10722
J. Am. Chem. Soc. 2000, 122, 10722-10723
Incorporation of N2 and CO into Organic Molecules:
Amide Formation by Palladium-Catalyzed
Carbonylation and Nitrogenation
Scheme 1. Plan for Synthesis of Amide
Kazutaka Ueda, Yoshihiro Sato, and Miwako Mori*
Scheme 2. Reaction of 1a, CO, and Titanium-Nitrogen
Complexes
Graduate School of Pharmaceutical Sciences
Hokkaido UniVersity, Sapporo 060-0812, Japan
ReceiVed July 24, 2000
1
Nitrogen fixation is a very interesting process. NH
3
has been
used as a nitrogen source in various fields, and it has been
synthesized from N and H under conditions of high pressure
2
2
and high temperature using a transition metal catalyst. We have
developed a novel nitrogen fixation method under very mild
conditions (1 atm pressure at room temperature) using a Li-
2
TiX
4
-TMSCl system. Recently, we developed a novel method
for synthesizing nonsubstituted anilines from aryl halides and
titanium-nitrogen complexes using a palladium catalyst. It is
3
thought that the reaction proceeds via transmetaltion of nitrogen
from titanium-nitrogen complexes to a palladium complex.
Here we report the synthesis of benzamides from aryl halides,
N
2
, and CO. Our plan is shown in Scheme 1.
To a THF solution of Pd (dba) ‚CHCl (2.5 mol %), DPPF
10 mol %), and NaO Bu (3 equiv) was added a THF solution of
Scheme 3. Conversion of 6a and 7a into 2a
2
3
3
t
(
2
a
titanium-nitrogen complexes (2 equiv), prepared from Ti-
i
4
(O Pr) , Li, TMSCl, and nitrogen (1 atm), and then a THF solution
of aryl halide 1a (1 equiv) was added. The atmosphere of nitrogen
was changed to an atmosphere of carbon monoxide (1 atm), and
the solution was heated at reflux overnight (Scheme 2). After
hydrolysis of the reaction mixture, amide 2a, imide 3a, and nitrile
6
4
N-formylbenzamide 6a or acylamidine 7a was obtained, but
4a were obtained in 4, 1, and 6% yields, respectively, along with
benzimide 3a was not produced. However, there were no
remarkable differences in the combined yields of the products.
Interestingly, in the absence of a base, the total yield of the
products was 87% (Table 2, run 1, condition A). On the other
hand, when propionitrile was used as the solvent in the absence
of NaO Bu, only a low yield of the desired products was obtained
Table 1, run 9). In this case, NaO Bu might act as a ligand.
Compound 6a or 7a was treated with K CO in MeOH to give
amide 2a in good yield. This indicates that the reaction of an
aryl halide with titanium-nitrogen complexes under carbon
monoxide (1 atm) in the presence of a palladium catalyst gives
amide 2a and nitrile 4a in high yields (Scheme 3).
Various aryl bromides were treated in a similar manner, and
the corresponding products were obtained in good to high yields
aniline derivative 5a in 16% yield (Table 1, run 1). Although the
combined yields of the products obtained by the carbonylation-
nitrogenation process were low (11% yield), gaseous CO and N
2
could be introduced directly into aryl halide under mild conditions.
To try to increase the yield of the desired products, the reaction
t
5
was carried out under various conditions (Table 1). As a solvent,
t
7
(
DMF gave good results, and amide 2a, imide 3a, and N-
formylbenzamide 6a were obtained in 24, 11, and 26% yields,
respectively (run 4). Propionitrile could also used (run 5).
When BINAP was used as a ligand, nitrile 4a was obtained as
2
3
the main product (runs 6 and 7). The use of Pd(OAc)
less efficient (run 8).
2 3
-PPh was
Subsequently, we chose DMF as the solvent, and the base was
t
changed from NaO Bu to a weak base, such as Li
2
CO
3 2 3
, K CO ,
8
i
(Table 2). Both the electron-donating and electron-withdrawing
2 3 3 2 3
Cs CO , NaHCO , Pr NEt, or NEt . In each case, amide 2a,
groups on the aromatic ring can be used.
(
1) (a) Hidai, M.; Mizobe, Y. Chem. ReV. 1995, 95, 1115. (b) Vol’pin, M.
The reaction is presumed to proceed by transmetalation of
nitrogen from titanium-nitrogen complexes to acylpalladium
complex 8 (Figure 1), because the reaction proceeded in the
absence of a base. Then 9 is converted into amide-titanium
E.; Shur, V. B. Dokl. Akad. Nauk SSSR 1964, 156, 1102. (c) Vol’pin, M. E.;
Ilatovskaya, M. A.; Kosyakova, L. V.; Shur, V. B. J. Chem. Soc., Chem.
Commun. 1968, 1074. (d) van Tamelen, E. E.; Seeley, D.; Schneller, S.; Rudler,
H.; Cretney, W. J. Am. Chem. Soc. 1970, 92, 5251. (e) van Tamelen, E. E.
Acc. Chem. Res. 1970, 3, 361. (f) Yamamoto, A.; Ookawa, M.; Ikeda, S. J.
Chem. Soc., Chem. Commun. 1969, 841. (g) Shiina, K. J. Am. Chem. Soc.
(6) Compound 7a would be formed from acylpalladium complex 8,
titanium-nitrogen complex and DMF as shown in Figure 1. The structure of
7a was determined by X-ray crystallography.
1
972, 94, 9266. (h) Mori, M.; Uozumi, Y.; Shibasaki, M.; Tetrahedron Lett.
987, 28, 6187. (i) Uozumi, Y.; Kawasaki, N.; Mori, E.; Mori, M.; Shibasaki,
1
M. J. Am. Chem. Soc. 1989, 111, 3725. (j) Uozumi, Y.; Mori, M.; Shibasaki,
M. J. Chem. Soc., Chem. Commun. 1991, 81.
(7) (a) Mann, G.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 13109. (b)
Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144.
(
2) (a) Kawaguchi, M.; Hamaoka, S.; Mori, M. Tetrahedron Lett. 1993,
(8) Typical procedure for carbonylation-nitrogenation: A solution of Ti-
i
3
4, 6907. (b) Hori, M.; Mori, M. J. Org. Chem., 1995, 60, 1480. (c) Mori,
(O Pr)
4
(0.3 mL, 1 mmol), Li (69.8 mg), and TMSCl (1.27 mL, 10 mmol) in
M.; Hori, K.; Akashi, M.; Hori, M.; Sato, Y.; Nishida M. Angew. Chem., Int.
Ed. 1998, 37, 636.
THF (15 mL) was stirred under nitrogen (1 atm) at room temperature overnight.
To this solution was added DMF (5 mL), and then the excess amount of
TMSCl was removed upon heating with THF. To this DMF solution was
(
(
3) Hori, K.; Mori, M. J. Am. Chem. Soc. 1998, 120, 7651.
4) Synthesis of nitrile from benzoyl chloride and N has been reported.
2
2 3 3
added Pd (dba) ‚CHCl (12.9 mg, 0.0125 mmol) and DPPF (28.8 mg, 0.05
van Tamelen, E. E.; Rudler, H. J. Am. Chem. Soc. 1970, 92, 5253.
mmol) and then a solution of aryl halide 1a (100 mg, 0.5 mmol) in DMF (5
mL), and then the nitrogen atmosphere was changed to a carbon monoxide
atmosphere (1 atm). The solution was warmed at 90 °C for 14 h. After
hydrolysis of the reaction mixture, 2a (12 mg, 14%), 4a (20 mg, 27%), 6a
(5 mg, 5%), and 7a (45 mg, 41%) were obtained.
(
5) Titanium-nitrogen complexes were prepared in THF. If it is desirable
that the solvent be changed from THF to another solvent, an appropriate solvent
is added to the THF solution of titanium-nitrogen complexes, and THF is
removed upon heating.
1
0.1021/ja002707r CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/14/2000
Ueda
