Simple ZnEt2 as a catalyst in carbodiimide hydroalkynylation: Structural and mechanistic studies

Article abstract of DOI:10.1039/c7dt02700a

Expanding the possibilities of the use of simple and available ZnEt₂ as a catalyst, the hydroalkynylation of carbodiimides with a variety of alkynes to obtain unsaturated substituted amidines is described in this work. Different stoichiometric

Full text of DOI:10.1039/c7dt02700a

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ISSN 1477-9226
PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
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a Zr-metal–organic
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ARTICLE
Simple ZnEt2 as catalyst in carbodiimide hydroalkynylation:
structural and mechanistic studies
Antonio Martínez,a Sonia Moreno-Blázquez,a Antonio Rodríguez-Diéguez,b Alberto Ramos,a Rafael
Fernández-Galán,a Antonio Antiñolo*a and Fernando Carrillo-Hermosilla*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Expanding the possibilities of use of simple and available ZnEt2 as catalyst, the hydroalkynylation of carbodiimides with a
variety of alkynes to obtain unsaturated substituted amidines is described in this work. Different stoichiometric studies
allow to propose that amidinate complexes are intermediates in this catalytic process, produced by easy activation of the
C-H bond of the alkyne, formation of alkynyl derivatives followed by a carbodiimide insertion step. Kinetics studies allowed
the generation of a rate law for the hydroalkynylation of N,N’-diisopropylcarbodiimide with phenylacetylene which is
second order in [carbodiimide], first order in [catalyst] and zero order in [alkyne], with a negligible PhC≡CH/PhC≡CD
isotopic effect, consistent with a rate-determining state involving carbodiimide insertion. The hydroalkynylation reaction
has been coupled with isocyanate (and isothiocyanate) insertion and intramolecular hydroamination to obtain
imidazolidin-2-ones (or thione). The structures of different plausible intermediates have been determined by X-ray
www.rsc.org/
diffraction
studies.
this compound without auxiliary ligands are rare.5
Introduction
Alkynes are among the most valuable functional groups in
organic synthesis since they can be transformed to build new
C-C or C−N bonds by catalytic methods.6 On the other hand,
carbodiimides are members of the heterocumulene family and
they are part of a plethora of NH addition reactions mediated
by metal complexes to obtain guanidines.7
Metal catalysis has a great impact in industrial processes
including the production of "commodities" and fine chemicals.
Nevertheless, the commercial use of the least abundant
transition metals (e. g, Pd, Rh, Ru, Ir) in catalytic processes, as
well as the growing trend in modern catalysis research
towards the use of derivatives of the lanthanoids, show some
disadvantages due to their low availability, high prices, or
toxicity, which implies additional purification processes,
especially when the final product has a pharmaceutical use.
Hence, part of the actual research is focused, on the one hand,
on their replacement by cheaper and less toxic metals with
simple ligand systems, and, on the other hand, on the
discovery of new protocols with such metals.1 Therefore, the
use of inexpensive, biocompatible and environmentally benign
zinc compounds can be of great interest.2 For example, well-
Amidines, analogous to guanidines but with a CN2 core, are
synthesized by different methods involving amides, thioamides
or nitriles.8 Propiolamidines (or propargylamidines)
(RN=C(C≡CR’)(NHR)), which contain
a C−C triple bond,
introduce a new factor of potential reactivity, which can be
exploited in the synthesis of complex organic heterocycles.9
Although these molecules can be obtained by nucleophilic
attack of alkynyllithium derivatives to carbodiimides, the yields
are often low and the work−up, involving hydrolysis of the
obtained amidinate salts, could lead also to the hydrolysis of
the final moisture−sensitive amidine product.10 As a new
strategy, a wide variety of metal catalysts have successfully
been employed in the atom−economic synthesis of these
propiolamidines by addition of terminal alkynes to
carbodiimides. Pioneering work was carried out by Süss−Fink
known diethylzinc is
a commonly used transmetallation
reagent,3 with an affordable price which makes it a very
attractive precursor for applications in catalytic synthesis. In
general, ZnEt2 has been used as a precursor for well-defined or
in situ formed complexes in a literature dominated by
polymerization chemistry.4 In contrast, the examples of use of
who employed
a bimetallic Ru−Co cluster to obtain
propiolamidines at high temperature.11 Since then, the
majority of the few and recent studies has focused on
rare−earth
metal
catalysis.10,12
Outstandingly,
carbonylpropiolamidine derivatives with potential biological
applications were also prepared under mild conditions via a
copper−catalysed multicomponent reaction (MCR) between
terminal alkynes, acid chlorides and carbodiimides.13
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A valuable alternative has been tabled by using main group transition metals or by multistep processes with their
metal catalysts. On the one hand, simple lithium respective undesired subproducts.19 In the elegant process
hexamethyldisilazide (LiN(SiMe3)2) opened the way to these described by Hill, the reaction takes place via a consecutive
earth−abundant elements, allowing to obtain propiolamidines formation of propiolamidine, the addition of an isocyanate and
in practically quantitative yields.14
the consequent intramolecular hydroamination (Scheme 2).
In the last years, our laboratory has been actively engaged in
developing the catalytic guanylation of amines employing
ZnEt2.20 In these processes, ZnEt2 activates amine N−H bonds
to obtain reactive amido species towards the carbodiimide
insertion. Although references about Zn−catalysed reactions
involving the functionalization of alkynes are well
documented,6g to the best of our knowledge no cases of the
use on those hydroalkynylation reactions have been reported
so far. As part of our ongoing research regarding the chemistry
of ZnEt2 as a catalyst, we now focused our attention into the
use this simple compound in the catalytic activation and
addition of terminal alkynes to carbodiimides to obtain
substituted propiolamidines. Propiolamidinate zinc complexes
have been obtained and fully characterized, and proposed as
plausible intermediates. Mechanistic studies are also
presented to propose a catalytic cycle. Finally, the reaction
was coupled to the addition of isocyanates (and
isothiocyanate) allowing the synthesis of substituted
imidazolidinones through intramolecular hydroamination of
intermediate ureas.
Scheme 1. Proposed catalytic synthesis of propiolamidines.
Results and Discussion
Catalytic hydroalkynylation studies
As stated previously, ZnEt2
1 shows excellent results for the
construction of C−N bonds of guanidines.20 Encouraged by
these results we decided to expand the scope of this catalyst
into the realm of C−C bond formation.
Scheme 2. Proposed catalytic coupling and cyclization of propiolamidines and
isocyanates.
Table 1. Optimization of the reaction conditions
For example,
a calcium amido−β−diketinimato complex
catalysed the reaction between phenylacetylene and
carbodiimide, in a process where the catalyst lost the ligands
to give the real undetected active species.15 Finally, the related
work of Coles with magnesium reagents, as well as the use of
homoleptic heavier alkaline earth amido compounds by Hill,
are good benchmarks for the research on simple and available
catalysts for this efficient C−C bond formation reaction.16
In all cases, these catalytic reactions were proposed to
proceed via propiolamidinate intermediates, produced by the
insertion of a carbodiimide molecule into a reactive metal–
acetylide bond. The catalytic cycle restarts by protonolysis
with acetylene to release the propiolamidine as shown in
Scheme 1.
Entry
Catalyst
Solvent
T (°C)
t (h)
Yield
(%)a
24
1
2
3
4
5
6
7
8
ZnEt2
ZnEt2
ZnEt2
ZnEt2
ZnEt2
ZnEt2
ZnEt2
ZnMe2
Toluene-d8
Toluene-d8
Toluene-d8
Toluene-d8
Toluene-d8
THF-d8
25
70
70
70
70
70
70
70
24
1
51
7
65
16
24
24
24
24
75
90
48
CD2Cl2
0
Toluene-d8
75
Recently, Hill has reported the preparation of
imidazolidinones, and other similar heterocycles, using a
strontium amido derivative as an efficient catalyst.17 The
synthesis of these cyclic ureas are of special interest as they
are found in many biologically active molecules, including
potent anti−HIV agents.18 Many of these heterocycles can be
synthesized by other catalytic methods based in less abundant
aYields obtained via spectroscopic 1H NMR. Reactions carried out using 0.5 mL of
solvent, 0.5 mmol of PhC≡CH, 0.5 mmol of DIC, and 0.015 mmol of catalyst (3
mol%).
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The effectiveness of
1
in the catalytic addition of terminal intermediates.16a Unfortunately, reactions of ZnEt2 with
alkynes to carbodiimides was initially investigated on an NMR PhC≡CH give, in addition to ethane, a very insoluble white
scale in toluene−d8 using N,N’−diisopropylcarbodiimide and solid, likely due to the formation of polymeric aggregates of
phenylacetylene, as a model reaction (Table 1). A control Zn(C≡CPh)2 or ZnEt(C≡CPh).21 Surprisingly, addition of excess of
reaction confirmed that the propiolamidine was not formed in PhC≡CH and DIC results in the redissoluꢀon of this precipitate
the absence of 1. In contrast, a catalyst loading of 3 mol% to form complex mixtures which, after warming at 70 °C for
yielded 24% of the amidine [iPrN=C(C≡CPh)(NHiPr)] 2a after 24 several hours, yield the corresponding amidine 2a. These facts
h at room temperature (Table 1, entry 1). More respectable allow us to conclude that additional alkyne or carbodiimide
yields were obtained with increased temperature and reaction form soluble adducts with the polymeric alkynyl species, as
times (Table 1, entries 2−5), with good yields (∼90%) at 70 °C was previously observed with phosphanes or THF coordinated
and 24 h. An important solvent effect was observed when the to ZnEt(C≡CPh).22
more polar THF−d8, with greater coordination ability, or CD2Cl2
were employed. In the latter case, the reaction was inhibited
(Table 1, entries
6 and 7). Finally, the use of the
closely−related, but more expensive ZnMe2 did not lead to
higher yields (Table 1, entry 8).
Table 2. Hydroalkynylation of carbodiimides.
Entry
Alkyne
PhC≡CH
Carbodiimide
DIC
Yield (%)a
2a/90
2b/89
2c/55
2d/83
2e/90
2f/85
1
2
3
4
5
6
7
PhC≡CH
DCC
EtNCNtBu
PhC≡CH
pFC6H4C≡CH
pCF3C6H4C≡CH
pCF3OC6H4C≡CH
pMeOC6H4C≡CH
DIC
DIC
DIC
DIC
2g/90
aYields obtained via spectroscopic 1H NMR. Reactions carried out using 0.5 mL of
solvent (toluene-d8), 0.5 mmol of alkyne, 0.5 mmol of carbodiimide, and 0.015
mmol of catalyst (3 mol%), at 70 °C, for 24 h.
Scheme 3. Synthesis of zinc propiolamidinates.
In fact, labile coordination of carbodiimide to an yttrium
complex has been proposed as intermediate in catalytic
hydroalkynylation,12d and two zinc complexes with
coordinated carbodiimide have been isolated.23 The
requirement of this coordination to the metal center could be
the origin of the observed negative effect of THF on the
catalytic activity (Table 1, entry 6).
Further studies were performed with a range of terminal
alkynes and carbodiimides (Table 2). All reactions went
smoothly providing the corresponding propiolamidines. Like
N,N’−diisopropylcarbodiimide
(DIC),
N,N’−dicyclohexylcarbodiimide (DCC) also reacts with
phenylacetylene with good conversions, whereas the steric
demand of bulkier N,N’−EtNCNtBu slightly affects the yield
(Table 2, entries 1−3). The reactions using alkynes with
electron−withdrawing or donor substituents at the phenyl ring
occur also with good yields (Table 2, entries 4−7). It is worth
Among the known routes to obtain new guanidinate or
amidinate complexes, the direct reaction between the
proligand and a metal complex containing ligands that are
susceptible to cleavage by protonolysis has been widely used.
noting that catalyst
1 displayed remarkable functional group
24
As an alternative to obtain these amidinate complexes as
tolerance and groups such as F or OR were unaffected under
the reaction conditions used. This catalytic activity is
comparable to that reported using magnesium alkyls or
strontium amides as precatalysts.16
plausible central active species, stoichiometric reactions of
ZnEt2 and preformed amidine 2a were performed in 1:1 and
1:2 metal:amidine ratios (Scheme 3).
In the first case, 1H NMR spectroscopy showed complete
conversion after a few minutes at room temperature. This new
Stoichiometric and Mechanistic studies
complex
3 shows a simple pattern in its spectra (See Figure
The knowledge of the catalytic mechanisms is of the utmost
importance because it helps design new catalysts and leads to
further synthetic developments. In this context, to gain
mechanistic insights into this catalytic process, a series of
stoichiometric reactions were carried out. From Scheme 1, it
seems reasonable to assume from previous reports that the
catalytic cycle starts with the initial metalation of the terminal
carbon of the alkyne,6f to form a reactive zinc acetylide which,
after insertion of the corresponding carbodiimide via an
S1). In addition to phenyl protons, methyl and methine
protons of the isopropyl groups appear as a doublet and a
septuplet at
triplet and a quadruplet, at
assigned to a Zn−ethyl moiety, a finding that indicates the
structure of very symmetric complex of formula
[ZnEt{C(C≡CPh)(NiPr)2}]
. It should be noted the excellent
δ
1.37 and 4.25 ppm, respectively, along with a
δ
1.67 and 0.82 ppm, respectively,
a
3
selectivity of the process towards the heteroleptic
associative
bond
metathesis,
affords
amidinate
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mono−chelated complex, stable in solution for days, under dinuclear compound with two types of amidinate ligands, one
coordinated in a chelate κ2− fashion and the other one
inert atmosphere.
κ1 κ1− fashion, which
from a saturated solution in hexane. The molecular structure produces a distorted pseudotetrahedral coordination around
Fortunately, suitable X−ray quality crystals of
3
were obtained bridging both metal nuclei in a
ꢀ− −
and the atomic numbering scheme are shown in Figure 1. The the zinc atoms, with a bite angle for the chelate ligand of 65.1°
complex appears to be
a dinuclear eight−membered and a N1−Zn1−N3 angle of 130.2°. Like compound 3, complex 4
metallacycle system in solid state, which adopts a boat−type shows delocalization at the amidinate core in both chelate and
conformation in which every zinc metal center bears a bridging ligands (C−N ~1.33 Å, sum of bond angles at C1 and
terminal ethyl group and an amidinate ligand acting as bridging C31 ~ 360°).
monodentate ꢀ−κ1−κ1 donor in remarkable contrast with
most amidinate complexes, which typically adopt a chelate
mode.
.
Figure 2. Molecular structure of compound 4: H atoms are omitted for clarity and
Figure 1. Molecular structure of compound 3: H atoms are omitted for clarity and
ORTEP ellipsoids are plotted at 50% probability level.
ORTEP ellipsoids are plotted at 50% probability level.
The distribution of the ligands in complex
4 explains the
The chelate coordination was ruled out since the Zn1−N1
distance of 2.893 Å (and Zn2−N3, 2.838 Å) exceeds the typical
distance for a dative Zn−N bond of 2.4 Å.25 As a result of this
coordination mode, the zinc atoms adopt a trigonal−planar
coordination geometry (sum of bond angles at Zn1 360°; Zn2
359.5°). We would like to note that, although
pseudotetrahedral is the habitual coordination mode in zinc
amidinate complexes in the solid state,26 very few examples of
zinc amidinate complexes with trigonal coordination have
been previously described, usually with bulky substituents on
nitrogen atoms.23,26b,f,g,i The bond lengths Zn1−N2 or Zn2−N1
presence of only two of the three sets of signals assigned to
1
isopropyl groups observed in the H NMR spectra. When these
C6D6 solutions where heated, a reversible decrease in intensity
of two of the doublets and the concomitant increase of the
less shielded one was observed. In fact, a thermodynamic
equilibrium between two different species was reached at
room temperature, lying towards a symmetric species upon
heating. This behavior was studied in more detail and the
equilibria were monitored by 1H NMR variable temperature
experiments (See Figure S3). Changes in the relative intensity
of methyl protons were followed, this allowing us to calculate
Keq at different temperatures. The thermodynamic parameters
(2.007 and 2.004 Å, respectively) are comparable with those of
[{EtC(NiPr)2}ZnEt]2.
23b
Finally, the amidinate ligands show a
ꢁ
H0 of 95.5 kJ.mol-1 and
ꢁ
S0 of 278.9 J.mol-1K-1 were obtained
from the corresponding van’t Hoff plot, wich allowed us to
uniform delocalization in the CN2 core (C7−N1 1.342 Å, C7−N2
1.320 Å, sum of bond angles at C7 360°).
calculate a value for
S4).
ꢁ
G0 of 12.0 kJ.mol-1 at 298K (See Figure
When a 1:2 metal:amidine ratio was used, the complete
conversion of the starting reagents takes place after 2h at
1
room temperature. H NMR spectra in C6D6 show, at the end
These results are in accordance with an associative process at
lower temperatures, to obtain the characterized dinuclear
compound, albeit low energy is needed to produce the
inverse, dissociative, process to give a mononuclear compound
with two equivalent amidinate ligands (shown as chelate
ligands, although a hemi−labile form cannot be completely
ruled out), as depicted in Scheme 4. This kind of equilibrium
has not been observed previously in propiolamidinate systems,
of the reaction, three similar doublets and their corresponding
septuplets, assigned to three inequivalent isopropyl groups, a
pattern hard to fit with the expected symmetric bisamidinate
complex [Zn{C(C≡CPh)(NiPr)2}2] (see Figure S2). To obtain more
information about the real structure of this new complex,
suitable X−ray quality crystals were obtained from a saturated
solution in hexane. Diffraction studies (Figure 2) reveal a
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although a similar equilibrium was found in a magnesium the N=C nitrogen atom, with a C1−N1 bond distance (1.306Å)
dimer compound with [CMe(NiPr)2]- ligands and the slightly shorter than that of the C1−N2 bond (1.352 Å). The
rearrangement of the propiolamidinate units from a chelating Zn−C≡C angles (174.30°) were very close to the linearity
into a bridging binding mode has also been postulated in the necessary to form a
synthesis of zinc clusters.27,26g
A reasonable mechanism for the formation of
π−interaction between free alkyne and the Lewis acidic center
of complex . Such coordination could to enhance the acidity
σ−bonded alkynyl ligand.
5
involves initial
4
of the C−H bond. The Brönsted basicity of the labile
non−coordinated N atom of the amidinate ligands prompts
deprotonation of the alkyne−CH bond affording coordinated
amidines and the alkynyl−zinc groups. This proposal is
reminiscent of the C−H bond activation occurring in frustrated
Lewis pairs (FLP) for terminal alkynes (Scheme 5).30
iPr
iPr
Zn
iPr
iPr
C
C
C
iPr
N
N
N
N
N
N
N
Zn
iPr
C
N
iPr
iPr
iPr
iPr
N
N
C
Zn
C
2
N
N
iPr
iPr
Scheme 4. Equilibrium between dimeric and monomeric forms of 4.
Figure 3. Molecular structure of compound 5: H atoms, excepting H2, are omitted for
Although different examples of propiolamidinate complexes of
10,12c,d,g,i,15,16a,c,28
rare−earth and group 2 metals are known,
clarity and ORTEP ellipsoids are plotted at 50% probability level.
iPr
these are the first examples of fully characterised zinc
propiolamidinates and promising candidates with potential
applications in catalysis and materials chemistry as analogous
NH
Ph
Ph
C
Ph
iPr
iPr
C
N
iPr
1
guanidinate complexes.26j,29 In fact, H NMR monitoring of the
Zn
iPr
iPr
N
N
Ph
H
2
N C
reaction of an equimolar mixture of DIC and PhC≡CH in the
Zn
Ph
N
N
Zn
Ph
H
N
Ph
presence of 3 mol% of complexes
formation of amidine 2a in 80% yield after 24 h at 70 °C,
showing a similar efficiency to that found for compound . This
3 or 4 indicated the catalytic
H
C
iPr
∼
iPr
1
5
Ph
confirms the involvement of amidinate intermediates in the
catalytic cycle (vide supra). When carrying out the reaction
4 and two equivalents of PhC≡CH, in C6D6
Scheme 5. Proposed mechanism for the formation of 5.
between complex
An intramolecular NH---C hydrogen bond (2.125 Å) was
observed between a nitrogen atom of the neutral guanidine
solution in a NMR tube, a fast transformation takes place, to
obtain a new compound (or mixture of compounds), the main
(N2) and the Cα atom of the alkynyl ligand, well below the sum
feature of which being a broad peak near
δ 9 ppm, along with
of Van der Waals radii for these atoms (1.20 Å for H, 1.70 Å for
C).31 That could cause the observed downfield shift of the NH
proton in NMR spectra and the broadening of this and other
peaks, by a probable fast exchange of the labile proton atom
between the nitrogen and carbon atoms. When crystals of
broad peaks assigned to phenyl and isopropyl groups, and free
alkyne, as observed in its 1H NMR spectra (See Figure S5).
Surprisingly, when PhC≡CD (99% deuterated) was used, that
peak was considerably reduced, the rest of the spectrum
remaining unaltered.
compound
were identical to those obtained from the reaction between
5
were dissolved in C6D6, their 1H NMR spectra
In order to stablish the exact structure of this new compound,
4
suitable X−ray quality crystals were obtained from
toluene−pentane solution. Diffraction studies (Figure 3) reveal
a four−coordinate Zn center, with two −bonded alkynyl and
a
and two equivalents of alkyne. A variable temperature 1H NMR
experiment in toluene−d8 reveals a complex equilibrium
between different species showing simultaneously dynamic
processes. We observed that the relative intensity of the peak
σ
two neutral amidine ligands, the latter coordinated through
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assigned to the CH proton of free alkyne decreases as this case, the apparent constant rate was observed to be
temperature was lowered. Alongside, the broad peak near reduced by one order of magnitude due to the reduction of
ppm starts to decrease in intensity and a new broad signal the initial alkyne concentration by also one order, suggesting a
near 9.8 ppm began to emerge already at -10 °C, being a dependence on this initial concentration. Kinetic analysis of
clear doublet at -90 °C. The latter peak was coupled with a the reaction using PhC≡CD in the same conditions yielded a
multiplet near
4 ppm, which were assigned to NH and CH(iPr) negligible kinetic isotopic effect (KIE) of kH/kD = 0.88, thus the
δ
9
δ
δ
groups, respectively, in a coordinated amidine, probably protonolysis of ZnEt2, or that of an intermediate amidinate
affected by the NH---C weak interaction commented above. complex, by the alkyne are unlikely to be rate–determining
Another doublet at near
NH(iPr) group can be also observed at this temperature. In ([amidine]0 = 120 mM) does not result in any substantial
addition, two pairs of broad doublets were tentatively variation of the reaction rate (Figure S7), in contrast with the
δ 3.7 ppm assigned to an unaffected (Figure 5, left). Furthermore, initial addition of the amidine
assigned to methyl groups in two types of coordinated product inhibition observed with
a strontium amido
amidines (see Figure S6).
complex.16c
5 participates in the The first order rate of reaction with respect to catalyst
We believe that a complex similar to
catalytic cycle as the resting state of the catalyst, as the concentration was confirmed conducting experiments at
characteristic peak at 9 ppm was observed in the NMR different catalyst precursor concentrations and fixing the
δ
spectra at the end of most of the described catalytic studies. carbodiimide to alkyne molar ratio at 1:10 (Figure 5, right).
Thus, coordinated amidines could be easily removed by two
carbodiimide molecules, followed by carbodiimide insertion to
restart the cycle. For the first time, this kind of necessary
intermediate in hydroalkynylation processes has been
detected, isolated and structurally characterized. In addition, it
should also be pointed out that, as commented before,6g the
alkynyl zinc derivatives show interesting applications in organic
synthesis, so such straightforward activation of terminal
40
30
20
10
0
0.26
0.24
0.22
0.20
0.18
0.16
0.14
0.12
0.10
m = -0,0001
R² = 0,98
m = 0,0237
R² = 0,996
alkynes by means of the complex
4 opens interesting reactivity
0
500
1000
1500
0
1000
avenues for this complex beyond the hydroalkynylation
t (min)
t (min)
process, potentially including the activation of other σ−bonds,
via FLP chemistry.
Figure 4. Left: second order kinetic analysis of the NMR scale reaction of
N,N'−diisopropylcarbodiimide (0.23 M) with PhC≡CH (2.3 M) in toluene−d8 (total
volume 0.8 ml) with 3 mol% of 1 at 70 °C. Right: zero order kinetic analysis of the NMR
scale reaction of N,N'−diisopropylcarbodiimide (2.3 M) with PhC≡CH (0.23 M) in
toluene−d8 (total volume 0.8 ml) with 3 mol% of 1 at 70 °C.
To gain further insight into the formation of propiolamidines,
quantitative kinetic data of the catalytic hydroalkynylation of
N,N'−diisopropylcarbodiimide with PhC≡CH in the presence of
ZnEt2
1 as catalyst were carried out in toluene−d8. The
reaction rates of the hydroalkynylation reaction at 70 °C were
monitored over a period of three half−lives by 1H NMR
spectroscopy, using tetrakis(trimethylsilyl)silane as internal
standard. Initially the order of the reaction with respect to DIC
concentration ([DIC]0 = 230 mM) was determined keeping the
concentration of alkyne virtually unaltered. The study started
11
0.30
10
9
0.25
0.20
0.15
0.10
0.05
0.00
m = 0,0036
R² = 0,997
R² = 0,97
8
7
m = 0,0041
R² = 0,995
by using 3 mol% of catalyst
1 ([1] = 7 mM), and the
6
carbodiimide to alkyne molar ratio was stablished at 1:10 to
keep approximately zero−order conditions for the alkyne. A
5
0
5
Catalyst loading (mol%)
10
0
500
t (min)
1000
plot of ln[DIC] against time did not provide
a linear
relationship, and the data fit better with a second−order
kinetic behavior (Figure 4, left). The observed second order
behavior with respect to [DIC] could implicate the formation of
Figure 5. Left: second order kinetic analysis of the NMR scale reaction of
N,N'−diisopropylcarbodiimide (0.23 M) with PhC≡CH (blue) or PhC≡CD (red) (0.23 M) in
toluene−d8 (total volume 0.8 ml) with 3 mol% of 1 at 70 °C. Right: linear correlation
between the observed rate constant k and catalyst loading (mol%).
a compound similar to
5 with two coordinated molecules of
carbodiimide and the consequent insertion of these
carbodiimides in the Zn−C bond, as the rate−determining step.
Next, we determined the order of the reaction with respect to
the concentration of PhC≡CH. During this study we stablished a
relative PhC≡CH to DIC ratio of 1:10. Variation of the alkyne
concentration provided evidence of a zero−order dependence
of the reaction rate on alkyne concentration (Figure 4, right).
Global pseudo−second order with respect to DIC concentration
was confirmed when the reaction was monitored using
equimolar concentrations of both reagents (Figure 5, left). In
On the basis of these analyses, we propose the formulation of
a
rate
law
for
the
hydroalkynylation
of
N,N’−diisopropylcarbodiimide with phenylacetylene catalysed
by 1 of the form shown in Equation (1).
ꢀꢁ[ꢂꢃꢄ]
= k.[ꢆ][ꢇℎꢈꢈꢉ]ꢊ.[ꢋꢌꢈ]ꢍ
(1)
ꢁꢅ
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C7DT02700A
Journal Name
ARTICLE
Catalytic intramolecular hydroamination studies
regardless of the isocyanate used, the almost quantitative
formation of open ureas of the type RC≡C(NR’)(NR’(CO)NHR”)
Considering the effectiveness of compound
1 as catalyst for
in few minutes at room temperature, displaying
a
hydroalkynylation under mild conditions, we decided to study
the possibility of coupling this reaction with the addition of
isocyanates, analogously to the reported catalytic activity
proved by group 2 metal amido species.17 The proposed
pathway implied isocyanate insertion in an amidinate
intermediate to obtain a κ2−N,O−chelate which isomerises to
the κ2−N,N form necessary for an intramolecular
hydroamination process, followed by protonolysis by an
characteristic downfield shifted peak, assigned to the NH
moiety in the NMR spectra. These would be the true starting
reagents to be transformed into the corresponding
heterocycles. In fact, after warming for 24 h at 70 °C, the
corresponding cyclic ureas were obtained in good yields (Table
t
3). The open urea obtained from BuNCO did not undergo the
intramolecular cyclization probably due to the bulkyness of the
isocyanate substituent (entry 7, Table 3).
amidine
molecule,
to
obtain
the
corresponding
Single crystals adequate for X−ray diffraction studies were
imidazolidin−2−ones (see Scheme 2).
obtained
from
the
NMR
scale
reaction
for
On the other hand, ZnEt2, activated by [PhNMe2H][B(C6F5)4],
has been recently described to show high reaction rates for
the addition of aniline derivatives to primary alkynes in an
intermolecular hydroamination process.32 Likewise, the
cyclization of alkynyl amides to form the corresponding
nitrogen−containing heterocycles mediated by ZnEt2 has also
been reported.5d
(4Z,5E)−4−benzylidene−3−(2,6−dimethylphenyl)−1−isopropyl−
5−(isopropylimino)imidazolidin−2−one 6f (entry 6, Table 3).
The molecular structure is displayed in Figure S8. The bond
lengths and angles are within the range expected for these
imidazolidin−2−ones.17
We propose that the reaction could take place through an
insertion reaction of the isocyanate into a zinc amidinate, as
occurs for group 2 catalysts. To gain insights into these
hydroamination reactions, we carried out the reaction of
Table 3. Alkyne, carbodiimide and heterocumulene scope for the catalytic synthesis of
imidazolidin−2−ones (or thione).
complex
4
with 2,6−Me2C6H4NCO. Regardless of the
stoichiometry, only one equivalent of isocyanate reacts with
the zinc complex, to obtain the heteroleptic imidamidate
complex 7, in quantitative yield in few minutes (Scheme 6).
Entry
Alkyne
Carbodiimide
RNCX
Yield
(%)a
1
2
PhC≡CH
PhC≡CH
DIC
DCC
EtNCNtBu
DIC
PhNCO
PhNCO
6a/95
6b/88
6c/83
6d/91
6e/90b
6f/95
6g/0c
6h/91
6i/94
6j/90
6k/90
3
PhC≡CH
PhNCO
4
PhC≡CH
PhNCS
5
PhC≡CH
DIC
pMeC6H4SO2NCO
2,6-Me2C6H4NCO
tBuNCO
PhNCO
6
PhC≡CH
DIC
7
PhC≡CH
DIC
8
pF-PhC≡CH
pCF3PhC≡CH
pCF3OPhC≡CH
pMeOPhC≡CH
DIC
9
DIC
PhNCO
10
11
DIC
PhNCO
DIC
PhNCO
[a] Yields obtained via spectroscopic 1H NMR with respect to the urea.
Reactions carried out using 0.5 mL of solvent, 0.5 mmol of alkyne, 0.5 mmol
of carbodiimide, and 0.015 mmol of catalyst (3 mol%), at 70 °C, for 24 h, and
then 0.5 mmol of isocyanate (or isothiocyanate), at 70 °C, for 24h. [b]
Obtained after 7h of reaction. [c] The reaction yields the urea without
cyclization.
Scheme 6. Synthesis of complex 7.
1
The H NMR spectra of
7
in C6D6 show, in addition to aromatic
1 and 1.9 ppm, coupled in
pairs with two multiplets at near 4.15 and 4.5 ppm, and
assigned to isopropyl groups. One singlet in the 2.5 ppm
peaks, four doublets between
δ
δ
δ
region indicates that the rotation of the 2,6−dimethylphenyl
group is not hindered in this molecule at room temperature
(See Figure S9).
Keeping this in mind, the catalytic activity of ZnEt2 with
different alkynes, carbodiimides and isocyanates (and one
isothiocyanate) was checked in order to test the versatility of
Crystals of compound
7 suitable for an X−ray diffraction study
the simple zinc compound
1 (Table 3). As one can draw from
were grown from a concentrated toluene/hexane solution and
the molecular structure is represented in Figure 6.
Scheme 2, the reaction is favoured with electron−withdrawing
substituents in the C≡C triple bond, increasing the
electron−deficiency and assisting the nucleophilic attack.
Following the catalytic cycle, in a first step, the amidines were
obtained as described previously, followed by the addition of
the heterocumulene molecule. The first observation was,
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Journal Name
ZnEt2
N
X
H
+
R'
C
R'
N
R'
N
N
ZnEt2-x
x
X
N
R'
C
R'
slow
X
R'
N
x =1,2
NH
X
fast
R'
R'
R'
X
H
NH
C
X
R'
C
RNCO
Zn
N
N
N
R'
HN
X
R'
O
X
fast
RNCO
R
R'
N
N
fast
X
N
Figure 6. Molecular structure of compound 7: H atoms are omitted for clarity and
R'
ORTEP ellipsoids are plotted at 20% probability level.
R'
O
R'
R
O
R'
N
N
N
N
X
This study revealed complex
complex with an amidinate and an imidamidate N,N’−chelate
ligands, the latter forming 6−membered [ZnNCNCN]
7 to be a pseudotetrahedral zinc
slow
X
Zn
O
HN R
N
R
N
N
N
LZn
R'
R'
R'
N R'
X
X
a
N
R'
L = propiolamidinate
boat−like metallacycle. This contrasts with the structure
obtained for a similar bis(imidamidate) magnesium complex,
where the ligands adopt a N,O−chelate ligand coordination,
which would require an isomerization prior to the
intramolecular hydroamination (See Scheme 2), no longer
Figure 7. Proposed coupled catalytic cycles.
In a first step, alkyne and carbodiimide were catalytically
transformed in propiolamidine (top cycle in Figure 7), through
amidinate and alkynyl zinc intermediate complexes, followed
by a rapid reaction of this amidine with isocyanate to obtain
the open urea. This urea undergoes a catalysed intramolecular
cyclization to produce the final imidazolidinone, through an
imidamidate intermediate complex (bottom cycle in Figure 7).
necessary for the zinc complex.17 Although complex
7 appears
to be chiral in the solid state, a rapid dynamic boat−to−boat
inversion of the metallacycle in solution results in the
equivalence of both isopropyl groups of the amidinate ligand.
However, the methyl groups within these isopropyl groups are
diastereotopic. This would explain the presence of four similar
1
doublets in the H NMR spectra, two of them assigned to the
isopropyl moieties in the metallacycle and the other two
corresponding to each pair of equivalent diastereotopic
methyls. This was confirmed by the presence of only three
peaks assigned to the methine carbon atoms by means of
gHSQC experiments (See Figure S10).
Conclusions
In summary, the hydroalkynylation of carbodiimides has been
achieved for the first time using a simple and low−cost zinc
compound, ZnEt2, as precatalyst, which offers
a
straightforward, atom−economic route to N,N’−disubstituted
propiolamidines. Stoichiometric studies have allowed the
isolation and full characterization of two zinc amidinates which
have been proposed as plausible intermediates in this catalytic
transformation, as well as a bisalkynyl−bisamidine complex, as
the possible resting state of the catalyst. The rate law for the
hydroalkynylation was deduced to be second order dependent
on the carbodiimide concentration but to be zero order with
respect to the alkyne, with a negligible kinetic isotopic effect,
thus indicating that the C−H activation of the alkyne was
favoured and the insertion of the carbodiimide in an alkynyl
intermediate is the rate determining step of this reaction.
Coupling this catalytic reaction with the addition of
isocyanates (or isothiocyanates) allows to obtain ureas that
were transformed into the corresponding imidazolidinones or
–thione in a one−pot high atom−efficient process. This last
process seems to occur through imidamidate intermediates,
one of them was isolated and fully characterized, via an
intramolecular hydroamination reaction catalysed by a zinc
Also, unlike the aforementioned magnesium derivative,
compound
atmosphere, with no proof of isocyanate de−insertion.
Participation of imidamidate species, similar to , in the
catalytic process of intramolecular hydroamination was
confirmed, using as catalyst in the coupling and cyclization of
7 was stable in solution for days, under inert
7
7
2a and 2,6−Me2C6H4NCO. As commented above, instantaneous
reaction between amidine and isocyanate gives rise to the
corresponding open urea. After warming for 24 h at 70 °C, full
conversion of this urea to the cyclic form was obtained.
Taking into account the different studies presented here, the
coupled catalytic cycles for both hydroalkynylation and
intramolecular hydroamination are proposed in Figure 7.
compound.
Further
stoichiometric
and
catalytic
transformations involving the use of these Zn−based
compounds are currently under study in our group.
8 | J. Name., 2012, 00, 1-3
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ARTICLE
Experimental Section
Synthesis of [Zn{C(C≡CPh)(NiPr)2}2]2 4.
General Considerations.
To a ZnEt2 (1 mmol) solution in toluene (5 mL), amidine 2a
(0.43 g, 2 mmol) was added. After 2 h stirring at room
temperature, the solvent was eliminated under reduced
pressure and 5 mL of pentane were added. The solution was
All reactions were performed using standard Schlenk and
glove−box techniques under an atmosphere of dry nitrogen.
Solvents were purified by passage through a column of
activated alumina (Innovative Tech.), degassed under nitrogen
and stored over molecular sieves in the glove−box prior to use.
Microanalyses were carried out with a Perkin−Elmer 2400 CHN
analyzer. NMR spectra were recorded on a Varian FT−400
spectrometer using standard VARIAN−FT software. Mass
spectroscopic analyses were performed on an Advion
expression CMS instrument (electron impact). ZnEt2 (1 M in
hexane), ZnEt2 (1.1 M in toluene), ZnMe2 (2 M in toluene),
alkynes, carbodiimides and isocyanates were purchased from
Aldrich and used as received.
stored at
complex
−20 °C overnight affording light yellow crystals of
(0.49 g, 94 %). H NMR (400 MHz, 298 K, C6D6) As a
1
4
mixture of dimer and monomer δ (ppm) = 7.49, 7.39, 6.94 (m,
C6H5, dimer and monomer), 4.45 (m, 4H, CH, dimer), 4.31
(sept, 2H, CH, monomer, J = 6.3 Hz), 1.68 (broad d, 12H, CH3,
dimer), 1.56 (broad d, 12H, CH3, dimer), 1.36 (broad d, 12H,
CH3, monomer). 13C{1H} NMR (100 MHz, 298 K, C6D6) δ (ppm) =
158.29, 155.18, 132.30, 132.27, 132.26, 129.38, 129.31,
129.00, 128.72, 128.62, 122.92, 122.50, 122.26, 96.82, 96.10,
82.37, 81.37, 79.76, 52.62, 49.07, 48.35, 26.34, 25.70, 25.21.
Anal Calcd for C30H38N4Zn: C, 69.29; H, 7.37; N, 10.77. Found,
C, 70.01; H, 7.41; N, 10.82.
Procedure for hydroalkynylation reactions at NMR tube scale
Catalytic reactions were performed on a small scale in an NMR
tube fitted with a concentric Teflon valve with 0.5 mmol of
alkyne, 0.5 mmol of carbodiimide and the adequate amount of
catalyst in the adequate solvent (toluene−d8 preferentially)
under nitrogen. Conversion of the starting material to product
was determined by integration of the product resonances
relative to the substrate peaks in the 1H NMR spectrum.
Compounds 2a−g were identified by comparing their NMR
spectra with the literature data.10,11,12b,14,16a,17
Synthesis of [Zn{C(C≡CPh)(NiPr)(NHiPr)}2(C≡CPh)2}]
Phenylacetylene (62 l, 0.60 mmol) was added to a toluene
solution (5 mL) of compound (0.150 g, 0.29 mmol). After
5.
ꢀ
4
stirring for 15 min at room temperature, the solution was
concentrated under reduced pressure and 3 mL of pentane
were added and the reaction mixture was kept at
h, affording colorless crystals of complex (0.085 g, 40 %).
Partial spectroscopic data from
solutions (see the text): 1H
−20 °C for 16
5
5
NMR (400 MHz, 298 K, C6D6) δ (ppm) = 9.05 (bs, NH), 7.9−6.9
(m, C6H5), 4.45 (sept, CH, J = 6.5 Hz), 4.24 (m, CH), 2.00−1.35
(bs, CH3), 1.45 (d, CH3, J = 6.5 Hz). 13C{1H} NMR (100 MHz, 298
Preparative Scale Reaction for 2a.
In the glovebox, phenylacetylene (3 mL, 27 mmol) and
N,N’−diisopropylcarbodiimide (4.2 mL, 27 mmol) in toluene (10
mL) were added in a Schlenk tube. ZnEt2 (0.8 mmol) was then
added to the above reaction mixture. The Schlenk tube was
taken outside the glovebox and the reaction was stirred at 70
°C for the 24 h. Then, the solution was concentrated under
reduced pressure, hexane was added and the mixture was
K, C6D6) δ (ppm
)
=
155.25, 151.85, 131.72, 129.48, 128.29,
125.74, 121.74, 121.00, 113.38, 110.53, 108.21, 107.77, 97.14,
96.19, 81.39, 78.20, 53.54, 49.22, 43.94, 24.63, 22.71. Anal
Calcd for C46H50N4Zn: C, 76.28; H, 6.96; N, 7.74 Found, C, 75.99;
H, 6.90; N, 7.68.
placed in a refrigerator at −20 °C for 16 h. After filtration the
product was obtained as yellowish microcrystalline solid. The
General procedure for kinetic experiments.
Kinetic experiments were performed using a Varian FT−400
mother liquor was reconcentrated in vacuo and placed in a
MHz spectrometer. A standard solution 0.11 M of catalyst
1
refrigerator at
−20 °C for 16 h to obtain a second crop of
was made, obtained from a 1.1 M solution in toluene and
diluted in deuterated toluene. The described kinetic
crystals. Total isolated yield 85%.
Synthesis of [ZnEt{C(C≡CPh)(NiPr)2}]2 3.
experiments
were
carried
out
on
the
N,N’−disopropylcarbodiimide and phenylacetylene (or
To a ZnEt2 (1 mmol) solution in toluene (5 mL), amidine 2a
(0.23 g, 1 mmol) was added. After stirring for 15 min at room
temperature, the solvent was eliminated under reduced
pressure and 3 mL of pentane were added. The solution was
stored at −20 °C overnight affording colorless crystals of
deuterated phenylacetylene) to form the corresponding
propiolamidine 2a
.
The reactions were carried out in J−Young NMR tubes and the
reaction rates were measured by monitoring the
disappearance of carbodiimide (or alkyne) relative to the
internal standard tetrakis(trimethylsilyl)silane (6 mg) by 1H
NMR spectroscopy at the described intervals over more than
three half−lives. All data were processed using Varian integral
analysis software. Reaction rates were derived by fitting data
to zero, first or second order equations by using linear trend
lines generated by Microsoft Excel software.
complex
3
(0.29 g, 90 %). 1H NMR (400 MHz, 298 K, C6D6) δ
(ppm) = 7.33 (m, 2H, C6H5), 6.96 (m, 3H, C6H5), 4.25 (sept, 2H, J
= 6.3 Hz, CH), 1.67 (t, 3H, J = 8.2 Hz, ZnCH2CH3), 1.37 (d, 12H, J
= 6.3 Hz, Me), 0.82 (2H, q, J = 8.2 Hz, ZnCH2CH3). 13C{1H} NMR
(100 MHz, 298 K, C6D6) δ (ppm) = 154.51 (CN2), 131.87, 129.13,
128.29, 121.58 (C6H5), 96.10 (PhC≡C), 80.55 (PhC≡C), 50.80
(CH), 25.31 (CH3), 12.87 (ZnCH2CH3), 4.16 (ZnCH2CH3). Anal.
Calcd. for C17H24N2Zn: C, 63.46; H, 7.52; N, 8.71. Found, C,
63.39; H, 7.45; N, 8,60.
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Journal Name
Procedure for isocyanate insertion and hydroamination reactions
at NMR tube scale.
CCDC, 12 Union Road, Cambridge, CB2 1EZ, U.K. (Fax:
+44−1223−335033; e−mail: deposit@ccdc.cam.ac.uk or
http://www.ccdc.cam.ac.uk).
Catalytic reactions were performed on a small scale in an NMR
tube fitted with a concentric Teflon valve with 0.5 mmol of
alkyne, 0.5 mmol of carbodiimide and ZnEt2 (3 mol%) in
toluene−d8 under nitrogen, at 70 °C for 24 h. Then 0.5 mmol of
the corresponding isocyanate or isothiocyanate were added to
the NMR tube inside the glovebox, and the mixture was
further heated at 70 °C for 24 h. Compounds 6a, d, g were
identified by comparing their NMR spectra with the literature
data.[17]
Acknowledgements
We gratefully acknowledge Spanish Ministerio de Economía,
Industria
y
Competitividad
(projects
Nos.
CTQ2014−51912−REDC and CTQ2016−77614−P) and the
Universidad de Castilla−La Mancha (grant No. GI20174020) for
financial support. A. R. acknowledges a postdoctoral contract
funded by the “Plan Propio de I+D+i” of the Universidad de
Castilla−La Mancha, co−funded by the Social European Fund.
Synthesis of
[Zn{C(C≡CPh)(NiPr)2}{(N(2,6−Me2C6H3))(CO)(NiPr)C(C≡CPh)(NiPr)}]
7.
2,6−Me2C6H3NCO (54
ꢀ
solution (5 mL) of compound
l, 0.38 mmol) was added to a toluene
(0.20 g, 0.38 mmol) . After
Notes and references
4
1
a) I. T. Horváth and P. T. Anastas, Chem. Rev., 2007, 107,
stirring for 15 min at room temperature, the solution was
concentrated under reduced pressure and 5 mL of hexane
were added and the mixture was placed in a refrigerator at
2169; b) L. L. Schafer, P. Mountford and W. E. Piers, Dalton
Trans., 2015, 44, 12027; c) M. S. Holzwarth and B.
Plietker, ChemCatChem, 2013, 5, 1650; d) R.Rochat, M. J.
Lopez, H. Tsurugi and K. Mashima, ChemCatChem, 2016, 8,
−
20 °C for 16 h, affording colorless microcrystals of complex 7
(0.24 g, 95%). 1H NMR (400 MHz, 298 K, C6D6) δ (ppm) =
7.33−6.87 (m, 13H, C6H5, C6H3), 4.42 (m, 2H, CH), 4.13 (m, 2H,
CH), 2.55 (s, 6H, Me2C6H3), 1.89 (d, 6H, CH3, J = 6.5 Hz), 1.39 (d,
6H, CH3, J = 6.6 Hz), 1.19 (d, 6H, CH3, J = 6.6 Hz), 0.98 (d, 6H,
CH3, J = 6.3 Hz). 13C{1H} NMR (100 MHz, 298 K, C6D6) δ (ppm) =
156.03, 155.13, 148.83, 146.09, 133.77, 132.36, 132.23,
130.62, 129.37, 128.91, 128.60, 128.51, 128.13, 127.88,
124.05, 122.03, 120.50, 100.20, 97.15, 54.87, 54.57, 47.62,
26.13, 25.59, 24.21, 22.20, 19.42. Anal Calcd for C39H47N5OZn:
C, 70.21; H, 7.10; N, 10.50 Found, C, 70.25; H, 7.16; N, 10.58.
10; e) M. S. Hill, D. J. Liptrot and C. Weetman, Chem. Soc.
Rev., 2016, 45, 972; f) V. Rodriguez-Ruiz, R. Carlino, S.
Bezzenine-Lafollée, R. Gil, D. Prim, E. Schulz and J.
Hannedouche, Dalton Trans., 2015, 44, 12029.
R. J. P. Williams in Zinc in Human Biology (Ed. I. Macdonald),
SpringerVerlag, New York, 1989, ch 2.
a) P. Knochel and R. D. Singer, Chem. Rev., 1993, 93, 2117; b)
J. H. Kim, Y. O. Ko, J. Bouffard and S.-Q. Lee, Chem. Soc. Rev.,
2015, 44, 2489.
a) X.-F. Wu and H. Neumann, Adv. Synth. Catal., 2012, 354,
3141. b) X.-F. Wu, Chem. Asian J., 2012, 7, 2502. c) S.
2
3
4
Enthaler ACS Catal. 2013, 150. d) Zinc Catalysis:
3
,
Applications in Organic Synthesis (Eds. S. Enthaler, X.-F. Wu),
Wiley-VCH, Weinheim, 2015; e) A. Otero, J. Fernandez-
Baeza, A. Lara-Sánchez and L. F. Sánchez-Barba, Coord.
Chem. Rev., 2013, 257, 1806; f) I. dos S. Vieira and S. Herres-
Pawlis, Eur. J. Inorg. Chem., 2012, 765; g) J. Wu, T.-L. Yu, C.-T.
Chen and C.-C. Lin, Coord. Chem. Rev., 2006, 250, 602.
X−ray diffraction studies
X−ray data collection of suitable single crystals of compounds
3, 4, 5 and 7 were done at 100(2) K on a Bruker VENTURE area
detector, while compound 6f was measured on APEX area
detector, both equipped with graphite monochromated
Mo−Kα radiation (λ = 0.71073 Å) by applying the ω−scan
method. The data reduction was performed with the APEX2
software and corrected for absorption using SADABS.33,34
Crystal structures were solved by direct methods using the
SIR97 program and refined by full−matrix least−squares on F2
including all reflections using anisotropic displacement
parameters by means of the WINGX crystallographic
package.35,36 All hydrogen atoms were included as fixed
contributions riding on attached atoms with isotropic thermal
displacement parameters 1.2 times or 1.5 times those of their
5
6
a) O. O. Kovalenko and H. Adolfsson, Chem. Eur. J., 2015, 21
2785; b) R. Cariou and J. W. Shabaker, ACS Catal., 2015,
,
,
5
4363; c) A.Lühl, L. Hartenstein, S. Blechert and P.W. Roesky,
Organometallics, 2012, 31, 7109; d) Y. Yin, W. Ma, Z. Chai, G.
Zhao, J. Org. Chem., 2007, 72, 5731; e) Y. Wei, X.-Y. Li, X.-B.
Jing, X.-S.Chen and Y.-B. Huang, Chem. Res. Chin. Univ., 2013,
29, 177; f) C. D. Smith and M. F. Greaney, Org. Lett., 2013,
4826.
8
,
a) D. F. Harvey and Dina M. Sigano, Chem. Rev., 1996, 96
271; b) R. Severin and S. Doye, Chem. Soc. Rev., 2007, 36
,
,
1407; c) T. E. Müller, K. C. Hultzsch, M.l Yus, F. Foubelo and
M. Tada, Chem. Rev., 2008, 108, 3795; d) M. C. Willis, Chem.
Rev., 2010, 110, 725; e) J. P. Brand and J. Waser, Chem. Soc.
Rev., 2012, 41, 4165; f) A. Fürstner, Angew. Chem., Int. Ed.,
2013, 52, 2794; g) M. J. González, L.A. López and R. Vicente,
Tetrahedron Lett., 2015, 56, 1600; h) C. Wanga, D. Ikhlef, S.
Kahlal, J.-Y. Saillard and D. Astruc, Coord. Chem. Rev., 2016,
316, 1; i) M.Patel, R. K. Saunthwal and A. K. Verma, Acc.
Chem. Res., 2017, 50, 240.
a) C. Alonso–Moreno, A. Antiñolo, F. Carrillo–Hermosilla and
A. Otero, Chem. Soc. Rev., 2014, 43, 3406; b) W.-X. Zhang, L.
Xuv Z. Xi, Chem. Commun., 2015, 51, 254; c) L. Xu, W.-
X.Zhang and F. Xi, Organometallics, 2015, 34, 1787.
parent atoms for the organic ligands. In compound
5, H2
atoms were located with the aim to study the intramolecular
NH---C hydrogen bond. Details of the structure determination
and refinement of compounds are summarized in Table S1.
Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited with the
Cambridge Crystallographic Data Center as supplementary
publication nos. CCDC 1554604−1554608. Copies of the data
can be obtained free of charge on application to the Director,
7
8
A. A. Aly and A. M. Nour-El-Din, ARKIVOC, 2008, 153.
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 11 of 13
Journal Name
a) W. Weingärtner and G. Maas, Eur. J. Org. Chem., 2012,
View Article Online
DOI: 10.1039/C7DT02700A
ARTICLE
9
Fernández-Galán,
E.
Villaseñor
and
A.
Otero,
6372; b) K. Drandarov, I. Tiritiris, O. Wassiljew, H.-U. Siehl
and W. Kantlehner, Chem. Eur. J., 2012, 18, 7224.
10 W.-X. Zhang, M. Nishiura and Z. Hou, J. Am. Chem. Soc.,
2005, 127, 16788.
11 G. F. Schmidt and G. Siüss-Fink, J. Organomet. Chem., 1988,
356, 207.
Organometallics, 2012, 31, 1840; c) D. Elorriaga, F. Carrillo-
Hermosilla, A. Antiñolo, I. López-Solera, R. Fernández-Galán
and E. Villaseñor, Chem. Commun., 2013, 49, 8701; d) D.
Nieto, S. Bruña, A. M. González-Vadillo, J. Perles, F. Carrillo-
Hermosilla, A. Antiñolo, J. M. Padrón, G. B. Plata and I.
Cuadrado, Organometallics, 2015, 34, 5407.
12 a) X. Gu, X. Zhu, Y. Wei, S. Wang, S. Zhou, G. Zhang and X. 21 a) E. Jeffery and T. Mole, J. Organomet. Chem., 1968, 11
Mu, Organometallics, 2014, 33, 2372; b) S. Zhou, S. Wang, G.
Yang, Q. Li, L. Zhang, Z. Yao, Z. Zhou and H.-B. Song,
,
393; b) L. Ma, J. Falkowski, C. Abney and W. Lin Nature
Chem., 2010, , 838.
2
Organometallics, 2007, 26, 3755; c) F. Zhang, J. Zhang, Y. 22 E. E. Wilson, A. G. Oliver, R. P. Hughes and B. L. Ashfeld,
Zhang, J. Hong and X. Zhou, Organometallics, 2014, 33, 6186; Organometallics, 2011, 30, 5214.
d) L. Xu, Y.-C. Wang, W.-X. Zhang and Z. Xia, Dalton Trans., 23 a) S. Schmidt, S. Schulz, D. Bläser and C. Wölper, Main Group
2013, 42, 16466; e) Y. Wu, S.Wang, L. Zhang, G. Yang, X. Zhu,
Z. Zhou and H. Zhu, S. Wu, Eur. J. Org. Chem., 2010, 326; f)
W. Yi, J. Zhang, M. Li, Z. Chen and X. Zhou, Inorg. Chem., 24 a) J. Barkerm and M. Kilner Coord. Chem. Rev. 1994, 133
Met. Chem., 2012, 35, 35; b) S. Schulz, M. Münch and U.
Flörke, Z. Anorg. Allg. Chem., 2008, 634, 2221.
,
2011, 50, 11813; g) Z. Du, W. Li, X. Zhu, F. Xu and Q. Shen, J.
Org. Chem., 2008, 73, 8966; h) F. M. Sroor, C. G. Hrib, L.
219; b) T. Chlupatý and A. Růžička, Coord. Chem. Rev., 2016,
314, 103.
Hilfert, S. Busse and F. T. Edelmann, New J. Chem., 2015, 39
,
25 H. Schumann, J. Gottfriedsen, S. Dechert and F.Girgsdies, Z.
Anorg. Allg. Chem., 2000, 626, 747.
13 X. Xu, J. Gao, D. Cheng, J. Li, G. Qiang and H.Guo, Adv. Synth. 26 a) S. Anga, I. Banerjee and T. K Panda, J. Chem. Sci., 2016,
7595.
Catal., 2008, 350, 61.
14 T.-G. Ong, J. S. O’Brien, I. Korobkov and D. S. Richeson,
Organometallics, 2006, 25, 4728.
15 A. G. M. Barrett, M. R. Crimmin, M. S. Hill, P. B. Hitchcock, S.
L. Lomas, M. F. Mahon, P. A. Procopiou and K.
Suntharalingam, Organometallics, 2008, 27, 6300.
128, 867; b) B. Gutschank, M. Bayram, S. Schulz, D. Bläser
and C. Wölpe,r Eur. J. Inorg. Chem., 2013, 5495; c) S.
Schmidt, B. Gutschank, S.Schulz, D. Bläser, R. Boese and C.
Wölper, Eur. J. Inorg. Chem., 2011, 4464; d) S. Schmidt, S.
Schulz, D. Bläser, R.Boese and M. Bolte, Organometallics,
2010, 29, 6097; e) B. Gutschank, S. Schulz, U. Westphal,
Dieter Bläser and R. Boese, Organometallics, 2010, 29, 2093;
f) C. Jones, L. Furness, S. Nembenna, R. P. Rose, S. Aldridge
and A. Stasch, Dalton Trans., 2010, 39, 8788; g) S. Schmidt, S.
Gondzik, S. Schulz, D.Bläser and R. Boese, Organometallics,
2009, 28, 4371; h) G. Glatz, S. Demeshko, G. Motz and R.
Kempe, Eur. J. Inorg. Chem., 2009, 1385; i) S. Schmidt, S.
Schulz and M. Bolte, Z. Anorg. Allg. Chem., 2009, 635, 2210;
j) L. F. Sánchez-Barba, C. Alonso-Moreno, A. Garcés, M.
Fajardo, J. Fernández-Baeza, A. Otero, A. Lara-Sánchez, A. M.
Rodríguez and I.López-Solera, Dalton Trans., 2009, 8054; k)
M. Münch, U. Flörke, M. Bolte, S. Schulz and D. Gudat,
Angew. Chem. Int. Ed., 2008, 47, 1512; l) N. Nimitsiriwat, V.
C. Gibson, E. L. Marshall, P. Takolpuckdee, A. K. Tomov, A. J.
P. White, D.J. Williams, M. R. J. Elsegood and S. H. Dale,
Inorg. Chem., 2007, 46, 9988; m) S. J. Birch, S. R. Boss, S. C.
Cole, M. P. Coles, R. Haigh, P. B. Hitchcock and A. E. H.
Wheatley, Dalton Trans., 2004, 3568; n) M. L. Cole, D. J.
16 a) R. J. Schwamm and M. P. Coles, Organometallics, 2013, 32
,
5277; b) R. J. Schwamm, B. M. Day, N. E. Mansfield, W.
Knowelden, P. B. Hitchcock and M. P. Coles, Dalton Trans.,
2014, 43, 14302; c) M. Arrowsmith, M. R. Crimmin, M.S. Hill,
S. L. Lomas, M. S. Heng, P. B. Hitchcock and G. K.- Köhn,
Dalton Trans., 2014, 43, 14249
17 a) M. Arrowsmith, M. S.Shepherd, M. S. Hill and G. K.- Köhn,
Chem. Commun., 2014, 50, 12676; b) M. Arrowsmith, M. S.
Hill and G. K.- Köhn, Chem. Eur. J., 2015, 21, 10548; c) M. S.
Hill, D. J. Liptrot and M. F. Mahon, Angew. Chem., Int. Ed.,
2013, 52, 5364.
18 (a) J. Dumas, Curr. Opin. Drug. Disc. Dev., 2002, 5, 718; b) E.
De Clercq, Biochim. Biophys. Acta, 2002, 1587, 258; c) J.-M.
Kim, T. E. Wilson, T. C. Norman and P. G. Schultz,
Tetrahedron Lett., 1996, 37, 5309; d) W. M. Kazmierski, E.
Furfine, Y. Gray-Nunez, A.Spaltenstein and L. Wrigh,t Bioorg.
Med. Chem. Lett., 2004, 14, 5685; e) H. B. Broughton and I.
A. Watson, Mol. J. Graphics Modell., 2005, 23, 51; f) L. Zhang,
X.-M. Peng, G. L. V. Damu, R.-X. Geng and C.-H. Zhou, Med.
Res. Rev., 2014, 34, 340; g) N. Rani, A. Sharma and R. Singh,
Mini-Rev. Med. Chem., 2013, 13, 1812.
Evans, P. C. Junk and L. M. Louis, New J. Chem., 2002, 26
,
1015; o) F. A. Cotton, L. M. Daniels, L. R. Falvello, J. H.
Matonic ,C. A. Murillo, X. Wang and H. Zhou, Inorg. Chim.
Acta, 1997, 266, 91; p) J.-K. Buijink, M. Noltemeyer and F. T.
Edelmann, Z. Naturforsch., 1991, 46b, 328.
19 a) J. A. Fritz, J. S. Nakhla and J. P. Wolfe, Org. Lett., 2016, 8,
2531; b) Y. Yuan, Y. Li, A. S. K. Hashmi, A. M. Schuster, M. 27 A. R. Sadique, M. J.Heeg and C.H. Winter, Inorg. Chem., 2001,
Schmuck and F. Romninger, Eur. J. Org. Chem., 2011, 4595; c) 40, 6349.
L. Zhang and Y. Wu, Chem. Eur. J., 2013, 19, 1496; d) S. Li, Z. 28 a) F. M. Sroor, C. G. Hrib, L. Hilfert, P. G. Jones and F. T.
Li, H. v. Wachenfeldt, P. Röse, F. Paulsen, N. Loganathan and
D. Strand, Chem. Eur. J., 2013, 19, 7982; e) J. E. Hein and V.
V. Fokin, Chem. Soc. Rev., 2010, 39, 1302; f) M. Yoshida, T.
Mizuguchi and K. Shishido, Chem. Eur. J., 2012, 18, 15578; g)
Edelmann, J. Organomet. Chem., 2015, 785, 1; b) P. Dröse, C.
G. Hrib and F. T. Edelmann, J. Organomet. Chem., 2010, 695
1953; c) F. M. Sroor, C. G. Hrib and F.T. Edelmann,
Inorganics, 2015, , 429.
,
3
X. Zhang, W. T. Teo and P. W. H. Chan, J. Organomet. Chem., 29 F. T. Edelmann, Adv. Organomet. Chem., 2013, 61, 55.
2011, 696, 331; h) S. Doherty, J. G. Knight, A. S. K. Hashmi, C. 30 a) D. W. Stephan, J. Am. Chem. Soc., 2015, 137, 10018; b) A.
H. Smyth, N. A. B. Ward, K. J. Robson, S. Tweedley, R. W.
Harrington and W. Clegg, Organometallics, 2010, 29, 4139; i)
Y. Kayaki, N. Mori and T. Ikariya, Tetrahedron Lett., 2009, 50,
6491; j) B.Heller, M. Hapke, Chem. Soc. Rev., 2007, 36, 1085;
Antiñolo, F. Carrillo-Hermosilla, R. Fernández-Galán, J.
Martínez-Ferrer, C. Alonso-Moreno, I. Bravo, S. Moreno-
Blázquez, M. Salgado, E.Villaseñor and J. Albaladejo, Dalton
Trans., 2016, 45, 10717.
k) Y. H. Hoberg, S. Schaefer, G. Burkhart, C. Krüger and M. J. 31 R. Taylor and O. Kennard, J. Am. Chem. Soc., 1982, 104, 5063.
Romao, J. Organomet. Chem., 1984, 266, 203.
20 [a) C. Alonso-Moreno, F. Carrillo-Hermosilla, A. Garcés, A.
32 A. Lühl, L. Hartenstein, S. Blechert, P. W. Roesky,
Organometallics, 2012, 31, 7109.
Otero, I. López-Solera, A. M. Rodríguez and A. Antiñolo, 33 Bruker Apex2, Bruker AXS Inc., Madison, Wisconsin, USA,
2004.
Organometallics, 2010, 29, 2789; b) D. Elorriaga, F. Carrillo-
Hermosilla, A. Antiñolo, I. López-Solera, B. Menot, R.
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Journal Name
34 G. M. Sheldrick, SADABS, Program for Empirical Adsorption
Correction, Institute for Inorganic Chemistry, University of
Gottingen: Germany, 1996.
35 A. Altomare, M. C. Burla, M. Camilla, G. L. Cascarano, C.
Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori and
R. Spagna, SIR97: a new tool for crystal structure
determination and refinement. J. Appl. Crystallogr., 1999, 32,
115.
36 a) G. M. Sheldrick, SHELX-2014, Program for Crystal Structure
Refinement; University of Göttingen, Göttingen, Germany,
2014. b) L. J. Farrugia, WinGX Suite for small-molecule single-
crystal crystallography. J. Appl. Cryst., 1999, 32, 837.
12 | J. Name., 2012, 00, 1-3
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FOR TABLE OF CONTENTS ONLY
The well-known simple ZnEt2 is an efficient catalyst for the addition of terminal alkynes to
carbodiimides through the formation of amidinate intermediate complexes and straightforward C-H
bond activation of alkynes. Consecutive isocyanate addition allows to obtain imidazolidinones via
intramolecular catalytic hydroamination.