Gold and palladium combined for the Sonogashira-type cross-coupling of arenediazonium salts

Article abstract of DOI:10.1039/c001277g

The Sonogashira-type cross-coupling of arenediazonium salts is reported for the first time using a Pd-Au dual catalytic system. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/c001277g

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Gold and palladium combined for the Sonogashira-type cross-coupling
of arenediazonium saltsw
Biswajit Panda and Tarun K. Sarkar*
Received (in Cambridge, UK) 19th January 2010, Accepted 3rd March 2010
First published as an Advance Article on the web 1st April 2010
DOI: 10.1039/c001277g
The Sonogashira-type cross-coupling of arenediazonium salts is
reported for the first time using a Pd–Au dual catalytic system.
Arenediazonium salts are both attractive and useful partners
in palladium-catalysed Heck, Suzuki, Stille and carbon-
heteroatom type cross-couplings.1 There are several advantages
Scheme 1 Sonogashira coupling of arenediazonium salts.
of working with arenediazonium salts which include their
the desired product. Accordingly, all other experiments in
Table 1 were conducted with 4 mol% of Pd- and 1 mol% of
Au-catalyst. Further screening identified 2,6-lutidine in MeCN
as a suitable option for this variant of the Sonogashira coupling
reaction where no traces of the competing Hay/Glaser type
homocoupling product 3 was formed (entry 5); in other
solvents the latter product was isolated, and especially in entry
8 where Et3N was used as base the homocoupling product was
the major by-product. A bulky pyridine base, namely 2,6-di-
tert-butyl-4-methylpyridine (DBMP), is also effective in this
reaction (entry 9); an added advantage here is that after use
the base can be recovered (>95%) at the chromatographic
purification stage. The only complication here (entries 5 and 9)
was the similar polarity of the coupled product and some
associated highly colored impurities, requiring multiple purifi-
cations by silica gel chromatography to obtain the product in
pure form. Incorporation of 5 mol% of bis-2,6-diisopropyl-
phenyl dihydroimidazolium chloride (IPr NHC) in the reac-
tion milieu prevented those side reactions leading to the
formation of the colored materials (entry 10). Although there
was no significant enhancement in yield in this case (compare
ready availability from anilines, their superior reactivity com-
pared to the corresponding aryl halides or triflates, and their
insensitivity to the electronic nature of the substituents they
might otherwise adorn in coupling reactions.2 Given these
attributes of arenediazonium salts it is surprising that there are
no reports of their use in a Sonogashira-type cross-coupling to
date. For years, the Sonogashira reaction3 has remained a
staple of organic synthesis due to the efficiency with which aryl
alkynes and conjugated enynes, which are prevalent inter-
mediates for the synthesis of a diverse array of natural products,
pharmaceuticals and molecular organic materials, are accessible.4
In particular many different variants of the Sonogashira
reaction have appeared, the recent thrust being on using
cheaper catalyst(s),5a inexpensive aryl partners5b as well as
effecting the reaction at ambient temperature.6 Within this
context we report for the first time the use of arenediazonium
salts in a Sonogashira-type cross-coupling reaction at room
temperature effected by a Pd–Au dual catalytic system.7,8
For an uneventful Sonogashira reaction with arenedi-
azonium salts, it is imperative to avoid use of phosphine-based
ligands on palladium and replace copper by a metal, such as
gold, which is resistant to oxidation.1,9 Following our success
with a Pd–Au dual catalytic Sonogashira reaction on aryl
halides, as described in a recent communication,7a we chose
the ligandless PdCl2/AuCl as the catalytic duo and ran the first
experiment on the diazonium tetrafluoroborate 1 and phenyl
acetylene in the presence of 2,6-lutidine as base in THF
(Scheme 1). The result was encouraging: the Sonogashira
product 2 was obtained in 54% yield accompanied by 8% of
the Hay/Glaser product 3.
Table 1 Optimization studies
Yield
Yield
Entry Solvent
Base
(%) of 2a (%) of 3a
The stage was thus set for optimization studies (Table 1)
wherein the solvents and bases used were varied to arrive at
the most suitable combination for high-yielding Sonogashira
coupling of arenediazonium salts. As can be seen from entry 1,
use of a higher loading of the Pd-catalyst improved the yield of
1
2
3
4
5
6
7
8
THF
1,4-Dioxane
H2O
2,6-Lutidine 62
2,6-Lutidine 74
2,6-Lutidine 62
8
5
14
MeCN–H2O (1 : 1) 2,6-Lutidine 76
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
2,6-Lutidine 74
0
Trace
Trace
51
0
K2CO3
Cs2CO3
Et3N
42
66
15
Department of Chemistry, Indian Institute of Technology, Kharagpur,
Kharagpur 721302, India. E-mail: tksr@chem.iitkgp.ernet.in;
Fax: (+)91-3222-255303
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data, ORTEP diagram of compound
6. CCDC 753368. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c001277g
9
10
11
DBMP
DBMP
DBMP
75
80b
11c
0
0
a
b
c
Isolated yield. 5 mol% IPr NHC was added. 1 mol% AgOTf was
used instead of AuCl.
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Chem. Commun., 2010, 46, 3131–3133 | 3131

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entries 9 and 10), we shall see later (vide infra) that this
modified condition was most effective for the Sonogashira
coupling of arenediazonium salts containing electron with-
drawing nitro groups as well as in the in situ protocol.
Furthermore, independent experiments were carried out to
see the role of Pd and Au separately in entry 10. While the
gold-only procedure gave 2 and 3 in 30% and 11% isolated
yields, respectively, the Pd-only process afforded 2 and 3 in
isolated yields of 10% and 28%, respectively. Finally, in entry
11, a silver salt was used in place of gold; however, the yield of
the product dropped to 11%.
nicely with aryl as well as alkyl acetylenes (entries 1–5). Even
highly electron-rich arenediazonium salts (entries 8–10) are
also amenable to this process. Alkynes containing an electron
withdrawing group (directly attached to the ethynyl carbon)
are usually poor substrates for the Sonogashira coupling.10 It
is gratifying to note that our catalytic system allows such a
coupling with methyl propiolate, albeit in modest yield (entry 6).
Cross-coupling of arenediazonium salts with alkynes bearing
an N,N-dimethylanilino group is a demanding case, since it is
common knowledge that N,N-dimethylanilines readily undergo
azo-coupling with arenediazonium salts. As can be seen
from entries 7 and 12 (Table 2), such couplings are possible
under these conditions. This method is also tolerant of
ortho-substitution in arenediazonium salts (entries 8, 11 and 12).
In addition, sterically hindered arenediazonium salts (entry 13)
also enter into Sonogashira coupling under this dual catalytic
condition. Entries 14 and 15 present the challenging11 reaction
of 3- and 4-nitrobenzenediazonium tetrafluoroborates with
phenylacetylene which gives the Sonogashira product
in 64 and 61% yields, respectively, accompanied by traces
(approx. 5%) of dediazotized product, namely nitrobenzene.
This reactivity profile is gratifying, given the high redox
potential of diazonium salts containing electron withdrawing
groups which makes them prone to preferential reduction.
Furthermore, these examples fully underscore the advantage
of using the conditions as given in entry 10 (Table 1) over
the one in entry 5 (Table 1), since use of the latter gives the
products in significantly reduced yields as shown in paren-
theses. That classical Sonogashira conditions (Pd/Cu) are not
suitable12 for the cross-coupling of arenediazonium salts is
borne out by replacing AuCl with CuI (entries 5 and 15,
Table 2) when no trace of the desired product was observed.
At this stage it was of interest to study the Sonogashira
coupling of 2-nitroarenediazonium salts; in this case there is
the possibility that the product o-(alkynyl)nitrobenzenes might
undergo a tandem cyclization catalyzed by gold leading to
isatogens/anthranils, as described by Yamamoto et al.13 As
expected, the coupling of 2- nitrobenzenediazonium tetrafluro-
borate 4 with phenylacetylene gave the anthranil 5 in 29%
yield accompanied by a somewhat polar (TLC) product 6
(33%); however, no trace of the isatogen 7 could be detected in
the crude reaction mixture (Scheme 2). The structure of 6 was
confirmed by X-ray crystal structure determination (see ESIw).z
The utility of our Pd–Au dual catalytic system is further
illustrated by the flexibility of being able to start with an
aniline substrate and employ an in situ diazonium formation
step. As can be seen from Table 3, the cross-coupled products
were isolated in moderate to good yield. Here again the
efficacy of the conditions given in entry 10 (Table 1) over
the one in entry 5 (Table 1) is apparent on examination of the
yields of products formed under both conditions (entries 1,2,6,
The synthetic efficacy of this reaction was studied with a range
of arenediazonium salts and the acetylenes, which produced the
Sonogashira coupled products (Table 2). As can be seen, both
electron-neutral and electron-rich arenediazonium salts couple
Table 2 Dual catalytic cross-coupling of arenediazonium salts
ꢁ
Entry ArN2+BF4
Product
Yield (%)a
1
2
80
80
3
4
78
62
5
6
7
71b
59
54
8
75
9
76
78
72
10
11
12
13
51
70
14
15
64 (38)c
61 (32)b,c
a
b
Isolated yield. Replacement of AuCl by CuI yielded no trace
c
(TLC) of the desired products. Yields in parentheses refer to those
obtained under conditions given in entry 5, Table 1.
Scheme
2
Tandem reactions of 2-nitrobenzenediazonium
tetrafluoroborate.
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Table 3 In situ aniline Sonogashira coupling
the preformed gold acetylide 8 (1 mol%) was used as a gold
catalyst to give the product in 58% isolated yield.
In conclusion, we have reported for the first time the
Sonogashira coupling of arenediazonium salts. The scope and
limitation of the new methodology as well as the unravelling of
its detailed mechanistic pathway is currently underway in this
laboratory.
This work was supported by DST and CSIR, Government
of India.
Entry
Ar-
Product
Yield (%)a
62 (50)b
1
2
Notes and references
64 (51)b
z Crystal data of compound 6: C14H8N2O4, Mr = 268.22, T = 293 K,
monoclinic, space group I 2/a, a = 13.0640(10), b = 12.9928(10), c =
14.0524(11) A, V = 2375.2(3) A3, Z = 7, Final indices R1 = 0.0552,
wR2 = 0.1114. CCDC 753368.
3
4
61
66
1 For an excellent review on palladium catalyzed cross- coupling
reactions of diazonium salts, see: A. Roglans, A. Pla-Quintana and
M. Moreno-Manas, Chem. Rev., 2006, 106, 4622.
2 M. Dai, B. Liang, C. Wang, J. Chen and Z. Yang, Org. Lett., 2004,
6, 221.
3 K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett.,
1975, 16, 4467.
4 For recent reviews on Sonogashira reaction, see: (a) R. Chinchilla
and C. Najera, Chem. Rev., 2007, 107, 874; (b) H. Doucet and
J. C. Hierso, Angew. Chem., Int. Ed., 2007, 46, 834; (c) H. Plenio,
Angew. Chem., Int. Ed., 2008, 47, 6954.
5 (a) M. Carril, A. Correa and C. Bolm, Angew. Chem., Int. Ed.,
2008, 47, 4862; (b) C. Torborg, J. Huang, T. Schulz, B. Schaffner,
A. Zapf, A. Spannenberg, A. Borner and M. Beller, Chem.–Eur. J.,
2009, 15, 1329 and references cited therein.
5
6
66
67 (48)b
7
56 (46)b
a
b
Isolated yield. Yields in parentheses refer to those obtained under
conditions given in entry 5, Table 1.
6 A. D. Finke, E. C. Elleby, M. J. Boyd, H. Weissman and
J. S. Moore, J. Org. Chem., 2009, 74, 8897 and references cited
therein.
and 7, Table 3). Furthermore, no trace of Hay/Glaser type
homocoupling of alkynes could be observed (TLC) in any of
the reactions described in Table 2 and 3.
On the basis of our previous work in a related area,7a it may
be assumed that gold acetylides are intermediates here which
enter into Pd catalytic cycle. This conjecture is supported by a
simple experiment (Scheme 3) wherein the coupling of 1 was
carried out as usual (cf. entry 3, Table 2), but instead of AuCl
7 For recent work dealing with Au/Pd dual catalytic system with
unique reactivity, see: (a) B. Panda and T. K. Sarkar, Tetrahedron
Lett., 2010, 51, 301; (b) A. S. K. Hashmi, C. Lothschutz, R. Dopp,
M. Rudolph, T. D. Ramamurthi and F. Rominger, Angew. Chem.,
Int. Ed., 2009, 48, 8243; (c) Y. Shi, K. E. Roth, S. D. Ramgren and
S. A. Blum, J. Am. Chem. Soc., 2009, 131, 18022 and references
cited therein.
8 For a recent review on gold-catalyzed transformations, see:
D. J. Gorin, B. D. Sherry and F. D. Toste, Chem. Rev., 2008,
108, 3351.
9 H. C. Shen, Tetrahedron, 2008, 64, 7847.
10 G. Zou, J. Zhu and J. Tang, Tetrahedron Lett., 2003, 44, 8709 and
references cited therein.
11 (a) F. X. Felpin, E. Fouquet and C. Zakri, Adv. Synth. Catal.,
2008, 350, 2559; (b) J. T. Kuethe and K. G. Childers, Adv. Synth.
Catal., 2008, 350, 1577 and references cited therein.
12 S. Sengupta and S. K. Sadhukhan, Tetrahedron Lett., 1998, 39,
715.
Scheme 3 Sonogashira coupling using preformed gold acetylide as
13 N. Asao, K. Sato and Y. Yamamoto, Tetrahedron Lett., 2003, 44,
5675.
catalyst.
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This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 3131–3133 | 3133