5
272
J . Org. Chem. 2001, 66, 5272-5274
Dou ble Ca r bon yla tion of Ar yl Iod id es w ith
P r im a r y Am in es u n d er Atm osp h er ic
Sch em e 1
P r essu r e Con d ition s Usin g th e P d /P P h
DABCO/THF System
3
/
Yasuhiro Uozumi,* Taro Arii, and Toshihiro Watanabe†
†
Institute for Molecular Science (IMS), Nishi-Gonaka 38,
Myodaiji, Okazaki 444-8585, J apan, and Faculty of
Pharmaceutical Sciences, Nagoya City University,
Mizuho-ku, Nagoya 467-8603, J apan
Sch em e 2
Received April 17, 2001
In tr od u ction
The palladium-catalyzed double carbonylation of aryl
halides to give R-keto acids, esters, and amides has been
1
extensively studied. However, in contrast to the wide-
spread synthetic use of catalytic single carbonylations,2
catalytic double carbonylations are less convenient to
employ.4 One of the major problems associated with
double carbonylations lies in the experimental manipula-
tion where an air-sensitive alkylphosphine ligand and
high-pressure conditions are frequently required to pro-
mote the double carbonylation selectively. A typical
example is shown in Scheme 1. We report herein a new
practical protocol for the palladium-catalyzed double
carbonylation of aryl halides under atmospheric pressure
of carbon monoxide at ambient temperature using tri-
,3
Ta ble 1. P a lla d iu m -Ca ta lyzed Ca r bon yla tion of P h I (1a )
w ith n -Bu NH2a
b
yield (%)
selectivity (%)
entry ligand solvent
base
2a
3a
of 3a
1
2
3
4
5
6
7
8
9
0
PPh3
PPh3
n-Bu3P THF
dppe
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
THF
THF
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
7
21
86
73
92
77
c
d
THF
Et2O
DMF
16
59
51
62
23
15
39
38
18
51
42
<1
48
40
43
23
69
54
<1
5
phenylphosphine as a ligand.
DMSO DABCO
Resu lts a n d Discu ssion
THF
THF
THF
3
Et N
pyridine 36
DBU 72
We have examined several phosphine ligands, solvents,
and bases for the double carbonylation of iodobenzene
1
a
All reactions were carried out at 25 °C for 12 h under 1 atm
3
of CO. The catalyst was generated in situ by mixing [PdCl(η -
C3H5)]2 and a phosphine ligand. The ratio of 1a (mol)/n-BuNH2
(mol)/[Pd] (mol)/ligand (mol)/base (mol)/solvent (L) ) 1.0/3.0/0.03/
0.06/3.0/10. b Isolated yield. c Pd(PPh3)4 (5 mol %) was used. No
reaction.
*
To whom correspondence should be addressed. Fax: (+81)564-
5
5-5245.
†
Nagoya City University.
d
(
1) (a) Ozawa, F.; Soyama, H.; Yamamoto, T.; Yamamoto, A.
Tetrahedron Lett. 1982, 23, 3383. (b) Kobayashi, T.; Tanaka, M. J .
Organomet. Chem. 1982, 233, C64. (c) Ozawa, F.; Yamamoto, T.;
Yamamoto, A. J . Synth. Org. Chem. J pn. 1985, 43, 442. (d) Ozawa,
F.; Sugimoto, T.; Yuasa, Y.; Santra, M.; Yamamoto, T.; Yamamoto, A.
Organometallics 1984, 3, 683. (e) Ozawa, F.; Yanagihara, H.; Yama-
moto, A. J . Org. Chem. 1986, 51, 415. (f) Sakakura, T.; Yamashita,
H.; Kobayashi, T.-A.; Hayashi, T.; Tanaka, M. J . Org. Chem. 1987,
(Scheme 2). Reaction of iodobenzene (1a ) with n-butyl-
amine in the presence of palladium-phosphine com-
plexes and bases under atmospheric pressure of carbon
monoxide at 25 °C for 12 h gave a mixture of N-
butylbenzamide (2a ) and N-butylphenylglyoxamide (3a ).
The selectivity producing the double carbonylation prod-
5
2, 5733. (g) Son, T.-I.; Yanagihara, H.; Ozawa, F.; Yamamoto, A. Bull.
Chem. Soc. J pn. 1988, 61, 1251-1258. (h) Ozawa, F.; Yamagami, I.;
Nakano, M.; Fujiwara, F.; Yamamoto, A. Chem. Lett. 1989, 125. (i)
Urata, H.; Ishii, Y.; Fuchikami, T. Tetrahedron Lett. 1989, 30, 4407.
(
j) Yamamoto, A. Bull. Chem. Soc. J pn. 1995, 68, 433. (k) Lin, Y.-S.;
Yamamoto, A. Organometallics 1998, 17, 3466.
2) For reviews, see: (a) Tsuji, J . Palladium Reagents and Catalysts;
1
uct 3a was determined by H NMR analysis of the crude
mixture, and the benzamide 2a and R-keto amide 3a were
readily isolated by silica gel column chromatography.
Representative results are summarized in Table 1. It was
found that the combination of triphenylphosphine, tet-
rahydrofuran, and 1,4-diazabicyclo[2.2.2]octane (DABCO)
is essential to construct an efficient catalyst system with
much higher selectivity for the double carbonylation
product. Thus, when a mixture of 1a , n-butylamine (3
equiv), and DABCO (3 equiv) was stirred at 25 °C under
1 atm of carbon monoxide for 12 h in the presence of 3
mol % of a palladium catalyst generated in situ by mixing
(
J ohn Wiley and Sons: Chichester, 1995. (b) Heck, R. F. Palladium
Reagents in Organic Synthesis; Academic Press: New York, 1985. (c)
Colquhoun, H. M.; Thompson, D. J .; Twigg, M. V. Carbonylation;
Plenum Press: New York, 1991.
(3) For some examples reported by the author’s group, see: (a) Mori,
M.; Uozumi, Y.; Ban, Y. Tetrahedron Lett. 1985, 26, 5947. (b) Mori,
M.; Uozumi, Y.; Ban, Y. J . Chem. Soc., Chem. Commun. 1986, 7, 841.
(c) Mori, M.; Uozumi, Y.; Ban, Y. Heterocycles 1986, 24, 1257. (d)
Uozumi, Y.; Kawasaki, N.; Mori, E.; Mori, M.; Shibasaki, M. J . Am.
Chem. Soc. 1989, 111, 3725. (e) Suzuki, T.; Uozumi, Y.; Shibasaki, M.
J . Chem. Soc., Chem. Commun. 1991, 1593-1595.
(4) Recent examples, see: (a) Couve-Bonnaire, S.; Carpentier, J .-
F.; Castanet, Y.; Mortreux, A. Tetrahedron Lett. 1999, 40, 3717-3718.
b) Lin, Y.-S.; Alper, H. Angew. Chem., Int. Ed. Engl. 2001, 40, 779-
81.
5) It has been reported that palladium-catalyzed carbonylation of
PhI with HNEt gives N,N-diethyl phenylglyoxamide with high
(
3
3
3 5 2
di(µ-chloro)bis(η -allyl)dipalladium(II) ([PdCl(η -C H )] )
7
(
and triphenylphosphine (P/Pd ) 2/1), the double carbo-
nylation took place with 92% selectivity to give 7% and
2
selectivity under atmospheric pressure conditions in the presence of
copper iodide as a cocatalyst at 50 °C, see: Satoh, T.; Kokubo, K.;
Miura, M.; Nomura, M. Organometallics 1994, 13, 4431.
8
6% isolated yields of 2a and 3a , respectively (Table 1,
entry 1). The selectivity giving the double carbonylation
1
0.1021/jo0156924 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/27/2001