An atom-efficient palladium-catalyzed cross-coupling reaction of triarylbismuths with acid chlorides: synthesis of diaryl and alkyl aryl ketones

Article abstract of DOI:10.1016/j.tetlet.2006.07.129

The cross-coupling reaction of triarylbismuths with acid chlorides using a catalytic amount of PdCl₂/PPh₃ afforded the corresponding ketones in high yields. The reactions of aromatic and aliphatic acid chlorides occurred with atom efficiency, as 3 equiv of acid chlorides coupled effectively with 1 equiv of triarylbismuths to yield 3 equiv of the corresponding diaryl and alkyl aryl ketones.

Full text of DOI:10.1016/j.tetlet.2006.07.129

Tetrahedron Letters 47 (2006) 6975–6978
An atom-efficient palladium-catalyzed cross-coupling reaction
of triarylbismuths with acid chlorides: synthesis of diaryl and
alkyl aryl ketones
*
Maddali L. N. Rao, Varadhachari Venkatesh and Deepak N. Jadhav
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
Received 14 June 2006; revised 18 July 2006; accepted 25 July 2006
Available online 14 August 2006
2 3
Abstract—The cross-coupling reaction of triarylbismuths with acid chlorides using a catalytic amount of PdCl /PPh afforded the
corresponding ketones in high yields. The reactions of aromatic and aliphatic acid chlorides occurred with atom efficiency, as 3 equiv
of acid chlorides coupled effectively with 1 equiv of triarylbismuths to yield 3 equiv of the corresponding diaryl and alkyl aryl
ketones.
ꢀ
2006 Elsevier Ltd. All rights reserved.
Metal-catalyzed cross-coupling reactions of acid
chlorides with organometallic reagents is an efficient
methodology for the synthesis of ketones. Ketones
can be used effectively for C–C bond formation. Recent
efforts in this direction have led to the development of
new organobismuth compounds for C–C bond forma-
1
5
represent a distinct class of organic compounds, and
are important building blocks in organic synthesis.
The traditional method for the synthesis of aromatic
ketones involves Friedel–Crafts acylation in the pres-
tion under palladium-catalyzed conditions. In particu-
lar, the use of triarylbismuths for C–C bond formation
would be atom efficient, as 3 equiv of electrophilic part-
ners can be used for the cross-coupling reaction. Barton
2
ence of Lewis acids, which is limited by problems asso-
et al. reported the cross-coupling reaction of BiPh with
3
6
ciated with regioselectivity. In this respect, the cross-
coupling reactions of acyl chlorides with organometallic
reagents provide flexibility for improving regioselectiv-
benzoyl chloride under palladium-catalyzed conditions.
Subsequently, no effort has been made in this direction
to expand the scope of this reaction. In this letter, we
1
ity. Thus, several metal-catalyzed cross-coupling reac-
a
Table 1. Screening of the reaction of benzoyl chloride with BiPh
3
tions of acid chlorides with organoboron, organotin,
organozinc reagents, etc. have been reported for the
O
O
3
synthesis of ketones. Although efficient, some of these
cat.PdCl2 / PPh3
Cl
methods suffer from disadvantages such as toxicity of
the organometallic reagents and harsh reaction condi-
3
3
+
BiPh3
base, 80 oC, solvent
3
b
tions. Further, the low atom efficiency that necessarily
Entry
Solvent
Base (equiv.)
KOAc (4)
Time (h)
Conv. (%)
results due to the use of stoichiometric amounts of the
1
2
3
4
5
6
7
1,4-Dioxane
1,4-Dioxane
THF
CH CN
3
DMA
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
3
3
3
3
3
3
3
4
10
61
67
69
5
90
88
95
organometallic reagent is an added drawback.3
K
2
K
2
K
2
CO
CO
CO
3
3
3
(4)
(4)
(4)
The utility of organobismuth compounds under transi-
tion metal-catalyzed conditions has not been explored
K CO (4)
2
3
4
in detail for C–C bond formation. Organobismuth
NEt
NEt
NEt
3
3
3
(4)
(1)
(1)
compounds are generally low or non-toxic, and hence
c
8
a
Equivalent ratios with respect to BiPh
PPh (0.2 equiv), PhCOCl (5.0 equiv).
Based on GC analysis.
3 2
(1 equiv): PdCl (0.1 equiv)/
Keywords: Cross-coupling; Triarylbismuths; Acid chlorides; Diaryl
ketones; Alkyl aryl ketones; Palladium catalyzed.
3
b
c
*
Corresponding author. Tel./fax: +91 512 2597532; e-mail: maddali@
iitk.ac.in
Equivalent ratios with respect to BiPh (1 equiv): PdCl (0.09 equiv)/
3
2
PPh
3
(0.18 equiv), PhCOCl ( 3.3 equiv).
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.129

6976
M. L. N. Rao et al. / Tetrahedron Letters 47 (2006) 6975–6978
a,b,c
Table 2. Cross-coupling reaction of triarylbismuths with acid chlorides
Entry
BiAr
3
Acid chloride
Ketone
Yield (%)
O
O
1
2
3
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
R = –H
R = –CH
3
R = –OCH
93
92
76
Cl
3
R
3
3
O
O
O
4
5
6
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
Cl
Br
R = –H
R = –CH
3
R = –OCH
89
78
66
Cl
3
Cl
Br
R
R
3
3
3
O
7
8
9
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
R = –H
R = –CH
3
R = –OCH
87
86
63
Cl
3
3
O
O
1
1
1
0
1
2
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
F
R = –H
R = –CH
3
R = –OCH
89
89
61
Cl
3
F
R
3
3
3
O
O
13
14
15
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
MeO
R = –H
R = –CH
3
R = –OCH
76
75
48
Cl
3
MeO
R
3
O
O
1
1
1
6
7
8
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
Me
R = –H
R = –CH
3
R = –OCH
90
86
66
Cl
3
Me
Me
R
3
3
3
3
3
3
3
3
3
3
O
O
19
20
21
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
R = –H
R = –CH
3
R = –OCH
79
90
68
Cl
3
Me
R
O
O
MeO
22
23
24
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
R = –H
R = –CH
3
R = –OCH
86
90
71
Cl
3
MeO
R
O
COCl
25
26
27
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
R = –H
R = –CH
3
R = –OCH
92
94
81
3
R
O
28
29
30
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
O
R = –H
R = –CH
3
R = –OCH
66
73
66
3
Cl
R
Me
O
O
O
O
3
3
1
2
BiPh
Bi(p-tolyl)
3
R = –H
R = –CH
65
40
Cl
3
3
Me
OMe
Cl
R
R
R
OMe
O
3
3
4
BiPh
3
3
R = –H
27
64
Cl
Cl
O
3
BiPh
R = –H
Cl
O
35
36
37
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
3
CH COCl
Me
R = –H
R = –CH
3
R = –OCH
82
85
61
3
R
3
3

M. L. N. Rao et al. / Tetrahedron Letters 47 (2006) 6975–6978
6977
Table 2 (continued)
Entry
BiAr
3
3
Acid chloride
Ketone
Yield (%)
O
38
39
40
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
CH
3
2
CH COCl
R = –H
R = –CH
3
R = –OCH
78
88
69
Et
3
3
R
3
O
O
41
42
43
BiPh
Bi(p-tolyl)
Bi(p-anisyl)
3
R = –H
R = –CH
R = –OCH
95
90
76
Cl
3
3
R
3
3
a
b
c
Conditions for aromatic acid chlorides. Equivalent ratios with respect to BiAr
0.18 equiv), Et N (1 equiv), 1,4-dioxane (3 mL), 80 ꢁC, 4 h.
Conditions for aliphatic acid chlorides. Equivalent ratios with respect to BiAr
0.30 equiv), Et N (5 equiv), 1,4 dioxane (3 mL), 80 ꢁC, 4 h.
Isolated yields obtained after column chromatography. All the products were characterized by H, C NMR, IR and mass spectral analysis.
3
: acid chloride (3.3 equiv), BiAr
3
(1 equiv), PdCl
2
(0.09 equiv)/PPh
3
(
3
3
3 2
: acid chloride (5 equiv), BiAr (1 equiv), PdCl (0.15 equiv)/PPh
3
(
3
1
13
report a general and atom-efficient cross-coupling reac-
tion of a variety of acid chlorides with triarylbismuths
using a catalytic amount of PdCl /PPh for the synthesis
of this cross-coupling reaction. In addition, the cross-cou-
pling reaction of b-naphthoyl chloride with triarylbis-
muths produced the corresponding naphthyl phenyl
ketones in excellent yields (entries 25–27). In contrast,
the reaction of a-naphthoyl chloride led to a moderate
yield of the corresponding ketones (entries 28–30). In a
similar manner, the cross-coupling reaction of sterically
encumbered aromatic acid chlorides containing o-substit-
uents (o-methyl, o-methoxy and o-chloro) led to low to
moderate yields of the corresponding ketones (entries
31–34). This clearly shows that the cross-coupling reac-
tion is influenced to some extent by steric factors.
2
3
of a range of diaryl and alkyl aryl ketones.
Initial experiments using benzoyl chloride (5 equiv) with
BiPh (1 equiv) were carried out with various bases in
3
acetone as the solvent at 65 ꢁC for 3 h in the presence
of PdCl (0.1 equiv)/PPh (0.2 equiv). It was found that
2
3
bases such as Na CO , Cs CO , KF and KOAc were
2
3
2
3
ineffective in providing the corresponding cross-cou-
pling product. To find suitable conditions for efficient
cross-coupling of benzoyl chloride with BiPh , a variety
3
of other bases and solvents were screened (Table 1). As
can be seen from Table 1, the cross-coupling reaction of
Further, the cross-coupling of aliphatic acid chlorides
with triarylbismuths under the conditions employed
above led to low yields of the corresponding ketones
benzoyl chloride with BiPh was found to be inefficient
3
with KOAc as base in 1,4-dioxane solvent (entry 1).
However, an increase in the cross-coupling reactivity
was observed with K CO under similar conditions
(30–40%). However, when the acid chloride and Et N
3
were employed in 5 M equiv with respect to BiAr along
3
with PdCl2 (0.15 equiv)/PPh3 (0.30 equiv), the corre-
sponding ketones were formed in high yields (entries
35–43). As shown in Table 2, both acetyl chloride and
propionoyl chloride yielded the corresponding acetoph-
enone and propiophenone in high yields (entries 35–40).
The cross-coupling reaction of cyclohexane carbonyl
chloride was also found to be efficient with triarylbis-
muths (entries 41–43).
2
3
(
entry 2). Further screening with K CO in different
2 3
solvents such as THF and CH CN led to moderate
3
conversions (entries 3 and 4), while DMA proved to
be unsuitable as the solvent (entry 5). However, a
dramatic increase in the conversion was observed in
1
,4-dioxane in the presence of Et N as base (entry 6).
3
It was established from further experiments that 1 equiv
of Et N in the presence of PdCl (0.09 equiv) and PPh
3
3
2
(
0.18 equiv) in 1,4-dioxane at 80 ꢁC led to 95% conver-
In conclusion, we have disclosed a Pd-catalyzed cross-
coupling reaction of acid chlorides with triarylbismuths
for the synthesis of a variety of diaryl and alkyl aryl
sion in 4 h with 3.3 equiv of benzoyl chloride (entry 8).
7
At this stage, we chose BiPh , Bi(p-tolyl) and Bi(p-ani-
ketones. The use of 3 equiv of acid chlorides with
3
3
syl) as representative triarylbismuths to investigate the
1 equiv of triarylbismuth constitutes an atom-efficient
process in addition to the fact that the catalytic system,
that is, PdCl /PPh employed is inexpensive and readily
accessible. The high cross-coupling reactivity of different
triarylbismuths with no perceptible differences in terms
of the isolated yields of the corresponding ketones
underscores the broad utility of this protocol for the
syntheses of diaryl and alkyl aryl ketones.
3
cross-coupling reactions further with a number of acid
chlorides under the conditions established above. The
results are summarized in Table 2. The cross-coupling
of a variety of para-functionalized aromatic acid chlorides
2
3
(
p-fluoro, p-chloro, p-bromo, p-methyl and p-methoxy)
proceeded effeciently with all the three triarylbismuths
to give excellent yields ofthe corresponding diaryl ketones
(
entries 1–18). Similarly, m-methyl and m-methoxy
substituted aromatic acid chlorides also produced high
yields of the diaryl ketones (entries 19–24). Thus, the
results observed with various functionalized aromatic
acid chlorides and triarylbismuths show that the elec-
tronic factors intrinsic to the acid chlorides as well as
the triarylbismuths play little or no role in the outcome
Acknowledgements
The authors thank DST and IITK for financial support.
V.V. and D.N.J. thank UGC, India, and CSIR, India,
respectively, for research fellowships.

6
978
M. L. N. Rao et al. / Tetrahedron Letters 47 (2006) 6975–6978
Chem. 2002, 659, 117; (d) Venkatraman, S.; Li, C. J.
References and notes
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.11 g), PdCl
2
(0.023 mmol, 0.004 g), PPh
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(0.045 mmol,
2
0
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3
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ethyl acetate extract was washed with dilute HCl (5 mL),
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3
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4
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(
4
2 · 5 mL) and dried over MgSO . The crude product
mixture thus obtained after removing the solvent was
subjected to column chromatography and pure benzophe-
none was isolated in 93% yield. The product was charac-
terized by H, C NMR, IR and mass spectral analysis.
For aliphatic acid chlorides, the same procedure was
followed, but with the following conditions: RCOCl
1
13
5
(
(
Et
1.25 mmol, 5 equiv), BiPh
0.0375 mmol, 0.15 equiv), PPh
N (1.25 mmol, 5 equiv), 1,4-dioxane (3 mL), 80 ꢁC, 4 h.
3
(0.25 mmol, 1 equiv), PdCl
2
3
(0.075 mmol, 0.30 equiv),
3