Synthesis of a (N,C,C) Au(iii) pincer complex: Via Csp3-H bond activation: Increasing catalyst robustness by rational catalyst design

Article abstract of DOI:10.1039/c8cc05489d

A (N,C^Ar,C^Alk) Au(iii) pincer complex has been synthesized from Au(OAc)₃ (OAc = OCOCH₃) and 2-(3,5-di-tert-butylphenyl)pyridine (L₁) involving a C_sp³-H bond activation by electrophilic substitution. In agreement with DFT calculations, the resulting complex significantly improves the performance of Au(tpy)(OAc^F)₂ (tpy = 2-(p-tolyl)pyridine, OAc^F = OCOCF₃) in the catalytic trifluoroacetylation of acetylene.

Full text of DOI:10.1039/c8cc05489d

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DOI: 10.1039/C8CC05489D.
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DOI: 10.1039/C8CC05489D
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Synthesis of a (N,C,C) Au(III) Pincer Complex via Csp3-H Bond
Activation: Increasing catalyst robustness by rational catalyst
design
Received 00th January 20xx,
Accepted 00th January 20xx
Marte Sofie Martinsen Holmsen,a Ainara Nova,*b Knut Hylland,a David S. Wragg,a Sigurd Øien-
Ødegaard,a Richard H. Heyn,c and Mats Tilset *a
DOI: 10.1039/x0xx00000x
www.rsc.org/
a Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo,
Norway
b Hylleraas Centre for Quantum Molecular Sciences, Department of Chemistry, University
of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
c SINTEF Industry, P.O. Box 124 Blindern, N-0314 Oslo, Norway
A (N,CAr,CAlk) Au(III) pincer complex has been synthetized from using Au(OAcF)2(tpy) as a catalyst precursor ( , Figure 2).15 The
A
Au(OAc)3 (OAc = OCOCH3) and 2-(3,5-di-tert-butylphenyl)pyridine combined experimental and computational study of the
(L1) involving a Csp3-H bond activation by electrophilic substitution. reaction mechanism showed that the active catalyst was the
In agreement with DFT calculations, the resulting complex structurally characterized Au(III) vinyl complex
significantly improves the performance of Au(tpy)(OAcF)2 (tpy = 2- undergoes formal insertion of acetylene into the Au-OAcF bond
(p-tolyl)pyridine, OCOCF3) in the catalytic furnishing (not observable), followed by protolytic cleavage of
OAcF
B, which
=
C
trifluoroacetylation of acetylene.
the Au-vinyl bond trans to tpy-C to release the vinyl
trifluoroacetate product. However, the protolytic cleavage of
the Au-CAr bond in
C
competes with the protolytic cleavage in
the catalytic cycle, leading to reductive elimination of (1E,3E)-
1,4-bis(trifluoroacetoxy)-1,3-butadiene and catalyst
deactivation. 15 In order to prevent this detrimental off-cycle
reaction, a (N,CAr,CAlk) Au(III) pincer complex such as
(Figure 2)
The use of pincer ligands in Au(III) chemistry has gained
popularity due to their ability to stabilize the metal centre, in
particular with respect to reductive processes.1-7 One of the
most widely explored systems is the (C,N,C)-pincer complexes
derived from 2,6-diarylpyridines,8 which are commonly
synthesized via transmetalation from organomercury
compounds.9 Another class of Au(III) pincer complexes involves
(C,N,N) and (N,C,N) ligands that commonly contain aryl-C
substituents (CAr) and give access to cationic complexes.1 A few
years ago, Nevado and co-workers reported the two-step,
mercury-free synthesis of (N,CAr,CAr) Au(III) pincer complexes via
initial, pyridine-N coordination of 2-biphenylpyridine, followed
by cyclometallation under microwave conditions.10 While such
processes, which involve the activation of a Csp2-H bond, are
common in the synthesis of cyclometalated Au(III) species, only
few examples of Csp3-H bond activation at Au(III) are reported.
1
was envisioned, because the tridentate chelating nature of this
system should suppress the protolytic cleavage of the Au-CAr
bond. Should any cleavage occur, the reductive elimination step
is also expected to be less favourable due to the sp3
hybridization of the C trans to pyridine-N. 15
These include the syntheses of the cationic (N,N,CAlk 11
)
and
12-13
neutral (N,CAlk
)
cyclometalated Au(III) complexes shown in
Figure 1. Previously reported (N,N,CAlk
complexes.11-13
) ) Au(III) cyclometalated
and (N,CAlk
Figure 1, in which the C-H bond activations were promoted by
either silver salts or Na2CO3. These scarce examples underscore
the limited mechanistic information on Au(III) mediated Csp3-H
bond activation processes and the unexplored reactivity of
these systems. 1,2,14
Complex
in 74-78% yield by following the same microwave strategy used
to prepare (Figure 2). The presumed intermediate
(arylpyridine)Au(OAcF)2
1 was successfully synthesized from Au(OAc)3 and L1
A
We recently reported the catalytic transformation of acetylene
into vinyl trifluoroacetate in trifluoroacetic acid (HOAcF), by
(2
) (Figure 2) was not observed.
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Complex
reaction times (see ESI). Complex
MS, X-ray diffraction analysis, and elemental analysis. In the H
NMR spectrum of , a characteristic resonance for the AuCH2
1
could also be prepared thermally with prolonged
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DOI: 10.1039/C8CC05489D
1
was characterized by NMR,
1
1
protons from the activated tert-butyl methyl group is observed
at δ 3.16, while the signal from the two unactivated methyl
groups is at δ 1.40. The 19F NMR spectrum of
1
one shows one
resonance at δ -76.9 arising from the OAcF ligand trans to aryl-
C, similar to that of OAcF trans to tpy-C in
(δ -77.0) and other
related complexes.15,17,18 The molecular structure of
(Figure 3
and ESI) is in full agreement with that observed by NMR.
Complex exhibits the typical distorted square planar geometry
A
1
1
for cyclometalated Au(III) complexes, with the N1-Au1-C1 and
C1-Au1-C2 chelate angles slightly deviating from the idealized
90o (80.36(13)o and 81.66(15)o, respectively). The Au1-N1 bond
(2.135(3) Å) is similar, but slightly shorter than that observed in
the (N,N,CAlk)-system reported by Cinellu and co-workers
(Figure 1) (2.151(5) Å), while the opposite trend was found for
Figure 3. ORTEP plot of 1 with 50% ellipsoids. Selected bond distances [Å] and angles
[o]: Au1-N1, 2.135(3); Au1-C1, 1.944(3); Au1-O1, 2.119(3); Au1-C2, 2.049(4); C2-C3,
1.557(6); O1-Au1-N1, 99.62(11); N1-Au1-C1, 80.36(13); C1-Au1-C2, 81.66(15); C2-
Au1-O1, 98.30(14); C1-Au1-O1, 179.34(13); N1-Au1-C2, 161.36(14).
the Au-C2 bond (2.049(4) Å in
system). 11
1
vs 2.028(7) Å in the (N,N,CAlk)-
Compared to
further from the ideal square planar, e. g. the OAcF-Au-OAcF
angle in
(82.3o) is further from 90o compared to (88.0o), and
the same is observed for the cis CAr-Au-OAcF angle, which is
94.6o in and 103.5o in
. The steric repulsion between the tert-
A, the optimized geometry of 2 deviates even
2
A
A
2
butyl group ortho to Au(III) and the OAcF anion also forces C(3)
out of the Au-C(1)-C(2) plane by 9.1o (see Figure 4). This
distortion probably favours the associative substitution of OAcF
by the tert-butyl substituent to furnish the agostic intermediate
3
. In
3
, there is a highly activated C-H bond (d(C-H) = 1.18 Å vs
). The ligand substitution step has an energy barrier of
1.09 in
2
13.6 kcal/mol and is followed by an almost barrier-less proton
abstraction by the OAcF anion. Experimental and theoretical
evidences for related Au(III)-(C-H) bond agostic interactions
have already been reported by Bourissou and co-workers. 19,20
The formation of complex
22.5 kcal/mol), and consequently the reverse reaction – the
protolytic cleavage of the Au(III)-CAlk bond in
, which might lead
1 from 2 is highly exergonic (G = -
1
to catalyst deactivation – is expected to be highly unfavourable.
Initially, the low energy barrier involved in the Csp3-H bond
activation in
2 was attributed to the steric repulsion between
the tert-butyl and OAcF groups, which promotes the OAcF
dissociation, and to the weak trans influence of the pyridine
ligand in this complex. Indeed, the Au-N bond is elongated from
2.00 in
2 to 2.18 Å in 1. In order to evaluate the effect of the
Figure 2. Synthesis of complexes A and 1 from Au(OAc)3 and tpyH and L1 respectively.
On top, mechanism previously reported for the trifluoroacetylation of acetylene with
A. 15
trans influence, the ligand 2-(tert-butyl)-6-(p-tolyl)pyridine (L2
)
was synthesized and the corresponding Au complexes were
tested both computationally and experimentally for the
analogous reaction (Figure 4, blue energy profile). Surprisingly,
the energy barriers obtained for this system do not differ
significantly from those with ligand L1. The transition state for
the Csp3-H bond activation (TS3’-1’) is only 3.5 kcal/mol higher
than TS3-1. In contrast with this moderate impact on the
kinetics, the influence on the thermochemistry is dramatic – the
reaction is much less exergonic (ΔG = - 4.6 kcal/mol, 17.9
kcal/mol higher), attributable mainly to the larger trans
influence of the aryl-C compared to pyridine-N.
In order to understand the mechanism for the Csp3-H bond
activation observed with ligand L1, DFT calculations were
performed at the PBE0 level using the continuum model SMD to
include solvation by HOAcF (see ESI for computational details),
using the cyclometalated complex 2 as energy reference (Figure
4). The formation of this species, although experimentally not
observed, is expected upon cyclometalation (Figure 2).
2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C8CC05489D
Figure 4. Reaction pathway for the Csp3-H bond activation from the cyclometalated Au(III) Finally, in order to assess the performance of complex
1 in the
complexes 2 (bottom, in black) and 2b (top, in blue). Gibbs energies in HOAcF (SMD) are
catalytic trifluoroacetylation of acetylene, the energy profile for
this process was calculated and compared with the reported
given in kcal/mol. The optimized geometries for all energy minima are represented with
the relevant distances (Å) and angles (o) with omission of the non-reacting hydrogen
atoms.* Estimated energy for the dissociative ligand substitution transition state. 21
energies for
transition states leading to the formation of vinyl
trifluoroacetate with do not change significantly from those
obtained with
G‡ < 1 kcal/mol), the energy for the
B
(Figure 2 and 5). 25 While the energies for the
1
Experimentally, the reaction of L2 with Au(OAc)3 under the same
B
(
conditions used to prepare
1 was however unsuccessful, as no
transition state of the Au-CAr protolytic cleavage increases by
3.6 kcal/mol (13.5 kcal/mol in TS6-7 vs 9.9 kcal/mol with the tpy
system).15 Hence, the difference in energy between the
transition state yielding the desired vinyl trifluoroacetate
product (TS6-8) and the one promoting catalyst decomposition
Au(III) (CAr,N,CAlk) pincer complex was obtained. Only L2H+ was
1
observed in the reaction mixture by H NMR. The calculated
kinetics (
kcal/mol) for the formation of 2’ from Au-L2 did not account for
the lack of reactivity with L2 (eq. 1) However, the formation of
Au-L2 from [Au(OAcF)4]- and [L2H]+, which are the species
probably present in solution,22-23 is endergonic (eq 2,
G = 4.7
kcal/mol) whereas the formation of Au-L1 from [Au(OAcF)4]- and
[L1H]+ is exergonic (eq 3,
G = -6.2 kcal/mol) (see ESI for details).
 G = -16.3
G‡ = 21.4 kcal/mol) and thermodynamics (
.
(
TS6-7) is 4.8 kcal/mol, which is significantly larger than that of
the tpy system (1.8 kcal/mol). 15 This energy difference should
make catalyst decomposition less prone from than from and
therefore make a more robust catalyst than (Figure 2). In
order to further check this hypothesis, complex was tested
experimentally for the catalytic trifluoroacetylation of
acetylene using the same reaction conditions as for
15 During

6
C
1
A

1
These experimental and computational results suggest that the
inability to produce 1’ from Au(OAc)3 and L2 may be due to the
inhibition of ligand coordination to Au(III). Attempts to
synthesise 1’ from other Au(III) precursors were also
unsuccessful (see ESI). Even though this complex could not be
obtained, the protonolysis of the (CAr,N,CAlk) ligand at CAr, similar
to the reactivity observed at a (CAr,N,CAr) pincer Au(III) complex
A
.
these experiments, turnover numbers (TONs) of 3.0, 5.0 and 18
(average numbers) were obtained at 30 min, 1h and 24h. With
catalyst A, measurements under the same conditions yielded
TONs of 1.8, 3.1 and 14 (see Table S1 and Figure S2). The larger
TONs obtained with
However, the rapid decomposition of
1H NMR15 and visually (see Figure S3), suggests that the
improved TONs of might more likely be attributed to a larger
concentration of this catalyst in solution. Indeed, complete
decomposition of is observed after 24 h. whereas a maximum
of ca. 10 % decomposition of was observed in multiple
experiments. The improved stability of toward catalyst
1
could indicate a higher activity of
1.
24
reported by Bochmann, was evaluated by computing the
A
, which is observed by
kinetics and thermodynamics for the reaction shown in
equation (4). The energy barrier for this reaction (
kcal/mol) is significantly lower than the one for the protonolysis
of Au-CAlk in 1’ G‡ = 18.4 kcal/mol) and G‡ = 32.8 kcal/mol,

G‡ = 11.8
1
(

1 (
A
Figure 4), showing the important influence of the hybridization
at C and trans effect in these reactions. In addition, the process
in equation (4) is clearly exergonic (G = -11.7 kcal/mol), and
1
1
decomposition under reaction conditions is therefore in
qualitative agreement with the DFT calculations.
therefore the protolytic cleavage of the Au(III)-CAr bond in the
putative complex 1’ would be expected to proceed in the
presence of acids.
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In conclusion, the synthesis of the first neutral (N,C,C) Au(III) 6 M. Joost, A. Zeineddine, L. Estevez, S. Mallet−LadeVirieaw, AKr.ticle Online
DOI: 10.1039/C8CC05489D
Miqueu, A. Amgoune, and D. Bourissou, J. Am. Chem. Soc. 2014,
136, 14654.
pincer complex containing a Au-Csp3 bond has been achieved by
a double cyclometalation reaction starting from Au(OAc)3 and
2-(3,5-di-tert-butylphenyl)pyridine. The Csp3-H bond activation
involved in this reaction proceeds via electrophilic substitution
assisted by trifluoroacetate. The steric bulk of the tert-butyl
substituent promotes this reaction by directing the activated C-
7 D.-A. Roşca, D. A. Smith, D. L. Hughes, M. Bochmann, Angew.
Chem. Int. Ed. 2012, 51, 10643.
8 K.-H. Wong, K.-K. Cheung, M. C.-W. Chan, C.-M. Che,
Organometallics 1998, 17, 3505.
9 W. Henderson in Adv. Organomet. Chem., Vol. 54 (Eds.: W.
Robert, F. H. Anthony), Academic Press, 2006, pp. 207–265.
10 R. Kumar, A. Linden and C. Nevado, Angew. Chem. Int. Ed.
2015, 54, 14287.
H
bond towards the Au(III) center. The resulting
(N,CAr,CAlk)Au(OAcF) complex outperforms the original catalyst
for the trifluoroacetylation of acetylene due to its greater
stability towards ligand protonation.
11 M. A. Cinellu, A. Zucca, S. Stoccoro, G. Minghetti, M.
Manassero and M. Sansoni, J. Chem. Soc., Dalton Trans., 1996,
0
, 4217.
12 J. Vicente, M. T. Chicote, M. I. Lozano, S. Huertas,
Organometallics, 1999, 18, 753–757
13 D. Fan, E. Meléndez, J. D. Ranford, P. F. Lee, J. J. Vittal, J.
Organomet. Chem. 2004, 689, 2969.
14 M. Joost, A. Amgoune, and D. Bourissou Angew. Chem. Int. Ed.
2015, 54, 15022.
15 M. S. M. Holmsen, A. Nova, D. Balcells, E. Langseth, S. Øien-
Ødegaard, R. H. Heyn, M. Tilset, and G. Laurenczy, ACS Catal.,
2017, 7, 5023.
16 The reductive elimination of Csp3-Csp2 is less favourable than
the corresponding Csp2-Csp2. See ref. 14 and D. Balcells, O.
Eisenstein, M. Tilset and A. Nova, Dalton Trans., 2016, 45, 5504.
17 E. Langseth, C. H. Görbitz, R. H. Heyn, and M. Tilset,
Organometallics, 2012, 31, 6567.
18 E. Langseth, A. Nova, E. Aa. Tråseth, F. Rise, S. Øien, R. H.
Heyn, and M. Tilset, J. Am. Chem. Soc., 2014, 136, 10104.
19 F. Rekhroukh, L. Estévez, C. Bijani, K. Miqueu, A. Amgoune,
and D. Bourissou Angew. Chem. Int. Ed. 2016, 55, 3414.
20 (a) F. Rekhroukh, L. Estevez, S. Mallet-Ladeira, K. Miqueu, A.
Amgoune, and D. Bourissou, J. Am. Chem. Soc. 2016, 138, 11920.
(b) J. Serra, P. Font, E. D. S. Carrizo, S. Mallet-Ladeira, S. Massou,
T. Parella, K. Miqueu, A. Amgoune, X. Ribas and D. Bourissou,
Figure 5. Reaction pathway proposed for the catalytic
trifluoroacetylation of acetylene by
protolytic cleavage of the Au-CAr in
energies in HOAcF (SMD) are given in kcal/mol. In dashed lines
the corresponding pathways reported from complex , where
the (N,CAr,CAlk)Au(III) fragment is replaced by (N,CAr)Au(III)(vinyl)
(see Figure 2,
). Error! Bookmark not defined.
1
(solid, black line) and the
6
(solid, red line). Gibbs
B
A-D
Chem. Sci., 2018,
9
, 3932–3940.
21
The energy of [LAuOAcF]+ + AcFO- has been used to estimate
the energy barrier for the dissociative ligand substitution of the
OAcF anion by the tBu group.
We thank the Research Council of Norway for the funding
provided through the grants 221801/F20 (M.S.M.H) and
250044/F20 (A.N.), its Centres of Excellence scheme (262695)
and the Norwegian NMR Platform, NNP (226244/F50).
Furthermore, we thank the Norwegian Metacenter for
Computational Science (NOTUR, nn4654k), Osamu Sekiguchi,
University of Oslo, for performing the MS experiments, and
University of Oslo NMR centre for the NMR facilities.
22 The computed

G for the formation of [Au(OAcF)4]- and [L1H]+
or [L2H]+ from Au(OAc)3, L1 or L2 and HOAcF are -54.8 kcal/mol
with L1 and -56,5 kcal/mol with L2
.
23 For the crystal characterization of related [AuX4]-[PyH]+ (PyH =
pyridine derivatives) species see: (a) L. Cao, M. C. Jennings, and
R. J. Puddephatt, Inorg. Chem., 2007, 46, 1361. (b) Z. D. Hudson,
Ch. D. Sanghvi, M. A. Rhine, J. J. Ng, S. D. Bunge, K. I.
Hardcastle, M. R. Saadein, C. E. MacBeth and J. F. Eichler,
Dalton Trans., 2009, 7473.
Notes and references
1 R. Kumar and C. Nevado, Angew. Chem. Int. Ed. 2017, 56, 1994.
2 W. Henderson, The Chemistry of Cyclometallated Gold(III)
Complexes with C,N-Donor Ligands. In Adv. Organomet. Chem.,
West, R.; Hill, A. F., Eds. Academic Press: 2006, 54, 207.
3 M. W. Johnson, A. G. DiPasquale, R. G. Bergman, and F. D.
Toste, Organometallics, 2014, 33, 4169.
24 (a) N. Savjani, D.-A. Rosca, M. Schormann, and M. Bochmann,
Angew. Chem. Int. Ed. 2013, 52, 874. (b) L. Rocchigiani, J.
Fernandez-Cestau, G. Agonigi, I. Chambrier, P. H. M. Budzelaar
and M. Bochmann, Angew Chem Int Ed Engl. 2017, 56, 13861.
25
The same methodology has been used for both systems
4
J. Grajeda, A. Nova, D. Balcells, Q. J. Bruch, D. S. Wragg, R. H.
Heyn, A. J. M. Miller, and M. Tilset, Eur. J. Inorg. Chem. DOI:
10.1002/ejic.201800019
5 M. Bochmann, I. Chambrier, L. Rocchigiani, D. L Hughes, P.
HM Budzelaar, Chem. A. Eur. J. DOI: 10.1002/chem.201802160.
4 | J. Name., 2012, 00, 1-3
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TOC
The synthesis of a (N,C,C) Au(III) catalyst via Csp3-H bond activation has been achieved
following a rational catalyst design approach.