 1H, CCCH), 2.93
(ddd, J = 11.3, 7.8, 6.7 Hz, 1H, NC(H)H), 2.59 (ddd, J = 11.4, 7.9, 6.1 Hz,
1H, N-CHH), 1.59 – 1.48 (m, 2H, NCH2CH2CH3), 1.06 (s, 9H, C(CH3)3),
0.96 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz,
CDCl3): δ = 131.9, 129.6 (q, J = 32.6 Hz), 127.7 (q, J = 1.2 Hz), 125.2 (q,
J = 3.8 Hz), 124.1 (q, 1JC-F = 272.0 Hz, CF3), 93.9, 83.1, 61.2, 50.9, 35.2,
26.6, 23.2, 11.9 ppm. HRMS (ESI) m/z calculated for [C17H22NF3+H]+:
298.1766; found 298.1776.
6,6-Diethoxy-2,2-dimethyl-N-propylhex-4-yn-3-amine (3au): 1H NMR
(400 MHz, CDCl3): δ = 5.31 (d, J = 0.9 Hz, 1H, CH(OEt)2), 3.74 (dq, J =
9.2, 7.1 Hz, 2H, CH(OCH2CH3)OCH2CH3), 3.60 (dq, J = 9.2, 7.1 Hz, 2H,
CH(OCH2CH3)OCH2CH3), 2.99 (d, J = 1.1 Hz, 1H, NCH), 2.85 (ddd, J =
11.3, 8.0, 6.6 Hz, 1H, NC(H)H), 2.50 (ddd, J = 11.3, 8.0, 6.1 Hz, 1H,
NC(H)H), 1.55 – 1.39 (m, 2H, NCH2CH2), 1.23 (t, J = 7.1 Hz, 6H,
(OCH2CH3)2), 0.99 (s, 9H, C(CH3)3), 0.92 (t, J = 7.4 Hz, 3H, CH2CH3),
NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 91.6, 86.7, 79.6,
60.7, 60.7, 60.5, 50.6, 34.8, 26.5, 23.1, 15.1, 11.8 ppm. HRMS (ESI) m/z
calculated for [C15H29NO2+H]+: 256.2271; found 256.2277.
1-(4-Fluoro-3-methylphenyl)-4,4-dimethyl-N-propylpent-1-yn-3-amine
(3ap): H NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 7.3 Hz, 1H, aromatic),
7.22– 7.17 (m, 1H, aromatic), 6.90 (t, 1H, J = 8.9 Hz, aromatic), 3.12 (s,
1H, CCCH), 2.92 (ddd, J = 11.3, 7.9, 6.6 Hz, 1H, NC(H)H), 2.57 (ddd, J
= 11.4, 8.0, 6.1 Hz, 1H, NC(H)H), 2.23 (d, J = 1.7 Hz, 3H, PhCH3), 1.58 –
1.46 (m, 2H, NCH2CH2CH3), 1.05 (s, 9H, C(CH3)3), 0.95 (t, J = 7.4 Hz, 3H,
7-Bromo-2,2-dimethyl-N-propylhept-4-yn-3-amine (3av): 1H NMR (400
MHz, CDCl3): δ = 3.43 (t, J = 7.2 Hz, 2H, CH2Br), 2.91 (t, J = 1.9 Hz, 1H,
NCH), 2.84 (ddd, J = 11.3, 8.0, 6.6 Hz, 1H, NC(H)H), 2.77 (td, J = 7.2,
1.9 Hz, 2H, CH2CH2Br), 2.49 (ddd, J = 11.3, 8.1, 6.1 Hz, 1H, NC(H)H),
1.46 – 1.42 (m, 2H, NCH2CH2CH3), 0.98 (s, 9H, C(CH3)3), 0.92 (t, J = 7.4
Hz, 3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ =
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
83.4, 80.5, 60.6, 50.7, 34.8, 30.3, 26.5, 23.4, 23.1, 11.8 ppm. HRMS
(CC), 82.0 (CC), 54.3, 46.0, 34.8, 26.4, 23.8, 12.0, 9.0 ppm. HRMS
(ESI) m/z calculated for [C15H20NCl+H]+: 250.1357; found 250.1362.
(ESI) m/z calculated for [C12H22NBr+H]+: 260.1008; found 260.1010.
1
5,5-Dimethyl-4-(propylamino)hex-2-yn-1-yl acetate (3aw): 1H NMR
(400 MHz, CDCl3): δ = 4.71 (d, J = 1.8 Hz, 2H, CH2O), 2.96 (t, J = 1.8 Hz,
1H, NCH), 2.83 (ddd, J = 11.3, 8.0, 6.6 Hz, 1H, NC(H)H), 2.48 (ddd, J =
11.3, 8.0, 6.1 Hz, 1H, NC(H)H), 2.08 (s, 3H, COCH3), 1.54 – 1.42 (m, 2H,
N-CH2CH2CH3), 0.98 (s, 9H, C(CH3)3), 0.92 (t, J = 7.4 Hz, 3H, CH2CH3),
NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 170.3, 88.1, 77.7,
60.6, 52.7, 50.6, 34.8, 26.5, 23.1, 20.8, 11.8 ppm. HRMS (ESI) m/z
calculated for [C13H23NO2+H]+: 226.1802; found 226.1809.
1-(Cyclohex-1-en-1-yl)-3-methyl-N-propylpent-1-yn-3-amine (5bs): H
NMR (400 MHz, CDCl3): δ = 6.08 – 5.97 (m, 1H, C=CH), 2.68 – 2.62 (m,
2H, NCH2), 2.10 – 2.07 (m, 4H), 1.66 – 1.54 (m, 6H), 1.54 – 1.46 (m, 2H),
1.23 (s, 3H, CqCH3), 0.99 (t, 3H, J = 7.4 Hz, CH3), 0.95 (t, 3H, J = 7.4 Hz,
CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 133.5, 120.8,
91.0, 84.8, 54.1, 45.9, 34.9, 29.7, 26.6, 25.6, 23.8, 22.4, 21.6, 12.0, 8.9
ppm. HRMS (ESI) m/z calculated for [C15H25N+H]+: 220.2060; found
220.2050.
General experimental procedure for the synthesis of ketimine-
alkyne coupling
N-Butyl-3,5-dimethyl-1-phenylhex-1-yn-3-amine (5ca): 1H NMR (400
MHz, CDCl3): δ = 7.40 - 7.37 (m, 2H, aromatic), 7.28 - 7.26 (m, 3H,
aromatic), 2.82 – 2.72 (m, 2H, NCH2), 1.99 – 1.89 (m, 1H, CH(CH3)2),
1.63 (dd, J = 13.7, 6.0 Hz, 1H, C(H)HCH), 1.55 (dd, J = 13.8, 5.7 Hz, 1H,
C(H)HCH), 1.52 – 1.46 and 1.44 – 1.34 (2×m, 2×2H, CH2CH2CH3), 1.40
(s overlap, 3H, CqCH3), 1.05 (d, J = 6.8 Hz, 3H, CH(CH3)CH3), 1.03 (d, J
= 6.9 Hz, 3H, CH(CH3)CH3), 0.94 (t, J = 7.2 Hz, 3H, CH2CH3), NH not
visible ppm. 13C NMR (100 MHz, CDCl3): δ = 131.5, 128.2, 127.7, 123.8,
94.6, 83.2, 53.5, 50.9, 43.5, 32.8, 27.6, 24.9, 24.7, 24.5, 20.6, 14.0 ppm.
HRMS (ESI) m/z calculated for [C18H27N+H]+: 258.2216; found 258.2210.
In an oven dried 10 mL vial containing 1 mL of toluene and a stirring bar,
the ketimines 4a-o (0.5 mmol), the acetylenes (0.5 mmol, 1 equiv) and
Zn(OTf)2 (0.027 g, 0.75 mmol) were added successively and the vial was
sealed under air. The reaction mixture was stirred at 100 ºC for 24 h.
Afterwards the reaction mixture was diluted with CH2Cl2 (10 mL) washed
and extracted with 0.5 N NaOH (10 mL). The organic phase was dried
over MgSO4 and the solvent was evaporated under reduced pressure.
Crude reaction mixture was purified by silica gel column chromatography
using EtOAc/n-Heptane (10:90) as solvent system to get the final product.
1
3,5-Dimethyl-1-phenyl-N-propylhex-1-yn-3-amine (5dd): H NMR (400
1-(Phenylethynyl)-N-propylcyclohexan-1-amine (5aa): 1H NMR (400
MHz, CDCl3): δ = 7.43 – 7.40 (m, 2H, aromatic), 7.31 – 7.24 (m, 3H,
aromatic), 2.77 (t, J = 7.3 Hz, 2H, NCH2), 1.97-1.90 (m, 2H, cHex), 1.72 –
1.39 (m, 8H, overlapped signal cHex), 1.30-1.19 and 0.84-0.91 (2 × m, 2
× 1H, cHex), 0.96 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible ppm. 13C
NMR (100 MHz, CDCl3, referenced to solvent δC 77.00): δ = 131.6,
128.1, 127.6, 123.8, 93.7, 84.4, 54.9, 45.2, 38.2, 25.9, 23.8, 23.0, 11.9
ppm. HRMS (ESI) m/z calculated for [C17H23N+H]+: 242.1903; found
242.1904.
MHz, CDCl3): δ = 7.31 (d, J = 8.1 Hz, 2H, aromatic), 7.11 (d, J = 8.1 Hz,
2H, aromatic), 2.77 (ddd, J = 10.5, 7.8, 7.0 Hz, 1H, NC(H)H), 2.69 (ddd, J
= 10.6, 8.1, 6.5 Hz, 1H, NC(H)H), 2.80 – 2.66 (m, 2H), 2.62 (q, J = 7.6 Hz,
2H, PhCH2CH3), 2.00 – 1.87 (m, 1H, CH(CH3)2), 1.62 (dd, J = 13.7, 6.0
Hz, 1H, C(H)HCH), 1.57 – 1.46 (m, 3H, C(H)HCH and CH2CH3), 1.39 (s,
3H, CqCH3), 1.21 (t, J = 7.6 Hz, 3H, PhCH2CH3), 1.05 (d, J = 6.9 Hz, 3H,
CH(CH3)CH3), 1.03 (d, J = 6.9 Hz, 3H, CH(CH3)CH3), 0.96 (t, J = 7.4 Hz,
3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ = 144.0,
131.5, 127.8, 121.0, 93.7, 83.3, 53.5, 51.0, 45.8, 28.8, 27.7, 24.9, 24.7,
24.5, 23.8, 15.4, 12.0 ppm. HRMS (ESI) m/z calculated for [C17H25N+H]+:
272.2373; found 272.2370.
3-Methyl-1-phenyl-N-propylpent-1-yn-3-amine (5ba): 1H NMR (400
MHz, CDCl3): δ = 7.43 – 7.40 (m, 2H, aromatic), 7.28 – 7.27 (m, 3H,
aromatic), 2.81 – 2.66 (m, 2H, NCH2), 1.77 – 1.60 (m, 2H, CH3CH2), 1.58
– 1.49 (m, 2H, CH3CH2CH2 ), 1.38 (s, 3H, CqCH3), 1.05 (t, J = 7.5 Hz, 3H,
CH3CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3CH2CH2), NH not visible ppm. 13C
NMR (100 MHz, CDCl3): δ = 131.6 (CHmeta), 128.2 (CHortho), 127.7
(CHpara), 123.7 (Cq arom), 94.0 (MeCqCC), 83.1 (CCCq arom), 54.3
(CqCH3), 46.0 (NCH2), 34.9 (CH3CH2), 26.5 (CqCH3), 23.8 (CH3CH2CH2),
12.0 (CH3CH2CH2), 8.9 (CH3CH2) ppm. HRMS (ESI) m/z calculated for
[C15H21N+H]+: 216.1747; found 216.1740.
N-Butyl-3,4-dimethyl-1-(p-tolyl)pent-1-yn-3-amine (5ex): 1H NMR (400
MHz, CDCl3): δ = 7.29 (d, J = 8.1 Hz, 2H, aromatic), 7.08 (d, J = 7.9 Hz,
2H, aromatic), 2.81 – 2.68 (m, 2H, NCH2), 2.33 (s, 3H, PhCH3), 1.87
(septet, J = 6.7 Hz, 1H, CH(CH3)2), 1.51 – 1.37 (m, 4H), 1.30 (s, 3H,
CqCH3), 1.07 (d, J = 6.7 Hz, 3H, CH(CH3)CH3), 1.02 (d, J = 6.8 Hz, 3H,
CH(CH3)CH3), 0.93 (t, J = 7.2 Hz, 3H, CH2CH3), NH not visible ppm. 13C
NMR (100 MHz, CDCl3): δ = 137.6, 131.5, 129.0, 120.8, 93.1, 83.5, 57.6,
43.5, 36.7, 32.9, 23.2, 21.4, 20.7, 18.1, 17.2, 14.1 ppm. HRMS (ESI) m/z
calculated for [C18H27N+H]+: 258.2216; found 258.2210.
1-(4-Methoxy-2-methylphenyl)-3-methyl-N-propylpent-1-yn-3-amine
(5bi): 1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8.5 Hz, 1H, aromatic),
6.63 (d, J = 2.2 Hz, 1H, aromatic), 6.56 (dd, J = 8.5, 2.2 Hz, 1H,
aromatic), 3.67 (s, 3H, OCH3), 2.72 – 2.60 (m, 2H, NCH2), 2.31 (s, 3H,
PhCH3), 1.68 – 1.52 (m, 2H, CH2CH3), 1.50 – 1.39 (m, 2H, CH2CH3),
1.29 (s, 3H, CqCH3), 0.98 (t, J = 7.5 Hz, 3H, CH2CH3), 0.87 (t, J = 7.4 Hz,
3H, CH2CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3 referenced
to solvent δC 77.00): δ = 159.0, 141.3, 132.9, 115.6, 114.8, 111.0, 96.1,
81.5, 55.0, 54.3, 45.9, 34.8, 26.5, 23.7, 20.9, 11.8, 8.8 ppm. HRMS (ESI)
m/z calculated for [C17H25NO+H]+: 260.2009; found 260.2014.
2-(Phenylethynyl)-N-propylbicyclo[2.2.1]heptan-2-amine (5fa): 1H
NMR (400 MHz, CDCl3): δ = 7.40 - 7.38 (m, 2H, aromatic), 7.30 - 7.24
(m, 3H, aromatic), 2.80 (ddd, J = 10.9, 7.6, 6.7 Hz, 1H, NC(H)H), 2.50
(ddd, J = 10.9, 7.8, 6.6 Hz, 1H, NC(H)H), 2.42 (broad d, J = 3.5 Hz, 1H),
2.24 (broad t, J = 4.0 Hz, 1H), 2.13 (ddd, J = 12.2, 4.7, 3.0 Hz, 1H), 1.94
(broad d, J = 9.9 Hz, 1H), 1.87 – 1.82 (m, 1H), 1.57 - 1.47 (m, 2H), 1.39 –
1.25 (m, 4H), 1.20 (dd, J = 12.3, 2.9 Hz, 1H), 0.96 (t, J = 7.4 Hz, 3H,
CH2CH3), NH overlapping ppm. 13C NMR (100 MHz, CDCl3): δ = 131.5,
128.2, 127.5, 124.1, 96.4, 82.3, 60.3, 47.8, 47.5, 46.8, 38.6, 36.5, 29.3,
23.8, 21.6, 12.1 ppm. HRMS (ESI) m/z calculated for [C18H23N+H]+:
254.1903; found 254.1913.
1-(4-Chlorophenyl)-3-methyl-N-propylpent-1-yn-3-amine (5bm): 1H
NMR (400 MHz, CDCl3): δ = 7.32 (d, J = 8.5 Hz, 2H, aromatic), 7.25 (d,
J = 8.5 Hz, 2H, aromatic), 2.79 – 2.64 (m, 2H, NCH2), 1.74 – 1.56 (m, 2H,
CH2CH3), 1.56 – 1.48 (m, 2H, CH2CH3), 1.36 (s, 3H, CqCH3), 1.04 (t, J =
7.4 Hz, 3H, CH2CH3), 0.96 (t, J = 7.4 Hz, 3H, CH2CH3), NH not visible
ppm. 13C NMR (100 MHz, CDCl3): δ = 133.7, 132.9, 128.5, 122.2, 95.0
N-Benzyl-3-methyl-1-phenylhept-6-en-1-yn-3-amine (5ga): 1H NMR
(400 MHz, CDCl3): δ = 7.41 – 7.39 (m, 2H, aromatic), 7.30 - 7.25 (m, 3H,
aromatic), 5.88 (ddt, J = 16.8, 10.2, 6.5 Hz, 1H, CH=CH2), 5.07 (ddd, J =
17.1, 3.4, 1.6 Hz, 1H, CH=C(H)H), 4.97 (dd, J = 10.2, 1.8 Hz, 1H,
CH=C(H)H), 2.78 – 2.68 (m, 2H, NCH2), 2.33 – 2.26 (m, 2H), 1.82 – 1.68
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
(m, 2H), 1.56 – 1.50 (m, 2H), 1.40 (s, 3H, CqCH3), 1.28 (broad s, 1H, NH),
0.97 (t, J = 7.4 Hz, 3H, CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ =
138.6, 131.6, 128.2, 127.8, 123.6, 114.5, 93.8, 83.3, 53.7, 45.9, 41.2,
29.1, 27.1, 23.8, 12.0 ppm. HRMS (ESI) m/z calculated for [C17H23N+H]+:
242.1903; found 242.1900.
62.0 (major), 53.5 (minor), 53.2 (major), 51.5 (minor), 51.4 (major), 45.5
(major), 44.3 (minor), 32.6 , 28.0 (minor), 27.5 (major), 19.5 (minor &
major), 18.4 (minor), 18.4 (major), 17.94 (major), 17.89 (minor), 14.5
(minor), 14.4 (major) ppm. HRMS (ESI) m/z calculated for
[C19H27NO2+H]+: 302.2115; found 302.2115.
N-Butyl-3-methyl-1-phenylhex-1-yn-3-amine (5ha): 1H NMR (400 MHz,
CDCl3): δ = 7.41 – 7.38 (m, 2H, aromatic), 7.29 – 7.25 (m, 3H, aromatic),
2.83 – 2.71 (m, 2H, NCH2), 1.67 – 1.48 (m, 6H), 1.42 – 1.41 (m, 1H),
1.38 (s, 3H, CqCH3), 1.22 (broad s, 1H, NH), 0.97 (t, J = 7.0 Hz, 3H, CH3),
0.94 (t, J = 7.1 Hz, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ =
131.6, 128.2, 127.7, 123.7, 94.2, 83.0, 53.8, 44.6, 43.7, 32.8, 27.1, 20.6,
17.9, 14.5, 14.0 ppm. HRMS (ESI) m/z calculated for [C17H25N+H]+:
244.2060; found 244.2050.
Methyl (1-(phenylethynyl)cyclohexyl)-D-valinate (5ma): 1H NMR (400
MHz, CDCl3): δ = 7.39 – 7.37 (m, 2H, aromatic), 7.27 – 7.24 (m, 3H,
aromatic), 3.55 (s, 3H, OCH3), 3.35 (d, J = 5.6 Hz, 1H, NHCH), 1.99 (s,
1H, NH), 1.95 – 1.82 (m, 3H, Cy), 1.68 – 1.46 (m, 6H, Cy), 1.38 (dt, J =
12.1, 3.4 Hz, 1H), 1.27 – 1.18 (m, 1H), 0.95 (d, J = 7.1 Hz, 3H,
CH(CH3)CH3), 0.93 (d, J = 7.1 Hz, 3H, CH(CH3)CH3) ppm. 13C NMR (100
MHz, CDCl3): δ = 176.9, 131.6, 128.1, 127.7, 123.6, 93.3, 84.9, 61.5,
54.4, 51.4, 39.3, 38.1, 32.6, 25.8, 23.1, 22.8, 19.5, 18.4 ppm. HRMS
(ESI) m/z calculated for [C22H27NO2+H]+: 314.2115; found 314.2117.
3-Methyl-1-phenyl-N-propylhex-1-yn-3-amine (5ia): 1H NMR (400 MHz,
CDCl3): δ = 7.41 - 7.39 (m, 2H, aromatic), 7.29 - 7.25 (m, 3H, aromatic),
2.79 - 2.69 (m, 2H, NCH2), 1.67-1.50 (m, 6H), 1.38 (s, 3H, CqCH3), 1.25
(broad s, 1H, NH), 0.99 (t, 3H, J = 7.1 Hz, CH3), 0.98 (t, 3H, J = 7.4 Hz,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 131.6, 128.2, 127.7, 123.7,
94.2, 83.0, 53.8, 46.0, 44.6, 27.1, 23.8, 17.9, 14.5, 12.0 ppm. HRMS
(ESI) m/z calculated for [C16H23N+H]+: 230.1903; found 230.1916.
Methyl (3,4-dimethyl-1-phenylpent-1-yn-3-yl)-D-alaninate (5na): 1H
NMR (400 MHz, CDCl3): δ = 7.39 – 7.37 (m, 2H, aromatic), 7.28 – 7.26
(m, 3H, aromatic), 3.70 (q, J = 7.1 Hz, 1H, NHCHCH3), 3.61 (s, 3H,
OCH3), 1.91 – 1.84 (m, 1H, CH(CH3)2), 1.56 (broad s, 1H, NH), 1.31 (d, J
= 7.1 Hz, 3H, NHCHCH3), 1.29 (s, 3H, CH3Cq), 1.08 (d, J = 6.7 Hz, 3H,
CH(CH3)CH3), 1.01 (d, J = 6.8 Hz, 3H, CH(CH3)CH3) ppm. 13C NMR (100
MHz, CDCl3): δ = 177.8 (C=O), 131.6, 128.2, 127.8, 123.5 (Cq arom),
93.1 and 84.1 (PhCC), 57.3 (CqCH3), 52.5 (NHCHCH3), 51.9 (OCH3),
36.9 (CH(CH3)2), 23.8 (CH3Cq), 21.1 (NHCHCH3), 18.3 (CH(CH3)CH3),
17.0 (CH(CH3)CH3) ppm. HRMS (ESI) m/z calculated for
[C17H23NO2+H]+: 274.1802; found 274.1811. Methyl (3,4-dimethyl-1-
1
3-Ethyl-1-phenyl-N-propylhept-1-yn-3-amine (5ja): H NMR (400 MHz,
CDCl3): δ = δ = 7.41 – 7.39 (m, 2H, aromatic), 7.28 – 7.26 (m, 3H,
aromatic), 2.67 (t, J = 7.2 Hz, 2H, NCH2), 1.70 – 1.61 (m, 4H), 1.52 (q, J
= 7.2 Hz, 2H, CqCH2CH3), 1.44 – 1.35 (m, 4H), 1.00 (t, 3H, J = 7.4 Hz,
1
CH3), 0.97 (t, 3H, J = 7.4 Hz, CH3), 0.94 (t, 3H, J = 7.1 Hz, CH3) ppm. 13
C
phenylpent-1-yn-3-yl)-D-alaninate (5na'): H NMR (400 MHz, CDCl3): δ
= 7.38 – 7.35 (m, 2H, aromatic), 7.27 – 7.26 (m, 3H, aromatic), 3.65 (q, J
= 7.1 Hz, 1H, NHCHCH3), 3.56 (s, 3H, OCH3), 1.84 – 1.77 (m, 1H,
CH(CH3CH3)), 1.31 – 1.29 (m overlapped, 3H, NHCHCH3), 1.31 (s
overlapped, 3H, CH3Cq), 1.11 (d, J = 6.7 Hz, 3H, CH(CH3)CH3), 1.05 (d,
J = 6.8 Hz, 3H, CH(CH3)CH3), NH not visible ppm. 13C NMR (100 MHz,
CDCl3): δ = 177.6, 131.6, 128.1, 127.8, 123.5, 92.5, 84.5, 57.5, 52.1,
51.8, 37.8, 24.6, 21.7, 17.9, 17.7 ppm.
NMR (100 MHz, CDCl3): δ = 131.6, 128.2, 127.6, 123.9, 93.9, 83.7, 57.3,
45.5, 38.0, 31.3, 26.1, 23.9, 23.1, 14.1, 12.0, 8.4 ppm. HRMS (ESI) m/z
calculated for [C18H27N+H]+: 258.2216; found 258.2220.
Methyl (3,4-dimethyl-1-phenylpent-1-yn-3-yl)-D-valinate (5ka): 1H
NMR (400 MHz, CDCl3): δ = 7.39 – 7.34 (m, 2H, minor & major,
aromatic), 7.26 – 7.23 (m, 3H, minor & major, aromatic), 3.58 (s, 3H,
OCH3 minor), 3.51 (s, 3H, OCH3 major), 3.40 (d, J = 5.6 Hz, 1H, NCH
minor), 3.27 (d, J = 5.6 Hz, 1H, NCH major), 2.01 (broad s, 1H, NH minor
& major), 1.88 – 1.78 (m, 3H, CH(CH3)2 minor & major), 1.26 (s, 3H,
CqCH3 minor & major), 1.10 (d, J = 6.7 Hz, 3H, CH(CH3)CH3 major), 1.09
(d, J = 6.6 Hz, 3H, CH(CH3)CH3 minor), 1.06 (d, J = 6.7 Hz, 3H,
CH(CH3)CH3 major), 1.09 (d, J = 6.6 Hz, 3H, CH(CH3)CH3 minor), 0.96 (d,
Methyl N2-acetyl-N6-(3,4-dimethyl-1-phenylpent-1-yn-3-yl)-L-lysinate
(5oa): 1H NMR (400 MHz, CDCl3): δ = 7.41 – 7.39 (m, 2H, aromatic),
7.33 – 7.23 (m, 3H, aromatic), 6.05 (d, J = 7.6 Hz, 1H, NHCOCH3), 4.61
(dt, J = 7.5, 5.6 Hz, 1H, CHCO2Me), 3.72 (s, 3H, OCH3), 2.77 (td, J =
11.3, 6.8 Hz, m, 1H, NC(H)H), 2.70 (td, J = 10.8, 7.3 Hz, m, 1H, NC(H)H),
2.00 (s, 3H, NHCOCH3), 1.91 – 1.84 (m, 2H, NCH2CH2), 1.76 – 1.63 (m,
1H, CH(CH3)2), 1.55 – 1.46 (m, 3H), 1.45 – 1.35 (m, 2H), 1.30 (s, 3H,
CH3Cq), 1.07 (d, J = 6.7 Hz, 3H, CH(CH3)CH3), 1.01 (d, J = 6.8 Hz, 3H,
CH(CH3)CH3), NH not visible ppm. 13C NMR (100 MHz, CDCl3): δ =
173.2 (CO2Me), 169.8 (CONH), 131.6 (CHarom), 128.2 (CHarom), 127.7
(CHarom), 123.7 (Cipso), 93.6 (CC), 83.5 (CC), 57.5 (CH3Cq), 52.3
(OCH3), 52.1 (CHCO2Me), 43.4 (NCH2), 36.64, 36.63, 32.4 (CH2), 30.2
(CH2), 23.17, 23.15 (CH2), 23.0, 18.1 (CH(CH3)CH3), 17.14, 17.13
(CH(CH3)CH3) ppm. HRMS (ESI) m/z calculated for [C22H32N2O3+H]+:
373.2486; found 373.2480.
J
= 7.6 Hz, 3H, CH(CH3)CH3 minor), 0.94 (d, J = 6.9 Hz, 3H,
CH(CH3)CH3 minor & major), 0.92 (d, J = 7.0 Hz, 3H, CH(CH3)CH3 major)
ppm. 13C NMR (100 MHz, CDCl3): δ = 177.1 (C=O, minor), 176.8 (C=O,
major), 131.6 (minor & major), 128.2 (minor), 128.1 (minor), 127.72
(minor), 127.66 (major), 123.6 (Cq arom minor & major), 93.3 (CC, minor),
93.2 (CC, major), 84.3 (CC, major), 84.2 (CC, minor), 62.4 (NCH,
minor), 61.9 (NCH, major), 57.4 (CqMe, minor), 56.8 (CqMe, major), 51.5
(OCH3, minor), 51.4 (OCH3, major), 38.2 (major), 36.7 (minor), 32.8
(minor), 32.7 (major), 24.1, 24.0 (minor), 19.6 (minor), 19.5, 18.5 (minor),
18.4, 18.3 (minor), 17.9, 17.6, 17.2 (minor) ppm. HRMS (ESI) m/z
calculated for [C19H27NO2+H]+: 302.2115; found 302.2120.
Methyl N2-acetyl-N6-(3,4-dimethyl-1-(p-tolyl)pent-1-yn-3-yl)-L-lysinate
1
Methyl (3-methyl-1-phenylhex-1-yn-3-yl)-D-valinate (5la): 1H NMR
(400 MHz, CDCl3): δ = 7.36 – 7.34 (m, 2H, aromatic), 7.27 – 7.24 (m, 3H,
aromatic), 3.57 (s, 3H, OCH3 minor), 3.53 (s, 3H, OCH3 major), 3.36 (d, J
= 5.6 Hz, 1H, NCH minor), 3.28 (d, J = 5.6 Hz, 1H, NCH major), 2.03
(broad s, 1H, NH minor & major), 1.85 – 1.80 (m, 1H, CH(CH3)2 minor &
major), 1.60 – 1.55 (m, 4H, CH2CH2CH3 minor & major), 1.36 (s, 3H,
CH3Cq minor), 1.32 (s, 3H, CH3Cq major), 1.00 – 0.87 (m, 9H, minor &
major) ppm. 13C NMR (100 MHz, CDCl3): δ = 176.9 (C=O minor), 176.8
(C=O major), 131.6 (minor & major), 128.14 (minor), 128.11 (major),
127.75 (minor), 127.72 (major), 123.5 (minor & major), 93.7 (CC, minor),
93.6 (CC, major), 83.7 (CC, major), 83.4 (CC, minor), 62.2 (minor),
(5ox): H NMR (400 MHz, CDCl3): δ = 7.29 (d, J = 7.8 Hz, 2H, aromatic),
7.09 (d, J = 7.9 Hz, 2H, aromatic), 6.16 (d, J = 7.7 Hz, 1H, NHCOCH3),
4.60 (td, J = 5.6, 7.5 Hz, 1H, CHCO2Me), 3.72 (s, 3H, OCH3), 2.77 (td, J
= 11.5, 7.3 Hz, 1H, NC(H)H), 2.70 (td, J = 10.8, 7.3 Hz, 1H, NC(H)H),
2.33 (s, 3H, CH3Ph), 2.00 (s, 3H, NHCOCH3), 1.90 – 1.82 (m, 2H,
NCH2CH2), 1.75 – 1.65 (m, 2H), 1.54 – 1.35 (m, 3H), 1.29 (s, 3H, CH3Cq),
1.07 (d, J = 6.7 Hz, 3H, 3H, CH(CH3)CH3), 1.01 (d, J = 6.8 Hz, 3H,
CH(CH3)CH3), NH overlapping ppm. 13C NMR (100 MHz, CDCl3): δ =
173.2 (CO2Me), 169.9 (CONH), 137.7 (Cq aromCH3), 131.5 (CHortho), 129.0
(CHmeta), 120.6 (Cipso), 92.6 (ArCC), 83.6 (ArCC), 57.6 (CqMe), 52.3
(OCH3), 52.2 (CHCO2Me), 43.3 (NCH2), 36.63 (CH), 36.62 (CH(CH3)2),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
32.3 (CH2), 30.1 (CH2), 23.2 (CH2), 23.1 (Me), 23.0 (CH3CONH), 21.4
(CH3Ph), 18.1 CH(CH3)CH3), 17.1 CH(CH3)CH3) ppm. HRMS (ESI) m/z
calculated for [C23H34N2O3+H]+: 387.2642; found 387.2643.
[4]
[5]
a) Punja. N. Patent US4325966, 1982; b) C. Swithenbank, P. J.
McNulty, K. L. Viste, J. Agric. Food Chem. 1971, 19, 417-421.
For chemical transformations see: a) M. A. Huffman, N. Yasuda, A. E.
DeCamp, E. J. J. Grabowski, J. Org. Chem. 1995, 60, 1590-1594; b) M.
Miura, M. Enna, K. Okuro, M. Nomura, J. Org. Chem. 1995, 60, 4999-
5004; c) A. Jenmalm, W. Berts, Y. L. Li, K. Luthman, I. Csoregh, U.
Hacksell, J. Org. Chem. 1994, 59, 1139-1148; d) R. Robles-Machin, J.
Adrio, J. C. Carretero, J. Org. Chem. 2006, 71, 5023-5026; e) A.
Ranjan, R. Yerande, P. B. Wakchaure, S. G. Yerande, D. H. Dethe, Org.
Lett. 2014, 16, 5788-5791; f) Y. Yamamoto, H. Hayashi, T. Saigoku, H.
Nishiyama, J. Am. Chem. Soc. 2005, 127, 10804-10805; g) A. Sinai, D.
Vangel, T. Gati, P. Bombicz, Z. Nova, Org. Lett. 2015, 17, 4136-4139;
h) A. S. K. Hashmi, A. M. Schuster, M. Schmuck, F. Rominger, Eur. J.
Org. Chem. 2011, 4595-4602; i) V. A. Peshkov, O. P. Pereshivko, P. A.
Donets, V. P. Mehta, E. V. Van der Eycken, Eur. J. Org. Chem. 2010,
4861-4867; j) E. Vessally, L. Edjlali, A. Hosseinian, A. Bekhradnia, M. D.
Esrafili, RSC Adv. 2016, 6, 49730-49746; k) E. Vessally, RSC Adv.
2016, 6, 18619-18631; l) Y. Liu, ARKIVOC, 2013, 2014, 1-20.
a) V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken, Chem. Soc.
Rev. 2012, 41, 3790-3807; b) A. Beillard, T.-X. Métro, X. Bantreil, J.
Martinez, F. Lamaty, Eur. J. Org. Chem. 2017, 4642-4647.
Methyl N2-acetyl-N6-(1-(4-methoxyphenyl)-3,4-dimethylpent-1-yn-3-
1
yl)-L-lysinate (5oh): H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 8.5 Hz,
2H, arom CHmeta), 6.82 (d, J = 8.5 Hz, 2H, arom CHortho), 6.09 (d, J = 6.8
Hz, 1H, NHCOCH3), 4.60 (dt, J = 7.5, 5.4 Hz, 1H, CHCO2Me), 3.80 (s,
3H, OCH3), 3.72 (s, 3H, OCH3), 2.78 (dt, J = 13.2, 6.9 Hz, 1H, NC(H)H),
2.71 (dt, J = 10.9, 7.3 Hz, 1H, NC(H)H), 2.01 (s, 3H, NHCOCH3), 1.91 –
1.86 (m, 3H), 1.72 - 1.67 (m, 1H), 1.54 – 1.38 (m, 3H), 1.30 (s, 3H,
CH3Cq), 1.07 (d, J = 6.7 Hz, 3H, CH(CH3)CH3), 1.01 (d, J = 6.8 Hz, 3H,
CH(CH3)CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 173.2 (COOCH3),
169.9 (CONH), 159.3 (Cq aromOCH3), 133.0 (CHmeta), 115.8 (Cipso), 113.9
(CHortho), 91.61 and 91.58 (ArCC), 83.49 and 83.47 (ArCC), 57.8 and
57.7 (CqMe), 55.3 (COOCH3), 52.3 (CHCO2Me), 52.2 (Cq aromOCH3), 43.3
(NCH2), 36.61 and 36.60 (CH(CH3)2), 32.4, 30.06 and 30.04 (CH3Cq),
23.2, 23.0, 18.1 (CH(CH3)CH3), 17.2 (CH(CH3)CH3) ppm. HRMS (ESI)
m/z calculated for [C23H34N2O4+H]+: 403.2591; found 403.2598.
[6]
[7]
Methyl N2-acetyl-N6-(3,4-dimethyl-1-(4-(trifluoromethyl)phenyl)pent-
a) Y. Imada, M. Yuasa, I. Nakamura, S.-I. Murahashi, J. Org. Chem.
1994, 59, 2282-2284; b) S. Czernecki, J.-M. Valéry, J. Carbohydr.
Chem. 1990, 9, 767-770; c) B. Castro, C. Selve, Bull. Soc. Chim. Fr.
1971, 4368; d) G. F. Hennion, R. S. Hanzel, J. Am. Chem. Soc. 1960,
82, 4908-4912; e) I. E. Kopka, A. Fataftah, M. W. Rathke, J. Org. Chem.
1980, 45, 4616-4622; f) P.-Q. Huang, W. Ou, F. Han, Chem. Commun.
2016, 52, 11967.
1
1-yn-3-yl)-L-lysinate (5oo): H NMR (400 MHz, CDCl3): δ = 7.55 (d, J =
8.3 Hz, 2H, aromatic), 7.50 (d, J = 8.2 Hz, 2H, aromatic), 6.05 (d, J = 7.4
Hz, 1H, NHCOCH3), 4.62 (dt, J = 5.7, 7.6 Hz, 1H, CHCO2Me), 3.73 (s,
3H, OCH3), 2.80 – 2.68 (m, 2H, NCH2), 2.01 (s, 3H, NHCOCH3), 1.93 –
1.83 (m, 3H), 1.74 – 1.65 (m, 1H), 1.56 – 1.37 (m, 3H), 1.32 (s, 3H,
CH3Cq), 1.08 (d, J = 6.7 Hz, 3H, CH(CH3)CH3), 1.02 (d, J = 6.8 Hz, 3H,
CH(CH3)CH3), NH overlapping ppm. 13C NMR (100 MHz, CDCl3): δ =
173.2 (CO2Me), 169.85 and 169.84 (CONH), 131.9 (CHmetaCCF3), 129.6
[8]
[9]
J. P. Guthrie, Can. J. Chem. 1975, 53, 898-906.
O. P. Pereshivko, V. A. Peshkov, E. V. Van der Eycken, Org. Lett. 2010,
12, 2638-2641.
2
3
(q, JC-F = 32.6, CipsoCF3), 127.4 (CHparaCCF3), 125.2 (q, JC-F = 3.7,
1
CHorthoCCF3), 124.0 (q, , JC-F = 272.1, CF3), 96.13 and 96.11 (ArCC),
[10] a) M. Cheng, Q. Zhang, X-Yu Hu, Bo-G. Li, Jian-Xin Ji, Albert S. C.
Chan, Adv. Synth. Catal. 2011, 353, 1274-1278; b) N. Gommermann, C.
Koradin, K. Polborn, P. Knochel, Angew. Chem. 2003, 115, 5941-5944;
Angew. Chem. Int. Ed. 2003, 42, 5763-5766; c) N. Gommermann, P.
Knochel, Chem. Eur. J. 2006, 12, 4380-4392.
82.6 (ArCC), 57.81 and 57.79 (Cq), 52.4 (COOCH3), 52.1 (CHCO2Me),
43.40 and 43.39 (NCH2), 36.5 (CH(CH3)2), 32.5 (CH3Cq), 30.1, 30.0, 23.2,
23.1, 22.8, 18.1 (CH(CH3)CH3), 17.1 (CH(CH3)CH3) ppm. HRMS (ESI)
m/z calculated for [C23H31N2O3F3+H]+: 441.2360; found 441.2357.
[11] C. E. Meyet, C. J. Pierce, C. H. Larsen, Org. Lett. 2012, 14, 964-967.
[12] X. Tang, J. Kuanga, S. Ma, Chem. Commun. 2013, 49, 8976-8978.
[13] C. J. Pierce, C. H. Larsen, Green Chem. 2012, 14, 2672.
[14] L. Yin, Y. Otsuka, H. Takada, S. Mouri, R. Yazaki, N. Kumagai, M.
Shibasaki, Org. Lett. 2013, 15, 698-701.
Acknowledgments
This work was financed by Erasmus mundus, the FWO-Flanders,
University of Antwerp (BOF), and the Hercules Foundation.
[15] C. J. Pierce, M. Nguyen, C. H. Larsen, Angew. Chem. 2012, 124,
12455-12458; Angew. Chem. Int. Ed. 2012, 51, 12289-12292.
[16] a) Z. L. Palchak, D. J. Lussier, C. J. Pierce, H. Yoo, C. H. Larsen. Adv.
Synth. Catal. 2015, 357, 539-548; b) M. Periasamy, P. O. Reddy, I.
Satyanarayana, L. Mohan, A. Edukondalu. J. Org. Chem. 2016, 81,
987-999; c) M. Biyikal, M. Porta, P. W. Roesky, S. Blechert, Adv. Synth.
Catal. 2010, 352, 1870-1875.
Keywords: A3-coupling; KA2-coupling; Alkyne; amines; Zinc
[1]
For medicinal and pharmacological applications see: a) P. H. Yu, B. A.
Davis, A. Boulton, J. Med. Chem. 1992, 35, 3705-3713; b) J. L. Wright,
T. F. Gregory, S. R. Kesten, P. A. Boxer, K. A. Serpa, L. T. Meltzer, L.
D. Wise, J. Med. Chem. 2000, 43, 3408-3419; c) M. Weinstock, C.
Bejar, R. H. Wang, T. Poltyrev, A. Gross, J. P. M. Finberg, M. B. H.
Youdim, J. Neural. Transm. Suppl. 2000, 60, 157-169; d) O. Weinreb, S.
Mandel, O. Bar-Am, Y. Falach, M. Y. A. Tirosh, T. Amit, M. B. H.
Youdim, Neurotherapeutics 2009, 6, 163-174; e) B. A. Orit, A. Tamar,
W. Orly, Y. B. H. Moussa, M. Silvia, J. Alzheimer's Dis. 2010, 21, 361-
371.
[17] C. J. Pierce, H. Yoo, C. H. Larsen, Adv. Synth. Catal. 2013, 355, 3586-
3590.
[18] H. Guo, X. Liu, Q. Xie, L. Wang, D. L. Peng, P. S. Branco, M. B.
Gawande, RSC Adv. 2013, 3, 19812-19815.
[19] H. Naeimi, M. Moradian, Appl. Organometal. Chem. 2013, 27, 300-306.
[20] M. Srinivas, P. Srinivasu, S. K. Bhargava, M. L. Kantam, Catalysis
Today 2013, 208, 66-71.
[21] R. Hudson, S. Ishikawa, C. J. Li, A. Moores, Synlett 2013, 24, 1637-
1642.
[2]
[3]
A. H. V. Schapira, Oxidative Stress and Neuroprotection. The use of
rasagiline in Parkinson's disease. Vol. 71, (Eds.: H. Parvez, P.
Riederer), Vienna Springer, Austria, 2006, pp. 157.
[22] R. Fässler, C. S. Tomooka, D. E. Frantz, E. M. Carreira, Proc. Nat.
Acad. Sc. 2004, 101, 5843-5845.
[23] D. E. Frantz, R. Fässler, E. M. Carreira, J. Am. Chem. Soc. 1999, 121,
11245-11246.
a) A. Hoepping, K. M. J. George, J. F. Anderson, A. P. Kozikowski, J.
Med. Chem. 2000, 43, 2064-2071; b) V. Bavetsias, J. H. Marriott, C.
Melin, R. Kimbell, Z. S. Matusiak, F. T. Boyle, A. L. Jackman, J. Med.
Chem. 2000, 43, 1910-1926; c) N. Miyachi, F. Kanda, M. Shibasaki, J.
Org. Chem. 1989, 54, 3511-3511.
[24] B. Jiang, Y.-G. Si, Angew. Chem. 2004, 116, 218-220; Angew. Chem.
Int. Ed. 2004, 43, 216-218.
[25] B. Jiang, Z. Chen, W. Xiong, Chem. Commun. 2002, 1524-1525.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
[26] C. C. Malakar, B. U. W. Maes, K. Abbaspour Tehrani, Adv. Synth. Catal.
2012, 354, 3461-3467.
[32] a) H. Sterckx, J. De Houwer, C. Mensch, I. Caretti, K. Abbaspour
Tehrani, W. A. Herrebout, S. Van Doorslaer, B. U. W. Maes, Chem. Sci.
2016, 7, 346-357; b) H. Sterckx, J. De Houwer, C. Mensch, W.
Herrebout, K. Abbaspour Tehrani, B. U. W. Maes, Beilstein J. Org.
Chem. 2016, 12, 144-153.
[27] M. Zille, A. Stolle, A. Wild, U. S. Schubert, RSC Adv. 2014, 4, 13126-
13133.
[28] W. J. Moran, A. Rodríguez, Org. Biomol. Chem. 2012, 10, 8590-8592.
[29] Y. Ma, E. Lobkovsky, D. B. Collum, J. Org. Chem. 2005, 70, 2335-2337.
[30] B. Miriyala, S. Bhattacharyyab, J. S. Williamson, Tetrahedron 2004, 60,
1463-1471.
[33] N. Sharma, U. K. Sharma, N. M. Mishra, E. V. Van der Eycken, Adv.
Synth. Catal. 2014, 356, 1029-1037.
[34] L. Zhao, O. Basl, C.-J. Li, Proc. Natl. Acad. Sci. USA, 2009, 106, 4106-
4111.
[31] D. G. Korton, V. E. Haury, F. C. Davis, I. J. Mitchell, S. A. Ballard, J.
Org. Chem. 1954, 19, 1054-1066.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701567
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
FULL PAPER
Propargylamines
Syeda Aaliya Shehzadi, Aamer Saeed,
Filip Lemière, Bert U. W. Maes and
Kourosch Abbaspour Tehrani*
Page No. – Page No.
Text for Table of Contents
Zinc(II)-catalyzed synthesis of
propargyl amines by coupling of
aldimines and ketimines with alkynes
Imines derived from unactivated aldehydes or ketones and primary amines or α-amino acid esters, react with a wide variety of
terminal alkynes under Zn(II) triflate catalysis to give secondary propargyl amines bearing give tri- (from aldimines) and tetra- (from
ketimines) substituted -carbons.
This article is protected by copyright. All rights reserved.