One-pot sequential N and C arylations: An efficient methodology for the synthesis of trans 4-N,N-diaryl aminostilbenes

Article abstract of DOI:10.1002/anie.200462938

(Chemical Equation Presented) A double-amination/intermolecular-Heck- reaction sequence is used as a one-pot methodology for sequential C-N and C-C bond formations. 4-Aminostyrene was coupled with aryl bromides and aryl iodides using a [Pd₂(dba)₃]/proazaphosphatrane catalyst system (dba = dibenzylideneacetone; see scheme) to form irons 4-N,N-diaryl aminostilbene derivatives in high yields, which are comparable to those of previously reported multistep syntheses.

Full text of DOI:10.1002/anie.200462938

Angewandte
Chemie
and Stille[16] couplings. The substrates for these coupling
reactions included aryl chlorides, which encompassed elec-
tron-poor, neutral, and electron-rich examples. Moreover,
proazaphosphatranes can also function as strong non-ionic
stoichiometric bases that facilitate a variety of useful organic
transformations.[17]
Herein, we report a one-pot synthesis of trans 4-N,N-
diaryl aminostilbenes from commercially available starting
materials using a double Buchwald–Hartwig amination/inter-
molecular Heck reaction sequence in the presence of [Pd2-
(dba)3]/1 (dba = dibenzylideneacetone) as the catalytic
À
Arylation
system. Recently, transition-metal-catalyzed sequential C C
À
and C heteroatom bond-forming reactions have attracted
One-Pot Sequential N and C Arylations: An
Efficient Methodology for the Synthesis of
trans 4-N,N-Diaryl Aminostilbenes**
synthetic chemists because of their ability to facilitate the
formation of more than one bond in a one-pot reaction.
Reports of palladium-catalyzed amination/intramolecular
cyclization reaction sequences for the synthesis of indole
derivatives[18] illustrate the importance of such coupling
reactions. A one-pot two-catalyst synthesis of 1,3-diphenylin-
dazoles using a combination of copper-catalyzed N-arylation
and palladium-catalyzed C-arylation reactions has also been
reported.[19] To the best of our knowledge, a one-pot double
amination/intermolecular Heck reaction sequence has not
been described to date. Herein, we present the preliminary
results of such a one-pot protocol.
Mecheril V. Nandakumar and John G. Verkade*
N,N-Diaryl aminostilbenes and N,N-diaryl aminostyrenes are
versatile compounds that have found exciting applications in
the field of photochemistry; most of these compounds are
patented and they are widely used as electro-photographic
photoconductors and photoreceptors.[1] Recent reports have
demonstrated, for example, that these compounds can exhibit
an amino-conjugation effect in their fluorescence enhance-
ment spectra[2] and can act as ionophores for transition
metals,[3] and have several other applications.[4] The synthetic
routes to these compounds begin from aniline and the
corresponding aryl halides through a three-step process
involving an Ullmann/Vilsmeier/Wittig[5] reaction sequence
or from triphenylamine through a Vilsmeir/Wittig/palladium-
catalyzed arylation sequence.[6] Recently, the synthesis of
trans 4-N,N-diaryl aminostilbenes from the corresponding
halostilbenes or aminostilbenes by palladium-catalyzed ami-
nation reactions has also been reported.[2,3]
Our studies commenced with the coupling of 4-amino-
styrene with bromobenzene under the conditions given in
Scheme 1. Optimization studies were carried out (Table 1),
Palladium-catalyzed cross-coupling reactions, facilitated
by a variety of ligands, are exceedingly powerful and reliable
[7]
methods for C C and C heteroatom[8] bond formations and
have a vast number of applications in the pharmaceutical,[9]
dye,[10] agriculture,[11] and polymer[12]
À
À
industries. In recent years, our studies
of commercially available proazaphos-
phatranes,[13] such as 1, which were first
synthesized by us, have shown them to
be efficient ligands in palladium-cata-
Scheme 1. a) [Pd2(dba)3] (2 mol%), 1 (4 mol%), NaOtBu (3.5 equiv),
aryl halide (3.2 equiv), dry toluene (10 mL), under argon atmosphere.
lyzed N arylations[14] and the Suzuki[15]
[*] Dr. M. V. Nandakumar, Prof. Dr. J. G. Verkade
Department of Chemistry
and it was initially found that when the reaction was carried
out at 608C with ligand 1 over 3 h (entry 1), the only coupling
observed was a double amination (product 4); the Heck
reaction required a minimum of 1108C for the protocol to be
efficient (entry 3). When iodobenzene was used instead, the
Heck reaction occurred at 1008C (entries 7 and 8) but faster
conversion was realized at 1108C (entry 9). In addition, other
phosphines, such as davephos (2-dicyclohexylphosphino-2’-
(N,N-dimethylamino)biphenyl), tBu3P, and rac-binap (2,2’-
Iowa State University
Ames, IA 50011-3111 (USA)
Fax: (+1)515-294-0105
E-mail: jverkade@iastate.edu
[**] We thank the National Science Foundation for support of this work
and Aldrich for research samples.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200462938
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Table 1: Optimization of the one-pot double amination/intermolecular Heck reaction.
mobenzene under the same conditions gave
the analogous product 6b in moderate yield
(Scheme 2). Our yield of 6a (86%) is
comparable to that reported in a patented
procedure (89%) involving the single-step
reaction of 4-methyldiethylbenzylphospho-
nate with 4-N,N-diphenylaminobenzaldehy-
de.[22a] However, our yield of 6a is substan-
tially better than the yield achieved through
a Wittig reaction of 4-methylbenzyltriphe-
nylphosphonium chloride with the afore-
mentioned aldehyde (72%)[22a] and the
overall yield (46%) of a previously reported
three-step synthesis.[22bc] Although 6b has
been reported previously, no yield was
given.[1]
Entry
Aryl halide
Ligand
t [h]
T [8C]
Yield [%][a]
Total yield [%]
4+5
4
5
1
2
3
4
5
6
7
8
1
3
12
16
3
16
16
12
24
16
16
16
16
60
100
110
60
110
110
100
100
110
110
110
110
90
92
9
53
69
56
32
0
0
2
83
0
90
94
92
53
83
90
98
94
93
85
56
88
davephos
14
34
66
rac-binap
1
94 (78)[b]
9
0
74
0
93
11
56
61
10
11
12
tBu3P
rac-binap
davephos
27
[a] Yield of isolated product. [b] Reported yield for a two-step, two-pot synthesis.[2]
In a similar manner, unsymmetrically N-
bis(diphenylphosphino)-1,1’-binapthyl), were found to be
inefficient ligands (entries 4–6 and 10–12).
substituted diaryl aminostilbenes 7a,b were synthesized in
very good yields by using aryl iodides instead of aryl bromides
Next, we examined the coupling of a variety of aryl
bromides and iodides with 4-aminostyrene to test the general-
ity of this methodology (Table 2). The major products formed
were trans N,N-diaryl aminostilbenes 5, except when 4-
bromoanisole and 3-bromoanisole were the substrates
(entries 5 and 6, respectively). The yields of 5 from 4-
bromotoluene and 4-iodotoluene as the substrates (entries 1
and 9, respectively) were similar to those reported previ-
ously,[20] whereas the yields of 5 from 4-bromoanisole and 4-
iodoanisole were poor (entries 5 and 8). On the other hand,
the yields of 5 from 4-bromotoluene and 4-iodotoluene
(entries 1 and 9) were superior to the overall yield (55%)
from a three-step procedure involving an Ullmann/Vilsmeier/
Wittig reaction series.[20,21] All other products derived from
this reaction series have not been previously reported
(entries 2–4, 6 and 7).
It is evident from the results of optimization experiments
given in Table 1 that the reaction pathway to 5 is a double
amination followed by an intermolecular Heck reaction. As
the amination reactions were completed within 3 h at 608C
and the Heck reactions required an elevated temperature and
a longer reaction time, we were able to utilize this difference
in coupling activity for the one-pot synthesis of 5 with two
identical aryl groups at the nitrogen atom and a different one
at the opposite terminus of 5 (Scheme 2). The first step of this
one-pot procedure afforded the bisamination product in three
hours, as monitored by TLC. The addition of 4-bromotoluene
(1.2 equiv) in the second step afforded 6a in very good yield.
Reaction of 4-aminostyrene with 4-bromoanisole and bro-
Table 2: One-pot double amination/intermolecular Heck reactions of
4-aminostyrene with aryl bromides and aryl iodides.
Entry
Aryl halide
Yield [%][a]
Total yield [%]
4
5
4+5
1
2
11
84
61
95
98
37
28
3
60
88
4
5
6
27
47
60
59
34
34
86
81
94
7
32
63
41
95
8
9
0
0
41
87
87 (83%)[b]
[a] Yield of isolated product. Reaction conditions: [Pd2(dba)3] (2 mol%),
1 (4 mol%), NaOtBu (3.5 equiv), aryl halides (3.2 equiv), dry toluene
(10 mL), 1108C, 16 h, under argon atmosphere. [b] Reported yield.[20]
Scheme 2. a) [Pd2(dba)3] (2 mol%), 1 (4 mol%), NaOtBu (3.5 equiv), dry toluene (10 mL), in an argon atmosphere. 6a, R1 =H, R2 =CH3 (86%);
6b, R1 =4-OMe, R2 =H (60%).
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Scheme 3. a) [Pd2(dba)3] (2 mol%), 1 (4 mol%), NaOtBu (3.5 equiv), dry toluene (10 mL), in an argon atmosphere. 7a, R1 =CH3, R2 =H (78%);
7b, R1 =4-OMe, R2 =H (79%).
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(4-methylphenyl)-N-phenylamino)benzaldehyde and diethyl-
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Received: December 15, 2004
Published online: April 14, 2005
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À
Keywords: amination · C C coupling · cross-coupling ·
Heck reaction · palladium
.
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Communications
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