Pd(0)/C-catalyzed cross-couplings of acyl chlorides with triarylbismuths as atom-efficient sub-stoichiometric multi-coupling reagents

Article abstract of DOI:10.1016/j.tetlet.2009.05.003

Aromatic and hetero-aromatic acyl chlorides were efficiently cross-coupled with triarylbismuths as atom-efficient nucleophilic organometallic coupling reagents in sub-stoichiometric amounts using catalytic Pd(0)/C. Thus, the coupling reactions of various triarylbismuths with a variety of acyl chlorides furnished a plethora of both symmetrical/unsymmetrical aromatic and hetero-aromatic ketones in high yields.

Full text of DOI:10.1016/j.tetlet.2009.05.003

Tetrahedron Letters 50 (2009) 4268–4271
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Pd(0)/C-catalyzed cross-couplings of acyl chlorides with triarylbismuths
as atom-efficient sub-stoichiometric multi-coupling reagents
*
Maddali L. N. Rao , Deepak N. Jadhav, Varadhachari Venkatesh
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Aromatic and hetero-aromatic acyl chlorides were efficiently cross-coupled with triarylbismuths as
atom-efficient nucleophilic organometallic coupling reagents in sub-stoichiometric amounts using cata-
lytic Pd(0)/C. Thus, the coupling reactions of various triarylbismuths with a variety of acyl chlorides fur-
nished a plethora of both symmetrical/unsymmetrical aromatic and hetero-aromatic ketones in high
yields.
Received 29 March 2009
Revised 30 April 2009
Accepted 4 May 2009
Available online 8 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Triarylbismuths
Palladium
Coupling
Acid chlorides
Ketones
Sub-stoichiometric
Organometallic coupling reactions such as the Suzuki, Negishi,
and Stille have enriched the art of organic synthesis in recent times.1
This has attracted the attention to develop various palladium-cata-
lyzed protocols using organo-boron, -zinc, -tin, and other organome-
tallic reagents.1,2 In general, palladium catalytic protocols often
utilize palladium pre-catalysts in combination with a variety of
phosphine ligands.2 While the use of Pd(0)/C as catalyst with or
without phosphines is still limited for coupling reactions,3 utility
of Pd(0)/C in catalytic hydrogenations is well known in organic syn-
thesis. Thus, there is a wide scope for the development of new proto-
cols using Pd(0)/C.3–6 The importance of Pd(0)/C stems from the fact
that this catalytic system is heterogeneous in nature, can be easily
separated from product, which is cheap and easily available.3
Synthesis of aromatic ketones using cross-coupling methodol-
ogy outweighs the traditional Friedel–Crafts acylation,7 as this ap-
proach facilitates the synthesis of isomeric ketones in a facile
manner. Further, use of higher amounts of Lewis acid is another
inevitable draw back associated with Friedel–Crafts method. On
the other hand, coupling reactions of acyl chlorides with 1 equiv
of aryl-boron, -zinc, or -tin are useful for the synthesis of ketones
under metal-catalyzed conditions.8,9 Notably in this context, tria-
rylbismuths as atom-efficient, sub-stoichiometric, and multi-cou-
pling reagents provides an additional coupling opportunity with
its three aryl groups under metal-catalyzed conditions.10a Thus, if
all the three aryl groups react, sub-stoichiometric amount
(ꢀ0.33 equiv) of triarylbismuth is enough to cross-couple with
1 equiv of acyl chloride to obtain 1 equiv of the corresponding ke-
tone stoichiometrically. This advantage of triarylbismuths will
have direct bearing in large-scale preparations involving such cou-
pling reactions. As known, triarylbismuths are non-toxic, stable,
and can be easily prepared using standard methods.11a Our recent
interest to develop triarylbismuths as an atom-efficient, sub-stoi-
chiometric, and multi-coupling organometallic reagents unraveled
new efficient cross-coupling reactivity of these reagents under pal-
ladium catalysis in short reaction times.10 In continuation, we re-
port herein, the Pd(0)/C-catalyzed coupling reaction of acyl
chlorides with sub-stoichiometric amounts of triarylbismuths for
atom-efficient synthesis of ketones.
The catalytic activity of Pd(0)/C was studied with triphenylbis-
muth and benzoyl chloride as a model coupling reaction (Table 1).
The coupling was carried out with Pd(0)/C (0.003 equiv) and PPh3
(0.075 equiv) in the presence of triethylamine (0.3 equiv) at 80 °C
for 3 h in tetrahydrofuran solvent. Significantly, the reaction fur-
nished 69% cross-coupling conversion and 51% isolated yield of
cross-coupled product, benzophenone (entry 1). Encouraged by
this, the reactivity of Pd(0)/C was further studied with different
catalytic loadings. These combinations provided good to moderate
conversions (entries 2–4). Importantly, the coupling reaction car-
ried out without triphenylphosphine provided very poor conver-
sion (entry 5). With the additional screening carried out in
different solvents, it was found that 1,4-dioxane, toluene,
1,2-dimethoxyethane, and acetonitrile are not suitable for this
reaction (entries 6–9).
* Corresponding author. Tel./fax: +91 512 259 7532.
E-mail address: maddali@iitk.ac.in (M.L.N. Rao).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.003

M. L. N. Rao et al. / Tetrahedron Letters 50 (2009) 4268–4271
4269
Table 1
Table 2
Screening conditionsa–c
Cross-coupling of different triarylbismuths with benzoyl chloride13,14
O
O
Cat. Pd/C,
Cat. PPh3
Bi
10% Pd/C (0.009 equiv Pd)
PPh3 (0.036 equiv)
O
+
O
Cl
BiAr3
( 0.3 equiv )
+
Ar
Base, solvent,
80oC, 3 h
3
Cl
Et3N (0.3 equiv), THF
80 oC, 3 h
(0.3 equiv)
Entry
Catalyst (equiv)
Ligand (equiv)
NEt3 (equiv)
Solvent
Conv (%)
Entry
Ar (BiAr3)
Ketone
Yielda–c (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0.003
0.003
0.015
0.003
0.003
0.003
0.003
0.003
0.003
0.006
0.009
0.009
None
0.009
0.075
0.012
0.06
0.3
THF
THF
THF
THF
69 (51)
73
66
44
04
25
6
5
None
None
None
0.3
None
None
None
None
None
None
None
None
0.3
O
0.006
None
0.012
0.012
0.012
0.012
0.024
0.036
0.036
0.036
0.036
1
2
THF
90
(1)
(2)
Dioxane
Toluene
DME
MeCN
THF
THF
THF
THF
THF
O
1
88 (82)
89 (86)
42 (41)d
6
89
85
95
85
71
75
Me
Me
O
91 (90)
3
a
Conditions: PhCOCl (1 equiv), BiPh3 (0.303 equiv), solvent (3 mL).
(3)
(4)
(5)
(6)
(7)
b Conversions are based on GC analysis of the crude reaction mixture. Isolated yield
based on benzoyl chloride given in parentheses.
MeO
F
OMe
c
Homo-coupling biphenyl from triarylbismuths formed as side product.
Reaction carried out at 60 °C.
O
d
4
F
Further, catalyst Pd(0)/C loading up to 0.009 equiv provided
increased conversion along with 86% of isolated ketone (entries
10 and 11). Lowering the temperature to 60 °C produced inferior
conversion to ketone (entry 12). A control carried out without
Pd(0)/C did not produce appreciable amount of ketone (entry
13). Importantly, we have also observed some inconsistency in
yields when reactions were carried out without triethylamine.
So, we further studied the reaction in presence of triethylamine
and obtained ketone upto 90% isolated yield (entry 14). Hence,
we decided to utilize acyl chloride (1 equiv), BiAr3 (0.303 equiv),
Pd/C (0.009 equiv), PPh3 (0.036 equiv), and NEt3 (0.30 equiv) in
THF at 80 °C for our further studies with different triarylbismuths
and acyl chlorides.
The new efficient protocol thus obtained above with Pd(0)/C
was studied further for elaboration with different triarylbismuths
and acyl chlorides.12 Firstly, efforts were made to establish cross-
coupling ability of various electronically diverse triarylbismuths
and heteroarylbismuths with benzoyl chloride. The various func-
tionalized triarylbismuths with both electron-rich and -deficient
aryl groups substituted with -methyl, -methoxy, -fluoro, -chloro,
-formyl, and -acetyl groups were studied with benzoyl chloride
as given in Table 2. This study revealed an efficient cross-coupling
reactivity of various triarylbismuths to give high yield of ketones
with benzoyl chloride. (entries 1–9). The coupling reactivity of tri-
thiophen-2-ylbismuth was efficient with benzoyl chloride and fur-
nished the corresponding mixed ketone in good yield (entry 10).
Further, it also clearly establishes the atom-efficient and multi-
coupling reactivity of triarylbismuths, as we have used only
0.3 equiv of triarylbismuth for cross-coupling reaction with 1 equiv
of acyl chloride in all these reactions.
O
5
Cl
Cl
O
6
OHC
CHO
O
7
MeOC
Me
COMe
O
Me
8
87
81
(8)
(9)
O
9
MeO
S
OMe
O
S
10
76
(10)
a Conditions: PhCOCl (0.825 mmol, 1.0 equiv), BiPh3 (0.25 mmol, 0.303 equiv), NEt3
(0.25 mmol, 0.30 equiv), 10% Pd/C (0.0075 mmol, 0.009 equiv Pd), PPh3 (0.03 mmol,
0.036 equiv), THF (3 mL), 80 °C, 3 h.
b
Isolated yields are reported based on acyl chlorides used. All products were
characterized by 1H NMR, 13C NMR, IR, and in comparison with literature data.
c
The striking atom-efficient and multi-coupling reactivity ob-
served with different triarylbismuths under Pd(0)/C catalysis
prompted our further study with a variety of divergent aryl and
heteroaryl acyl chlorides (Table 3). From this, the Pd(0)/C-based
protocol proved to be efficient to couple a variety of functionalized
electron-rich and-deficient acyl chlorides with different triarylbis-
muths. Thus, benzoyl chlorides with 4-methyl and 4-methoxy
groups reacted efficiently furnishing high yields of the ketones
with different triarylbismuths (compounds 11–16). Additionally,
5–10% Homo-coupling bi aryls from triarylbismuths formed.
benzoyl chlorides substituted with 3-methyl and 3-methoxy
groups also produced corresponding isomeric ketones in good
yields (compounds 17–22). The 4-nitrobenzoyl chloride rendered
moderate coupling reactivity due to strong electron-withdrawing
nature of the nitro group (compounds 23–25). The cross-coupling
reactivity of both 1- and 2-naphthoyl chlorides was found to be

4270
M. L. N. Rao et al. / Tetrahedron Letters 50 (2009) 4268–4271
Table 3
Cross-coupling of triarylbismuths with aromatic acyl chlorides13,14
O
10% Pd/C (0.009 equiv Pd)
PPh3 (0.036 equiv)
O
Bi
+
Cl
R'
R
Et3N (0.3 equiv), THF
80 oC, 3 h
R'
R
3
(0.3 equiv )
O
O
O
OMe
90%
66%
58%
52%
50%
74%
83%
71%
90%
83%
85%
87%
88%
86%
92%
94%
83%
84%
86%
83%
80%
72%
79%
Me
Me
Me
Br
MeO
MeO
(33)
(11)
(22)
O
O
O
87%
86%
73%
74%
76%
83%
80%
80%
63%
60%
Me
NO2
MeO
Br
(23)
(34)
(12)
O
O
O
MeO
Me
Cl
NO2
(24)
(35)
(13)
O
O
O
Me
NO2
OMe
Me
Cl
(14)
(36)
(25)
O
O
O
Me
OMe
MeO
Cl
(37)
(26)
(15)
O
O
O
O
MeO
OMe
Me
(16)
(38)
(27)
O
O
O
Me
O
Me
MeO
(39)
(17)
(28)
O
O
O
Me
O
MeO
Me
(18)
(29)
(40)
O
O
O
Me
S
MeO
Me
(30)
(41)
(19)
O
O
O
OMe
S
MeO
H3C
(31)
(20)
(42)
O
O
O
OMe
S
MeO
Br
Me
(32)
(21)
(43)
Note: (a) Conditions: ArCOCl (0.825 mmol, 1.0 equiv), BiAr3 (0.25 mmol, 0.303 equiv), NEt3 (0.25 mmol, 0.30 equiv), 10% Pd/C (0.0075 mmol, 0.009 equiv Pd), PPh3
(0.03 mmol, 0.036 equiv), THF (3 mL), 80 °C, 3 h. (b) Isolated yields are reported based on acyl chlorides used. (c) All products were characterized by 1H NMR, 13C NMR, IR, and
in comparison with literature data. (d) In general, ꢀ5–10% of homo-coupling bi aryls formed from triarylbismuths. (e) In reactions yielding moderate cross-coupled ketones,
homo-coupling bi aryls from triarylbismuths invariably formed in appreciable amounts.

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4271
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excellent, furnishing high yields of ketones with triarylbismuths
(compounds 26–31). The coupling reactions with 4-bromo and
4-chloro benzoyl chlorides were found to be efficient with che-
mo-selective coupling furnishing the corresponding halo-benz-
ophenones in high yields (compounds 32–37). The couplings of
furan-2-carbonyl chloride and thiophene-2-carbonyl chloride were
efficient with triarylbismuths and produced mixed ketones in good
yields (compounds 38–43).
As described above, the Pd(0)/C-catalyzed coupling of a variety
of acyl chlorides with triarylbismuths provided novel atom-effi-
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matic and hetero-aromatic ketones. This method also proved to
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and chloro benzophenones. The regio-selective synthesis of certain
isomeric ketones (Tables 2 and 3) through cross-coupling demon-
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Thus, we have disclosed Pd(0)/C-catalyzed coupling reaction of
acyl chlorides with triarylbismuths as atom-efficient, sub-stoichi-
ometric, and multi-coupling reagents for the synthesis of aromatic
and hetero-aromatic ketones. The coupling reactions involving tri-
arylbismuths proved to be very efficient and notably involves con-
version of three Bi–C bonds to three C–C bonds in one-pot
operation under Pd(0)/C catalysis.
Acknowledgments
11. (a)Organobismuth Chemistry; Suzuki, H., Matano, Y., Eds.; Elsevier, 2001; (b)
Rao, M. L. N.; Yamazaki, O.; Shimada, S.; Tanaka, T.; Suzuki, Y.; Tanaka, M. Org.
Lett. 2001, 3, 4103–4105.
12. Aromatic acyl chlorides were prepared using the literature procedures: (a)
Chaudhari, S. S.; Akamanchi, K. G. Synlett 1999, 1763–1765; (b) Bessard, Y.;
Crettaz, R. Heterocycles 1999, 51, 2589–2602.
The authors thank the Department of Science and Technology
(DST), New Delhi for financial support of this work. In addition,
D.N.J. thanks CSIR, New Dehi and V.V. thanks UGC, New Delhi for
research fellowships.
13. Representative coupling procedure: An oven-dried Schlenk tube was charged
with PhCOCl (0.825 mmol, 0.116 g), BiPh3 (0.25 mmol, 0.11 g), 10% Pd(0)/C
(0.0075 mmol of Pd, 0.024 g), PPh3 (0.03 mmol, 0.0078 g), and Et3N
(0.25 mmol, 0.025 g) followed by anhydrous THF (3 mL) under nitrogen
atmosphere. The reaction mixture in Schlenk tube was stirred in an oil bath
at 80 °C for 3 h. In the end, the reaction mixture was cooled to room
temperature, quenched with water, and extracted with ethyl acetate
(2Â15 mL). The combined ethyl acetate extract was washed with dilute
hydrochloric acid (5 mL), saturated sodium bicarbonate solution (5 mL), brine
(2Â5 mL), and dried over anhydrous magnesium sulfate and was concentrated
under vacuo to obtain the crude product. The crude product was further
purified on silica gel by column chromatography to afford benzophenone (1)
(0.123 g) in 90% yield based on the amount of based on acyl chlorides used.
14. In all the reactions, 1 equiv of BiPh3 was used with 3.3 equiv of acyl chloride.
15. (a) Gooben, L. J.; Ghosh, K. Angew. Chem., Int. Ed. 2001, 40, 3458–3460; (b)
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