Highly active phosphite gold(i) catalysts for intramolecular hydroalkoxylation, enyne cyclization and furanyne cyclization

Article abstract of DOI:10.1039/c4cc00839a

New and highly active mononuclear phosphite gold(i) catalysts are described. Turn-over numbers up to 37-000 for the furan-yne reaction and up to 28-000-000 for the two-fold hydroalkoxylation of alkynes are reported.

Full text of DOI:10.1039/c4cc00839a

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Highly active phosphite gold(I) catalysts for
intramolecular hydroalkoxylation, enyne
cyclization and furanyne cyclization†
Cite this: Chem. Commun., 2014,
50, 4937
Received 30th January 2014,
Accepted 27th March 2014
Maria Camila Blanco Jaimes,a Frank Rominger,a Mariette M. Pereira,b
Rui M. B. Carrilho,b Sonia A. C. Carabineiroc and A. Stephen K. Hashmi*ad
´
DOI: 10.1039/c4cc00839a
www.rsc.org/chemcomm
New and highly active mononuclear phosphite gold(I) catalysts are using dissymmetric gold(I) N-heterocyclic carbene complexes.7
described. Turn-over numbers up to 37 000 for the furan–yne More recently, our group reported a TON of 32 000 000 for the
reaction and up to 28 000 000 for the two-fold hydroalkoxylation two-fold addition of alcohols to an alkyne, and proved that high
of alkynes are reported.
TONs can also be achieved in reactions following an entirely
different mechanism.8 That is how a TON of 5720 could be
During the last decade, homogeneous gold catalysis has evolved accomplished in the gold(I)-catalyzed furan–yne reaction. On the
to a highly active and innovative field.1 The yearly numbers of other hand, the use of gold nanoparticles as catalysts for the oxida-
publications are still increasing; most of them focus on the tion of glucose by oxygen, reported by Rossi and coworkers,
synthesis of new gold complexes, new methodologies and allowed a TOF of 50 120 hÀ1.9 Small gold clusters (with 3 to 5 gold
applications in total synthesis,2 as well as studies on reaction atoms) have been recently described by Corma and coworkers,
mechanisms.3 The high catalyst loading (1–10 mol%), usually who reported a remarkable TON of 10 000 000 and TOF of
employed in gold-catalyzed reactions, indicates the need for the 100 000 hÀ1 in the ester-assisted hydration of alkynes.10
design of more stable and active catalysts able to achieve high
turn-over numbers (TONs), which would allow the use of smaller to prove that excellent catalytic activity can be achieved using
amounts of catalysts.
homogeneous and mononuclear gold catalysts,8 we decided to
Based on our previous results and in continuation of our efforts
There are only a few reports in the literature concerning high synthesize, characterize and investigate the catalytic activity of
TON or turnover frequencies (TOFs) with gold catalysts.4–10 phosphite gold(I) complexes. In earlier work, cationic phosphite
In homogeneous gold catalysis, the highest TONs and TOFs gold(I) complexes have been recognized to possess high kinetic
reported so far all cover the addition of alcohols to alkynes. activities, but low stabilities due to the easy dissociation of these
The first study was described by Teles and coworkers,4 who weak donor ligands.4 On the other hand, we had assumed that
achieved TONs up to 100 000 and TOFs up to 5400 hÀ1. In 2004, the sterical shielding of the gold(I) center in our highly active
Hayashi, Tanaka and coworkers reported a TOF to 15 600 hÀ1 NAC–gold(I) complex avoids catalyst decomposition by preventing
using CO and acids as co-catalysts.5 In 2009, Nolan and gold–gold interactions.8 If this hypothesis is correct, the use of a
coworkers6 reached a TON of 84 000 and TOF of 4667 hÀ1 even bulky phosphite ligand instead of a bulky NAC ligand should also
using the less nucleophilic water instead of alcohols. Thieleux and lead to high TONs and fast kinetics. Here we report our findings
coworkers achieved a TON of 800 000 and a TOF of 294 000 hÀ1 when using such very bulky phosphite ligands.
We synthesized the phosphite gold(I) chlorides 1–3 (Fig. 1)
a
¨
Organisch-Chemisches Institut, Ruprecht-Karls-Universitat Heidelberg,
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
E-mail: hashmi@hashmi.de; Fax: +49-711-685-4205
by reaction of DMS–gold chloride (DMS = dimethylsulfide) with
the phosphite ligands prepared according to previously described
methods.11 For 1 and 3, suitable single crystals for X-ray crystal
structure analysis could be obtained, which show the different
sterical demand of the ligands.12
The gold-catalyzed cycloisomerization of 1,6-enynes was first
used to study the catalytic activity of phosphite gold(I) complexes.
Table 1 summarizes the results for catalysts 2 and 3, which show
high TONs (up to 420) in comparison to best value published so far
for the homogeneous gold-catalyzed cycloisomerization of enyne 4
(TON of only 39–41 with 2 mol% of Au).13 These preliminary results
b
´
´
Centro de Quımica de Coimbra, Departamento de Quımica,
Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal
c LCM - Laboratory of Catalysis and Materials - Associate Laboratory LSRE/LCM,
Faculdade de Engenharia, Universidade do Porto, Rua Dr Roberto Frias,
4200-465 Porto, Portugal
d Chemistry Department, Faculty of Science, King Abdulaziz University,
Jeddah 21589, Saudi-Arabia
† Electronic supplementary information (ESI) available: Detailed experimental
procedures and analytical data. CCDC 983150 and 983151. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c4cc00839a
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Table 2 Gold-catalyzed phenol synthesis
Entry Catalyst [Au] (mol%) Conversiona (%) Yielda (%) TONb
1
2
3
1
2
3
0.1
0.01
0.001
100
60
40
73
42
31
730
4200
31 000
4
5
6
0.1
0.01
0.001
100
75
50
88
50
37
880
5000
37 000
Fig. 1 Phosphite gold(I) complexes 1–3 and solid state molecular struc-
tures of 1 and 3.
7
8
9
0.1
0.01
0.001
100
85
65
74
54
34
740
5400
35 000
Table 1 Gold-catalyzed 1,6-enyne cycloisomerization
Unless otherwise stated, the experiments were carried out in a NMR
tube using 0.2 mmol of the substrate in 500 mL of solvent. a Determined
by 1H NMR using TTBB (1,3,5-tri-tert-butylbenzene) as internal standard.
b
TON: n(product)/n(catalyst).
Entry Catalyst
[Au] (mol%) Conversiona (%) Yield 5 : 6a (%) TONb
which was first studied with Rh and Ir catalysts by Messerle and
coworkers,17 was recently investigated by our group using a highly
sterically demanding NAC–gold(I) catalyst, which was able to achieve
a TON of 32 000 000.8 We were curious how the activity of those
catalysts bearing a silsesquioxane group compares to that of the new
phosphite gold(I) catalysts 1–3.
Table 3 shows the results obtained for the gold-catalyzed two-
fold hydroalkoxylation reaction with substrate 9, forming the
spiro-compounds 10 and 11. With 0.1 mol% of the catalysts 1–3
1
2
3
4
5
2
2
3
3
0.50
0.10
0.50
0.10
72
31
88
47
50
28 : 40
9 : 19
17 : 61
9 : 33
136
280
156
420
44
(PhO)3PAuCl 0.50
10 : 12
The experiments were carried out in a NMR tube using 0.2 mmol of the
substrate in 500 mL of solvent. Determined by 1H NMR using TTBB
a
b
(1,3,5-tri-tert-butylbenzene) as internal standard. TON: n(product)/
n(catalyst).
of increasing the TON for the reaction of the 1,6-enyne 4 by a factor (entries 1–3), a complete conversion was observed in less than 2 hours
of ten, already indicated a high potential of this new series of at room temperature; catalyst (PhO)3PAuNTf2 needed 3 h for the same
catalysts. The use of sterically less hindered triphenylphosphite result (entry 4). A decrease of the catalyst loading to 0.01 mol% (entries
ligand gave a much lower TON (entry 5).
5–7) and 0.001 mol% (entries 9–11) still allowed complete conversions
Motivated by these results, we decided to investigate the at room temperature, which correspond to TONs up to 9700 and
catalytic activity of the phosphite gold(I) complexes 1–3 in the 96 000, respectively. When a catalyst loading of 0.0001 mol% or less
furan–yne reaction.14 Furan–yne 7 is a very useful substrate was employed,18 it was necessary to increase the temperature to 40 1C
among the enyne compounds family, delivering phenols; it has and/or double the concentration of the substrate in the reaction
been already used as model substrate for evaluation of new mixture in order to avoid extremely long reaction times. In these
catalysts,15 achieving a TON of 1180.15b When the reaction was entries (PhO)3PAuNTf2 could not keep up with the other catalysts
performed using 0.1 mol% of the respective catalyst with in situ (entries 8, 12 and 16). Even with a loading of 0.00001 mol% almost
activation according to Gagosz,16 we were delighted to detect full complete conversion was accomplished in 72 hours (entries 17–19)
conversion with TON up to 880 (Table 2). Under the same reaction achieving TONs up to 9 700 000. Only when the catalyst loading was
conditions it was possible to decrease the catalyst loading to 0.000001 mol%, the reaction did not proceed to completion, with
0.001 mol% reaching a remarkable TON of 37 000. The three catalysts conversions between 18–29% being observed after 72 hours, reaching
1–3 achieved comparable TONs, which indicated that their stability TONs between 18 000 000 and 28 000 000, which correspond to TOFs
and catalytic activity is quite similar. With these results a new record between 250 000 and 380 000 hÀ1 (entries 20–22). No conversion was
for the gold-catalyzed phenol synthesis has been established. Here we observed under the same conditions without gold catalysts. Since it
did not include the (PhO)3P ligand in the screening, as in the group was already reported for substrate 9 that, under the same reaction
there already have been many previous efforts to optimize the ligands conditions, silver salts alone or Brønsted acids does not show any
for that reaction, including this phosphite, phosphines and carbene comparable catalytic activity,8 the gold catalysts have to be the species
ligands as well as heterogeneous gold catalysts.14b
responsible for the high TONs reached.
As mentioned above, in homogeneous gold catalysis the addition
In order to establish the rate by which the catalysts 1–3 convert
of alcohols to alkynes has reached the highest TONs and TOFs so far substrate 9 into the corresponding spiro-compounds 10 and 11,
reported.4–10 Thus, we now decided to investigate the catalytic activity time/conversion curves for each catalysts were measured using a
of the phosphite gold(I) catalysts 1–3 in the intramolecular two-fold catalyst loading of 0.0001 mol% at 40 1C. The curves showed that the
hydroalkoxylation reaction of substrate 9. This test substrate, three catalysts convert the substrate at the same rate, having only a
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Table 3 Gold-catalyzed formation of spiro-compounds 10–11
conversion of the substrate is increased, the rate of decomposition
of the catalyst becomes slower. Furthermore, a new record for
the gold catalyzed phenol synthesis was accomplished with a
TON of 37 000.
M. C. Blanco J. is grateful to DAAD for a fellowship. S.A.C.
Carabineiro acknowledges financial support from ‘‘Investigador
FCT’’ program. M. M. P. and R. M. B. C. thank the financial support
from FCT-Portugal and QREN/FEDER (COMPETE – Programa
Operacional Fatores de Competitividade, PTDC/QUI-QUI/112913/
˜
Entry [Au] (mol%)
T
Conversionb (%) TONb,c
1a
2a
3a
4a
0.10, 1
0.10, 2
0.10, 3
0.10, (PhO)3PAuCl
r.t.
r.t.
r.t.
r.t.
100
100
100
100
980
980
980
980 2009). Authors also thank Fundaçao das Universidades Portuguesas
˜
˜
and DAAD for the bilateral project Açao Integrada Luso-Alema
5a
6a
7a
8a
0.01, 1
0.01, 2
0.01, 3
0.01, (PhO)3PAuCl
r.t.
r.t.
r.t.
r.t.
100
100
100
100
9700
9700
2012 – Ref.a A-19/12. Gold salts were generously donated by
9600 Umicore AG & Co. KG.
9700
Notes and references
1 For recent general reviews on gold catalysis: (a) N. Krause and C. Winter,
Chem. Rev., 2011, 111, 1994; (b) A. S. K. Hashmi and M. Rudolph, Chem.
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9a
0.001, 1
0.001, 2
0.001, 3
0.001, (PhO)3PAuCl
r.t.
r.t.
r.t.
r.t.
100
97
98
96 000
94 000
96 000
60 000
10a
11a
12a
62
´
Chem. Rev., 2008, 108, 3351; (d) E. Jimenez-Nu´nez and A. M. Echavarren,
13a
14a
15a
16a
0.0001, 1
0.0001, 2
0.0001, 3
40 1C
40 1C
40 1C 100
98
98
960 000
940 000
980 000
120 000
Chem. Commun., 2007, 333; (e) A. Fu¨rstner and P. W. Davies,
Angew. Chem., 2007, 119, 3478 (Angew. Chem., Int. Ed., 2007, 46, 3410);
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0.0001, (PhO)3PAuCl 40 1C
14
2 (a) A. S. K. Hashmi and M. Rudolph, Chem. Soc. Rev., 2008, 37, 1766;
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17d
18d
19d
0.00001, 1
0.00001, 2
0.00001, 3
40 1C
40 1C
40 1C
98
93
97
9 700 000
9 200 000
9 400 000
20d
21d
22d
0.000001, 1
0.000001, 2
0.000001, 3
40 1C
40 1C
40 1C
25
29
18
24 000 000
28 000 000
18 000 000
a
In a NMR tube using 0.1 mmol of the substrate in 500 mL of solvent.
´
6 N. Marion, R. S. Ramon and S. P. Nolan, J. Am. Chem. Soc., 2009, 131, 448.
b
A ratio of 10 : 11 = 1 : 2 determined by 1H NMR using TTBB (1,3,5-tri-
´
7 M. Bouhrara, E. Jeanneau, L. Veyre, C. Coperet and C. Thieuleux,
c
tert-butylbenzene) as internal standard. TON: n(product)/n(catalyst).
Dalton Trans., 2011, 40, 2995.
d
The reaction was carried out with 0.2 mmol of substrate in 500 mL of
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slight difference in the conversion at the end. That is how after
´
40 hours, catalyst 1 and 2 showed complete conversion (100%) 10 (a) J. Oliver-Meseguer, J. R. Cabrero-Antonino, I. Domınguez, A. Leyva-
´
Perez and A. Corma, Science, 2012, 338, 1452; (b) for a discussion, see:
and catalyst 3 reached 97%. The same outcome was observed at
0.000001 mol% catalyst loading when catalyst 3 achieved the
lowest TON of 18 000 000, compared to the 28 000 000 obtained
with catalyst 2. In perfect agreement with our initial hypothesis,
this difference could be explained in terms of the stabilizing
effect of the bulky19 substituents on the gold catalysts. There-
fore catalyst 3, which is bearing only adamantyl substituents,
is the less stabilized catalyst, showing a faster deactivation and
achieving lower TONs than the other two phosphite catalysts,
bearing bulkier binaphthyl substituents.
A. S. K. Hashmi, Science, 2012, 338, 1434.
¨
´
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´
´
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´
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32 000 000 using NAC–gold(I) complex,8 it was proved that 14 (a) A. S. K. Hashmi, T. M. Frost and J. W. Bats, J. Am. Chem. Soc., 2000,
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activity by introducing bulky substituents, which stabilize the
gold complex.
(d) A. S. K. Hashmi, T. Hengst, C. Lothschu¨tz and F. Rominger, Adv.
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Our investigation supports the hypothesis that high catalytic
activity is not limited to sub-nanoparticles20 or heterogeneous
catalysis; in contrast, it can be achieved not only by NAC–gold(I)
complexes but also by homogeneous, mononuclear, phosphorus-
containing gold catalysts. The steric bulkiness of the ligand is the
crucial factor for achieving long catalyst lifetimes – not the rate of
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¨
(i) A. S. K. Hashmi, M. Rudolph, J. P. Weyrauch, M. Wolfle, W. Frey and 18 The amount of catalysts was added by stock solutions using dilution
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Y. Yu and F. Rominger, Organometallics, 2012, 31, 895S; (k) S. Carrettin,
techniques. Stock solutions were prepared by stepwise dilution in
volumetric flasks.
M. C. Blanco, A. Corma and A. S. K. Hashmi, Adv. Synth. Catal., 2006, 19 The buried volume of the different complexes is: (a) for (PhO)3PAuCl:
348, 1283; many other ligands including (PhO)3P have been tested and
H. Clavier and S. P. Nolan, Chem. Commun., 2010, 46, 841–861 – 31.9%
for Au–C = 2.28 Å, sphere radius = 3.50 Å(b) for 3 35.7% for Au–C = 2.20 Å,
sphere radius = 3.50 Å; (c) for 1 51.6% for Au–C = 2.20 Å, sphere
radius = 3.50 Å.
showed low activity during these investigations.
15 (a) A. S. K. Hashmi, C. Lothschu¨tz, K. Graf, T. Haffner, A. Schuster
¨
and F. Rominger, Adv. Synth. Catal., 2011, 353, 1407; (b) A. S. K.
Hashmi, J. P. Weyrauch, M. Rudolph and E. Kurpejovic, Angew. 20 ESI MS and UV studies (see ref. 10) on the reaction mixtures did not
Chem., 2004, 116, 6707 (Angew. Chem., Int. Ed., 2004, 43, 6545).
provide any evidence for sub-nanoparticles or nanoparticles. In the
furan–yne reaction, the only nanoparticles that are active, are
supported on nanocrystalline CeO2 (but do not allow high turnover
numbers): S. Carrettin, M. C. Blanco, A. Corma and A. S. K. Hashmi,
Adv. Synth. Catal., 2006, 348, 1283.
´
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4940 | Chem. Commun., 2014, 50, 4937--4940
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