[Silver(I)(Pyridine-Containing Ligand)] Complexes as unusual catalysts for A3-coupling reactions

Article abstract of DOI:10.1021/jo500981r

Two original macrocyclic silver(I)(pyridine-containing ligand) complexes [Ag(I)(Pc-L)] were synthesized and characterized. Their ability to catalyze the coupling among aldehydes, terminal alkynes and amines (A³-coupling) was demonstrated. The reaction could be performed under conventional as well as dielectric heating. The catalysts were effective in both cases, but dielectric heating allowed a lower catalyst loading and reduced ratio among reaction partners in shorter reaction times. The reaction scope was broad, including aryl/alkyl aldehydes, aryl/alkyl acetylenes and secondary aliphatic amines. Some unprecedented propargylamines have been prepared. The new catalytic system was also tested with more challenging coupling partners such as aniline and ketones.

Full text of DOI:10.1021/jo500981r

Subscriber access provided by MEMORIAL UNIV
Article
[Silver(I)(Pyridine-Containing Ligand)] complexes
as unusual catalysts for A3-coupling reactions
Michael Trose, Monica Dell'Acqua, Tommaso Pedrazzini, Valentina Pirovano,
Emma Gallo, Elisabetta Rossi, Alessandro Caselli, and Giorgio Abbiati
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo500981r • Publication Date (Web): 22 Jul 2014
Downloaded from http://pubs.acs.org on August 1, 2014
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 16
The Journal of Organic Chemistry
1
2
3
4
5
6
[Silver(I)(Pyridine-Containing Ligand)] complexes as
unusual catalysts for A3-coupling reactions
7
8
9
Michael Trose,a,b Monica Dell’Acqua,a Tommaso Pedrazzini,b Valentina Pirovano,a
Emma Gallo,b Elisabetta Rossi,a Alessandro Casellib* and Giorgio Abbiatia*
10
11
12
13
14
15
16
17
18
a Dipartimento di Scienze Farmaceutiche, Sezione di Chimica Generale e Organica “A. Marchesini”,
Università degli Studi di Milano, Via Venezian, 21, 20133 Milano, Italy
b Dipartimento di Chimica, Università degli Studi di Milano,
and CNR - Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133 Milano, Italy
Corresponding authors: e-mail: giorgio.abbiati@unimi.it
e-mail: alessandro.caselli@unimi.it
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Graphical Abstract
Abstract
Two original macrocyclic silver(I)(pyridine-containing ligand) complexes [Ag(I)(Pc-L)] were synthesized and
characterized. Their ability to catalyze the coupling among aldehydes, terminal alkynes and amines (A3-
coupling) was demonstrated. The reaction could be performed under conventional as well as dielectric
heating. The catalysts were effective in both cases, but dielectric heating allowed a lower catalyst loading
and reduced ratio among reaction partners in shorter reaction times. The reaction scope was broad,
including aryl/alkyl aldehydes, aryl/alkyl acetylenes and secondary aliphatic amines. Some unprecedented
propargylamines have been prepared. The new catalytic system was also tested with more challenging
coupling partners such as aniline and ketones.
Introduction
Multicomponent reactions (MCR’S) enable the synthesis of complex molecules starting from more than two
simple building blocks in a single operative step.1 These strategies allow reducing the overall time required
to obtain the desired product, beside a valuable solvents and energy saving, and the reduction of waste
production. The advantages from the ecological and economic point of view are significant. In this context,
the transition-metal catalyzed three-component reaction of an aldehyde, an amine and an alkyne, better
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 16
1
2
3
4
5
6
7
8
9
known as A3-coupling,2 represents a worthwhile approach to propargylamines, which are recurrent
moieties in biologically active compounds and valuable intermediates for the synthesis of more complex
nitrogen-containing molecules. Starting from the pioneering works of Dax3 and Dyatkin,4 the most popular
procedures for A3-coupling are based on copper(I) catalysis.5 Moreover, the other coinage metals, silver6
and gold,7 gave valuable results8 too, and some other metals such as iron,9 indium,10 zinc,11 nickel,12 cobalt13
and mercury14 demonstrated their skill to catalyze this transformation. In particular, regarding silver based
catalysts, it is worth noting that the catalytic systems most frequently used are simple silver(I) salts (e.g.,
AgX,6,15 Ag2O,16 or Ag3PW12O4017) occasionally as acetonitrile complexes18 or (N-heterocyclic carbene)Ag(I)
complexes.19 Interestingly, when this MCR was endeavoured in the presence of phosphine-based Ag(I)
complexes, a switch of activity was observed, and surprisingly the simple propargyl alcohol originated from
aldehyde-alkyne coupling was obtained.20 On the other hand, the asymmetric version of the A3-coupling
(the so-called AA3-coupling) is absolutely dominated by Cu-based complexes,21 and to the best of our
knowledge no examples have been already reported with any other transition metal.22
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In connection with our ongoing interest in the study of metal catalyzed domino23 and multicomponent24
processes involving alkynes, carbonyl compounds and ammonia/amines, we are pleased to report a
microwave enhanced synthesis of propargylamines, catalyzed by well-defined Ag(I) complexes which are
characterised by the presence of an original tetraaza-macrocyclic ligand. Macrocyclic ligands display a
series of peculiar properties, when compared with their non-cyclic analogues, which render their
coordination chemistry and the catalytic activity of their complexes an interesting field of inquiry. These
includes kinetic (resistance to ligand exchange), thermodynamic (large formation constants), spectral (high
ligand field strengths), and structural effects.25 A few years ago, we introduced a new class of 12-membered
macrocyclic ligands, called Pc-L (Pyridine containing Ligands), which can be synthesised in good yields,
starting from commercially available reagents, even in enantiopure form. These macrocycles were firstly
synthetized by the group of research of Stetter in 1981,26 and some years later they have been
rediscovered as ligands for the coordination of lanthanide ions in MRI contrasting agents.27 By appropriate
choice of the starting materials in the target macrocycle synthesis, we reasoned that the presence of a
pyridine ring fused to the macrocycle could provide an enhanced conformational preorganization to the
molecule, binding strongly to the metal atom while still allowing for the coordination of other molecules
directly involved in the desired reaction. With the optimized reaction conditions, a small library of Pc-Ls has
been obtained, including enantiomerically pure stereoisomers, and their copper and silver complexes
demonstrated to be effective in catalysis. The cyclopropanation reaction of alkenes,28 and the Henry
reaction29 were successfully catalyzed by some original copper based (Pc-L) complexes. Very recently, the
addition/cycloisomerization reaction of 2-alkynylbenzaldehydes and alcohols under mild reaction
conditions was effectively promoted by some new [Ag(I)(Pc-L)] complexes.30
Results and discussion
As mentioned above, we recently reported on the synthesis of some well-defined [Ag(I)(Pc-L)]+X- complexes
(X = BF4, OTf, N(Tf)2) characterized by the presence of a benzyl group on N6, capable to catalyze in good
yield the one pot addition/cycloisomerization reaction of 2-alkynylbenzaldehdehydes and alcohols to yield
3-substituted-1-alkoxyisochromenes (Figure 1, A).30 These silver complexes were quite stable, versatile and
could be used without the need of a protective atmosphere, but they have the disposition to soak moisture
from air to form mono-acquo species (Figure 1, B). We have already shown recently that the presence of a
1-(naphthyl)methyl substituent on the N6 of the macrocycle confers a good stability to the metal
2
ACS Paragon Plus Environment

Page 3 of 16
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
complexes of these Pc-Ls (i.e., copper(I) complexes),28b by providing a further coordination site for the
metal atom (Figure 1, C). This additional coordination site provided by the naphthyl group works as a
“protecting cap” for the metal center, so avoiding the formation of undesirable pentacoordinated species
with adventitious solvents or water. On the other hand, a suitable more electron-rich molecule in the
reaction environment could easily displace the naphthyl cap (Figure 1, D).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 1. [M(Pc-L)]+X- complexes used in the synthesis of isochromenes (A) and in this work (C).
For that reason in the present study we turned our attention to the use of the 1-(naphthyl)methyl
substituted Pc-L, 1, that can be obtained in good overall yield from commercially available starting
materials according to Scheme 1.28b The synthetic strategy involved the nucleophilic ring opening of 1-
tosylaziridine by naphthalen-1-ylmethanamine to give the corresponding 1,7-ditosyl-4-(naphthalen-1-
ylmethyl)-1,4,7-triazaheptane in quantitative yields. The approach has been improved by the use of
dielectric heating, that not only allowed an overall increase of the yield in shortened reaction times, but
moreover the product obtained was sufficiently pure to be used in the macrocyclization step, without need
of further purification. Thus, the so obtained bis-protected triamine was directly reacted with 2,6-
pyridinedimethanol 2,6-dimesylate in refluxing anhydrous acetonitrile in the presence of anhydrous K2CO3,
to yield the macrocycle 1 in 76% yield.
Scheme 1. Synthesis of pyridine-containing ligand 1 and its silver complexes 2a-b
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 16
1
2
3
4
5
6
7
8
9
The silver(I) complexes 2a-b were synthesized in good yields by simple reaction in 1,2-dichloroethane of
macrocyclic ligand with the proper silver salts.30 In the step of formation of the complex, the silver salts and
all silver containing solutions were kept in the dark and under protective atmosphere until the isolation of
the final products. The silver complexes were collected as white powder from n-hexane and once isolated
showed a remarkable stability in open air. They have been fully characterized by NMR, IR and UV-vis
spectroscopies and electrospray ionization mass spectrometry (ESI-MS) analyses. As already observed for
copper complexes,28b also the new silver complexes 2a-b displayed the η2 coordination of the naphthyl
substituent (Scheme 1) as established by 1H and 13C NMR studies in CDCl3 solution. In both 13C NMR spectra
of complexes 2a-b (that showed a very close signals pattern) a significant shift to lower frequencies of the
carbon a involved in the η2 bond with silver was observed, precisely from 125.1 ppm in the free ligand 1 to
112.3 and 112.4 ppm in the silver complexes 2a-b, respectively (see supporting information). Moreover, in
13C NMR APT (attached-proton test) experiments, the signal around 112 ppm appeared broadened,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
probably due to the coupling with the silver atom. An opposite effect could be observed in the H NMR,
where the proton directly bound to carbon a experienced a higher frequencies shift (i.e., from 8.13 ppm in
the free ligand 1, to 9.16 and 9.18 in complexes 2a and 2b, respectively). A similar high frequency shift,
although to a lesser extent, is observed also for the proton bound to carbon b (from 7.45 ppm in 1, to 7.90
1
and 7.92, respectively, in the metal complexes 2a-b). The observed coupling constant JC-H of 157 Hz for
1
carbon a in complex 2b provided a hint of a partial re-hybridization state from sp2 to sp3. A H-19F HOESY
(heteronuclear Overhauser effect spectroscopy) spectrum of complex 2a in deuterated chloroform showed
that the tetrafluoborate anion has weak proximity interactions only with the pyridine ring (see supporting
information). A comparison between the UV spectra of the ligand 1 and of the metal complexes 2a-b
showed that the shape of the absorption bands did not change upon complexation, and only modest
differences in the intensities were observed. The measured bands in the near UV were thus attributed to
ligand-centered transitions and were consistent with the absence of colour of the complexes 2a and 2b.
-
We started our study testing the [Ag(I)(Pc-L)]+ BF4 complex 2a on a model reaction involving simple and
easily available starting materials, i.e., benzaldehyde 3a, phenylacetylene 4a and pyrrolidine 5a. The results
are reported in table 1. In a first experiment, we tried the reaction in 0.5 mmol scale using the ratio among
reagents, the temperature, and the catalyst loading more frequently reported in the literature for A3-
couplings (i.e., ratio aldehyde/amine/alkyne = 1 : 1.5 : 1.5, T = 100 °C, cat. 3 mol %). Under these typical
reaction conditions, we briefly explored the effect of some different solvents with decreasing relative
polarity31 (Table 1, entries 1-5). We were pleased to find that complex 2a was able to catalyze the reaction
in all solvent tested. Higher yields were obtained performing the reaction in water, methanol and in
toluene (Table 1, entries 1, 2 and 5). It is interesting to note that, despite the low solubility in water of the
catalyst 2a and reactants 3a, 4a and 5a, the reaction however took place with fair yields (Table 1, entry 1),
although at the end of the reaction a great amount of free metallic silver(0) was observed in the bottom of
the test tube. A similar behaviour was detected when the reaction was performed in methanol (Table 1,
entry 2), whereas in toluene only traces of Ag(0) as silver mirror were observed on the internal surface of
the test tube (Table 1, entry 5), so this solvent was chosen to optimize the conditions. The addition of a
small amount of 3 Å molecular sieve did not strongly influence the reaction yields in both best solvents (i.e.,
methanol and toluene, Table 1, entries 6 and 7). Decreasing the temperature to rt the reaction became
extremely sluggish and the yield was poor (Table 1, entry 8). Conversely, increasing the catalyst loading to 6
mol % a improvement in yield up to 87% was observed (Table 1, entry 9). Moreover, changing the counter
-
ion of the complex from BF4 (2a) to the slightly more coordinating32 TfO- (2b) an additional rise in yield was
observed (Table 1, entry 10).
4
ACS Paragon Plus Environment

Page 5 of 16
The Journal of Organic Chemistry
1
2
3
Table 1. Exploring the best reaction conditions under conventional heatinga
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry cat. (mol %)
solv.
molecular sieves T (°C) t (h)
6a (yieldb %)
4 Å
1
2
3
4
5
6
7
8
9
2a (3)
2a (3)
2a (3)
2a (3)
2a (3)
2a (3)
2a (3)
2a (3)
2a (6)
2b (6)
Water
MeOH
DMF
-
-
-
-
-
100
100
100
100
100
100
100
rt
4
4
4
4
4
3
3
90
5.5
4.5
65
62
26
22
60
57
54
31
87
96
DCE
Ph-Me
MeOH
Ph-Me
Ph-Me
Ph-Me
Ph-Me
yes
yes
yes
-
100
100
10
-
a Reaction conditions: 3a (0.53 mmol), 4a (0.80 mmol), 5a (0.80 mmol), solvent (1 mL),
cat., screw capped tube, oil bath, 100 °C. b Yields of pure isolated product.
In spite of the remarkable results obtained, the approach suffers for the relatively long reaction times (4-5
h) and quite high catalyst loading (6 mol %). To improve the efficiency of the approach we decide to change
the energy source. The ability of dielectric heating to promote different type of Cu(I) catalyzed A3-coupling
has been well established and described by Leadbeater,33 Tu34 and Van der Eycken,35 so we decide to
proceed our study under microwave irradiation (Table 2). It is well known that the efficiency of dielectric
heating is strongly related to the nature and the polarity of the solvent.36 For this reason we repeated the
solvent screening (Table 2, entries 1-6) and, somewhat surprisingly, we found that also under microwave
heating toluene demonstrated to be the best solvent (Table 2, entry 5); the reaction was complete in 15
min with excellent yield. Moreover, we found that the ratio among reaction partners could be
advantageously reduced to 1 : 1.03 : 1.03 without loss of efficiency. Furthermore, we tried to reduce also
the catalyst loading (Table 2, entries 7 and 8) and we found that 3 mol % of the catalyst was sufficient to
obtain excellent results (Table 2, entry 7) whereas in the presence of 1 mol % of catalyst the yield drop-out
to 67% (Table 2, entry 8). Also the reaction time can be reduced to 10 min without appreciable loss of
efficiency (Table 2, entry 9), whereas 5 min resulted in slightly lower yield (Table 2, entry 10). Finally, we
performed two control experiments under the optimized reaction conditions in the presence of simple
silver triflate as catalyst (Table 2, entries 11 and 12). Though the model reaction in the presence of 3 mol %
of AgOTf gave the product 6a in very good yield, the activity of complex 2b appeared superior (Table 2, cf.
entry 7 and 11) ─ in particular when the catalyst loading was reduced to 1 mol % (Table 2, cf. entry 8 and
12) ─ thus confirming a certain ligand effect. To be sure that also under this relatively harsh reaction
conditions, the active catalytic species were actually the Ag[Pc-L] complexes and not degradation products
or an in situ generated silver nanoparticles, we made two additional experiments. The complex 2a was
heated at 150 °C in toluene (complex 2a is slightly soluble in toluene at rt, but dissolves at 150 °C) by
dielectric heating for 10 min. Despite at the end of the heating we observed a small amount of dark
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 16
1
2
3
1
precipitate in the test tube, the H NMR of the solution revealed that the silver(I) complex was still intact.
Moreover, we performed the model reaction under conventional heating at 120 °C in the presence of a
drop of mercury as np-inhibitor:37 after two hours, we obtain the desired propargylamine 6a in 36 % yield.
4
5
6
7
8
9
Table 2. Exploring the best reaction conditions under microwave heatinga
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry
1
2
3
4
5
6
7
8
cat. (mol %)
2b (6)
solvent
MeOH
Me-CN
DCE
t (min)
15
15
15
15
15
15
15
15
10
5
6a (yieldb %)
46
62
68
9
96
61
95
67
96
93
88
52
2b (6)
2b (6)
2b (6)
2b (6)
2b (6)
2b (3)
2b (1)
2b (3)
Dioxane
Ph-Me
Cyclohexane
Ph-Me
Ph-Me
Ph-Me
9
10
11
12
2b (3)
AgOTf (3)
AgOTf (1)
Ph-Me
Ph-Me
Ph-Me
15
15
a Reaction conditions: 3a (0.53 mmol), 4a (0.55 mmol), 5a (0.55 mmol), solvent (1 mL), cat.,
microwave screw capped tube, mW, 150 °C. b Yields calculated via 1H NMR using dimethyl
terephthalate (DMT) as internal standard.38
With the best conditions in hands, we explored scope and limitation of the reaction. In particular, our
target was to verify the ability of our catalysts to promote the reaction among partners of different nature,
such as substituted aliphatic and aromatic aldehydes, alkynes substituted with alkyl or aryl moieties, and
secondary amines. The results are reported in table 3. EWGs and EDGs on arylalkyne partner were in
general well-tolerated (Table 3, entries 2, 3, 11-13), except for strongest EWG such as nitro group (Table 3,
entry 4). Benzaldehyde derivatives bearing EWGs or EDGs in any position of the ring gave satisfying results
(Table 3, entries 6-8) as well as cyclohexanecarbaldehyde (Table 3, entries 9 and 11). Nevertheless, also in
this case lower yields were obtained when the aldehyde was characterized by an acyclic alkyl substitution
(Table 3, entry 10). The nature of the amine seemed to be the more critical feature. Cyclic secondary
amines such as pyrrolidine and piperidine gave best results (Table 3, entries 1-3, 6-9, 11-13), whereas
acyclic secondary amines (Table 3, entries 15, 16), and less basic cyclic amines as morpholine (Table 3, entry
14) gave only fair to good reaction yields.
6
ACS Paragon Plus Environment

Page 7 of 16
The Journal of Organic Chemistry
1
2
3
Table 3. Scope of (Pc-L)-Ag(I) catalyzed A3-coupling with secondary amines
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aldehyde 3
R1
3a: Ph-
3a: Ph-
3a: Ph-
3a: Ph-
3a: Ph-
3b: p-MeO-Ph-
3c: m-Cl-Ph-
3d: o-OH-Ph-
3e: Cy-
alkyne 4
R2
4a: Ph-
amine 5
entrya cat.
R3
R4
6 (yieldb %)
6a 96
1
2
2b
2b
2b
2b
2b
2b
2a
2b
2b
2a
2b
2b
2b
2b
2bf
2b
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5b: -(CH2)5-
5b: -(CH2)5-
5c: -(CH2)2O(CH2)2-
4b: p-MeO-Ph-
4c: m-F-Ph-
4d: p-NO2-Ph-
4e: n-Pr-
4a: Ph-
6b 75
6c 83
3
4
5
6
-
6d 53c
6e 78c
6f 79
7
8
9
4a: Ph-
4a: Ph-
4a: Ph-
4a: Ph-
6g 83
6h 98 (81)d
6i 61 (62)e
6j 89
10
11
12
13
14
15
16
3f: n-Bu-
3e: Cy-
3a: Ph-
3e: Cy-
3a: Ph-
4b: p-MeO-Ph-
4b: p-MeO-Ph-
4c: m-F-Ph-
4a: Ph-
6k 91
6l 96
6m 59c
6n 57c (61)e
6o 61c
3a: Ph-
3a: Ph-
4a: Ph-
4a: Ph-
5d: Et-
5e: Bn-
Et-g
Bn-
a Reaction conditions: 3a (0.53 mmol), 4a (0.55 mmol), 5a (0.55 mmol), toluene (1 mL), cat. (3 mol%),
b
c
microwave screw capped tube, mW, 150 °C, 10 min. Yields of pure isolated products. Reaction
time: 20 min. With AgOTf as cat. (calculated as indicated in footnote e). Yields calculated via H
NMR using dimethyl terephthalate (DMT) as internal standard. Cat. loading = 6 mol %. Equiv of
amine = 2.
d
e
1
f
g
It is well known that the A3-coupling process was mainly optimized with aliphatic secondary amines for the
synthesis of tertiary propargylamines. Considerable work has been done also with anilines for the synthesis
of secondary N-arylpropargylamines, but it is difficult to find a single catalytic system capable to efficiently
catalyze both the transformations.34 Moreover, primary alkyl amines as well as ketones were generally
considered to be very difficult substrates. With the aim to broaden the scope of our approach, we tested
our [Ag(I)(Pc-L)] catalysts with some of these more challenging substrates, in particular aromatic amines
and ketones. A number of examples of A3-coupling reactions with anilines as amine partners have been
reported in the literature, mainly catalyzed by Cu(I) salts and complexes,21d,e, 39 or else Ru(III)-Cu(I),40 AuCl3-
CuBr,41 and InBr3,10b but only a single reaction catalyzed by a simple silver catalyst (silver iodide) was
published.42 On the other side, in the literature are reported some examples of that variant of A3-coupling,
called KA2-coupling, that involves the use of a ketone instead of an aldehyde to yield propargylamines
bearing a quaternary carbon. In most cases these reactions were performed with copper(I/II)43 salts as
catalysts, but also isolated examples catalyzed by gold(III)44 and Ti(IV)/Cu(II)45 salts were reported.
However, to the best of our knowledge, no examples of Ag catalyzed KA2-coupling have been already
reported.
The results of our exploratory study with more challenging substrates are summarized in table 4. The first
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 16
1
2
3
4
5
6
7
8
9
attempt was performed with benzaldehyde 3a, phenylacetylene 4a and aniline 5f. The reaction conditions
were slightly modified: the catalyst loading and the reaction time were increased to 6 mol % and 20 min,
respectively (Table 4, entry 1). Under these conditions, the corresponding propargylamine 6p was obtained
in a modest 28 % yield, beside a 68 % yield of the imine 7. Also in this case, the addition of molecular sieve
did not improve the yield of the desired product (Table 4, entry 2). Slightly better results were obtained by
increasing the amount of alkyne 4a, but also in these cases the imine 7 remained the main product (Table 4,
entries 3 and 4). Conversely, the use of a three-fold excess of amine and aldehyde partners was
unsuccessful (Table 4, entry 5). Based on these results we argued that the low yields obtained were not
related to the imine formation stage, but probably to a more difficult addition of the activated alkyne on
the less electrophilic carbon of the imine intermediate. With the aim to obtain a more reactive aryl-iminium
intermediate we tested the reaction with diphenylamine 5g, as secondary arylamine5a but in these cases
the reactions totally failed (Table 4, entries 6 and 7), and complex mixtures of unidentified products were
obtained.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Concerning the KA2-coupling, we briefly tested the reactivity of 2-pentanone 8a, phenylacetylene 4a and
pyrrolidine 5a in the reaction conditions adopted for the A3-couplings with aniline (i.e., toluene, 6 mol % of
catalyst, microwave heating, 150°C, 20 min), and different molar ratio between reactants were tested
(Table 4, entries 8-10). With the aim to facilitate the formation of the keto-iminium cation, 4Å molecular
sieves were added to the reaction mixture. Unfortunately, also in these cases the reaction yields were
unsatisfactory. Probably, the reaction is low yielding due to the intrinsic lower reactivity of ketones more
hindered and less electrophilic than aldehydes. This hypothesis was also supported by the complete failure
of the reaction with the less reactive acetophenone 8b and benzophenone 8c (table 4, entries 11 and 12).
Table 4. Study of the reaction with more challenging substrates
ratio
molecular
sieves 4 Å
6 or 9
(Yielda %)
6p: 28
6p: 24
6p: 34
6p: 42
6p: 30
-
7
entry
R1
R2
R3
R4
3 or 8 : 4 : 5
1 : 1.03 : 1.03
1 : 1.03 : 1.03
1.03 : 2 : 1
1 : 3 : 1.03
3 : 1 : 3
(Yielda %)
1
2
3
4
5
6
7
3a: Ph-
3a: Ph-
3a: Ph-
3a: Ph-
3a: Ph-
3a: Ph-
3e: Cy-
H-
H-
H-
H-
H-
H-
H-
5f: Ph-
5f: Ph-
5f: Ph-
5f: Ph-
5f: Ph-
5g: Ph-
5g: Ph-
H-
H-
H-
H-
H-
-
68
74
58
55
74b
-
yes
-
-
-
-
-
Ph-
Ph-
1 : 1.03 : 1.03
1 : 1.03 : 1.03
-
-
8
9
10
11
8a: n-Pr- Me-
8a: n-Pr- Me-
8a: n-Pr- Me-
5a: -(CH2)4-
1 : 1.03 : 1.03
2 : 1 : 2
1 : 2 : 1
1 : 1.03 : 1.03
1 : 1.03 : 1.03
yes
yes
yes
yes
yes
9a: 30
9a: 32
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
5a: -(CH2)4-
9a: 36c (33)d
9b: -
8b: Ph-
8c: Ph-
Me-
12
Ph-
9c: -
a
1
Yields calculated via H NMR using dimethyl terephthalate (DMT) as internal standard with respect to
limiting reagent. With respect to aniline. Under conventional heating at 100 °C for 1.5 h. Isolated
yield.
b
c
d
8
ACS Paragon Plus Environment

Page 9 of 16
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1H NMR experiments in CDCl3 at room temperature showed no interaction between the metal complexes
and the aldehyde, while a remarkable shift, especially for the signals originally involved in the η2
coordination of the naphthyl moiety to the silver atom were observed upon addition of both the
phenylacetylene 4a or pyrrolidine 5a. In the absence of any base, however, complex 2a reacts very easily
with a terminal alkyne to give the silver acetylide. This liberates acid, which protonates the ligand causing
partial decomplexation. This decomplexation does not happen in the presence of a stoichiometric amount
of pyrrolidine. Based on the experimental results and taking in mind the literature findings,6, 19c a tentative
mechanism was proposed: first the catalyst form the π-complex (I) with the alkyne 4 (an equilibrium with
the silver complex coordinated to the amine cannot be however ruled out). This increase the acidity of
acetylenic hydrogen which is removed by the amine (or more probably by the emiaminal intermediate
resulted from the reaction between the amine 5 and the aldehyde 3) to give silver acetylide II. The proton
assisted condensation between the amine 5 and the aldehyde 3 generate a molecule of water and the
iminium halide III, which reacts with the silver acetylide II to afford the desired propargylamine 6 and
regenerate the catalyst (Scheme 2).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Tentative mechanism proposed
Conclusions
In conclusion, we have synthesized and in depth characterized two original Ag(I)(Pc-L) complexes and their
catalytic activity was tested in A3-coupling MCR. We optimized the reaction conditions both under
conventional and microwave heating. The catalysts were effective in both cases, but dielectric heating
allowed a lower catalyst loading and a reduced ratio among reaction partners in shorter reaction times. The
reaction scope was broad when secondary aliphatic amines were used and some unprecedented
propargylamines have been prepared. This work represent the first example of A3-coupling catalyzed by
tetraaza-macrocyclic silver complexes. Moreover, some explorative experiments demonstrated that the
new catalysts worked with more challenging reaction partners such as aromatic amines and ketones too,
although the results, in these cases, are only modest. Current efforts are now devoting to design and
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 16
1
2
3
4
5
synthesize some new chiral [Pc-L]* ligands characterized by a well-planned chiral profile able to induce
stereoselectivity in this valuable MCR.
6
7
8
9
EXPERIMENTAL SECTION
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General Experimental Details. All of the reactions that involved the use of reagents sensitive to oxygen or
hydrolysis were carried out under an inert atmosphere. The glassware was previously dried in an oven at
110 °C and was set with cycles of vacuum and nitrogen. Also syringes, used to transfer reagents and
solvents, were previously set under a nitrogen atmosphere. The syntheses of the silver complexes were
carried out under a nitrogen atmosphere by employing standard Schlenk techniques. All chemicals and
solvents were commercially available and were used after distillation or treatment with drying agents. The
chromatographic column separations were performed by a flash technique, using silica gel (pore size 60 Å,
particle size 230−400 mesh, Merck grade 9385). For TLC, silica was used on TLC Alu foils with fluorescent
indicator (254 nm) and the detection was performed by irradiation with UV light (λ = 254 nm or 366 nm). 1H
NMR analyses were performed with 200, 300, or 400 MHz spectrometers at room temperature. The
coupling constants (J) are expressed in hertz (Hz), and the chemical shifts (δ) in ppm. 13C NMR analyses
were performed with the same instruments at 50.3, 75.5, and 100 MHz, and attached proton test (APT)
sequence was used to distinguish the methine and methyl carbon signals from those arising from
methylene and quaternary carbon atoms. All 13C NMR spectra were recorded with complete proton
decoupling. The 1H NMR signals of the ligand described in the following have been attributed by correlation
spectroscopy (COSY) and nuclear Overhauser effect spectroscopy (NOESY) techniques. Assignments of the
resonance in 13C NMR were made using the APT pulse sequence and heteronuclear single quantum
correlation (HSQC) and heteronuclear multiple bond correlation (HMBC) techniques. The 15N NMR signals
of the compound described have been attributed by HMBC technique. Low resolution MS spectra were
recorded with instruments equipped with electron ionization (EI), ESI/ion trap (using a syringe pump device
to directly inject sample solutions), or fast atom bombardment (FAB) (for Pc-L and metal complexes)
sources. The values are expressed as mass−charge ratio and the relative intensities of the most significant
peaks are shown in brackets. High resolution MS spectra were recorded with an instrument equipped with
an electrospray source and a ion cyclotron resonance-Fourier transform mass spectroscopy (ICR-FTMS)
analyzer. UV−vis spectra of the ligand and its silver complexes were recorded in CHCl3. The melting points
of the solid products are uncorrected. Microwave promoted reactions were performed with a single-mode
Personal Chemistry microwave synthesizer “Emrys Creator,” using sealed glass vessels. The temperature
was detected with an infrared sensor.
Synthesis of 1,7-ditosyl-4-(naphthalen-1-ylmethyl)-1,4,7-triazaheptane. A solution of tosyl aziridine (0.769
g, 3.90 mmol) and 1-naphthylmethylamine (0.283 g, 1.80 mmol) in MeOH (15 mL) was stirred and heated
by microwave irradiation for 1 h at 120 °C. The mixture was dried and used without any further purification.
Yield quantitative (0.993 g, 1.80 mmol). 1H NMR (300 MHz, CDCl3, δ): 8.14 (d, J = 8.3 Hz, 1H, Har), 7.86 (d, J =
8.3 Hz, 1H, Har), 7.78 (m, 1H, Har), 7.54 (d, J = 8.0 Hz, 4H, Har) overlapping with 7.61-7.49 (m, 2H, Har), 7.42-
7.32 (m, 2H, Har), 7.19 (d, J = 8.0 Hz, 4H, Har), 4.83 (bs, 2H, NH), 4.00 (s, 2H, CH2), 2.90 (m, 4H, CH2), 2.66 (m,
4H, CH2), 2.38 (s, 6H, CH3). The spectral data are consistent with those previously reported.28b
Synthesis of 6-(naphthalen-1-ylmethyl)-3,9-ditosyl-3,6,9,15-tetraazabicyclo[9,3,1]pentadeca-1(15),11,13-
triene 1. A solution of 1,7-ditosyl-4-(naphthalen-1-ylmethyl)-1,4,7-triazaheptane (2.053 g, 3.731 mmol),
2,6-bis(methanesulfonyloxymethyl)pyridine (1.101 g, 3.731 mmol) and micronized anhydrous potassium
10
ACS Paragon Plus Environment

Page 11 of 16
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
carbonate (1.547 g, 11.19 mmol) in freshly distilled acetonitrile (110 mL) was stirred and heated under
reflux for 16 h. The mixture was washed with water (150 mL) and extracted with ethyl acetate (3 x 80 mL).
The organic layers were dried with sodium sulphate and then evaporated to dryness under reduced
pressure. The crude product was then dissolved in hot ethyl acetate (60 mL), filtered while hot and layered
with n-hexane (35 mL). After cooling at 0 °C an amorphous yellowish solid fell out from the solution. The
solid was filtered off and the mothers liquors were evaporated to dryness, yielding a white solid. Yield =
1.857 g, 76%. 1H NMR (400 MHz, CDCl3, δ): 8.14 (d, J = 8.1 Hz, 1H, Hi), 7.91 (d, J = 7.8 Hz, 1H, Hd o Hf),7.87 (d,
J = 8.1 Hz, 1H, Hd o Hf), 7.78 (t, J = 7.8 Hz, 1H, Hr), 7.50 (d, J = 8.2 Hz, 4H, Hn)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
overlapping with 7.51-7.45 (m, 3H, Har), 7.39 (d, J = 7.8 Hz, 2H, Hq), 7.35 (d, J
2
= 6.9 Hz, 1H, Hb), 7.19 (d, J= 8.2 Hz, 4H, Ho), 4.31 (s, 4H, CH2 and CH210), 3.93
4
8
(s, 2H, CH213), 3.07 (m, 4H, CH2 and CH2 ), 2.40 (s, 6H, CH314), overlapping
5
7
with 2.36 (m, 4H, CH2 and CH2 ). 13C NMR (100 MHz, CDCl3, δ): 155.3 (C1),
143.7 (Cp), 139.2 (CrH), 136.2 (Cm), 134.9 (C), 134.3 (C), 132.8 (C), 130.1
(CoH), 128.8 (CArH), 128.5 (CArH), 127.7 (CArH), 127.4 (CnH), 126.04 (CArH),
125.98 (CArH), 125.7 (CArH), 125.1 (CiH), 124.4 (CqH), 58.5 (C13H2), 54.7 (C2H2),
50.9 (C5H2), 44.7 (C4H2), 21.9 (C14H3). 15N NMR (40 MHz; CDCl3, δ): 312 (N12),
95 (N-Ts), 32 (N6). MS (FAB): m/z (%) = 655 (100) [MH]+, 499 (34) [MH–Ts]+.
UV/vis (5.2 10-5 mol L-1, CHCl3 in 1-cm cuvettes): λmax [nm] = 242, 264, 283,
296 nm.
General procedure for the synthesis of silver complexes 2a-b. The silver salt and all silver-containing
solutions were kept in the dark until the final isolation of the product. The ligand 1 was dissolved in 1,2-
dichloroethane, the silver salt (weighed under a nitrogen atmosphere) was added and the mixture stirred
for one hour, then filtered to remove any unreacted solid. The solvent was evaporated to dryness, then n-
hexane was added and the product recovered by filtration in open air.
2a: 1 (MW = 654.84; 0.137 g; 0.209 mmol), AgBF4 (MW = 194.67; 0.041 g; 0.21 mmol), C2H4Cl2 (10 mL), n-
hexane (20 mL). Yield 0.161 g (MW = 849.51) 90 %. 1H NMR (300 MHz, CDCl3, δ): 9.16 (d, J = 8.1 Hz, 1H, Hi),
8.12 (d, J = 8.1 Hz, 1H, Hf), 7.99 (d, J =8.1 Hz, 1H, Hd), 7.90 (m, 1H, Hh), 7.81 (t, J = 7.9 Hz, 1H, Hr), 7.72 (m,
1H, Hb), 7.67-7.59 (m, 2H, Hc and Hg) overlapping with 7.59 (d, J = 7.8 Hz, 4H, Hn), 7.41 (d, J = 7.8 Hz, 4H, Ho),
2
7.24 (d, J = 7.9 Hz, 2H, Hq), 4.89 (d, J = 15.0 Hz, 2H, CH2 and CH210), 4.35 (br s, 2H, CH213), 3.50 (d, J = 15.0 Hz,
2H, CH22’ and CH210’) overlapping with 3.51-3.48 (m, 2H, CH2), 2.81 (m, 2H, CH2), 2.59 (m, 2H, CH2), 2.49 (s,
6H, CH314), 2.13 (m, 2H, CH2).13C NMR (75 MHz, CDCl3, δ): 154.0 (C1), 146.0 (Cp), 141.0 (CrH), 135.3 (Cm),
133.8 (C), 133.2 (C), 132.5 (CfH), 131.1 (C), 130.8 (CoH), 130.7 (CbH), 130.0 (CdH), 128.6 (CnH), 127.1 (ChH),
126.4 (CArH), 125.8 (CArH), 125.3 (CqH), 112.3 (CiH), 56.4 (C13H2), 56.3 (C2H2 and C10H2), 54.7 (CH2), 48.3 (CH2),
22.1 (C14H3). 19F NMR (282 MHz, CDCl3, δ): -152.8. MS (FAB): m/z (%) = 761/763 (90/100) [M – BF4]+, 655
(37) [MH – AgBF4]+. UV/vis (5.2 10-5 mol L-1, CHCl3 in 1-cm cuvettes): λmax [nm] = 242, 264, 284, 295 nm.
Anal. Calcd for C36H38AgBF4N4O4S2: C, 50.90; H, 4.51; N, 6.60. Found: C, 50.75; H, 4.61; N, 6.43.
2b: 1 (MW = 654.84; 0.867 g; 1.32 mmol), AgOTf (MW = 256.94; 0.340 g; 1.32 mmol), C2H4Cl2 (26 mL); n-
hexane (15 mL), Yield 1.077 g (MW = 911.78) 89 %. 1H NMR (300 MHz, CDCl3, δ): 9.18 (d, J = 8.4 Hz, 1H, Hi),
8.12 (d, J = 8.4 Hz, 1H, Hf), 8.00 (d, J =8.1 Hz, 1H, Hd), 7.92 (m, 1H, Hh), 7.84 (t, J = 7.7 Hz, 1H, Hr), 7.73 (m,
1H,Hb), 7.69-7.62 (m, 2H, Hc and Hg), 7.59 (d, J = 8.2 Hz, 4H, Hn), 7.41 (d, J = 8.2 Hz, 4H, Ho), 7.26 (d, J = 7.7
2
Hz, 2H, Hq), 4.88 (d, J = 15.0 Hz, 2H, CH2 and CH210), 4.36 (br s, 2H, CH213), 3.59 (d, J = 15.0 Hz, 2H, CH22’ and
CH210’) overlapping with 3.57-3.49 (m, 2H, CH2), 2.84 (m, 2H, CH2), 2.74 (m, 2H, CH2), 2.50 (s, 6H, CH314), 2.26
(m, 2H, CH2). 13C NMR (75 MHz, CDCl3, δ): 154.1 (C1), 146.0 (Cp), 141.0 (CrH), 135.3 (Cm), 133.7 (C), 133.2 (C),
132.7 (CfH), 131.2 (C), 130.8 (CoH) overlapping with 130.8 (CbH), 130.1 (CdH), 128.6 (CnH), 127.1 (ChH), 126.5
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 16
1
2
3
4
5
6
7
8
1
(CArH), 125.9 (CArH), 125.4 (CqH), 112.4 (CiH, J H-13C = 156.8 Hz), 56.6 (C13H2), 56.4 (C2H2 and C10H2), 54.8
(CH2), 48.3 (CH2), 22.1 (C14H3). 19F NMR (282 MHz, CDCl3): δ = -78.5. MS (FAB): m/z (%) = 761/763 (90/100)
[M – CF3SO3]+, 655 (35) [MH – AgCF3SO3]+. Anal. Calcd for C37H38AgF3N4O7S3: C, 48.74; H, 4.20; N, 6.14.
Found: C, 48.41; H, 4.52; N, 6.02.
9
General procedure for the A3-coupling under conventional heating. The reaction were performed in a 0.5
mmol scale in open air. The catalyst (2a or 2b, 0.03 mmol) was dissolved in dry toluene (1 mL) in a screw-
cap test tube equipped with a stirring bar. The suitable aldehyde (0.5 mmol), amine (0.75 mmol) and alkyne
(0.75 mmol) were added to the stirred solution, according to this order. The mixture was stirred and heated
with an oil-bath at 100 °C (for reaction times see table 1). The reaction mixture was diluted with ethyl
acetate (20 mL) and the organic layer was washed with water (20 mL) and brine (20 mL). The organic layer
was dried over sodium sulphate, and the solvent was evaporated under reduced pressure. The reaction
crude was purified by flash column chromatography over a silica gel column with gradients of n-
hexane/ethyl acetate as eluent. For reaction yields see table 1.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General procedure for the A3-coupling under dielectric heating. The reaction were performed in a 0.5
mmol scale in open air. The catalyst (2a or 2b, 0.015 mmol) was dissolved in dry toluene (1 mL) in a sealed
microwave vial equipped with a stirring bar. The suitable aldehyde (0.5 mmol), amine (0.515 mmol) and
alkyne (0.515 mmol) were added to the stirred solution, according to this order. The mixture was heated in
a single-mode microwave oven at 150 °C for 15 min. The reaction mixture was diluted with ethyl acetate
(20 mL) and the organic layer was washed with water (20 mL) and brine (20 mL). The organic layer was
dried over sodium sulphate, and the solvent was evaporated under reduced pressure. The reaction crude
was purified by flash column chromatography over a silica gel column with gradients of n-hexane/ethyl
1
acetate as eluent. (When the reaction yields were calculated by H NMR with the internal standard, a
1
precise amount of DMT (around 45 mg) was added to the reaction crude before the work-up, and the H
NMR was recorded with a prolonged delay time (d1 = 10)).
1
1-(1,3-Diphenylprop-2-yn-1-yl)pyrrolidine 6a.7d Pale yellow oil. Yield: 96% (125 mg). H NMR (200 MHz,
CDCl3, δ): 7.61 (dd, J = 7.8, 1.7 Hz, 2H, HAr), 7.53–7.44 (m, 2H, HAr), 7.42–7.27 (m, 6H, HAr), 4.89 (s, 1H, CH),
2.69 (pt, J = 6.7 Hz, 4H, N–CH2), 1.98–1.61 (m, 4H, CH2). Spectral data are in good agreement with literature
values.
1
1-(3-(4-Methoxyphenyl)-1-phenylprop-2-yn-1-yl)pyrrolidine 6b. Pale yellow oil. Yield: 75% (109 mg). H
NMR (200 MHz, CDCl3, δ): 7.60 (dd, J = 7.8, 1.2 Hz, 2H, Har), 7.42 (d, J = 8.9 Hz, 2H, Har), 7.37–7.27 (m, 3H,
Har), 6.84 (d, J = 8.9 Hz, 2H, Har), 4.86 (s, 1H, CH), 3.81 (s, 3H, O–CH3), 2.68 (pt, J = 6.6 Hz, 4H, N–CH2), 1.83–
1.75 (m, 4H, CH2). 13C NMR (50.3 MHz, CDCl3, δ): 159.7 (Cq), 139.9 (Cq), 133.4 (CHar), 128.54 (CHar), 128.46
(CHar), 127.8 (CHar), 115.6 (Cq), 114.2 (CHar), 87.0 (Csp), 85.3 (Csp), 59.4 (CH), 55.5 (O–CH3), 50.5 (N–CH2), 23.8
(CH2). MS ESI(+): m/z (%) = 292.1 (4) [M + H]+, 221.2 (100) [M – pyrrolidine]+. HRMS ESI (M + H)+ calcd for
C20H22NO+, 292.1696; found, 292.1701.
1
1-(3-(3-Fluorophenyl)-1-phenylprop-2-yn-1-yl)pyrrolidine 6c. Pale yellow oil. Yield: 83% (116 mg). H NMR
(200 MHz, CDCl3, δ): 7.67–7.53 (m, 2H, Har), 7.44–7.23 (m, 6H), 7.23–7.13 (m, 1H), 7.11–6.90 (m, 1H), 4.91
(s, 1H, CH), 2.71 (pt, J = 6.6 Hz, 4H, N–CH2), 1.88–1.76 (m, 4H, CH2). 13C NMR (50.3 MHz, CDCl3, δ): 162.6 (d,
3
1JC F = 246.4 Hz, Cq), 139.3 (Cq), 130.0 (d, JC F = 8.7 Hz, CHar), 128.54 (CHar), 128.47 (CHar), 127.92 (CHar),
−
−
127.89 (d, 4JC F = 3.2 Hz, CHar), 125.3 (d, 3JC F = 9.5 Hz, Cq), 118.8 (d, 2JC F = 22.7 Hz, CHar), 115.7 (d, 2JC F = 21.2
−
−
−
−
4
Hz, CHar), 88.5 (Csp), 86.0 (d, JC F = 3.3 Hz, Csp), 59.3 (CH), 50.5 (N–CH2), 23.7 (CH2). MS ESI(+): m/z (%) =
−
12
ACS Paragon Plus Environment

Page 13 of 16
The Journal of Organic Chemistry
1
2
3
4
5
280.2 (100) [M + H]+, 209.4 (48) [M – pyrrolidine]+. HRMS ESI (M + H)+ calcd for C19H19FN+, 280.1496; found,
280.1493.
6
7
1
1-(1-Phenylhex-2-yn-1-yl)pyrrolidine 6d. Pale yellow oil. Yield: 53% (60 mg). H NMR (200 MHz, CDCl3, δ):
8
9
7.53 (dd, J = 7.5, 1.5 Hz, 2H, Har), 7.44–7.19 (m, 3H, Har), 4.60 (t, J = 2.0, 1H, CH), 2.59 (pt, J = 6.2 Hz, 4H, N–
CH2), 2.26 (dt, J = 7.1, 2.0 Hz, 2H, CH2), 1.79–1.73 (m, 4H, CH2), 1.58 (ses, J = 7.1 Hz, 2H, CH2), 1.02 (t, J = 7.2
Hz, 3H, CH3). 13C NMR (50.3 MHz, CDCl3, δ): 140.3 (Cq), 128.5 (CHar), 127.6 (CHar), 87.2 (Csp), 77.3 (Csp), 59.0
(CH), 50.4 (N–CH2), 23.7 (CH2), 22.7 (CH2), 21.0 (CH2), 13.8 (CH3). MS ESI(+): m/z (%) = 228.1 (100) [M + H]+.
HRMS ESI (M + H)+ calcd for C16H22N+, 228.1747; found, 228.1750.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
1-(1-(4-Methoxyphenyl)-3-phenylprop-2-yn-1-yl)pyrrolidine 6e.46 Pale yellow oil. Yield: 78% (114 mg). H
NMR (200 MHz, CDCl3, δ): 7.46–7.54 (m, 4H, Har), 7.29–7.32 (m, 3H, Har), 6.89 (d, J = 8.6 Hz, 2H), 6.84 (d, J =
8.9 Hz, 1H, Har), 4.82 (s, 1H, CH), 3.81 (s, 3H, CH3), 2.71–2.64 (m, 4H, N–CH2), 1.82–1.76 (m, 4H, CH2).
Spectral data are in good agreement with literature values.
1-(1-(3-Chlorophenyl)-3-phenylprop-2-yn-1-yl)pyrrolidine 6f.47 Pale yellow oil. Yield: 79% (117 mg). 1H NMR
(200 MHz, CDCl3, δ): 7.63 (s, 1H, Har), 7.58–7.41 (m, 3H), 7.40–7.20 (m, 5H), 4.91 (s, 1H, CH), 2.84–2.60 (m,
4H, N–CH2), 1.96–1.67 (m, 4H, CH2). 13C NMR (50.3 MHz, CDCl3, δ): 141.9 (Cq), 134.4 (Cq), 132.0 (CHar), 129.7
(CHar), 128.6 (CHar), 128.5 (CHar), 128.5 (CHar), 128.0 (CHar), 126.6 (CHar), 123.2 (Cq), 87.7 (Csp), 85.9 (Csp), 58.7
(CH), 50.3 (N–CH2), 23.79 (CH2). MS ESI(+): m/z (%) = 298.1/296.1 (30/100) [M + H]+. Spectral data are in
good agreement with literature values.
2-(3-Phenyl-1-(pyrrolidin-1-yl)prop-2-yn-1-yl)phenol 6g.48 Pale yellow oil. Yield: 83% (115 mg). 1H NMR (200
MHz, CDCl3, δ): 7.57–7.50 (m, 3H, Har), 7.41–7.32 (m, 3H, Har), 7.29–7.17 (m, 1H, Har), 6.95–6.79 (m, 2H, Har),
5.29 (s, 1H, CH), 2.96–2.75 (m, 4H, N–CH2), 1.96–1.82 (m, 4H, CH2). Spectral data are in good agreement
with literature values.
1
1-(1-Cyclohexyl-3-phenylprop-2-yn-1-yl)pyrrolidine 6h.6 Colorless oil. Yield: 98% (131 mg). H NMR (200
MHz, CDCl3, δ): 7.48–7.38 (m, 2H, Har), 7.35–7.22 (m, 3H, Har), 3.36 (d, J = 8.4 Hz, 1H, CH), 2.80–2.60 (m, 4H,
N–CH2), 2.12–1.92 (m, 2H, C sp3H), 1.85–1.52 (m, 8H, C sp3H), 1.30–1.05 (m, 5H, CH2). 13C NMR (50.3 MHz,
CDCl3, δ): 131.9 (CHar), 128.4 (CHar), 127.9 (CHar), 123.9 (Cq), 88.1 (Csp), 86.0 (Csp), 61.5 (CH), 50.3 (N–CH2),
41.6 (CH), 30.9 (CH2), 30.5 (CH2), 26.9 (CH2), 26.5 (CH2), 23.8 (CH2). MS ESI(+): m/z (%) = 268.2 (100) [M +
H]+. Spectral data are in good agreement with literature values.
1
1-(1-Phenylhept-1-yn-3-yl)pyrrolidine 6i.6 Colorless oil. Yield: 61% (74 mg). H NMR (200 MHz, CDCl3, δ):
7.45–7.40 (m, 2H), 7.31–7.26 (m, 3H, Har), 3.67 (dd, J = 7.9, 6.7 Hz, 1H, CH, Har), 2.78–2.67 (m, 4H, N–CH2),
1.84–1.26 (m, 10H, CH2), 0.93 (t, J = 7.0 Hz, 3H, CH3). 13C NMR (50.3 MHz, CDCl3, δ): 131.9 (CHar), 128.4
(CHar), 127.9 (CHar), 123.8 (Cq), 88.7 (Csp), 85.4 (Csp), 55.4 (CH), 49.9 (N–CH2), 35.1 (CH2), 30.9 (CH2), 29.1
(CH2), 23.7 (CH2), 22.7 (CH2), 14.2 (CH3). MS ESI(+): m/z (%) = 242.1 (100) [M + H]+, 171.2 (12) [M –
pyrrolidine]+. Spectral data are in good agreement with literature values.
1
1-(1-Cyclohexyl-3-(4-methoxyphenyl)prop-2-yn-1-yl)pyrrolidine 6j. Colorless oil. Yield: 89% (132 mg). H
NMR (200 MHz, CDCl3, δ): 7.36 (d, J = 8.9 Hz, 2H, Har), 6.82 (d, J = 8.9 Hz, 2H, Har), 3.80 (s, 1H, O–CH3), 3.32
(d, J = 8.3 Hz, 1H, CH), 2.77–2.57 (m, 4H, N–CH2), 2.10–1.90 (m, 2H, C sp3H), 1.83–1.49 (m, 8H, C sp3H), 1.28–
1.04 (m, 5H, CH2). 13C NMR (75.5 MHz, CDCl3, δ): 159.6 (Cq), 133.4 (CHar), 116.3 (Cq), 114.2 (CHar), 86.7 (Csp),
85.9 (Csp), 61.7 (O–CH3), 55.7 (CH), 50.4 (N–CH2), 41.8 (CH), 31.1 (CH2), 30.7 (CH2), 27.1 (CH2), 26.6 (CH2),
23.9 (CH2). HRMS ESI (M + H)+ calcd for C20H28NO+, 298.2165; found, 298.2162.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 16
1
2
3
4
5
6
7
8
1
1-(3-(4-Methoxyphenyl)-1-phenylprop-2-yn-1-yl)piperidine 6k.49 Pale yellow oil. Yield: 91% (139 mg). H
NMR (200 MHz, CDCl3, δ): 7.66–7.60 (m, 2H, Har), 7.45 (d, J = 8.9 Hz, 2H, Har), 7.40–7.28 (m, 3H, Har), 6.86 (d,
J = 8.9 Hz, 2H, Har), 4.77(s, 1H, CH), 3.82 (s, 3H, CH3), 2.55 (pt, J = 5.2 Hz, 4H, N–CH2), 1.66–1.53 (m, 4H, CH2),
1.50–1.40 (m, 2H, CH2). Spectral data are in good agreement with literature values.
9
1
1-(1-Cyclohexyl-3-(3-fluorophenyl)prop-2-yn-1-yl)piperidine 6l.50 Pale yellow oil. Yield: 96% (144 mg). H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (200 MHz, CDCl3, δ): 7.32–7.18 (m, 2H, Har), 7.17–7.09 (m, 1H), 7.04–6.92 (m, 1H), 3.10 (d, J = 9.9 Hz,
1H, CH), 2.68–2.55 (m, 2H, N–CH2), 2.44–2.32 (m, 2H, N–CH2), 2.11–1.99 (m, 2H, CH2), 1.80–1.38 (m, 10H,
CH2), 1.33–0.88 (m, 5H, CH2). Spectral data are in good agreement with literature values.
4-(1,3-Diphenylprop-2-yn-1-yl)morpholine 6m.51 Colorless oil. Yield: 59% (82 mg). 1H NMR (200 MHz, CDCl3,
δ): 7.68–7.63 (m, 2H, Har), 7.57–7.50 (m, 2H), 7.44–7.31 (m, 6H), 4.81 (s, 1H, CH), 3.80–3.71 (m, 4H, O–CH2),
2.74–2.59 (m, 2H, N–CH2). 13C NMR (50.3 MHz, CDCl3, δ): 138.1 (Cq), 132.0 (CHar), 128.8 (CHar), 128.53 (CHar),
128.45 (CHar), 128.0 (CHar), 123.3 (Cq), 88.7 (Csp), 85.3 (Csp), 67.4 (O–CH2), 62.3 (CH), 50.2 (N–CH2) (one signal
obscured). MS ESI(-): m/z (%) = 276.5 (100) [M - H]-, 191.4 (75) [M – morpholine]-. Spectral data are in good
agreement with literature values.
N,N-Diethyl-1,3-diphenylprop-2-yn-1-amine 6n. Colorless oil. Yield: 57% (75 mg). 1H NMR (200 MHz, CDCl3,
δ): 7.73 (dd, J = 7.4, 0.8 Hz, 2H, Har), 7.57–7.52 (m, 2H, Har), 7.43–7.30 (m, 6H, Har), 5.09 (s, 1H, CH), 2.71–
2.53 (m, 4H, N–CH2), 1.11 (t, J = 7.1 Hz, 6H, CH3). 13C NMR (75.5 MHz, CDCl3, δ): 140.2 (Cq), 132.0 (CHar),
128.6 (CHar), 128.5 (CHar), 128.3 (CHar), 127.5 (CHar), 126.7 (Cq), 87.7 (Csp), 86.4 (Csp), 57.3 (CH), 44.8 (N–CH2),
13.9 (CH3) (one signal obscured). MS ESI(+): m/z (%) = 264.0 (100) [M + H]+, 191.4 (20) [M – diethylamine]+.
HRMS ESI (M + H)+ calcd for C19H22N+, 264.1747; found, 264.1744.
1
N,N-Dibenzyl-1,3-diphenylprop-2-yn-1-amine 6o.7a Colorless oil. Yield: 61% (118 mg). H NMR (200 MHz,
CDCl3, δ): 7.77 (d, J = 7.5 Hz, 2H, Har), 7.67 (dd, J = 6.0, 2.6 Hz, 2H, Har), 7.52–7.20 (m, 16H, Har), 4.98 (s, 1H,
CH), 3.84 (d, J = 13.5 Hz, 2H, N–CH2), 3.58 (d, J = 13.5 Hz, 2H, N–CH2). Spectral data are in good agreement
with literature values.
1
1-(3-methyl-1-phenylhex-1-yn-3-yl)pyrrolidine 9a. Colorless oil. Yield: 33% (40 mg). H NMR (200 MHz,
CDCl3, δ): 7.447–7.39 (m, 2H, Har), 7.31–7.27 (m, 3H, Har), 2.79 (t, J = 5.9 Hz, 4H, N–CH2), 1.88–1.48 (m, 8H,
CHsp3), 1.43 (s, 3H, CH3), 0.96 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (75.5 MHz, CDCl3, δ): 132.0 (CHar), 128.4 (CHar),
127.9 (CHar), 123.9 (Cq), 91.7 (Csp), 84.6 (Csp), 58.2 (Cq), 48.0 (N–CH2), 44.1 (CH2), 26.1 (CH3), 23.9 (CH2), 18.0
(CH2), 14.8 (CH3). MS ESI(+): m/z (%) = 264.1 (10) [M + Na]+, 242.1 (75) [M + H]+, 171.0 (100) [M –
pyrrolidine]+. HRMS ESI (M + H)+ calcd for C17H24N+, 242.1903; found, 242.1899.
Supporting information
1
Copies of H and 13C NMR, spectra of ligand 1, Ag complexes 2a−b, and propargylamines 6b,c,d,f,h,i,j,m,n
1
and 9a. H NMR spectra of propargylamines 6a,e,g,k,l,o. HOESY spectrum of complex 2a and HSQC NMR
experiments for the free ligand 1 and complex 2b. 1H NMR spectra of the reaction with aniline with internal
standard. This material is available free of charge via the Internet at http://pubs.acs.org.
14
ACS Paragon Plus Environment

Page 15 of 16
The Journal of Organic Chemistry
1
2
3
References
4
5
6
7
8
9
1
(a) Multicomponent Reactions; Zhu, J.; Bienaymé H. Eds.; Wiley-WCH: Weinheim, 2006; (b) B. Ganem, Acc. Chem.
Res. 2009, 42, 463–472.
2 (a) V. A. Peshkov, O. P. Pereshivko, E.V. Van der Eycken, Chem. Soc. Rev. 2012, 41, 3790–3807. (b) W.-Y. Yoo, L. Zhao,
C.-J. Li, Aldrichimica Acta, 2011, 44, 43–51. (c) C. Wei, Z. Li, C.-J. Li, Synlett, 2004, 1472–1483.
3 McNally, J. J.; Youngman, M. A.; Dax, S. L. Tetrahedron Lett. 1998, 39, 967-970.
4 Dyatkin, A. B.; Rivero R. A. Tetrahedron Lett. 1998, 39, 3647–3650.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5 Selected examples: (a) Park, S. B.; Alper, H. Chem. Commun. 2005, 1315–1317. (b) Sreedhar, B.; Reddy, P. S.; Prakash,
B. V.; Ravindra, A. Tetrahedron Lett. 2005, 46, 7019–7022. (c) Meyet, C. E.; Pierce, C. J.; Larsen, C. H. Org. Lett. 2012,
14, 964–967.
6 The first example: Wei, C.; Li, Z.; Li, C.-J. Org. Lett. 2003, 5, 4473–4475.
7 Selected examples: (a) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2003, 125, 9584–9585. (b) Lo, V. K.-Y.; Liu, Y.; Wong, M.-K.;
Che, C.-M. Org. Lett. 2006, 8, 1529–1532. (c) Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green Chem. 2007, 9,
742–745. (d) Zhang, X.; Corma, A. Angew. Chem., Int. Ed. 2008, 47, 4358–4361.
8 Abbiati, G.; Rossi, E. Beilstein J. Org. Chem. 2014, 10, 481–513.
9 (a) Li, P.; Zhang, Y.; Wang, L. Chem. Eur. J. 2009, 15, 2045–2049. (b) Chen, W.-W.; Nguyen, R. V.; Li, C.-J. Tetrahedron
Lett., 2009, 50, 2895–2898.
10 (a) Y. Zhang, P. Li, M. Wang and L. Wang, J. Org. Chem., 2009, 74, 4364–4367. (b) Yadav, J. S.; Subba Reddy, B. V.;
Hara Gopal, A. V.; Patil, K. S. Tetrahedron Lett. 2009, 50, 3493–3496.
11 (a) Ramu, E.; Varala, R.; Sreelatha, N.; Adapa, S. R. Tetrahedron Lett., 2007, 48, 7184–7190; (b) Kantam, M. Lakshmi;
Balasubrahmanyam, V.; Kumar, K. B. Shiva; Venkanna, G. T. Tetrahedron Lett. 2007, 48, 7332–7334.
12 Samai, S.; Nandi, G. C.; Singh, M. S. Tetrahedron Lett., 2010, 51, 5555–5558.
13 Chen, W.-W.; Bi, H.-P.; Li, C.-J. Synlett 2010, 475–479.
14 Li, P.; Wang, L. Chin. J. Chem., 2005, 23, 1076–1080.
15 Huang, B.; Yao, X.; Li, C.-J. Adv. Synth. Catal. 2006, 348, 1528–1532.
16 Liu, Q.; Lu, Y.; Sun, W.-Y.; Zhai, L.-L.; Zhao, Y.; Zhou, X. RSC Adv. 2013 , 3, 1732–1734.
17 Reddy, K. M.; Babu, N. S.; Suryanarayana, I.; Prasad, P. S. S.; Lingaiah, N. Tetrahedron Lett. 2006, 47, 7563–7566.
18 Zhang, Y.; Santos, A. M.; Herdtweck, E.; Mink, J.; Kühn, F. E. New J. Chem. 2005, 29, 366–370.
19 (a) Li, P.; Wang, L.; Zhang, Y.; Wang, M. Tetrahedron Lett. 2008, 49, 6650–6654. (b) He, Y.; Lv, M.-f.; Cai, C. Dalton
Trans. 2012, 41, 12428–12433. (c) Li, Y.; Chen, X.; Song, Y.; Fang, L.; Zou, G. Dalton Trans. 2011, 40, 2046–2052. (d)
Chen, M.-T.; Landers, B.; Navarro, O. Org. Biomol. Chem. 2012, 10, 2206–2208. (e) Cheng, C.-H.; Chen, D.-F.; Song, H.-
B.; Tang, L.-F. J. Organomet. Chem. 2013, 726, 1–8.
20 Yao, X.; Li, C.-J. Org. Lett. 2005, 7, 4395–4398.
21 Selected examples: (a) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124, 5638–5639. (b) Gommermann, N.; Koradin, C.;
Polborn, K.; Knochel, P. Angew. Chem., Int. Ed. 2003, 42, 5763–5766. (c) Aschwanden, P.; Stephenson, C. R. J.; Carreira,
E. M. Org. Lett. 2006, 8, 2437–2440. (d) Bisai, A.; Singh, V. K. Org. Lett. 2006, 8, 2405–2408. (e) Nakamura, S.;
Nakamura, Y.; Ohara, M.; Shibata, N.; Toru, T. Chem. Eur. J. 2010, 16, 2360–2362. (f) Bisai, A.; Singh, V. K. Tetrahedron
2012, 68, 3480–3486.
22
Some related examples of silver and gold catalyzed enantioselective addition of acetylenes on preformed imines
have been recently reported, see for example: with a gold phosphine catalyst: Campbell, M. J.; Toste, D. Chem. Sci.
2011, 2, 1369–1378; with a silver phosphine catalyst: Su, Y.; Lu, M.; Dong, B.; Chen, H.; Shi, X. Adv. Synth. Catal. 2014,
356, 692–696.
23 (a) Abbiati, G.; Arcadi, A.; Chiarini, M.; Marinelli, F.; Pietropaolo, E.; Rossi, E. Org. Biomol. Chem. 2012, 7801–7808.
(b) Dell’Acqua, M.; Abbiati, G.; Arcadi, A.; Rossi, E. Org. Biomol. Chem. 2011, 7836–7848. (c) Dell’Acqua, M.; Facoetti,
D.; Abbiati, G.; Rossi, E. Synthesis 2010, 2367–2378. (d) Alfonsi, M.; Dell’Acqua, M.; Facoetti, D.; Arcadi, A.; Abbiati, G.;
Rossi, E. Eur. J. Org. Chem. 2009, 2852–2862. (e) Facoetti, D.; Abbiati, G.; L.; Rossi, E. Eur. J. Org. Chem. 2009, 2872–
2882.
24 (a) Dell’Acqua, M.; Facoetti, D.; Abbiati, G.; Rossi, E. Tetrahedron 2011, 67, 1552–1556. (b) Facoetti, D.; Abbiati, G.;
Dell’Acqua, M.; Rossi, E. Tetrahedron 2011, 67, 6833–6837. (c) Dell’Acqua, M.; Facoetti, D.; A. Arcadi, G. Abbiati, E.
Rossi, Synlett, 2010, 2672–2676.
25 Curtis, N. F. In Comprehensive Coordination Chemistry II; 2003; vol. 1, pp. 447–474.
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 16
1
2
3
26 Stetter, H.; Frank, W.; Mertens, R. Tetrahedron, 1981, 37, 767–772.
4
5
6
7
8
9
27 (a) Aime, S.; Botta, M.; Crich, S. G.; Giovenzana, G. B.; Jommi, G.; Pagliarin, R.; Sisti, M. Inorg. Chem. 1997, 36, 2992–
3000. (b) Aime, S.; Gianolio, E.; Corpillo, D.; Cavallotti, C.; Palmisano, G.; Sisti, M.; Giovenzana, G. B.; Pagliarin, R. Helv.
Chim. Acta 2003, 86, 615–632.
28
(a) Caselli, A.; Cesana, F.; Gallo, E.; Casati, N.; Macchi, P.; Sisti, M.; Celentano, G.; Cenini, S. Dalton Trans. 2008,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4202–4205. (b) Castano, B.; Guidone, S.; Gallo, E.; Ragaini, F.; Casati, N.; Macchi, P.; Sisti, M.; Caselli, A. Dalton Trans.
2013, 42, 2451–2562. (c) Castano, B.; Zardi, P.; Honemann, Y. C.; Galarneau, A.; Gallo, E.; Psaro, R.; Caselli, A.; Dal
Santo, V. RSC Advances 2013, 3, 22199–22205. (d) Castano, B.; Gallo, E.; Cole-Hamilton, D. J.; Dal Santo, V.; Psaro, R.;
Caselli, A. Green. Chem. 2014, 16, 3202–3209.
29 Castano, B.; Pedrazzini, T.; Sisti, M.; Gallo, E.; Ragaini, F.; Casati, N.; Caselli, A. Appl. Organometal. Chem. 2011, 25,
824–829.
30
Dell’Acqua, M.; Castano, B.; Cecchini, C.; Pedrazzini, T.; Pirovano, V.; Rossi, E.; Caselli, A.; Abbiati G. J. Org. Chem
2014, 79, 3494–3505.
31 Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, 3rd ed., Wiley-VCH, Weinheim, 2003.
32 Díaz-Torres, R.; Alvarez, S. Dalton Trans. 2011, 40, 10742–10750.
33 Leadbeater, N.E.; Torenius, H. M.; Tye, H. Mol. Diversity 2003, 7, 135–144.
34 Shi, L.; Tu, Y. Q.; Wang, M.; Zhang F. M.; Fan, C. A. Org. Lett. 2004, 6, 1001–1003.
35 Bariwal, J. B.; Ermolat’ev D. S.; Van der Eycken, E. V. Chem. Eur. J. 2010, 16, 3281–3284.
36 AA.VV., Microwaves in Organic Synthesis, ed. A. Loupy, Wiley VCH, Weinheim, 2002.
37 Foley, P.; Di Cosimo, R.; Whitesides, G. M. J. Am. Chem. Soc. 1980, 102, 6713-6725.
38 Rundlöf, T.; Mathiasson, M.; Bekiroglu, S.; Hakkarainen, B.; Bowden, T.; Arvidsson, T. J. Pharm. Biomed. Anal. 2010,
52, 645–651.
39 (a) Nagaiah, K.; Naveenkumar, V.; Rao, R. S.; Subba Reddy, B. V.; Yadav, J. S. New. J. Chem. 2004, 28, 335–337. (b)
Mirzaei, M.; Sharifi, A.; Naimi-Jamal, M. R. J. Chem. Res. 2007, 129–132.
40 Li, C.-J.; Wei, C. Chem. Commun. 2002, 268–269.
41 Chen, Y.; Liu, Y.; Wang, J.; Xiao, F. Tetrahedron 2008, 64, 2755–2761.
42 Chen, L.; Li, C.-J.; Li, Z.; Wei, C.; Varma, R. S.; Li, Chao-Jun Tetrahedron Lett. 2004, 45, 2443–2446.
43 (a) Tang, X.; Kuang, J.; Ma, S. Chem. Commun.2013, 49, 8976-8978. (b) Pierce, C. J.; Larsen, C. H. Green Chem. 2012,
14, 2672–2676. (c) Meyet, C. E.; Pierce, C. J.; Larsen, C. H. Org. Lett. 2012, 14, 964-967. (d) Pereshivko, O. P.; Peshkov,
V. A.; Van der Eycken, E. V. Org. Lett. 2010, 12, 2638–2641.
44 Cheng, M.; Zhang, Q.; Hu, X.-Y.; Li, B.-G.; Ji, J.-X.; Chan, A. S. C. Adv. Synth. Cat. 2011, 353, 1274–1278.
45 Pierce, C. J.; Nguyen, M.; Larsen, C. H. Ange. Chem. Int. Ed. 2012, 51, 12289–12292.
46 Zhua, W.; Qiana, W.; Zhang, Y. J. Chem. Res. 2005, 410–412.
47 Lo, V. K.-Y.; Zhou, C.-Y.; Wong, M.-K.; Che, C.-M. Chem. Commun. 2010, 46, 213–215.
48 Dilman, A. D.; Arkhipov, D. E.; Belyakov, P. A.; Struchkova, M. I.; Tartakovsky V. A. Russ. Chem. Bull., Int. Ed. 2006,
55, 517–522.
49 Sreedhar, B.; Surendra Reddy, P.; Vamsi Krishna, C. S.; Vijaya Babu, P. Tetrahedron Lett. 2007, 48, 7882–7886.
50 Sreedhar, B.; Suresh Kumar, A.; Surendra Reddy P. Tetrahedron Lett. 2010, 51, 1891–1895.
51 Karimi, B.; Gholinejad, M.; Khorasani, M. Chem. Commun. 2012 , 48, 8961–8963.
16
ACS Paragon Plus Environment