Pd(0)/Au(i) redox incompatibilities as revealed by Pd-catalyzed homo-coupling of arylgold(i)-complexes

Article abstract of DOI:10.1039/c1cc11055a

A Pd(ii)-catalyzed homo-coupling of Au(i)-aryls is reported. The reaction is driven by a Pd(0)/Au(i) redox reaction that generates a gold mirror and Pd(ii), and illustrates one of the challenges for developing dual catalytic Au-Pd systems.

Full text of DOI:10.1039/c1cc11055a

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Pd(0)/Au(I) redox incompatibilities as revealed by Pd-catalyzed
homo-coupling of arylgold(I)-complexeswz
´
Dieter Weber and Michel R. Gagne*
Received 22nd February 2011, Accepted 17th March 2011
DOI: 10.1039/c1cc11055a
A Pd(II)-catalyzed homo-coupling of Au(I)-aryls is reported. The
reaction is driven by a Pd(0)/Au(I) redox reaction that generates
a gold mirror and Pd(II), and illustrates one of the challenges for
developing dual catalytic Au–Pd systems.
Pd(0)/Pd(II) catalyzed coupling reactions rely on five basic
elementary steps: oxidative addition, reductive elimination,
migratory insertion, b-elimination, and transmetallation.1
With the exception of transmetallation, gold complexes rarely
facilitate these basic transformations, a partial consequence of
their high barriers for Au(I)/Au(0) and Au(III)/Au(I) redox
transitions2 along with their preference for low coordination
numbers. Despite these differences Au(I)/Au(III) catalyzed
cross-coupling reactions have been reported3,4 under the
action of strong oxidants like selectfluor,5 PhI(OAc)2,6 or
peroxy acids.7 Mechanistic studies by Toste on systems
utilizing selectfluor suggest fascinating bimolecular reductive
elimination mechanistic possibilities.8,9
Fig. 1 Structures of Au-vinyl complexes A and B.
cross-coupling of isolated vinyl and arylgold(I)-complexes with
aryl-triflates.15 Unfortunately, attempts to couple complexes
A16 and B17 (Fig. 1) and TolOTf with various Pd-catalysts
failed.18 TLC and GC-MS analysis indicated that at best only
traces of the desired cross-coupled products were obtained
(24 h).
In contrast, the same reaction conditions converted
arylgold(I)-complex 1a into a variety of biaryl products
(eqn (1)). The reaction progress was accompanied by the
formation of brown particles, which gradually led to a gold
mirror on the glass surface. Once TLC indicated complete
conversion, GC-MS showed that three biaryl products, 2, 3,
and 4, were generated in an 8 : 85 : 7 ratio, respectively.19 The
Fueled by the seemingly orthogonal reactivity modes of Au
and Pd catalysts, are suggestions of tantalizing new cross-
coupling schemes that sequence the reactivities of Au and Pd.
Reports of at least partial success in interfacing Au- and Pd
catalysis in this manner have been published by Blum,10
Hashmi,11 Sarkar,12 and Sestelo.13 In particular, Blum has
reported an impressive example of bimetallic catalysis wherein
a gold-vinyl intermediate obtained from an allene activation
reaction could be intercepted by an in situ formed palladium
p-allyl species to perform a vinyl-allyl coupling that was
catalytic in both gold and palladium.14 We report herein that
undesirable redox reactions between Pd(0) and Au(I) can
interfere with the normal operation of several putative
catalytic cycles that could couple the reactivity of Au and
Pd. These observations may explain the difficulty of developing
reactions that are catalytic in both metals.
1
structure of 4 was confirmed by H NMR.
ð1Þ
A simple mechanistic scheme for the formation of 2 is
shown in cycle C, Scheme 1. Whereas cross-coupling to 2 is
initiated by oxidative addition of TolOTf, catalytic homo-coupling
of 1a to 3 requires a separate oxidant (cycle D, Scheme 1) to
Motivated by the potential of utilizing aryl and vinyl
electrophiles to model the reactivity of C(sp2)–Au intermediates
in Au(I)-catalysis, we studied the palladium-catalyzed
Caudill Laboratories, Department of Chemistry, University of North
Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
E-mail: mgagne@unc.edu
w This article is part of a ChemComm web-based themed issue on new
advances in catalytic C–C bond formation via late transition metals
z Electronic supplementary information (ESI) available: Experimental
details, NMR, and GC-MS data. See DOI: 10.1039/c1cc11055a
Scheme 1 Mechanistic schemes for cross- and homo-coupling of 1a.
c
5172 Chem. Commun., 2011, 47, 5172–5174
This journal is The Royal Society of Chemistry 2011

Table 1 Ligand screen and control experimentsa
Table 2 No addition of TolOTf and variation of substratea
Entry
Additive
[Pd]
L
Time
2 : 3 : 4f
Entry
Substrate
[Pd]
L0
Time
2 : 3 : 4f
1
2
3
4
5
6
7
8
TolOTf
TolOTf
TolOTf
TolOTf
TolOTf
TolOTf
TolOTf
TolOTf
TolOTf
TolOTf
None
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
dppfPdCl2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
L1
L3
L4
None
L1
L3
L4
None
L1
o19 h
o19 h
24 hd
o19 h
19 hd
24 hd
24 hd
o29 h
19 he
8 : 85 : 7
2 : 84 : 14
1 : 86 : 13g
11 : 74 : 15
13 : 73 : 14g
5 : 83 : 12g
7 : 81 : 12g
1 : 88 : 12
—
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1b
1c
1d
1a
1a
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
L1
L1
L1
L1
L2
L1
L1
None
PPh3
o19 h
o5 h
19 hc
5 hc
0 : 76 : 24
0 : 75 : 25
0 : 98 : 2g
19 : 80 : 1g
18 : 82 : 0g
—
—
0 : 83 : 17h
—
b
5 hc
5 hd
12 hd
o2 h
12 he
PEPPSI-IPrc
None
None
9
10
11
b
None
None
19 he
—
—
19 he
a
None
Reaction conditions: 5–10 mol% [Pd]/L; 10 mg (17.7 mmol) of
b
c
a
1a. 3.1 equivalents of PPh3 vs. 1a were added. Incomplete conversion
to coupled product was indicated by TLC; after the indicated period of
time, the reactions was analyzed by GC-MS which thermally converts 1
Reaction conditions: 5–10 mol% [Pd]/L; 2.5 equiv. TolOTf; 10 mg
b
(17.7 mmol) of 1a. dppf
ferrocene. PEPPSI-IPr
2-ylidene](3-chloropyridyl)palladium(II)
=
1,10-bis(diphenylphosphino)-
= [1,3-bis(2,6-diisopropylphenyl)imidazol-
c
d
e
d
dichloride. Incomplete
to 3. Only an initial burst to coupled product was observed. No
f
conversion indicated by TLC. Product ratio determined by GC-MS.
conversion to coupled product was indicated by TLC; after the
indicated period of time, the reactions was analyzed by GC-MS which
g
h
See ref. 19. An 0 : 84 : 16 mixture (NMR ratio) of products was
e
thermally converts unreacted 1a to 3. No conversion indicated by
isolated by flash column chromatography on silica (45% yield of 3,
and a 5% yield of 4).
f
TLC. Product ratio determined by GC-MS. See ref. 19.
g
regenerate Pd(II) after reductive elimination of 3. Since no
external oxidant was added (with the exception of TolOTf
which would facilitate cross-coupling) further studies were
initiated to gain insight.
phosphine ligand for Pd a small amount of 4 was also
observed, pointing to two ligand sources for the aryl group.
In the case of the non-phosphine NHC complexes (IPr-
NHC)AuAr (1c) and (IMes-NHC)AuAr (1d) (Ar = 3,5-Xyl)
only an initial burst of homo-coupling was observed, with
neither reaction progressing beyond this point (Table 2, entries
6 and 7). This experiment suggests that either the PAr3 ligand
is necessary to facilitate the reaction or that NHC ligands
sufficiently stabilize the Au(I) state to inhibit the redox process.
In the absence of added phosphine ligand Pd(OAc)2 fully
converted 1a within 2 h at 58 1C (Table 2, entry 8). Conversely,
3.1 equivalents of PPh3 completely inhibit the conversion to 3
(Table 2, entry 9), supporting the notion that stabilizing Au(I)
either through NHC’s or excess phosphine can inhibit the
redox reaction.22
As shown in Table 1, variation of the Pd catalyst did not
significantly increase the amount of 2 (Table 1, entries 1–8),
though reaction times did vary from catalyst to catalyst: Pd(II)
sources tended to be faster. Control experiments showed that
when no Pd catalyst was added, no conversion of 1a to
coupled products was observed by TLC (Table 1, entries
9–11). Note: thermolysis of 1a in the GC injector port leads
to 3.19
The source of 3 and 4 was investigated by examining the role
of each reaction component. When TolOTf was omitted, only
3 and 4 were formed (Table 2, entry 1), which clearly showed
that TolOTf did not act as the oxidant for the formation of 3.
Monitoring the reaction with Pd(OAc)2 by TLC indicated that
1a was consumed within 5 h (Table 2, entry 2), and that an
initial burst20 of coupled products was followed by a slower
but steady reaction. Using Pd2(dba)3 (Table 2, entry 3), the
initial burst was not observed and the reaction proceeded
slowly. A slightly faster rate could be regained using Pd2(dba)3
in combination with TolOTf, but the reaction time was still
not as rapid as when a Pd(II) source was used. These data
suggest that it is a Pd(II) species that first engages Au(I) to
produce homo-coupled products. Since the aryl groups of
PAr3 ligands are known to transfer in Ni, Pd, and Pt reductive
elimination reactions,21 the possibility that 4 was phosphine
derived was tested by utilizing (p-tol)3PAuAr (1b) (Table 2,
entries 4 and 5). Not surprisingly, a significant amount of 2
was observed. When Ph-Xphos (L1, Fig. 2) was utilized as the
We also attempted to elucidate whether the reaction
was homogenous or heterogeneous with a Hg drop test.23
Unfortunately, this led to an instant decomposition of 1a as
previously observed by Grandberg while studying the redox
potential of gold complexes on Hg electrodes (eqn (2)).24
2RAuPPh3 + Hg(0) - R2Hg + 2Au(0) + 2PPh3 (2)
Fig. 2 Various ligands utilized in attempted cross-coupling.
Chem. Commun., 2011, 47, 5172–5174 5173
c
This journal is The Royal Society of Chemistry 2011

2010, 16, 4739–4743; (h) A. S. K. Hashmi, T. D. Ramamurthi,
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The catalytic coupling of two nucleophiles requires an
oxidant. Based on the Grandberg redox precedent, the
observed gold mirror, and the experimental results we propose
that reduction of Au(I) to Au(0) accounts for the necessary
redox equivalents. As outlined in step a of Scheme 2, two
equivalents of Au(I) are consumed to regenerate Pd(II) with the
Au(0) eventually forming the gold mirror.25 Since the Hg drop
experiment failed, the role of Pd and/or Au nanoparticles
cannot be eliminated from consideration.
7 H. A. Wegner, S. Ahles and M. Neuburger, Chem.–Eur. J., 2008,
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¨
¨
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¨
¨
Scheme 2 Proposed mechanism for the homo-coupling of 1a.
In conclusion, a Pd-catalyzed homo-coupling of arylgold(I)-
complexes has been observed. While of limited applicability in
synthesis, these results have illuminated a point of incompat-
ibility between these two metals and suggested strategies
for overcoming these shortcomings. Since Au-mirrors are
relatively common occurrences in gold-catalyzed reactions,
these results demonstrate how two elements with orthogonal
reactivity profiles can be redox incompatible and thus impede
the development of dual Au(I)/Pd(0) catalysts.
12 (a) B. Panda and T. K. Sarkar, Chem. Commun., 2010, 46,
3131–3133; (b) B. Panda and T. K. Sarkar, Tetrahedron Lett.,
2010, 51, 301–305.
´ ´
13 M. Pena-Lopez, M. Ayan-Varela, L. A. Sandareses and
J. P. Sestelo, Chem.–Eur. J., 2010, 16, 9905–9909.
14 Y. Shi, K. E. Roth, S. D. Ramgren and S. A. Blum, J. Am. Chem.
Soc., 2009, 131, 18022–18023.
15 Sestelo has coupled p-acetylphenyl triflate with in situ formed
organometallic gold compounds (from RLi and Ph3PAuCl). Our
attempts to couple isolated Au-complexes 1a or PhAuPPh3 with
TolOTf or p-acetylphenyl-triflate under these published conditions
were unsuccessful (see the supporting informationz and ref. 13).
Financial support is gratefully acknowledged from the
Fulbright Foreign Student Program (DW) and the National
Institute of General Medicine (GM-60578).
16 (a) D. Weber, M. A. Tarselli and M. R. Gagne
´
, Angew. Chem., Int.
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18 For ligands commonly used to couple sulfonate electrophiles, see:
K. Dooleweerdt, B. P. Fors and S. L. Buchwald, Org. Lett., 2010,
12, 2350–2353, and references therein.
Notes and references
1 X.-F. Wu, P. Anbarasam, H. Neumann and M. Beller, Angew.
Chem., Int. Ed., 2010, 49, 9047–9050.
2 For an example of in situ reduction of Au(III) in catalysis, see:
A. S. K. Hashmi, M. C. Blanco, D. Fischer and J. W. Bats, Eur. J.
Org. Chem., 2006, 1387–1389.
3 For short reviews on oxidative coupling reactions with gold, see:
(a) H. A. Wegner, Chimia, 2009, 63, 44–48; (b) P. Garcia,
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4 Palladium impurities could play the key role in gold-only catalyzed
coupling reactions, especially if no oxidant is present:
19 GC-MS and GC data could not be used to determine the yield of
incomplete reactions, since arylgold(I)-complexes pass through
silica or florisil and homo-couple in the hot injector port (see the
supporting informationz).
20 The initial burst was qualitatively observed by TLC. It is best
explained by a fast first turnover of a Pd(II) source.
21 (a) J. Vicente, M. D. Bermudez and J. Escribano, Organometallics,
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´
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22 The exact nature of the inhibiting effect of PPh3 is unclear, but we
note that when it is in excess not even a single turnover occurs.
23 D. R. Anton and R. H. Crabtree, Organometallics, 1983, 2,
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25 While this paper was under review Blum disclosed a nickel-
catalyzed cross-coupling of organogold reagents: J. J. Hirner and
S. A. Blum, Organometallics, 2011, 30, 1299–1302. Notable
observations include redox chemistry between Au(I) and Ni(0) to
generate paramagnetic Ni(I) (i.e. single electron processes) and
gold mirrors. We are unable to confirm the presence of Pd(I)
intermediates in the present chemistry.
´
´
´
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5174 Chem. Commun., 2011, 47, 5172–5174
This journal is The Royal Society of Chemistry 2011