Solvent free amination reactions of aryl bromides at room temperature catalyzed by a (π-allyl)palladium complex bearing a diphosphinidenecyclobutene ligand

Article abstract of DOI:10.1021/jo049087n

An air- and moisture-stable (π-allyl)palladium complex bearing a unique diphosphinidenecyclobutene ligand effectively catalyzes amination reactions of aryl bromides with amines, where the reactions proceed under mild conditions without solvent, with 2 mol % of catalyst and 1 equiv of t-BuOK at room temperature. Under these conditions the amination products were obtained in good to excellent isolated yields.

Full text of DOI:10.1021/jo049087n

Solven t F r ee Am in a tion Rea ction s of Ar yl
Br om id es a t Room Tem p er a tu r e Ca ta lyzed
by a (π-Allyl)p a lla d iu m Com p lex Bea r in g a
Dip h osp h in id en ecyclobu ten e Liga n d
SCHEME 1
†
†
,†
Anil S. Gajare, Kozo Toyota, Masaaki Yoshifuji,* and
Fumiyuki Ozawa‡
Department of Chemistry, Graduate School of Science,
Tohoku University, Aoba, Sendai 980-8578, J apan, and
Institute for Chemical Research, Kyoto University, Uji,
Kyoto 611-0011, J apan
5
terization of diphosphinidenecyclobutenes (DPCB), con-
taining low-coordinated phosphorus atom(s). DPCBs are
phosphorus analogues of diimines and form stable chelate
rings with transition metal species and those complexes
are fairly stable toward air in solution as well as in solids.
yoshifj@mail.tains.tohoku.ac.jp
Received J une 1, 2004
2
The DPCB derivatives with sp -hybridized phosphorus
atoms have a marked propensity to engage in metal-to-
phosphorus π back-bonding, comparable to that of the
carbonyl ligand. We have been interested in the coor-
dination chemistry of DPCB and have characterized the
complexes with the group 6 as well as the group 8-10
transition metals.7 Indeed we found several organic
reactions catalyzed by DPCB-Pd complexes or DPCB-
Pt complexes,8 through the high coordination ability
of the ligand owing to σ-donation/ π-back-donation in-
teractions and the strong π-acceptor properties owing to
the low-lying LUMO (π*).
Abstr a ct: An air- and moisture-stable (π-allyl)palladium
complex bearing a unique diphosphinidenecyclobutene ligand
effectively catalyzes amination reactions of aryl bromides
with amines, where the reactions proceed under mild
conditions without solvent, with 2 mol % of catalyst and 1
equiv of t-BuOK at room temperature. Under these condi-
tions the amination products were obtained in good to
excellent isolated yields.
6
8
,9
,10
Aromatic amines are important compounds found
throughout the pharmaceutical, dye, agricultural, and
polymer industries. Uses for aromatic amines can range
from conducting polymers in material science to ligands
for asymmetric homogeneous catalyst chemistry. It there-
fore follows that catalytic aromatic carbon-nitrogen bond
forming reactions that are practical, relatively inexpen-
sive, and feasible over a broad range of substrates would
Herein we report that a (π-allyl)(dpcb)palladium com-
plex 2,9 prepared from DPCB 1 and [(π-allyl)PdCl]
b,c
2
followed by treatment with silver triflate, catalyzes
amination reactions of aryl bromides with amines with-
out solvent (Scheme 1). Those reactions proceed under
mild conditions, with 2 mol % of catalyst 2 at room
temperature.
For optimization studies we initially screened catalyst
and base as shown in Table 1. The amination of bromo-
benzene with aniline in the presence of 1 equiv of
t-BuOK/2 mol % of 2 at room temperature without
solvent gave the best results (entry 1). As shown in
entries 2 and 3, reactions conducted without catalyst or
base did not occur, and reactions with 1 or 0.5 mol % of
catalyst occurred to give products only in low yields
1
be valued in organic synthesis. In recent years a number
of reports have appeared on amination reactions; how-
ever, only a few methods are known at room temperature.
For some examples of room temperature aminations, see
ref 2.
We have been interested in developing sterically
protected and multiple-bonded organophosphorus com-
pounds.3 Utilizing the 2,4,6-tri-tert-butylphenyl group
4
(
abbreviated to Mes*) as a protecting group, we and
others have been successful in the isolation and charac-
(
entries 4 and 5). The reaction conducted with 2 equiv of
t-BuOK (entry 6) gave the product in slightly lower yield
†
Tohoku University.
Kyoto University.
‡
(
1) For reviews see: (a) Wolfe, J . P.; Wagaw, S.; Marcoux, J .-F.;
(5) (a) Appel, R.; Winkhaus, V.; Knoch, F. Chem. Ber. 1987, 120,
243. (b) M a¨ rkl, G.; Kreitmeier, P.; N o¨ th, H.; Polborn, K. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 927. (c) Yoshifuji, M.; Toyota, K.; Murayama,
M.; Yoshimura, H.; Okamoto, A.; Hirotsu, K.; Nagase, S. Chem. Lett.
1990, 2195.
(6) For reviews, see: (a) Le Floch, P.; Mathey, F. Coord. Chem. Rev.
1998, 179/180, 771. (b) Mathey, F. Acc. Chem. Res. 1992, 25, 90. (c)
Yoshifuji, M. J . Chem. Soc., Dalton Trans. 1998, 3343.
(7) (a) Yoshifuji, M. J . Synth. Org. Chem. J pn. 2003, 61, 1116. (b)
Ozawa, F.; Kawagishi, S.; Ishiyama, T.; Yoshifuji, M. Organometallics
2004, 23, 1325.
(8) Ikeda, S.; Ohhata, F.; Miyoshi, M.; Tanaka, R.; Minami, T.;
Ozawa, F.; Yoshifuji, M. Angew. Chem., Int. Ed. 2000, 39, 4512.
(9) (a) Toyota, K.; Masaki, K.; Abe, T.; Yoshifuji, M. Chem. Lett.
1995, 221. (b) Minami, T.; Okamoto, H.; Ikeda, S.; Tanaka, R.; Ozawa,
F.; Yoshifuji, M. Angew. Chem., Int. Ed. 2001, 40, 4501. (c) Ozawa, F.;
Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami, T.; Yoshifuji, M.
J . Am. Chem. Soc. 2002, 124, 10968.
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805. (b) Hartwig, J . F.
Angew. Chem., Int. Ed. Engl. 1998, 37, 2046. (c) Muci, A. R. Top. Curr.
Chem. 2002, 219, 131. (d) Littke, A. F.; Fu, G. C. Angew. Chem., Int.
Ed. 2002, 41, 4176. (e) Hartwig, J . F. In Modern Arene Chemistry:
Concepts, Synthesis, and Applications; Astruc, D., Ed.; Wiley Canada:
Ontario, Canada, 2002; p 107.
(
2) (a) Roy, A. H.; Hartwig, J . F. J . Am. Chem. Soc. 2003, 125, 8704.
b) Zim, D.; Buchwald, S. L. Org. Lett. 2003, 5, 2413. (c) Wolfe, J . P.;
Tomori, H.; Sadighi, J . P.; Yin, J .; Buchwald, S. L. J . Org. Chem. 2000,
(
6
1
5, 1158. (d) Wolfe, J . P.; Buchwald, S. L. Angew. Chem., Int. Ed. Engl.
999, 38, 2413. (e) Hartwig, J . F.; Kawatsura, M.; Hauck, S. I.;
Shaughnessy, K. H.; Alcazar-Roman, L. M. J . Org. Chem. 1999, 64,
575.
3) (a) Multiple Bonds and Low Coordination in Phosphorus Chem-
5
(
istry; Regitz, M., Scherer, O. J ., Eds.; Georg Thieme Verlag: Stuttgart,
Germany, 1990. (b) Dillon, K. B.; Mathey, F.; Nixon, J . F. Phosphorus:
Carbon Copy; Wiley: Chichester, UK, 1998.
(
4) Yoshifuji, M.; Shima, I.; Inamoto, N.; Hirotsu, K.; Higuchi, T. J .
(10) Ozawa, F.; Yamamoto, S.; Kawagishi, S.; Hiraoka, M.; Ikeda,
S.; Minami, T.; Ito, S.; Yoshifuji, M. Chem. Lett. 2001, 972.
Am. Chem. Soc. 1981, 103, 4587; 1982, 104, 6167.
1
0.1021/jo049087n CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/20/2004
6
504
J . Org. Chem. 2004, 69, 6504-6506

TABLE 1. Selection of Ca ta lyst a n d Ba se for Am in a tion
TABLE 2. Am in a tion Rea ction s a t Room Tem p er a tu r e
w ith ou t Solven t Ca ta lyzed by (π-Allyl)(d p cb)p a lla d iu m
Com p lexa
a
Rea ction
b
c
entry catalyst [mol %] base [equiv] solvent T, °C yield, %
b
entry
aryl bromide
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
p-MeOC6H4Br
p-EtOC(O)C6H4Br
o-MeOC6H4Br
p-t-BuC6H4Br
m,m′-Me2C6H3Br
p-C6H4Br2
p-C6H4Br2
amine
PhNH2
yield, %
1
2
3
4
5
6
7
8
9
0
1
2
2 [2]
K [1.00]
K [1.00]
rt
rt
rt
rt
rt
rt
rt
rt
98
NR
NR
45
24
81
70
70
33
1
2
3
4
5
6
7
8
9
98
82
80
69
60
62
99
2 [2]
2 [1]
2 [0.5]
2 [2]
2 [2]
2 [2]
2 [2]
e
Ph(CH2)2NH2
p-MeC6H4CH2NH2
R-NaphCH2NH2
PhCHMeNH2
CH3(CH2)15NH2
p-MeOC6H4NH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
K [1.00]
K [1.00]
K [2.00]
K [0.50]
K [0.25]
Cs [1.00]
K [1.00]
K [1.00]
K [1.00]
c
rt
63 [65 ]
d
1
1
1
100
100
100
4
53
95
97
97
78
d
e
f
g
g
10
11
d
50
1
1
1
2
3
4
a
b
Bromobenzene (1 equiv), aniline (1 equiv), 12 h. K ) t-BuOK
d
PhNH2
71
c
d
and Cs ) Cs2CO3; Isolated yields. No reaction at room tem-
perature. The catalyst was prepared in situ from 2 mol % of 1
and 2 mol % of (MeCN)2PdCl2. The catalyst was prepared in situ
from 2 mol % of 1 and 2 mol % of Pd(OAc)2. Toluene (2 mL) was
PhNH2e
71
e
f
a
Aryl bromide (1 mmol), amine (1 equiv), t-BuOK (1 equiv), 2
g
b
c
(2 mol %), at room temperature, 12 h. Isolated yields. Yield at
used as solvent.
100 °C. d Toluene (2 mL) was added. e Amine (2 equiv) was used.
than that with 1 equiv of t-BuOK. The use of 0.50 and
TABLE 3. Am in a tion Rea ction s w ith ou t Solven t
0
.25 equiv of t-BuOK (entries 7 and 8) afforded the
a
Ca ta lyzed by (π-Allyl)(d p cb)p a lla d iu m Com p lex
corresponding product in 70% yield. Although in some
cases milder bases such as Cs salts have been reported
to be effective in catalytic amination reactions on aro-
matic rings,11 cesium carbonate did not give good results
b
entry
aryl halide
PhBr
PhBr
PhBr
PhBr
PhBr
p-t-BuC6H4Br
PhBr
amine
PhNH2
PhNHMe
Ph2CdNH
morpholine
piperidine
piperidine
THIQf
T, °C
yield, %
(entry 9), indicating that a strong base is required in
1
2
3
4
5
6
7
100
100
rt
rt
rt
84c
these amination reactions. Catalysts generated in situ
from DPCB and bis(acetonitrile)dichloropalladium (en-
tries 10 and 11) or palladium acetate (entry 12) gave the
corresponding products only in low yields at 100 °C with
the use of toluene as solvent. In no reaction did we
observe arenes as side products, which would result from
â-hydride elimination from an amido intermediate.12
After exploring a wide array of conditions we deter-
mined that the amination of bromobenzene with aniline
in the presence of 1 equiv of t-BuOK and 2 mol % of 2 at
room temperature without solvent gave the best results
d
70
e
76 [81 ]
55 [58 ]
70 [73 ]
64 [74 ]
e
e
e
rt
100
51
a
Aryl halide (1 equiv), amine (1 equiv), t-BuOK (1 equiv), 2 (2
b
c
d
mol %), 12 h. Isolated yields. Aryl halide (2 equiv).
No
reaction at room temperature. e Yields at 100 °C. f Tetrahydroiso-
quinoline.
(
entry 1, Table 2 as well as Table 1).
We then examined various substrates as listed in Table
under the optimized conditions. Not only aromatic
1
4, the use of 2 equiv of aniline provided for sufficient
stirring without the use of toluene, giving only mono-
substituted product.
2
amines but also alkylamines gave the corresponding
products with bromobenzene in moderate to good yields
Table 3 shows the effect of temperature on the reaction.
Even when 2 equiv of bromobenzene was used and heated
with aniline for 12 h at 100 °C, diphenylamine was
obtained in 84% yield (entry 1), indicating monosubsti-
tution is predominant in these catalytic reactions. N-
Methylaniline reacted with bromobenzene to form the
corresponding tertiary amine in 70% yield at 100 °C, but
no reaction was observed at room temperature (entry 2).
(entries 2-6). An electron-donating substitutent on the
aniline ring gave an excellent result (entry 7). Substitu-
tion effects on the bromobenzene did not show any
disadvantage to the reaction with aniline (entries 9-10),
except for p-methoxybromobenzene (entry 8) either at
room temperature or at an elevated temperature. 4-tert-
Butylbromobenzene and 1-bromo-3,5-dimethylbenzene
reacted with aniline at room temperature to form the
corresponding N-aryl products in 78-97% yield (entries
2
Benzophenone imine, which contains an sp nitrogen
atom, formed the corresponding amination product in
good yield (entry 3).
1
1 and 12). In the case of entry 13, p-dibromobenzene, 2
Arylmorpholine and arylpiperidine are an important
class of medicinal compounds and have been prepared
by using palladium-catalyzed amination with aryl chlo-
mL of toluene was used to facilitate stirring to give a 71%
yield of monosubstitution product. In the case of entry
ride,13 aryl bromides, and iodides. By using the (π-
14
15
(
(
11) Wolfe, J . P.; Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6359.
12) (a) Paul, F.; Patt, J .; Hartwig, J . F. J . Am. Chem. Soc. 1994,
1
1
5
4
16, 5969. (b) Paul, F.; Patt, J .; Hartwig, J . F. Organometallics 1995,
4, 3030. (c) Hartwig, J . F.; Paul, F. J . Am. Chem. Soc. 1995, 117,
373. (d) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1995, 117,
708.
(13) (a) Beller, M.; Riemeier, T. H.; Reisinger, C.-P.; Herrmann, W.
A. Tetrahedron Lett. 1997, 38, 2073. (b) Stauffer, S. R.; Lee, S.;
Stambuli, J . P.; Hauck, S. I.; Hartwig, J . F. Org. Lett. 2000, 2, 1423.
(c) Reddy, N. P.; Tanaka, M. Tetrahedron Lett. 1997, 38, 4807.
J . Org. Chem, Vol. 69, No. 19, 2004 6505

allyl)(dpcb)palladium system, aryl bromides couple with
piperidine or morpholine to form the corresponding
N-aryl product in good yields, at room temperature as
well as at 100 °C. No significant temperature effect was
found on the yields (entries 4 and 5). The reaction of
conditions without solvent, with 2 mol % of catalyst 2 at
room temperature. It should be noted here that these
catalytic reactions can be carried out without a drybox.
Under these conditions the amination products were
obtained in good to excellent isolated yields.
4
-tert-butylbromobenzene with piperidine at room tem-
perature afforded only the desired product in 64% yield
and in 74% at 100 °C (entry 6), with no cleavage observed
Exp er im en ta l Section
1
5b
Ma ter ia ls a n d Meth od s. See the Supporting Information.
Gen er a l P r oced u r e for th e Am in a tion Rea ction s of Ar yl
Br om id es. All reactions were performed without a drybox, and
for 4-tert-butylbromobenzene. Tetrahydroisoquinoline
reacted with bromobenzene to afford the corresponding
N-phenyl product in an acceptable yield (entry 7).
Although we have discovered that the DPCB-Pd
complex exhibits unique reactivity for amination reac-
tions, we observed some limitations. No reaction was
observed at room temperature or at 100 °C with cyclo-
hexylamine, urea, pivaloyl amide or p-nitroaniline, and
bromobenzene.
2
and t-BuOK were weighed in air. An oven-dried Pyrex screw
tube was charged with t-BuOK (1 mmol) and 2 (2 mol %). The
tube was evacuated and filled with argon. To the mixture were
added aryl bromide (1 mmol) and amine (1 mmol) at room
temperature (the solution turned black). The viscous reaction
mixture was stirred vigorously at room temperature for 12 h.
After all starting material had been consumed, as judged by
TLC, the reaction mixture was diluted with ethyl acetate. After
water was added, the mixture was stirred vigorously to dissolve
the precipitates, then extracted with ethyl acetate 3 times. The
It seems likely a catalytic cycle for this amination
reaction involves a palladium(0) intermedate16 ligated
with DPCB (see Supporting Information for a proposed
2 4
combined organic extracts were dried over Na SO , filtered, and
concentrated in vacuo. Silica gel column chromatography (hex-
ane-EtOAc) of the crude material provided pure amination
products.
catalytic cycle). The formation of (dpcb)Pd(0) has already
been proposed in the reaction of 2 with amine.9b,17
In summary, we have demonstrated that a (π-allyl)-
palladium complex 2 bearing the unique DPCB ligand
effectively catalyzes amination reactions of aryl bromides
and amines, where the reactions proceed under mild
Ack n ow led gm en t. This work was supported in part
by Grants-in-Aid for Scientific Research (Nos. 13304049
and 14044012) from the Ministry of Education, Culture,
Sports, Science and Technology, J apan. A.S.G. is grate-
ful to the J apan Society for the Promotion of Science
for a Postdoctoral Fellowship for Foreign Researchers.
(
14) (a) Urgaonkar, S.; Xu, J .-H.; Verkade, J . G. J . Org. Chem. 2003,
8, 8416. (b) Wolfe, J . P.; Wagaw, S.; Buchwald, S. L. J . Am. Chem.
Soc. 1996, 118, 7215.
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6
(
(
Su p p or tin g In for m a tion Ava ila ble: Spectral data for
amination products, copies of H NMR spectra for amination
products, and proposed catalytic cycle for the amination
reaction. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
1
S. L. J . Am. Chem. Soc. 2002, 124, 14104. (b) Alcazar-Roman, L. M.;
Hartwig, J . F. J . Am. Chem. Soc. 2001, 123, 12905. (c) Guari, Y.; van
Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J . N. H.; Kamer, P. C. J .;
van Leeuwen, P. W. N. M. Chem. Eur. J . 2001, 7, 475.
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17) Ozawa, F.; Ishiyama, T.; Yamamoto, S.; Kawagishi, S.;
Murakami, H.; Yoshifuji, M. Organometallics 2004, 23, 1698.
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