Modular Access to Tetrasubstituted Imidazolium Salts through Acid-Catalyzed Addition of Isocyanides to Propargylamines

Article abstract of DOI:10.1002/ejoc.201500502

Propargylamines, prepared through A³-coupling of primary amines, aldehydes and terminal alkynes, react with isocyanides in an HCl-catalyzed process to yield tetrasubstituted imidazolium salts. The key step of the mechanism involves the generation of an amidine intermediate, from the isocyanide insertion into the N-H bond of the propargylamine, which in situ evolves by cyclization upon the alkyne moiety. The scope of the process is analyzed and only shows restrictions for aliphatic amines, whereas it is quite general regarding the aldehyde, alkyne and isocyanide inputs. The protocol allows the preparation of a wide array of adducts, tandem one-pot processes being also feasible. Mechanistic studies using selected substrates have been used to determine the profile of the reaction and some substitution and functional group limitations. Some post-synthetic transformations of the imidazolium salts have been performed as well. Propargylamines, synthesized through A³-coupling of primary amines, aldehydes and terminal alkynes, react with isocyanides in an HCl-catalyzed process to yield tetrasubstituted imidazolium salts. Tandem one-pot protocols allow direct access to these adducts from the commercially available inputs.

Full text of DOI:10.1002/ejoc.201500502

FULL PAPER
DOI: 10.1002/ejoc.201500502
Modular Access to Tetrasubstituted Imidazolium Salts through Acid-Catalyzed
Addition of Isocyanides to Propargylamines
[a]
[a]
[b]
[a,b]
Ouldouz Ghashghaei, Marc Revés, Nicola Kielland, and Rodolfo Lavilla*
Keywords: Synthetic methods / Homogeneous catalysis / Multicomponent reactions / Nitrogen heterocycles / N ligands
3
Propargylamines, prepared through A -coupling of primary
tions for aliphatic amines, whereas it is quite general regard-
amines, aldehydes and terminal alkynes, react with isocyan- ing the aldehyde, alkyne and isocyanide inputs. The protocol
ides in an HCl-catalyzed process to yield tetrasubstituted
imidazolium salts. The key step of the mechanism involves
the generation of an amidine intermediate, from the isocyan-
ide insertion into the N–H bond of the propargylamine,
which in situ evolves by cyclization upon the alkyne moiety.
The scope of the process is analyzed and only shows restric-
allows the preparation of a wide array of adducts, tandem
one-pot processes being also feasible. Mechanistic studies
using selected substrates have been used to determine the
profile of the reaction and some substitution and functional
group limitations. Some post-synthetic transformations of the
imidazolium salts have been performed as well.
double catalysis of Ag /Yb cations,[10] prompted us to
disclose our findings.
+
3+
Introduction
Multicomponent reactions (MCRs) and domino pro-
cesses, being transformations in which several bonds are
generated in a single step, represent an optimized way for
the synthesis of complex compounds in a fast manner, espe-
[
1]
cially suitable for the generation of chemical libraries. In
this context, following our interest in isocyanide MCR
[
2]
chemistry, we decided to tackle the interaction of these
substrates with alkynes.[3] So far, this interaction mostly in-
volves metal-catalyzed processes and conjugated additions
to electron-deficient alkynes.[ Although remarkable pro-
cesses have been described by the Van der Eycken group,
where the alkyne is a manifold substituent in some inputs of
4]
[
5]
the Ugi MCR; the direct transformation remains largely
unexplored. We envisaged a new reaction profile where the
isocyanide would undergo addition to an acid activated tri-
[
6]
ple bond, and the nitrilium ion so generated would be
captured by a nucleophilic amine (Scheme 1, pathway a) to
yield iminopyrrolines A or tautomeric species. Alternatively,
the process may proceed by isocyanide insertion[7] into the
N–H bond of the secondary amine, to trigger an intramo-
[
8]
lecular amidine addition upon the alkyne through a 5-
Scheme 1. Hypothetical mechanistic profiles on the interaction of
[
9]
exo-dig route (Scheme 1, pathway b) and [1,3]-H shift, isocyanides and propargylamines.
leading to the imidazolium salts B. The recent report of
Zhu and co-workers, describing an analogous process using
3
[11]
In this way, we prepared A adducts, arising from the
metal-catalyzed interaction of, a primary amine 1, an alde-
hyde 2 and a terminal alkyne 3, to afford propargylamines
[
[
a] Laboratory of Organic Chemistry, Faculty of Pharmacy,
University of Barcelona,
4
(Scheme 1). Then, these compounds were treated with iso-
Av. Joan XXIII sn, 08028 Barcelona, Spain
E-mail: rlavilla@pcb.ub.es
cyanides 5 under variety of acid catalysts (see below). These
processes allowed the formation of imidazolium salts 6
b] Barcelona Science Park,
Baldiri Reixac, 10–12, 08028 Barcelona, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500502.
(Scheme 2), thus revealing the prevalence of the latter mech-
anistic choice.
Eur. J. Org. Chem. 2015, 4383–4388
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4383

O. Ghashghaei, M. Revés, N. Kielland, R. Lavilla
Table 1. Range of the components.
FULL PAPER
1
2
3
4
Yield[a]
Entry Adduct
R , R , R , R
, pTol, Ph, 4-MeOC
pTol, Ph, Ph, tBu
4-MeOC , pTol, Ph, tBu
Bn, iPr, Ph, cHex
4-MeOC CH , Ph, Ph, cHex
4-MeOC , 4-ClC , pTol, tBu
4-MeOC , 4-ClC , n-C 11, tBu
pTol, Ph, Ph, cHex
pTol, Ph, Ph, EtCO CH
pTol, Ph, Ph, 2,6-(H C)
pTol, 4-ClC , Ph, 2-naphthyl
1
2
3
4
5
6
7
8
9
6a
6b
6c
6d
6e
6f
6g
6h
6i
4-MeOC
6
H
4
6
H
4
82%
82%
92%
23%[
6
H
4
b]
[
b]
6
H
4
2
10%
56%[
c]
6
H
4
6 4
H
H
6
H
4
6
4
5
H
85%
82%
[
c]
2
2
96%
27%
[d]
10
6j
3
2
C
6
H
3
e]
11
6k
6 4
H
75%[
[
a] Obtained from general procedure A (see Supporting Infor-
mation). [b] AcOH (1 equiv.) and AgTfO (20%) were used instead
of HCl (see SI). [c] The hydrolyzed betaine 6iЈ was also generated
during purification. [d] Reaction performed at 60 °C. [e] Reaction
Scheme 2. Synthesis of imidazolium salts through silver-catalyzed
propargylamine-isocyanide interaction.
performed with MeSO
3
H (1 equiv.) instead of HCl, due the low
solubility of the propargylamine hydrochloride.
Results and Discussion
First the preparation of propargylamines 4 was trouble- rank among the most active catalysts for Pd-coupling reac-
[
17]
some, as there are few reports involving the participation of tions.
Unfortunately the preparations of polysubstituted
[
11c]
primary amines.
patibility of the Cu cation used in the A couplings with ses.
We were concerned about the incom- imidazolium salts usually involve complex multistep synthe-
I
3
[18]
Therefore, many of the previously mentioned appli-
isocyanides 5, via the formation of inert complexes, there- cations have been tested only on simple, easily accessible
3
fore requiring purification of the A adducts. After much salts, usually obtained by alkylation of the parent imid-
[
19]
experimentation, it was shown that the concomitant use of azoles.
Ru /Cu catalysis in THF (Li-Wei method)
Thus, a general and direct access to these com-
III
I
[11d]
was pro- pounds would allow a programmed preparation of diversely
ductive and, importantly, allowed the subsequent isocyan- substituted derivatives and hence a finer and more rational
ide interaction to be performed in tandem (see below). The modulation of their properties.
aniline-derived substrates were prepared in this way,
Next the scope of the reaction was tested. Proparg-
whereas those arising from benzylamine were synthesized ylamines 4 having N-aromatic residues smoothly reacted
using van Eycken conditions.[
11c]
with isocyanides to afford the corresponding products
Next, the reaction of propargylamine 4a and isocyanide (Table 1, entries 1–3, 6–11). On the other hand, the N-
a was investigated (Scheme 2). Several Lewis acids such as benzyl derivatives afforded imidazolium salts 6d and 6e in
5
CuBr, InCl , AuCl , AgOTf, Sc(OTf) , I and ICl allowed lower yields (Table 1, entries 4 and 5), whereas N-alkyl de-
3
3
3
2
the detection of the corresponding salt 6a in low yields. rivatives did not react under these conditions. The use of
However, the combination of AgOTf/AcOH was more pro- milder acids (AcOH, citric acid) was inefficient, pTosOH
ductive and afforded the imidazolinium salt 6a in 33% gave low yields and the HCl-promoted addition remained
yield. The X-ray diffraction of a monocrystal of this com- as the only productive transformation (23% and 10%
pound secured the proposed structure.[
12]
respectively). This fact constitutes the main practical limita-
The best results were observed when propargylamine 4a tion of the procedure. Referring to the aldehyde moiety, the
was treated with a stoichiometric amount of HCl (dioxane process allows a wider scope; including aromatic (both elec-
solution), in a 1:1 mixture of ACN/THF at room temp., tron-rich and electron-poor, Table 1, entries 1–3, 5–11) and
affording the final adduct in 82% yield (Table 1). For un- alkyl derivatives (Table 1, entry 4). With respect to the ter-
known reasons, the imidazolium salts were better isolated minal alkyne substitution, a variety of aromatic (Table 1,
[13]
after aqueous Na CO extraction (clean HPLC profiles), entry 1–6, 8–11) and aliphatic residues (Table 1, entry 7) are
2
3
and analytical samples can be obtained by standard flash tolerated.
chromatography (SiO ), although some decomposition was
Finally, a wide range of isocyanides yielded the corre-
2
observed during purification. Consequently, we assume that sponding products, allowing the introduction of bulky ali-
the anion of the imidazolium species is CO32 , although its phatic groups such as tBu and cHex (Table 1, entries 2–8).
unequivocal identification was not possible (MS-Ve tech- Aromatic isocyanides were also productive, either dis-
–
nique).
playing electron-donating groups (MeO) or bulky residues
The use of imidazolium salts and their derivatives is such as xylyl and naphthyl groups (Table 1, entries 1, 10,
widespread in several areas such as medicinal chemistry or 11). Methyl isocyanoacetate afforded the corresponding
[
14]
biology.
Imidazolium salts belong to a very common imidazolium salt 6i (entry 9) and partially hydrolyzed dur-
class of ionic liquids,[ and constitute the primary source ing chromatographic purification, presumably to the beta-
of N-heterocyclic carbenes,[ frequently used ligands in or- ine 6iЈ (see SI). Although PhosMIC and TosMIC under-
ganometallic chemistry. In this respect, PEPPSI catalysts went satisfactory conversions, the corresponding adducts
15]
16]
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Eur. J. Org. Chem. 2015, 4383–4388

Modular Access to Tetrasubstituted Imidazolium Salts
(detected by HPLC/MS) quickly decomposed during chro-
matographic purification.
In order to further explore the range of the reaction upon
distinct substrates, we performed a series of experiments.
First of all, the intermolecular version of this interaction
was tested. In this way, disubstituted alkynes (diphenylace-
tylene or 1-phenyl-1-hexyne) were treated with primary an-
ilines and isocyanides, under a variety of catalysts, but no
imidazolium salts could be detected. This result reinforces
the need of an intramolecular mode of action. The o-alk-
ynylaniline 7 was treated with isocyanide 5b to afford indole
8
in 12% yield (31% with AuCl catalysis, Scheme 3). The
3
process may start with an N–H isocyanide insertion to gen-
erate amidine C, which would subsequently cyclize (5-endo-
dig) to afford the final product (Scheme 3), in a transforma-
tion related to the Larock indole synthesis.[ Noteworthy,
when 2-phenylindole reacted with isocyanide 5b under the
same conditions, product 8 was not formed, suggesting that
the formation of the amidine moiety takes place first.
20]
Scheme 4. Post-transformation reactions and application.
pled with phenylboronic acid to furnish biphenyl 15 (35%
yield, unoptimized, Scheme 4).
We next considered the feasibility of tandem procedures,
to speed up the overall process. In this way, the pregener-
I
ated imine 16 was subjected to alkyne addition under Cu /
III
Ru catalysis followed by in situ treatment with isocyanide
5c and HCl to successfully afford the imidazolium salt 6b
(64%; Scheme 5, A). Furthermore, the direct synthesis of
the same adduct by interaction of the four reactant inputs,
without isolation of any intermediates was achieved by link-
3
ing the standard A reaction with the isocyanide interaction
(Scheme 5, B). Interestingly, this tandem/one-pot pro-
cedure, albeit less productive (54%) and clean than the orig-
inal stepwise reaction, does not show synthetic restrictions
due to incompatibilities of isocyanides with metal cations
present in the medium. Likewise, imidazolium salts 6h
(49%) and 6i (68%) were also prepared following this pro-
tocol.
Scheme 3. Mechanistic probes.
Interestingly, the substituted anilines 9 and 10 afforded,
on interaction with isocyanides 5b and 5c, amidines 11
(96%) and 12 (91%) respectively (Scheme 3). The processes
stop at the amidine formation stage and the cyclizations
upon the π systems do not proceed, although imidazolium
rings have been formed this way in related systems.[ When
21]
attempting a different extraction procedure, using aq. Scheme 5. Tandem multicomponent approaches.
NaOH (1 m) as a basic quencher, the hydroxy derivative 13
(Scheme 4) cleanly precipitated, and was isolated in 76%
yield and purified simply by filtration. Its structure was
clearly established by spectroscopic methods. Interestingly,
H NMR showed two rotamers, probably due to the tert-
Conclusions
1
In conclusion, the formation of tetrasubstituted imid-
butyl steric hindrance, albeit displaying a single peak in the azolium salts by an HCl-promoted isocyanide/proparg-
HPLC profile. As a proof of concept, the PEPPSI-type cat- ylamine interaction has been described. The scope of the
alyst 14 was prepared from imidazolinium salt 6b, following process has been analyzed and some synthetic uses of the
[
22]
Organ’s procedure. The thus prepared palladium catalyst corresponding adducts determined. The reaction is not pro-
was used in a standard Suzuki reaction using 4-chlorotolu- ductive for aliphatic amines, whereas the Zhu reaction[10]
ene as representative substrate, which was successfully cou- works well for these substrates. However, the milder condi-
Eur. J. Org. Chem. 2015, 4383–4388
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4385

O. Ghashghaei, M. Revés, N. Kielland, R. Lavilla
tions used in our transformation allow the preparation of 1.2 mmol), CuCl (31 mg, 30mol-%), RuCl (6.5 mg, 3mol-%.) were
FULL PAPER
3
dissolved in THF (3 mL) under inert atmosphere. The mixture was
then stirred at 50 °C for 24 h. The solution was cooled to room
temp. and diluted with ACN (3 mL). Then, tert-butyl isocyanide
N-tert-butylimidazolium salts without elimination prob-
lems. Overall, our process shows that the stoichiometric use
of HCl leads to the desired products, however in lower
yields and parallels the mechanistic profile described for
this interaction. Although for some sensitive substrates, the
protic acid may be deleterious, the soft activation needed
and the consumption of this reagent may prevent unwanted
(
91 mg, 1.1 mmol.) was then added, followed by a 4 m HCl solution
in dioxane (0.125 mL, 1 equiv.). The resulting solution was stirred
at room temp. until reaction completion (24 h) and then quenched
with Na
2 3
CO (saturated aq. solution, 40 mL) and extracted with
AcOEt (3ϫ 20 mL). The combined organic phases were dried with
decomposition. Finally, tandem/one-pot protocols linking MgSO and concentrated in vacuo, to afford imidazolium salt 6b
4
3
the synthesis of the propargylamines, by an A reaction, (412 mgs, 64%). Analytically pure sample was obtained by flash
with the isocyanide addition step have been developed.
chromatography on silica (hexanes/EtOH).
Preparation of Hydroxyldihydroimidazole (13): N-(1,3-di-
phenylprop-2-ynyl)-4-methylaniline (149 mg, 0.5 mmol) was dis-
solved in 1.5 mL of THF and ACN (1.5 mL) under inert atmo-
sphere. tert-butyl isocyanide (50 mg, 0.6 mmol) was added, fol-
lowed by a 4 m HCl solution in dioxane (0.125 μL, 1 equiv.). The
solution was stirred at room temp. until reaction completion (24 h)
and then quenched with a NaOH aq. solution (1 m, 3 mL) was
added and the solution was stirred vigorously at room temperature
overnight. Hydroxyldihydroimidazole 13 (151 mg, 76%), precipi-
tated in the reaction mixture and was recovered by filtration,
washed with hexanes (1 mL) and dried in vacuo.
Experimental Section
Preparation of Propargylic Amines (4): N-(aryl)propargylamines
were prepared using a modification of Li and Wei’s procedure[
in non-aqueous media: In a Schlenk tube, 2.0 mmol (1.00 equiv.)
of aldehyde and 2.2 mmol (1.1 equiv.) of amine were dissolved in
11d]
5
mL of THF under inert atmosphere. The tube was sealed and the
mixture was heated at 60 °C until complete consumption of the
aldehyde (2 h). Next CuCl (30mol-%), RuCl (3mol-%) and the
3
alkyne (2.4 mmol, 1.2 equiv.) were added. The mixture was stirred
at room temp. (30 min), and then heated at 50 °C until consump-
tion of the imine (24 h). The solution was cooled, poured into
water, and extracted with DCM. The combined organic phases
Preparation of 2-(Phenylethynyl)aniline (7): Compound 7 was pre-
pared through a Sonogashira coupling reaction as reported by Li-
[23]
ang et al. in good yield (87%).
4
were washed with water, dried with MgSO and concentrated in
vacuo. Purification by flash chromatography on silica gel (hexanes/
AcOEt) afforded the corresponding propargylamines.
Preparation of N-[(2-Phenyl-1H-indol-1-yl)methylene]cyclohexan-
amine (8): 2-(Phenylethynyl)aniline (7) (97 mg, 0.5 mmol), and
AuCl
inert atmosphere in a microwave tube. Cyclohexyl isocyanide
82 mg, 0.75 mmol) was added. The sealed tube was irradiated for
h at 75 °C (power: 80 W). The reaction was quenched with satu-
rated aq. NaHCO (10 mL) and extracted with AcOEt (3ϫ
0 mL). The combined organic phases were dried with MgSO , fil-
3
(15 mg, 0.05 mmol), were dissolved in ACN (1 mL) under
N-benzylpropargylamines were prepared following the procedure
reported by Van der Eycken et al.[
11c]
(
2
General Procedure A: Propargylamine 4 (0.5 mmol, 1 equiv.) was
dissolved in THF (1.5 mL) and ACN (1.5 mL) under inert atmo-
sphere. Next isocyanide 5 (0.5 mmol, 1 equiv.) was added. A 4 m
HCl solution in dioxane (125 μL, 1 equiv.) was added and the mix-
ture stirred at room temp. until consumption of the propargylamine
3
1
4
tered, concentrated in vacuo and purified by flash chromatography
on silica gel (hexanes/AcOEt) to afford compound indole 8 (47 mg,
(
4 h). Next the reaction was quenched with saturated Na
solution (20 mL) and extracted with AcOEt (3ϫ 10 mL). The com-
bined organic phases were dried with MgSO and concentrated in
2 3
CO aq.
31% yield). Unreacted starting material was also recovered (58%).
The same reaction catalyzed by HCl (dioxane solution,1 equiv.)
gave the same compound in a modest 12% yield.
4
vacuo to afford the corresponding imidazolium salts. Analytically
pure samples of the products were obtained by flash chromatog-
raphy on silica gel (hexanes/EtOH).
N-Methyl-2-(phenylethynyl)aniline (9):[24] 2-(Phenylethynyl)aniline
(
7) (193 mg, 1.0 mmol) was dissolved in THF (5 mL) under inert
atmosphere and cooled to –78 °C. nBuLi solution (10 m in hexanes,
.11 mL, 1.1 equiv.) was added dropwise and the mixture was
General Procedure B (tandem): In a Schlenk tube, the aldehyde
0
(
(
1.0 equiv.) and the amine (1.05 equiv.) were dissolved in THF
3 mL) under inert atmosphere. The tube was sealed and the mix-
stirred for 1 h. Methyl iodide (213 mg, 1.5 mmol) was added and
the mixture was stirred at room temp. for 2 h. Upon reaction com-
pletion, the reaction was carefully quenched by dropwise addition
ture was heated at 60 °C until complete aldehyde consumption
(2 h.). Next CuCl (30mol-%), RuCl
3
(3mol-%.) and the alkyne
of NH
off, and the solution was added to of saturated aq. solution
NaHCO (10 mL) and extracted with AcOEt (3ϫ 10 mL). The
combined organic phases were dried with MgSO , filtered, and
4
Cl aq. solution (1 mL) at 0 °C. A precipitate was filtered
(1.2 equiv.) were added. The mixture was first stirred at room temp.
for 30 min, and then heated at 50 °C (24 h). The solution was
cooled to room temp. and diluted with ACN (3 mL). The isocyan-
ide (1.1 equiv.) was then added, followed by a 4 m HCl solution in
dioxane (0.125 μL, 1 equiv.). The solution was stirred at room
temp. until reaction completion (24 h) and then quenched with
3
4
concentrated in vacuo to yield aniline 9 (190 mg, 91% yield). The
crude was used without further purification as the spectroscopic
data matched with those described in the literature.
Na
2 3
CO (saturated aq. solution, 40 mL) and extracted with AcOEt
Preparation of NЈ-Cyclohexyl-N-methyl-N-[2-(phenylethynyl)phen-
yl]formimidamide (11) and N-Allyl-NЈ-tert-butyl-N-phenylformimid-
amide (12): Amidines 11 and 12 were prepared from N-methyl-2-
(
3ϫ 20 mL). The combined organic phases were dried with MgSO
4
and concentrated in vacuo, to afford the corresponding imid-
azolium salts. Analytically pure samples were obtained by flash
chromatography on silica gel (hexanes/EtOH). In this way, from
the corresponding inputs, imidazolium salts 6b (54%), 6h (49%),
(
phenylethynyl)aniline (9) and N-allylaniline (10) respectively in
96% and 91% yield using general procedure A.
6
i (68%) were obtained.
Typical Procedure C (tandem from the imine): In a Schlenk tube,
imine 16 (204 mg, 1.05 mmol.), phenylacetylene (122 mg,
6
b-PdCl -(3-chloropyridine) Complex (14): This catalysts was pre-
2
2
pared from imidazolium salt 6b, 3-chloropyridine and PdCl fol-
25]
3
lowing Organ’s procedure[ (yield 47%).
4386
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4383–4388

Modular Access to Tetrasubstituted Imidazolium Salts
4
-Methyl-1,1Ј-biphenyl (15): A mixture of 4-chlorotoluene (24 mg,
Lygin, A. de Meijere, Angew. Chem. Int. Ed. 2010, 49, 9094–
9124; Angew. Chem. 2010, 122, 9280–9311; c) for a recent ex-
0.205 mmol), phenylboronic acid (25 mg, 0.205 mmol), complex
ample of isocyanide insertion into an N–H bond in a MCR
[6b-PdCl
2
-(3-chloropyridine)] (14) (4 mg, 0.006 mmol), Cs
2 3
CO
process, see: F. Medda, C. Hulme, Tetrahedron Lett. 2014, 55,
(99 mg, 0.307 mmol) in dioxane was heated at 100 °C for 2 h under
3328–3331.
nitrogen atmosphere. The mixture was filtered through a celite pad
and concentrated under reduced pressure. The residue was purified
by flash column chromatography on silica gel (hexanes/ethyl acet-
ate) to obtain the desired product whose spectroscopic properties
matched with the described in the literature[ (12 mg, 35%).
[
[
8] a) For a related process involving an isocyanide-metal complex
interacting with a propargylamine, leading to N-heterocyclic
carbene complexes, see: J. Ruiz, B. F. Perandones, G. García,
M. E. G. Mosquera, Organometallics 2007, 26, 5687–5695; b)
Also see: M. Joshi, M. Patel, R. Tiwari, A. K. Verma, J. Org.
Chem. 2012, 77, 5633–5645.
9] For related transformations featuring 5-exo additions, see: a)
R. L. Giles, J. D. Sullivan, A. M. Steiner, R. E. Looper, Angew.
Chem. Int. Ed. 2009, 48, 3116–3120; Angew. Chem. 2009, 121,
3162–3166; b) D. S. Ermolatev, J. B. Bariwal, P. L. Steenackers,
S. C. J. De Keersmaecker, E. V. Van der Eycken, Angew. Chem.
Int. Ed. 2010, 49, 9465–9468; Angew. Chem. 2010, 122, 9655–
26]
Acknowledgments
This work was supported by the Spanish Dirección General de In-
vestigación Ciencia y Técnica (DGICYT) (project BQU-CTQ2012-
30930) and Generalitat de Cataluña (grant number 2014 SGR 137).
9
658; c) B. P. Zavesky, N. R. Babij, J. P. Wolfe, Org. Lett. 2014,
Profs. Carmen Nájera (Univ. Alicante), Rosario Fernández (Univ.
Sevilla) and José M. Lassaletta (CSIC Sevilla) are thanked for use-
ful suggestions.
16, 4952–4955; d) Also see: N. Kielland, C. J. Whiteoak, A. W.
Kleij, Adv. Synth. Catal. 2013, 355, 2115–2138, and references
cited therein.
[
10] S. Tong, Q. Wang, M.-X. Wang, J. Zhu, Angew. Chem. Int. Ed.
[
[
1] For overviews on multicomponent reactions and domino pro-
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[11] a) V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken, Chem.
Soc. Rev. 2012, 41, 3790–3807; b) W.-J. Yoo, L. Zhao, C.-J. Li,
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[12] CCDC-1043645, -1043646 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
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