Quantitative kinetic investigation of triazole-gold(i) complex catalyzed [3,3]-rearrangement of propargyl ester

Article abstract of DOI:10.1039/c3cc49351b

The triazole-gold(i) complex catalyzed [3,3]-rearrangement of propargyl ester has been quantitatively investigated through in situ IR. First order dependence of the initial rates on [Au] and [propargyl ester] suggested that the turnover-limiting step is the associative ligand substitution. The activation enthalpy was also determined to be 7.8 kcal mol^-1. TA-Au catalysts with different triazole derivatives were also tested, giving a linear free energy relationship with a ρ value of 0.74. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc49351b

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Quantitative kinetic investigation of triazole–
gold(I) complex catalyzed [3,3]-rearrangement
of propargyl ester†
Yumeng Xi,a Qiaoyi Wang,a Yijin Su,a Minyong Li*b and Xiaodong Shi*a
Cite this: Chem. Commun., 2014,
50, 2158
Received 10th December 2013,
Accepted 24th December 2013
DOI: 10.1039/c3cc49351b
www.rsc.org/chemcomm
The triazole–gold(I) complex catalyzed [3,3]-rearrangement of propargyl However, in our case, no indene was detected after 12 h using
ester has been quantitatively investigated through in situ IR. First order 1 mol% TA–Au. We view this phenomenon as a good opportunity for
dependence of the initial rates on [Au] and [propargyl ester] suggested the mechanistic study. The simplified system (over Nolan’s two-step
that the turnover-limiting step is the associative ligand substitution. The transformation) may allow for the collection of quantitative kinetic
activation enthalpy was also determined to be 7.8 kcal molÀ1. TA–Au information associated with TA–Au. In addition, it is also very
catalysts with different triazole derivatives were also tested, giving a important to understand why TA–Au offered the chemoselectivity
linear free energy relationship with a q value of 0.74.
with excellent stereochemistry control, while other [L–Au]+ com-
plexes led to rapid racemization at the propargyl position with poor
The past decade has witnessed the fast growing homogenous gold chemoselectivity (activation of both alkyne and allene). Herein, we
catalysis.1 Compared with the fast pace of new transformation devel- report our quantitative kinetic investigation of TA–Au catalyzed
opment, the mechanistic investigations are left much behind. Mean- propargyl ester [3,3]-rearrangement using in situ IR spectroscopy
while, with recent efforts to characterize catalytic intermediates using from a ‘live’ catalytic reaction.13
X-ray crystallography and NMR,2 more and more evidence suggests that
a much more complicated mechanism is operative in real case rather
than the oversimplified mechanism previously assumed. Furthermore,
the recent observation of the ‘‘silver effect’’,3 Au–Cl–Ag4 and Au–Cl–Au5
complexes, and ‘‘small gold cluster’’ catalysis6 further supports the
more complex mechanism, and stimulates the need for a mechanistic
study. In general, gold catalysis involves three important steps: coordi-
nation (to alkyne/alkene), protodeauration and gold decomposition
Scheme 1 TA–Au as a chemoselective catalyst for alkyne activation.
(side reaction).7 Thus, due to the mechanistic complexity (especially the
existence of fast decomposition), efforts to target each elementary step
To acquire meaningful kinetic data for a catalytic reaction,
in the catalytic cycle are not always fruitful.8 Thanks to the recent
the turnover-limiting step needs to be established. This is a
mechanistic studies from several laboratories, meaningful data were
challenging task for the LAuCl–AgX system, leading to the rapid
derived from some stoichiometric reactions,9 although they may not
catalyst decomposition over time. A unique advantage of the
TA–Au catalyst is its improved stability, which allows relatively
steady concentration of the catalyst for the kinetic study. Thus,
necessarily reflect the catalytic reactions accurately.
In 2009, our group introduced a 1,2,3-triazole bound cationic gold(I)
complex (TA–Au) as an improved thermally stable catalyst.10 Later it
we set out to evaluate the kinetic dependence of concentration
was discovered that the TA–Au complex could preferentially activate
of the substrate and TA–Au. The standard reaction was chosen
alkyne over allene in propargyl ester [3,3]-rearrangement,11 where
as the model reaction for the detailed investigation (eqn (1)).
indene was synthesized using 2 mol% IPrAuCl/AgBF4 (Scheme 1).12
a C. Eugene Bennett Department of Chemistry, West Virginia University,
(1)
Morgantown, WV 26506, USA. E-mail: Xiaodong.Shi@mail.wvu.edu;
Fax: +1-304-293-4904; Tel: +1-304-293-0179
b Department of Medicinal Chemistry, School of Pharmacy, Shandong University,
To avoid the potential influence of acid (formation of HOTf),
Jinan, Shandong, 250012, China. E-mail: mli@sdu.edu.cn
the N-Me-benzotriazole (instead of N–H) coordinated TA–Au 4
† Electronic supplementary information (ESI) available: Experimental proce-
dures, and kinetic and DFT data. See DOI: 10.1039/c3cc49351b
was selected.14 The dependence of the initial rates on the
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Fig. 1 Dependence of the initial rates on catalyst concentrations for
rearrangement of 1. Reaction conditions: 1 (0.10 M in DCE, 1.2 mL), 4
(0.002–0.008 M in DCE), 30 1C.
Scheme 2 Proposed mechanism for TA–Au catalyzed propargyl ester
[3,3]-rearrangement.
Fig. 2 Dependence of the initial rates on substrate concentrations for
rearrangement of 1. Reaction conditions: 1 (0.10–0.20 M in DCE, 1.2 mL), 4
(0.003 M in DCE), 30 1C.
Fig. 3 Kinetics profile at different temperatures. Reaction conditions: 1
(0.10 M in DCE, 1.2 mL), TA–Au (0.003 M in DCE), at 22, 32, 38, and 46 1C.
concentration of TA–Au catalyst 4 was studied with varied concen-
trations from 0.002–0.008 M. The initial rates in different runs were
calculated based on the kinetic profiles monitored by in situ IR.
A linear relationship is established as depicted in Fig. 1. The reaction
is therefore first-order dependent on [4], suggesting the involvement
of 4 in the turnover-limiting step.
A subsequent experiment was performed to determine the kinetic
order of [1]. Similarly, the initial rates were plotted against [1] varied
from 0.10–0.20 M. Again, a first-order dependence was observed, as
shown in Fig. 2. Combining the two experiments, we were able to
derive the rate law for this reaction: r = kobs[1]1[4]1. According to the
rate law, both the catalyst 4 and substrate 1 were involved, revealing
the electronic activation of alkyne (i.e. ligand exchange) as the
turnover-liming step. In situ monitoring by 31P NMR over the entire
course of reaction showed 4 as the resting state further supporting the
ligand exchange as the turnover-limiting step.
With these kinetic data, a tentatively proposed mechanism of
TA–Au catalyzed propargyl ester [3,3]-rearrangement is shown in
Scheme 2. First, the TA–Au complex undergoes the turnover-limiting
ligand exchange with the substrate to form the cationic gold(I) alkyne
p-complex. This complex then rapidly converts the propargyl ester to
the corresponding allene. It is clearly seen that the ligand exchange step
significantly slows the reaction rate compared to the use of free cationic
gold(I) (Scheme 1), which is consistent with the fact that the same
reaction catalyzed by IPrAu(L)+ (L = Et3N, py) was also slower.15
To further probe the physical organic nature of this elementary
step, a temperature dependent experiment was carried out in order
to obtain the activation energy quantitatively. As shown in Fig. 3, the
reactions were again monitored by in situ IR at different tempera-
tures (295–319 K). The activation enthalpy was determined to
be 7.8 kcal molÀ1 through the Erying equation after plotting the
ln(kobs/T) vs. 1/T. This value reveals that the ligand exchange step
itself is quite a facile process at room temperature. Similarly,
Echavarren reported even lower activation enthalpy values (3.7 and
6.2 kcal molÀ1) in his studies on the enyne cycloisomerization.16
Assuming that all the catalyst in the reaction remained active
throughout the reaction, [4]0 will be identical to active catalyst concen-
tration. Therefore, activation entropy was determined to be À36.6 eu.
This negative and relatively large value supports the associative ligand
substitution through a transient 3-coordinate gold(I) complex. However,
the possibility of the 3-coordinate gold(I) complex with TA attached as
the stable intermediate cannot be ruled out at this point. Further
support came from the fact that the reaction was inhibited if additional
1-methyl-benzotriazole (5, 4 equiv. toward TA–Au) was present. Unfor-
tunately, we were unable to determine the exact order of [5] due to the
extremely slow reaction rates. But a negative kinetic order of [5] is
anticipated, which is consistent with the proposed triazole–alkyne
exchange mechanism shown in Scheme 3.17
Finally, we prepared various TA–Au catalysts with different
substituted benzotriazoles in order to investigate the impact of the
electronic nature of the TA–Au catalysts.18 The 31P NMR peaks
corresponding to TA–Au catalysts provide direct information regard-
ing the electronic nature of the gold center. As expected, a more
electron-withdrawing group gives
a
more upfield 31P shift,
Scheme 3 Associative ligand substitution through a transient 3-coordinate
cationic gold(I) complex.
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TA–Au catalyzed alkyne activation. The discovery of associative ligand
exchange between TA–Au and alkyne as the turnover-limiting step
provided mechanistic insight, which will benefit future investigations.
We thank the NSF (CAREER-CHE-0844602 and CHE-1228336)
and NSFC (No. 21228204) for financial support.
Notes and references
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Fig. 4 Kinetics profile using various TA–Au catalysts. Reaction conditions:
1 (0.10 M in DCE, 1.2 mL), TA–Au (0.003 M in DCE), 26 1C.
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slowest reaction was observed with the 4-methoxyphenyl substituted
TA–Au catalyst, however, this reaction is still faster than the reaction
catalyzed by 4, suggesting the inherent electron-withdrawing nature of
the phenyl group attached to benzotriazole. The linear free energy
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The positive r value suggested partial positive charge building up
´
12 (a) N. Marion, S. Dıez-Gonzalez, P. Fremont, A. R. Noble and S. P. Nolan,
during the reaction, which is consistent with the associative ligand
substitution being the turnover-limiting step. The more electron-
deficient triazole undergoes ligand exchange more rapidly, which is
accounted for by the faster reaction rate. This result also highlights
the tunability of the TA–Au catalyst. Based on the different cases, the
more electron-deficient TA–Au will give a shorter reaction time, while
the more electron-rich TA–Au has a longer catalyst lifetime.
The chemoselectivity of the TA–Au catalysts (activation of alkyne
over allene) can also be explained by this ligand–substrate exchange
mechanism. The DFT calculation revealed that the HOMO of pro-
pargyl ester 1 is 20 kcal molÀ1 higher than the HOMO of allene 2.19
Thus, the ligand exchange is much slower between allene and TA–Au,
which supports the observed selective alkyne activation.20
In summary, the triazole–gold(I) complex (TA–Au) catalyzed pro-
pargyl ester [3,3]-rearrangement has been quantitatively investigated.
Considering that few physical organic studies have been reported
regarding gold catalyzed alkyne activation due to the poor catalyst
stability and complex reaction nature, this work provided direct
experimental evidence for understanding the elementary step in the
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17 The inhibition could be explained by either the formation of 3-coordinate
+
LAu(TA)2 -type complex or the competition of the external triazole
ligand with alkyne substrate. Unfortunately, our attempts to detect the
3-coordinate gold complex through MS and NMR were unfruitful with no
+
observation of any LAu(TA)2 type complexes. Thus, the equilibrium
between TA–Au and Au–alkyne p-complex is the likely explanation for
the observed decreased reaction rate when external TA ligands were used.
Detailed derivation of rate law is provided in ESI†.
18 K. Wang, M. Chen, Q. Wang, X. Shi and J. K. Lee, J. Org. Chem., 2013,
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19 DFT calculation was performed on Gaussian 03 program at the
B3LYP/6-311G level of theory.
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2160 | Chem. Commun., 2014, 50, 2158--2160
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