J. Am. Chem. Soc. 1998, 120, 7651-7652
7651
Synthesis of Nonsubstituted Anilines from Molecular
Scheme 1
Nitrogen via Transmetalation of Arylpalladium
Complex with Titanium-Nitrogen Fixation
Complexes
Katsutoshi Hori and Miwako Mori*
Graduate School of Pharmaceutical Sciences
Scheme 2
Hokkaido UniVersity, Sapporo 060-0812, Japan
ReceiVed April 29, 1998
1
Since Migita succeeded in synthesizing disubstituted aniline
derivatives from arylpalladium complex and dialkylstannane, a
method for synthesizing mono- and disubstituted aniline deriva-
tives from aryl halides using palladium catalyst has been
2
established by the ingenious studies of Buchwald and Hartwig.
However, synthesis of nonsubstituted aniline derivatives from
arylpalladium complex was not known because we must use NH
3
for that purpose. These results have stimulated us to synthesize
nonsubstituted aniline derivatives2v,3 by a one-step reaction from
arylpalladium complex and titanium-nitrogen fixation complexes
Table 1. Ligand Effects on Palladium-Catalyzed Amination of
1a
a
yields (%)
4 4
prepared from molecular nitrogen and the TiCl - or Ti(OiPr) -
Li-TMSCl system (Scheme 1).4
run
ligand
solvent
time (h)
3a
6a
If titanium-nitrogen fixation complexes 2 are transmetalated
with ArPdX 4, arylpalladium-nitrogen complex 5 would be
formed, and this should be followed by reductive elimination to
give nonsubstituted aniline derivatives 3 (Scheme 2).
When a THF solution of titanium-nitrogen complexes 2 (2.0
4
equiv), which was prepared from Ti(OiPr) (2.0 equiv), Li (20
1
2
3
4
5
6
7
P(o-tolyl)
3
THF
24
4
44
40
21
23
21
0
32
23
39
30
14
15
0
11
28
4
0
0
P(o-tolyl)3
P(o-tolyl)
toluene
toluene
toluene
toluene
toluene
toluene
3
(S)-BINAP
DPPF
DPPP
(S)-BINAPO
0
equiv), and TMSCl (20 equiv) in THF under an atmosphere of
4
a
nitrogen at room temperature for 8 h, was added to a THF
All reactions were carried out in the presence of 2.5 mol %
solution of Pd
2
(dba)
3
‚CHCl
3
(2.5 mol %), P(o-tolyl)
3
(10 mol %),
2 3
Pd (dba) , 5-10 mol % ligand, 2 equiv of Ti-N complexes, and 2.8
equiv of NaOtBu in toluene at 90 °C.
and NaOtBu (2.8 equiv), and the solution was refluxed overnight,
no nitrogen-containing products were produced and a dehaloge-
nation product was obtained along with the starting material (Table
Scheme 3
1
, run 1). Since it is known that THF is not the best solvent for
2a,b
palladium-catalyzed amination, the solvent was changed from
THF to toluene and the reaction was carried out in a similar
manner. As a result, we obtained 4-aminobiphenyl 3a in 32%
(
1) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927.
2) (a) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem., Int.
(
Ed. Engl. 1995, 34, 1348. (b) Louie, J.; Hartwig, J. F. Tetrahedron Lett. 1995,
6, 3609. (c) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117,
708. (d) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11598. (e)
3
4
yield along with secondary aniline 6a in 11% yield (run 2)
Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030. (f) Wolfe,
J. P.; Buchwald, S. L. J. Org. Chem. 1996, 61, 1133. (g) Hartwig, J. F.;
Richards, S.; Baranano, D.; Paul, F. J. Am. Chem. Soc. 1996, 118, 3626. (h)
Wolfe, J. P.; Wagaw. S.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 7215.
(Scheme 3). The result indicates that nonsubstituted aniline could
be synthesized from aryl halide and molecular nitrogen by a one-
5
step reaction using palladium-catalyzed amination. Various
(
i) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 7217. (j) Wolfe,
ligands were used for this reaction, and the results are shown in
Table 1. The longer reaction time increased the yield of the
secondary aniline 6a (run 3), and the use of (S)-BINAP as a ligand
gave good results (run 4). It seems likely that the bidentate ligand
predominantly gave primary aniline 3a (runs 4-7).
J. P.; Rennels, R. A.; Buchwald, S. L. Tetrahedron 1996, 52, 7525. (k) Wagaw,
S.; Buchwald, S. L. J. Org. Chem. 1996, 61, 7240. (l) Mann, G.; Hartwig, J.
F. J. Am. Chem. Soc. 1996, 118, 13109. (m) Louie, J.; Paul, F.; Hartwig, J.
F. Organometallics 1996, 15, 2794. (n) Wolfe, J. P.; Buchwald, S. L. J. Org.
Chem. 1997, 62, 1264. (o) Louie, J.; Driver, M. S.; Hamann, B. C.; Hartwig,
J. F. J. Org. Chem. 1997, 62, 1268. (p) Marcoux, J. F.; Wagaw, S.; Buchwald,
S. L. J. Org. Chem. 1997, 62, 1568. (q) Wolfe, J. P.; Buchwald, S. L. J. Am.
Chem. Soc. 1997, 119, 6054. r) Driver, M. S.; Hartwig, J. F. J. Am. Chem.
Soc. 1997, 119, 8232. (s) Wagaw, S.; Rennels, R. A.; Buchwald, S. L. J. Am.
Chem. Soc. 1997, 119, 8451. (t) Reddy, N. P.; Tanaka, M. Tetrahedron Lett.
NaOtBu was essential in this reaction, and if the reaction was
6
carried out in the presence of CsF instead of NaOtBu, the desired
product was not obtained. Various aryl bromides were used for
this reaction (Table 3, method A). The electron-donating group
accelerated the formation of secondary anilines 6 (runs 2, 3, and
4), while the aryl bromide having the electron-withdrawing group
1
997, 38, 4807. (u) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 1997, 62,
6
066. (v) Wolfe, J. P.; Ahmman, J.; Sadigihi, J. P.; Singer, R. A.; Buchwald,
S. L. Tetrahedron Lett. 1997, 38, 6367. (w) Wolfe, J. P.; Buchwald, S. L.
Tetrahedron Lett. 1997, 38, 6359.
(3) Synthesis of nonsubstituted aniline derivatives from aryl halides and
imine or allylamine derivative followed by hydrolysis (two steps) has been
developed. See ref 2v. See also: (a) J-Figueroa, S.; Liu, Y.; Muchowski, J.
M.; Putman, D. G. Tetrahedron Lett. 1998, 39, 1313. (b) Mann, G.; Driver,
M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 827.
(5) It has been reported that the reaction of excess PhLi with molecular N
(1-100 atm) in the presence of Cp TiCl gave aniline (3-15% yield based
on Cp TiCl ). (a) Vol’pin, M. E.; Shur, V. B.; Kudryavtsev, R. V.; Prodayko,
2
2
2
2
2
L. A. Chem. Commum. 1968, 1038. (b) Vol’pin, M. E. J. Organomet. Chem.
1980, 200, 319.
(
4) (a) Kawaguchi, M.; Hamaoka, S.; Mori, M. Tetrahedron Lett. 1993,
34, 6907. (b) Mori, M.; Kawaguchi, M.; Hamaoka, S. Heterocycles 1994, 39,
29. (c) Hori, M.; Mori, M. J. Org. Chem. 1995, 60, 1480. (d) Mori, M.;
(6) Since it was considered that the main species of titanium-nitrogen
7
3
complex is N(TMS) at this stage, CsF was used because we usually added
Hori, K.; Akashi, M.; Hori, M.; Nishida, M.; Sato, Y. Angew. Chem., Int. Ed.
Engl. 1998, 37, 636.
CsF in the reaction of titanium-nitrogen complexes 2 with organic com-
4
pounds.
S0002-7863(98)01465-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/18/1998