Experimental and theoretical investigation of the cycloisomerization of N-propargylcarboxamide catalyzed by NHC-Au-X in green solvents

Article abstract of DOI:10.1016/j.ica.2021.120372

For the first time, NHC-Au-X [NHC = (1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene, X^? = BF₄^?, OTf^?, OTs^?, TFA^?] catalysts were tested in the cycloisomerization of N-(prop-2-yn-yl)benzamide to 2-phenyl-5-vinylidene-2-oxazoline in a wide set of green solvents. We found that most of these solvents (cyclohexanone, isopropyl acetate, MIBK, ethyl lactate, furfuryl alcohol, γ-valerolactone, propylene carbonate and propionic acid) are comparable or better solvents with respect to traditional VOS. Furthermore, the catalyst activity is related to the basic strength of the anion and the performances of the catalysts decrease gradually with increasing basicity and hydrogen-bond acceptor power of X^?. Kinetic experiments and DFT calculations seem to indicate that both the characteristic of the solvent and counterion should be taken into account.

Full text of DOI:10.1016/j.ica.2021.120372

Inorganica Chimica Acta 522 (2021) 120372
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Research paper
Experimental and theoretical investigation of the cycloisomerization of
N-propargylcarboxamide catalyzed by NHC-Au-X in green solvents
,
c
,
d
,
,d
Jacopo Segatoa, Walter Barattaa, Paola Belanzonib
*, Leonardo Belpassic
,
,c,*
Alessandro Del Zottoa, Daniele Zuccacciaa
a
`
Dipartimento di Scienze Agroalimentari, Ambientali e Animali, Sezione di Chimica, Universita di Udine, Via Cotonificio 108, I-33100 Udine, Italy
b
c
`
Dipartimento di Chimica, Biologia e Biotecnologie, Universita degli Studi di Perugia, Via Elce di Sotto 8, I-06123 Perugia, Italy
`
Istituto di Scienze e Tecnologie Chimiche del CNR “Giulio Natta” (CNR-SCITEC), c/o Dipartimento di Chimica, Biologia e Biotecnologie, Universita degli Studi di
Perugia, Via Elce di Sotto 8, I-06123 Perugia, Italy
d Consortium for Computational Molecular and Materials Sciences (CMS)2, Via Elce di Sotto 8, I-06123 Perugia, Italy
A R T I C L E I N F O
A B S T R A C T
For the first time, NHC-Au-X [NHC = (1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene, Xꢀ = BF4ꢀ , OTfꢀ ,
OTsꢀ , TFAꢀ ] catalysts were tested in the cycloisomerization of N-(prop-2-yn-yl)benzamide to 2-phenyl-5-vinyl-
idene-2-oxazoline in a wide set of green solvents. We found that most of these solvents (cyclohexanone, isopropyl
acetate, MIBK, ethyl lactate, furfuryl alcohol, γ-valerolactone, propylene carbonate and propionic acid) are
comparable or better solvents with respect to traditional VOS. Furthermore, the catalyst activity is related to the
basic strength of the anion and the performances of the catalysts decrease gradually with increasing basicity and
hydrogen-bond acceptor power of Xꢀ . Kinetic experiments and DFT calculations seem to indicate that both the
characteristic of the solvent and counterion should be taken into account.
Keywords:
Gold catalysis
Cycloisomerization
Counterion effect
Green solvent
DFT
1. Introduction
A rationalization of the ‘counterion effects’ is still far from being fully
achieved, even if several experimental data in gold catalysis are present
In recent years, a fast growing area in organic chemistry is repre-
sented by homogeneous gold catalysis [1]. Most of the reactions in
which gold catalysts are involved can be classified as nucleophilic ad-
ditions to a carbon–carbon unsaturated bond promoted by L-Au-X
compounds (Scheme 1, ISIP = inner sphere ion pair, L = ancillary ligand
and Xꢀ = counterion). The gold metal fragment L-Au-X acts as a Lewis
acid coordinating unsaturated hydrocarbons, i.e., alkynes, in the pre-
equilibrium step (Scheme 1, intermediate OSIP = outer sphere ion
pair), which subsequently undergoes nucleophilic attack by Nu-H, with
the formation of organogold intermediates (Scheme 1, intermediate I).
The gold-carbon bonds in these intermediates are typically cleaved by a
proton, protodeauration, to give the desired products and regenerate the
catalyst. In-depth kinetic and mechanistic studies on gold(I)-catalyzed
nucleophilic addition to a carbon–carbon unsaturated bond have been
appearing in the literature [2], with the aim to understand the ligand
[3–9] and counterion [10–15] effects in the different steps of the cata-
lytic cycle.
in the literature [16]. Both coordination ability and basicity [17] of the
counterion may have a great impact on the catalytic performances of
gold complexes [16] and some of us [18,19] studied the Au-catalyzed
intermolecular methoxylation of alkynes and proposed that the nucle-
ophilic attack of nucleophile is assisted by the anion through the for-
mation of a hydrogen bond [20].
Counterion and ligand effects have been studied by some of us in the
cycloisomerization of N-propargylcarboxamides [21]. It is a well-
studied gold-catalyzed reaction [22] in which protodeauration is
considered the slow step (Scheme 1) [3a-d]. A pseudo-first order kinetic
with respect to catalyst concentration is observed [23], and the key vinyl
gold intermediate [24] (Scheme 1, intermediate I) has been identified
in the case of NHC-Au(I) [25] and PPh3-Au(I) [2,31] and in the case of
gold(III) [26]. These observations induce to believe that the formation of
the vinyl gold complex (intermediate I) is not the rate-determining step
[25]. We have found that the choice of the most efficient L-Au-X catalyst
for the cycloisomerization of N-propargylcarboxamides should not be
`
* Corresponding authors at: Dipartimento di Chimica, Biologia e Biotecnologie, Universita degli Studi di Perugia, via Elce di Sotto 8, I-06123 Perugia, Italy (P.
`
Belanzoni). Dipartimento di Scienze Agroalimentari, Ambientali e Animali, Sezione di Chimica, Universita di Udine, Via Cotonificio 108, I-33100 Udine, Italy (D.
Zuccaccia).
E-mail addresses: paola.belanzoni@unipg.it (P. Belanzoni), daniele.zuccaccia@uniud.it (D. Zuccaccia).
https://doi.org/10.1016/j.ica.2021.120372
Received 28 November 2020; Received in revised form 26 March 2021; Accepted 26 March 2021
Available online 30 March 2021
0020-1693/© 2021 Elsevier B.V. All rights reserved.

J. Segato et al.
Inorganica Chimica Acta 522 (2021) 120372
Scheme 1. Proposed gold catalytic cycle.
done by evaluating the properties of L [27] and Xꢀ alone, but rather on
the basis of their best combination.
On the other hand, most of the protocols that employ gold(I) com-
plexes as catalysts, are unsustainable from a green chemistry point of
view [28]: high catalyst loading, use of volatile organic solvent (VOS),
silver salts as halide scavenger, and non-recyclable catalysts represent
the major drawbacks [29]. A great effort was done in the area of neat
and silver-free gold catalyzed reactions [30–32].
Scheme 2. Cycloisomerization of N-(prop-2-yn-yl)benzamide to 2-phenyl-5-
vinylidene-2-oxazoline.
Table 1
NHC-Au-X catalyzed N-(2-Propynyl)benzamide isomerization at 50 ◦C.a
Recently, some of us investigated the activity of NHC-Au-X [NHC =
(1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene, Xꢀ = BArFꢀ , BF4ꢀ ,
SbFꢀ6 , ClOꢀ4 , OTfꢀ , NTf2ꢀ , OTsꢀ , and TFAꢀ ), BArFꢀ = tetrakis(3,5-bis
(trifluoro-methyl)phenyl)-borate] as catalysts in solvent-, acid- and
silver-free hydration of alkynes at room/mild temperature and with
suitable ionic additives [33].
Entry
Solvent
Conv.b
%
TOFc(hꢀ 1
)
εrd
VOS
1
2
3
4
5
Chloroform
Dichloromethane
Acetonee
90
89
10
65
67
354
406
43
4.81
8.93
21
3-Nitrotoluene
Nitromethane
281
274
22.2
35.87
Replacement of VOS with green solvents [34] is a key topic in
organic synthesis, and in many transition metal catalyzed organic pro-
cess bio-based solvents [35] such as water [36], γ-valerolactone (GVL)
[37], glycerol [38], lactic acid and its derivatives [39], d-limonene and
p-cymene [40] are employed instead of VOS. Other green solvents such
as biodiesel [41], scCO2 [42], perfluorinated hydrocarbons [43], poly-
ethylene glycol (PEG) [44], Deep Eutectic Solvent (DES) [45] and ionic
liquid (IL) [46] also find frequent use in organic synthesis. Use of green
solvents instead of VOS is rare in gold catalysis [47–49].
Green
6
Cyclohexanone
p-Cymene
47
15
11
94
16,7
39,6
90,9
23
13
49
62
73
39
12
47
5
206
63
2.02
2.24
2.4
7
8
Limonenee
50
9a
9b
9c
9d
10
11
12
13
14
15
16
17
18
19
20
21
Propionic acid
Propionic acidf
Propionic acidg
Propionic acidh
Cyrene
431
65
3.35
3.35
3.35
3.35
3.4
154
354
94
Anisolee
56
4.3
Some of us [50] investigated the alkoxylation and hydration of al-
kynes in a wide set of green solvents using NHC-Au-OTf as catalyst and
we found that polarity and functionalities present in the solvent influ-
ence the three steps of the reaction pathway (pre-equilibrium, nucleo-
philic attack, and protodeauration).
Isopropyl acetate
MIBK
223
250
317
148
50
6.3
13.1
15.4
16.85
27.7
36.9
46.7
64
Ethyl Lactate
Furfuryl alcohol
Propionitrilee
γ-Valerolactone
DMSO
Building on this state of the art, we investigate here the activity of
NHC-Au-X (Xꢀ = BFꢀ4 , OTfꢀ OTsꢀ , TFAꢀ ) catalysts in the cyclo-
isomerization of N-(prop-2-yn-yl)benzamide to 2-phenyl-5-vinylidene-
2-oxazoline (Scheme 2) conducted in green solvents. We found that
most of these solvents are comparable or better solvents with respect to
traditional VOS. Kinetic experiments coupled with DFT calculations
have allowed us to shed light on the mechanism of cycloisomerization in
green conditions. The results presented here show that the anion prop-
erties, both coordination ability and basicity (hydrogen-bond acceptor
power), should have a great impact on its “proton shuttle ability”.
192
21
Propylene carbonate
BMIM-OTf
49
28
21
180
120
90
–
–
Methyl levulinate
a
Catalysis conditions: NHC-Au-OTf (0.0025 mmol, 1.8 mg), N-(2-Propynyl)
benzamide (0.5 mmol, 79.6 mg), solvent (200 µL).
b
c
Determined by 1H NMR; average value of three measurements after 30 min.
TOF = (molproduct/molcatalyst)/t calculated after 30 min.
d
εr = dielectric constant.
e
f
slightly or not soluble.
NHC-Au-Cl (0.0025 mmol, 1.6 mg), 1.1 eq AgOTs.
g
2. Results and discussion
NHC-Au-Cl (0.0025 mmol, 1.6 mg), 1.1 eq AgTFA.
h
NHC-Au-Cl (0.0025 mmol, 1.6 mg), 1.1 eq AgBF4.
Gold complexes were synthesized according to literature procedures
(see Supporting Information for details). All complexes NHC-Au-X
(Scheme 2, Xꢀ = BFꢀ4 , OTfꢀ , OTsꢀ , TFAꢀ ) have been tested as cata-
lysts in the cycloisomerization of N-(prop-2-yn-yl)benzamide to 2-
phenyl-5-vinylidene-2-oxazoline (Scheme 2 and Table 1). Isolated
NHC-Au-OTf was directly employed, whereas in all other cases the
catalyst was prepared in situ in an NMR tube by mixing equimolar
amounts of the precursor NHC-Au-Cl and the appropriate silver salt
(Scheme 2 and Table 1). Interestingly, all the solvents were used as
2

J. Segato et al.
Inorganica Chimica Acta 522 (2021) 120372
delivered without further purification.
In addition, the higher coordination ability of TFAꢀ versus the NHC-Au+
fragment probably favors the formation of the precatalyst NHC-Au-TFA
during the catalysis.
A typical catalytic run was performed by dissolving N-(prop-2-ynyl)
benzamide (0.5 mM) in the presence of 0.5 mol% of NHC-Au-OTf (or 1:1
L-Au-Cl/AgX) at 50 ◦C in the appropriate solvent (0.2 mL). The progress
of reaction was monitored by NMR spectroscopy (see Supporting In-
formation for details).
In the case of propionic acid, OTfꢀ shows the best performance fol-
lowed by BFꢀ4 . OTsꢀ exhibited the lower activity according to the pre-
vious study [21]. On the other hand, the most basic anion TFAꢀ shows
better results probably due to the acid environment that is able to pro-
tonate TFAꢀ disfavouring the formation of NHC-Au-TFA.
Most reactions reached more than 90% of conversion within 8 h (see
Table S2 in the Supporting Information) except those run in acetone,
limonene, anisole and proprionitrile (Table 1, entries 3, 8, 11, and 16) in
which N-(prop-2-ynyl)benzamide resulted slightly soluble or even
insoluble, and in dimethyl sulfoxide (Table 1, entry 18) due to its strong
coordinative capability, as previously observed [50].
Summarizing, the experimental catalytic activity trend found here
for the cyclization of propargylamides, namely, TFAꢀ < OTsꢀ < OTfꢀ
<
BFꢀ4 , shows that the performances of the catalysts increase gradually
with decreasing coordinating ability and hydrogen-bond acceptor power
of Xꢀ (basicity and coordinating strength: BFꢀ4 < OTfꢀ < OTsꢀ < TFAꢀ ),
with TFAꢀ being by far the worst counterion. Thus, the results presented
here show that the anion properties, both coordination ability and ba-
sicity (hydrogen-bond acceptor power), should have a great impact on
its “proton shuttle ability”. To elucidate the gold(I) catalytic activity in
the cyclization of propargylamide, the NHC-Au-X (NHC = 1,3-dime-
thylimidazol-2-ylidene; Xꢀ = BF4ꢀ , BF4ꢀ /H2O, OTfꢀ , OTsꢀ ) complexes
have been considered as catalysts and N-(prop-2-ynyl)benzamide as the
substrate for the calculations (Scheme 2). On the basis of BFꢀ4 instability
to H+ with respect to the HF elimination and its low-coordinating na-
ture, an additional water molecule has been included in the calculations
to explore the catalytic activity of this anion (BFꢀ4 /H2O). The calculated
reaction energy profiles for the nucleophilic attack step are shown in
Fig. 2.
In order to compare the catalytic activity in different solvent, the
values of the initial turnover frequency, TOFi (Table 1) were calculated.
Chloroform and dichloromethane showed the best performance
among the volatile organic solvents (VOS) giving a TOFi of 354 and 406
h
ꢀ 1, respectively (Table 1, entries 1 and 2). Less efficiently, NHC-Au-OTf
promoted the formation of the reaction product with a very similar TOFi
of 281 and 274 in the higher polar solvents 3-nitrotoluene and nitro-
methane (Table 1, entries 4 and 5). Finally, the very low value of 43 was
obtained in acetone (Table 1, entry 3).
Turning into green solvents, very different catalytic performances
were observed, and although the green solvents showed, on average,
slower conversion with respect to VOS, propionic acid resulted to be the
best among all solvents with a TOFi of 431 hꢀ 1 (Table 1, entry 9). Me-
dium TOFi values in the range 150–300 hꢀ 1 were obtained in cyclo-
hexanone, isopropyl acetate, MIBK, ethyl lactate, furfuryl alcohol,
γ-valerolactone, and propylene carbonate (Table 1), while lower cata-
lytic performances (TOFis in the range 90–150 hꢀ 1) were observed for p-
cymene, BMIM-OTf and methyl levulinate (Table 1). Finally, limonene,
cyrene, anisole, propionitrile and DMSO gave the worst catalytic per-
formances (TOFis below 90 hꢀ 1) owing to coordination of the solvent to
the metal fragment (propionitrile in addition to DMSO) or low solubility
of the starting material.
The NHC-Au-X initial complex (IC), with the N-(prop-2-ynyl)benza-
mide in the second coordination sphere, has been considered as zero
energy reference structure for all the three anions. The displacement of
the coordinated anion has been calculated to be a thermodynamically
favorable process for BF4ꢀ (ꢀ 13.9 kcal/mol), BF4ꢀ /H2O (ꢀ 14.1 kcal/
mol), and OTfꢀ (ꢀ 5.7 kcal/mol), leading to the corresponding reactant
These results confirm our previous results concerning the hydration
and alkoxylation of alkynes: a sustainable production of chemicals with
homogeneous gold catalysts in green solvents is reachable [51] and
exploration of the use of gold catalysts in other nucleophilic addition
reactions on substrates with unsaturated bonds (especially alkynes) in
green solvents is mandatory.
In order to verify the importance of the acid-base nature and
hydrogen-bond acceptor powers of the counterion in this reaction we
have just considered (Fig. 1) the catalytic properties of NHC-Au-X (Xꢀ
=
BFꢀ4 , OTfꢀ , OTsꢀ , and TFAꢀ ) in CDCl3 [21] The catalyst activity is
related to the basic strength of the anion and the performances of the
catalysts decrease (Fig. 1) gradually with increasing basicity and
hydrogen-bond acceptor power of Xꢀ (basic strength: BF4ꢀ < OTfꢀ
<
OTsꢀ < TFAꢀ ). The plausible scenario for NHC-Au-X is that too basic
anions with higher hydrogen-bond acceptor power (OTsꢀ and TFAꢀ ) do
not easily release the proton to gold thus slowing down the reaction rate.
Fig. 2. Energy profiles for the nucleophilic attack step of the cyclo-
isomerization of N-propargylcarboxamides reaction mechanism catalyzed by
NHC-Au-X (Xꢀ = BF4ꢀ , BF4ꢀ /H2O, OTfꢀ , and OTsꢀ ). Energy values (kcal/mol)
refer to the corresponding ICX taken as zero.
Fig. 1. TOFi values for the cycloisomerization of N-(prop-2-yn-yl)benzamide to
2-phenyl-5-vinylidene-2-oxazoline catalyzed by NHC-Au-X (Xꢀ = BF4ꢀ , OTfꢀ ,
OTsꢀ , and TFAꢀ ) in CDCl231 and propionic acid.
3

J. Segato et al.
Inorganica Chimica Acta 522 (2021) 120372
complexes RCBF4, RCBF4/H2O and RCOTf, where N-(prop-2-ynyl)benza-
mide is coordinated to gold and the anion is in the second coordination
sphere weakly interacting with the NH moiety of the substrate through a
hydrogen bond. The OTsꢀ replacement with the substrate is instead a
thermoneutral process, yielding a RCOTs (0.1 kcal/mol) through a
calculated energy barrier of 7.8 kcal/mol and a tri-coordinated transi-
tion state where both N-(prop-2-ynyl)benzamide and OTsꢀ are bound to
gold (see Fig. S3 in the SI). The optimized geometries of all species are
shown in Figs. S4–S7. In all the RC complexes the counterion Xꢀ is
placed above gold, weakly interacting with the metal center with at least
one basic atom and forming a hydrogen bond with substrate NH group.
Starting from these RC adducts, the oxygen atom of the substrate CO
group intramolecular nucleophilic attack to one carbon atom of the
activated triple bond can easily occur, with relativity low energy bar-
riers (12.2, 10.1, 13.9 and 12.4 kcal/mol for BFꢀ4 , RCBF4/H2O, OTfꢀ and
OTsꢀ , respectively) (Fig. 2).
As it can be seen, this step requires a higher energy barrier than that
of the nucleophilic attack step for all the three anions, in full agreement
with the experimental observations. The geometries of TSII are
compared in Fig. 4, whereas PC structures are reported in Fig. S8 in the
SI.
The protodeauration energy barrier trend exactly matches both that
of the catalytic performances, and that of the anion basicity and
hydrogen-bond acceptor power (BFꢀ4 < OTfꢀ < OTsꢀ ), thus suggesting
an impact of the anion in controlling the reaction rate through
abstraction of the proton from the NH moiety and its releasing to the C2
atom bond to gold. Interestingly, inspection of the TSII structures in
Fig. 4 reveals that both the coordinating ability trend (Au… O = 3.523 Å
for OTsꢀ , Au… O = 3.611 Å for OTfꢀ , and Au… F = 3.914 Å for BFꢀ4 /
H2O) and the hydrogen-bond acceptor power (H… C2 = 3.079 Å for
OTsꢀ , H… C = 2.984 Å for OTfꢀ , and H… C = 2.288 Å for BF4ꢀ /H2O) are
able to account for the energy barrier trend. In addition, hydrogen
abstraction from substrate NH appears to be hindered by the coordi-
nating capability of the anion (H… N = 2.328 Å for OTsꢀ , H… N = 2.498
Å for OTfꢀ , and H… N = 4.444 Å for BF4ꢀ /H2O). Thus, the anion basicity
seems to be mainly responsible for the energy activation barrier value.
Overall, these results suggest that too basic anions, with higher
hydrogen-bond acceptor power (OTsꢀ ), do not easily abstract and
transfer the proton, thus slowing the reaction rate, consistently with
experimental findings, where the anion “proton shuttle ability” is found
to be crucial for the catalytic activity. Finally, a calculation has been
performed on the overall reaction path for NHC-Au-OTf, using the full
ligand (NHC = 1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene), to
test the reliability of the results previously obtained with the model
NHC. The optimized structures of IC, RC, TSI, I, TSII and PC and their
relative energies are reported in the SI (Fig. S9). The results show that
the interactions of the anion with the bulky NHC ligand do not affect the
energetics of the whole path, particularly at the transition states, which
show comparable energies with respect to the corresponding IC (for
model NHC E (TSIOTf) = 8.2 kacl/mol, E(TSIIOTf) = 21.9 kcal/mol vs. full
NHC E(TSIOTf) = 6.3 kcal/mol, E(TSIIOTf) = 21.6 kcal/mol).
Formation of the vinyl gold complex (intermediate I) from this step is
an exergonic process for all the anions (Fig. 2). In the intermediate I, the
anion, still forming a hydrogen bond with the substrate NH group,
moves from the gold center, localizing in the second coordination
sphere. The acidic NH hydrogen should then be transferred to the C2
carbon atom coordinated to Au by the anion, acting as proton shuttle. To
calculate the overall path starting from NH proton detachment, due to
the very large number of different conformations involved, molecular
dynamics simulations would be needed, which are beyond the scope of
this work.
However, starting our analysis of the protodeauration step from in-
termediate I, a transition state for the final proton transfer from the
anion to C2 (TSII) has been located, which allows to completely ratio-
nalize the experimental findings.
Energy profiles for the protodeauration step are shown in Fig. 3.
The energy barrier calculated from I follows the trend BFꢀ4 /H2O <
OTfꢀ < OTsꢀ (21.8, 25.0 and 27.4 kcal/mol, respectively).
3. Conclusion
In this work, we extended our previous works studying the cyclo-
isomerization of N-propargylcarboxamides promoted by NHC-Au-X
complexes in green solvents from an experimental and theoretical
point of view. At first, we investigated the effect of the solvent
employed. As a primary and important goal, we found that the reaction
proceeds very well in most of the alternative solvents employed, such as
cyclohexanone, isopropyl acetate, MIBK, ethyl lactate, furfuryl alcohol,
γ-valerolactone and propylene carbonate. TOFs are comparable or even
better with respect to those obtained using VOS. On the other hand,
when the reaction is performed in DMSO or propionitrile the TOFs are
much lower, owing to the presence of a coordinating functional group
–
–
– –
C N, respectively) that upon coordination to the metal
–
(>S O and
–
centre affords inactive NHC-Au(solvent)OTf species. We also observed
that the use of propionic acid resulted in a speed up of the reaction,
according to the view that protodeauration is the RDS.
Secondarily, we found, according to our previous work, that the
activity of the catalyst in propionic acid (in terms of TOF) seems to be
inversely correlated to the coordinating ability and hydrogen-bond
acceptor power of Xꢀ (basic and coordinating strength: BFꢀ4 < OTfꢀ
<
OTsꢀ < TFAꢀ ), with TFAꢀ being by far the worst counterion. This
behaviour is consistent with the active role of the counterion in all the
three steps of the reaction pathway (pre-equilibrium, nucleophilic attack
and protodeauration).
DFT calculations corroborate these peculiar experimental kinetic
findings showing an excellent agreement, and the proposed mechanism
fully rationalizes the experimental reactivity, which is highly dependent
on both anion and solvent effects.
Fig. 3. Energy profiles for the protodeauration step of the cycloisomerization of
N-propargylcarboxamides reaction mechanism catalyzed by NHC-Au-X (Xꢀ
=
BFꢀ4 /H2O, OTfꢀ , and OTsꢀ ). Energy values (kcal/mol) refer to corresponding
ICX (Fig. 2) taken as zero.
These results are indeed remarkable and suggest that a sustainable
4

J. Segato et al.
Inorganica Chimica Acta 522 (2021) 120372
Fig. 4. Transition state (TSIIX) geometries for the protodeauration step of the cycloisomerization of N- propargylcarboxamides reaction mechanism catalyzed by
NHC-Au-X (Xꢀ = BF4ꢀ ,BF4ꢀ /H2O, OTfꢀ , and OTsꢀ ). Bond lengths are in Å.
´
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P.B. gratefully acknowledges financial support from MIUR and the
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