A pronounced anionic effect in the Pd-catalyzed Buchwald-Hartwig animation reaction revealed in phosphonium salt ionic liquids

Article abstract of DOI:10.1002/ejoc.200700005

The Pd-mediated Buchwald-Hartwig animation reaction of aryl halides in a phosphonium salt ionic liquid consisting of a trihexyl(tetradecyl)phosphonium cation with a range of anions has been investigated. A pronounced anionic effect was uncovered with the reaction proceeding readily with weakly nucleophilic diarylamines only in the presence of noncoordinating anions. A mechanism is postulated to explain these results and it involves a rate-limiting ligand exchange step that proceeds through a dissociative pathway. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700005

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200700005
A Pronounced Anionic Effect in the Pd-Catalyzed Buchwald–Hartwig
Amination Reaction Revealed in Phosphonium Salt Ionic Liquids
[a]
[a]
[b]
[c]
James McNulty,* Sreedhar Cheekoori, Timothy P. Bender, and Jennifer A. Coggan
Keywords: Homogeneous catalysis / Amination / Phosphanes / Conducting materials
The Pd-mediated Buchwald–Hartwig amination reaction of
aryl halides in a phosphonium salt ionic liquid consisting of
a trihexyl(tetradecyl)phosphonium cation with a range of
anions has been investigated. A pronounced anionic effect
was uncovered with the reaction proceeding readily with
weakly nucleophilic diarylamines only in the presence of
noncoordinating anions. A mechanism is postulated to ex-
plain these results and it involves a rate-limiting ligand ex-
change step that proceeds through a dissociative pathway.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
methodology. Many factors contributing to the success of
this reaction have been investigated including solvent ef-
The use of transition metal complexes to catalyze cross- fects, where the superiority of noncoordinating solvents
coupling reactions between aryl and vinyl halides or their was demonstrated. To the best of our knowledge, no reports
[
7]
equivalents with amines has become a standard tool for the specifically on anionic effects have been reported on the
construction of complex amines.[
1–5]
Classic protocols uti- production of arylamines under Buchwald–Hartwig condi-
lizing copper salts (Ullmann reaction)[ suffer from many tions.
drawbacks in terms of reactivity. These methods require
high loadings of copper catalyst, high reaction temperatures
and/or times, the use of excess amine and the reactions
often result in the formation of side products. Tedious, ex-
pensive and wasteful product purification and the disposal
of metal-containing waste are further environmental con- tions of Pd-catalyzed and other cross-coupling reactions
cerns of the classic Ullmann reaction, which accentuates in phosphonium salt ionic liquids (ILs). Phosphonium-
the need for the development of “green” alternatives for based ILs are very thermally stable, nonvolatile, econom-
obtaining these valuable intermediates and products. On the ical and available on an industrial scale. Most IL research
basis of initial reports by Buchwald and Hartwig,[ a pleth- has been conducted in nitrogen-based solvents, especially
2]
Results and Discussion
Recently, we have been interested in developing applica-
[
8]
[9]
[
10]
3]
[
11]
ora of methods utilizing Pd complexes (now known as alkyl imidazolium salts,
whereas the phosphonium ana-
Buchwald–Hartwig amination) coupled with a variety of logues represent a largely unexplored area. We have re-
electron rich, bulky ligands have appeared over the last few ported the efficient Suzuki cross-coupling of aryl halides,
[
4]
years. A major impetus for these developments is the po- including chlorides, with a variety of boronic acids in the
tential utility of efficient amination protocols in the synthe- IL trihexyl(tetradecyl)phosphonium chloride. Efficient re-
sis of dyes, high-value pharmaceuticals[ and functionalized covery and recycling of the palladium catalysts was demon-
5]
[
8a]
triarylamines, which are the key components in a variety of strated, and this work has been extended to Suzuki and
materials including organic photoconductors, light-emitting other Pd-mediated reactions employing an organic solvent
diodes and photovoltaic cells.[ An expanding variety of nanofiltration technology. In addition to the “green” po-
arylamines have now been prepared under mild conditions tential of these processes, an interesting feature when utiliz-
and in a controlled, chemoselective manner by utilizing this ing these IL solvents is the tunability of the reaction that is
available through altering the nature of either the anion or
6]
[12]
phosphonium cation. For example, trihexyl(tetradecyl)-
280 Main Street West, Hamilton, Ontario, L8S 4M1, Canada phosphonium bis(trifluoromethylsulfonyl)imide (bistrifl-
[
a] Department of Chemistry, McMaster University,
1
Fax: +905-522-2509
E-mail: jmcnult@mcmaster.ca
imide) IL proved to be the optimal choice in a series of
[
9a,13]
[
[
b] Department of Chemical Engineering and Applied Chemistry, alklyation reactions investigated,
whereas with this
University of Toronto,
[8a]
same cation, the chloride IL proved optimal in Suzuki
2
00 College Street, Toronto, Ontario, M5S 3E5, Canada
[
8b]
and Heck
cross-coupling reactions, and finally, the dec-
c] Xerox Research Centre of Canada,
2
660 Speakman Drive, Mississauga, Ontario, L5K 2L1, Canada anoate salt was optimal in the catalysis of carbonyl addition
Eur. J. Org. Chem. 2007, 1423–1428
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1423

J. McNulty, S. Cheekoori, T. P. Bender, J. A. Coggan
SHORT COMMUNICATION
reactions.[9b] As an extension of this work, we recently in- conducted in toluene solvent.[15] Further experiments on
vestigated a Pd-mediated Buchwald–Hartwig amination re- the nature of the anionic effect were carried out with this
action of an aryl bromide in trihexyl(tetradecyl)phospho- optimal catalyst–precursor combination.
nium chloride and were surprised that little cross-coupling
took place (Scheme 1).
The cross-coupling reaction was screened in nine dif-
ferent trihexyl(tetradecyl)phosphonium ILs by varying the
electronic and, to some extent, the steric nature of the
anion; the results are summarized in Table 2 (Scheme 2).
The superiority of the bistriflimide derivative is striking;
this reaction went to completion within two hours, whereas
even other partly successful anions, decanoate and tetra-
fluoroborate, provided only 57 to 59% conversion over 24 h
under otherwise identical conditions. The saccharide
Scheme 1. Screening Pd sources and ligand in trihexyl(tetradecyl)-
phosphonium bistriflimide IL.
(imide) derivative was also successful but reacted slower to
This was surprising because this same substrate, under give 90% conversion over a 24 h reaction period. The inac-
otherwise similar conditions, readily enters into Suzuki tivity of the chloride and bromide derivatives is also star-
cross-coupling reactions with the same Pd source [Pd2- tling, particularly in view of the success of these media in
(
dba) ·CHCl ], the only difference being the nature of the promoting other Pd-mediated cross-coupling reac-
3 3
[8a,8b]
nucleophile (amine versus boronic acid). This negative re- tions.
The Buchwald–Hartwig amination reaction in
sult prompted us to further explore the reaction parameters tetradecyl(trihexyl)phosphonium bistriflimide was also suc-
in order to gain a deeper insight into this dichotomous ob- cessfully conducted by coupling 4-methoxyaniline (2b)
[
14a]
servation. Prior to this work, Pd-mediated amination
and direct nucleophilic amination of activated aryl ha- The reaction appears to be general and indicates that oxi-
(Scheme 3) with bromobenzene derivatives 1b–1d (Table 3).
[
14b]
lides
cases utilize tetrafluoroborate or hexafluorophosphate electron-deficient halides proceeds without difficulty.
counteranions. In this paper, we report the use of phospho- In general, the results in Table 2 show that nucleophilic
was reported in imidazolium ionic liquids, both dative addition of the catalyst to both electron-rich and
nium-based ILs in Pd-mediated Buchwald–Hartwig-type “coordinating” counteranions are detrimental to the suc-
amination reactions and uncover a pronounced anionic ef- cess of the amination reaction whereas diffuse, weakly or
fect and discuss its mechanistic implications.
noncoordinating anions, particularly the bistriflimide and
The target compound central to our investigation was saccharide derivatives, are superior. This result is in agree-
biphenyl-substituted triarylamine 3a, Scheme 1. The most ment with the solvent effect study recently reported in
direct route for its synthesis and structural analogues would which donor solvents were seen to be an inferior media.[
be from 4-bromobiphenyl (1a) and a diphenylamine such as It appears that the weakly nucleophilic nature of the di-
7]
[
6]
2a by using a Buchwald–Hartwig amination protocol.
arylamine employed in the present study inhibits its partici-
The cross-coupling shown (Scheme 1) did not proceed sig- pation in the Pd-mediated catalytic cycle where coordinat-
nificantly in trihexyl(tetradecyl)phosphonium chloride IL; ing anions and/or solvent are present. These results contrast
however, we quickly determined that it proceeded rapidly the success of the chloride-containing IL in the Suzuki
[
8a]
in the bistriflimide analogue, which allowed complete con- cross-coupling reaction. It seems unlikely that a different
version of the aryl bromide. The reaction independently re- Pd-catalyst is operative in the chloride-containing IL during
quires the addition of ligand and base. We screened two Pd0 the Suzuki process given the similarity of the reaction con-
sources and several ligands (Table 1) in this IL solvent and ditions. The above results and the generality of the amin-
determined that the source of the active palladium catalysts ation reaction to variously substituted aryl halides (Table 3)
was not crucial, although the combination of Pd dba · indicate that there is no problem with the oxidative addition
2
3
CHCl with the tertiary phosphane 1-isobutyl-2,2,6,6-tet- step in either catalytic cycle and that the explanation for the
3
ramethylphosphorinane proved optimal. We have recently dichotomy rests upon the nature of the ligand exchange
found this ligand to be valuable in various Pd-mediated step involving the weakly nucleophilic diarylamine (vide in-
cross-coupling reactions, including amination reactions fra).
Table 1. Screening different palladium sources and ligands in bistriflimide IL.
Entry Palladium source
Ligand
Temperature
°C]
Time
[h]
Conversion[a]
[%]
[
1
2
3
Pd
2
Pd
2
Pd
2
(dba)
(dba)
(dba)
3
3
3
tri(tert-butyl)phosphane
isobutylphosphorinane
tri(o-tolyl)phosphane
104
104
104
15
2
2
89
98
71
[
b]
4
5
6
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
tri(tert-butyl)phosphane
isobutylphosphorinane
tri(o-tolyl)phosphane
104
104
104
2
15
15
90
36
20
[a] Conversion determined by HPLC analysis. [b] 5 mol-% of palladium catalyst used.
1424
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1423–1428

Anionic Effect in the Pd-Catalyzed Amination Reaction
SHORT COMMUNICATION
Table 2. Phosphonium-based ionic liquid screen in a standard amination reaction.
Entry
Ionic liquid
Overnight conversion[a]
Isolated yield
[%]
[%]
1
2
trihexyl(tetradecyl)phosphonium chloride
trihexyl(tetradecyl)phosphonium bromide
1
2
2
NA
NA
NA
42
NA
73
35
9
65
[
b]
3
4
5
6
7
8
9
trihexyl(tetradecyl)phosphonium dicyanamide
trihexyl(tetradecyl)phosphonium decanoate
trihexyl(tetradecyl)phosphonium tosylate
trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide
trihexyl(tetradecyl)phosphonium tetrafluoroborate
trihexyl(tetradecyl)phosphonium dibutylphosphate
trihexyl(tetradecyl)phosphonium saccharide
57
2
98[
59
15
90
b]
[a] Conversion determined by HPLC analysis. [b] This reaction was complete in 2 h.
reaction in toluene had no effect on the reaction, with 98%
conversion being observed in the latter case. In contrast, the
addition of trihexyl(tetradecyl)phosphonium chloride poi-
soned the operative catalytic cycle in the cross-coupling re-
action in toluene. Although 1.0 equiv. of the chloride IL
was tolerated, the reaction did not proceed at all in toluene
when 5.0 equiv. of this soluble chloride were added. These
results correlate precisely with the activity observed in the
cross-coupling reaction as described purely in the IL sol-
vent, which confirms the generality of the anionic effect.
Extensive work has been carried out on the effects of
halides and other coordinating anions in palladium-medi-
ated cross-coupling reactions. The work of Amatore, Jutand
Scheme 2.
[
16a]
et al.
indicates that in the presence of such anions an
–
anionic complex of type L PdX is formed and that this is
2
Scheme 3.
an active species in the oxidative addition to the aryl halide.
At least two catalytic cycles are now generally accepted for
Having uncovered the anionic effect in the phosphonium such a cross-coupling reaction in the absence or presence of
salt ILs, we probed the effect in a typical organic solvent in added halide or other coordinating species.[16b] In contrast
order to ascertain if this effect is general or just a manifesta- to the above catalytic cycles, cases are known where added
tion of the overall polar or atypical nature of the reaction chloride retards the rate of a Pd-mediated cross-coupling
[
17]
medium. Further evidence for the general nature of the an- reaction, alters the regioselectivity in the case of a Heck
[
18]
ionic effect described above was gained from the following reaction or may promote the formation of complexes of
–
[19]
reactions. The cross-coupling reaction between 4-bromobi- type LPdX that undergo rapid oxidative addition. In ad-
phenyl (1a; 1 equiv.) and diphenylamine (2a, 1.05 equiv.) dition, excess salt can modify the process by simply increas-
also proceeded smoothly in toluene as solvent with the ing the polarity of the medium. These catalytic cycles also
same catalyst, ligand and base combination as shown in present an overall dichotomy; whereas added halide may
Scheme 1. The addition of trihexyl(tetradecyl)phosphonium expedite the initial steps of the cycle through the intermedi-
–
bistriflimide in various proportions ranging from 1.0 to acy of L PdX and rapid oxidative addition to the Ar–X
2
5.0 equiv. (relative to 4-bromobiphenyl) to the amination bond, a high concentration of halide is expected to hinder
Table 3. Cross-coupling of 4-methoxyaniline with aryl bromides.
Eur. J. Org. Chem. 2007, 1423–1428
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1425

J. McNulty, S. Cheekoori, T. P. Bender, J. A. Coggan
SHORT COMMUNICATION
subsequent ligand exchange steps that involve halide disso- pected to hinder this ionization step (Path C) in accord with
ciation. Since halide anions are released during many cross- Le Chatelier’s principle and thus hinder cross-coupling with
coupling reactions, oxidative addition is expected to acceler- weak nucleophiles. In contrast, a strong nucleophile, such as
ate, while ligand exchange is expected to become self-poi- an arylboronic acid/base combination, could allow ligand
soning to the cycle as the reaction proceeds. The contribut- exchange (or transmetallation) by a nucleophilically assisted
ing effect of anions on a given catalytic cycle is therefore process through either association to form an anionic palla-
far from clear-cut and must depend on the nature of the dium intermediate or directly through an interchange path-
active catalyst, the medium and intimate details of the con- way. A modification of the “textbook” catalytic cycle for
tributing steps. In the present case, the bistriflimide IL is halide-free cross-coupling taking into account the details of
considered to be a dipolar, halide-free medium. Rapid the ligand exchange is presented in Scheme 4. This process
cross-coupling takes place with a weakly nucleophilic di- also offers a satisfactory explanation for the successful Su-
arylamine. When this reaction is performed in toluene, zuki cross-coupling reactions reported in the chloride-con-
5.0 equiv. of a soluble chloride are enough to poison the taining IL and hence Scheme 4 may describe a unified view
catalytic cycle with this amine under conditions where of Pd-mediated cross-coupling reactions in phosphonium
stronger nucleophiles like arylboronic acids readily partici- salt ILs; the differences is accounted for by the nature of
pate. The most likely explanation involves the nature of the the ligand exchange processes available and competing
ligand-exchange step, the details of which are outlined in strong or weak nucleophiles present. While the Suzuki
Scheme 4. In principle, this may take place through either cross-coupling conducted in the chloride IL could take
–
an associative (Path A), interchange (Path B) or dissociative place via the involvement of the anionic complex (L PdCl ),
2
Path C) mechanism.[ In the case of the bistriflimide IL, the lack of coordinating solvent and high chloride ion con-
20]
(
the polar medium, absence of halide and excess of nonco- centration are expected to retard subsequent ligand ex-
ordinating anion are likely to promote the ionization of the change processes, which raises doubt that such a cycle is
halide from the oxidative addition intermediate to yield a operative.
+
[21]
cationic L PdAr complex. This complex can then com-
Taken together, the overall results of the amination reac-
2
bine with the weakly nucleophilic diarylamine, which pro- tion conducted in phosphonium salt ILs and toluene with
vides the next intermediate that undergoes N-deproton- the addition of soluble anions show that the general anionic
[
22]
ation
cycle.
and finally reductive elimination to complete the effect uncovered in our investigations in IL media are also
applicable to typical Buchwald–Hartwig amination reac-
tions conducted in a standard solvent such as toluene. In
retrospect, the use of the phosphonium salt IL media as the
solvent coupled with either coordinating or noncoordina-
ting anions proved to be an ideal media in which to isolate,
uncover and probe the anionic effect in this cross-coupling
reaction. The use of a media consisting of a diffuse phos-
phonium cation coupled to anions varying from Lewis-ba-
sic to noncoordinating has provided insight into the nature
of the Buchwald–Hartwig amination cycle. The anionic ef-
fects indicate ionization in noncoordinating media and the
intervention of a cationic palladium intermediate with the
weakly nucleophilic amine. Further investigations into the
nature of the active catalyst described in the bistriflimide
IL and its oxidative addition product, as well as the synthe-
sis of a variety of triarylamines by the cross-coupling of
weakly nucleophilic diarylamines utilizing this process, is
under investigation in our laboratories.
Experimental Section
General Information: Reactions were carried out under an argon
atmosphere in oven-dried glassware. All ionic liquids used were ob-
tained from Cytec Canada Inc., Niagara Falls, Ontario. Ionic li-
quids were degassed under high vacuum for at least one hour im-
mediately prior to use. All other solids were dried under high vac-
Scheme 4. Proposed catalytic cycle and dissociative ligand exchange
Path C) with weak nucleophiles in noncoordinating media.
uum. Toluene was distilled from sodium metal with benzophenone
indicator. CIMS were obtained with a Micromass Quattro Ultima
spectrometer fitted with a direct injection probe (DIP) with ioniza-
(
The presence of excess halide or other coordinating tion energy set at 70 eV and HRMS (CI) were performed with a
1
13
anion in the reaction conducted in the IL or toluene is ex- Micromass Q-Tof Ultima spectrometer. H and C NMR spectra
1426
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1423–1428

Anionic Effect in the Pd-Catalyzed Amination Reaction
SHORT COMMUNICATION
were recorded with a Bruker 500 or AV 700 spectrometer with TMS
as the internal standard. Chemical shifts are reported in ppm
downfield of TMS.
trihexyl(tetradecyl)phosphonium chloride (22 mg, 1.0 equiv.) and
dry toluene (3.0 mL), 4-bromobiphenyl (10 mg, 1 equiv.), sodium
tert-butoxide (7.7 mg, 1.8 equiv.), Pd
), 2,2,6,6-tetramethyl-1-isobutylphosphorinane ligand HBF
1.3 mg, 9 mol-%) and diphenylamine (8 mg, 1.05 equiv.) were se-
2
(dba)
3
·CHCl
3
(2 mg, 4 mol-
%
4
salt
General Procedure for Table 2: To a vial containing degassed tri-
hexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide
(
quentially added under an argon atmosphere. The vial was capped
and heated at 70 °C for 16 h at which time analysis (TLC or HPLC)
indicated the absence of 4-bromobiphenyl (limiting reagent) and
complete conversion to the triarylamine.
(
1.00 mL), 4-bromobiphenyl (100 mg, 0.44 mmol), sodium tert-but-
oxide (77.5 mg, 0.79 mmol), Pd (dba) ·CHCl (18.46 mg, 4 mol-%),
and 2,2,6,6-tetramethyl-1-isobutylphosphorinane ligand HBF
2
3
3
4
salt (12.2 mg, 9 mol-%) were sequentially added, followed by the
addition of diphenylamine (80 mg, 0.47 mmol) under an argon at-
mosphere. The vial was capped and heated at either 75 or 104 °C
for the duration specified. Reactions were terminated when TLC or
HPLC indicated full consumption of the bromoarene. The reaction
mixture was cooled to room temperature. The product was isolated
by using a hexane/water protocol. This results in partitioning of
the central ionic liquid phase between the lower water and upper
hexane layers with the palladium complex remaining in the ionic
liquid layer. The combined hexane fractions were dried with
Trihexyl(tetradecyl)phosphonium Chloride (5 equiv.): To a vial con-
taining degassed trihexyl(tetradecyl)phosphonium chloride
(115 mg, 5 equiv.) and dry toluene (3.0 mL), 4-bromobiphenyl
(10 mg, 1 equiv.), sodium tert-butoxide (7.7 mg, 1.8 equiv.),
Pd
2
(dba)
3
·CHCl
3
(2 mg, 4 mol-%), 2,2,6,6-tetramethyl-1-isobutyl-
salt (1.3 mg, 9 mol-%) and diphenyl-
phosphorinane ligand HBF
4
amine (8 mg, 1.05 equiv.) were sequentially added under an argon
atmosphere. The vial was capped and heated at 70 °C for 16 h at
which time analysis (HPLC or TLC) indicated that only starting
materials were present.
2 4
Na SO , the solvent was removed under reduced pressure and the
product was isolated from a silica column (hexane) to give the de-
sired product in 73% yield.
Acknowledgments
N-Biphenyl-N-diphenylamine (3a): The general procedure was fol-
lowed throughout Table 2 with the various ionic liquids at 104 °C.
We thank NSERC, Xerox Research Centre of Canada and McMas-
ter University for financial support of this work and Cytec Canada
Inc. for provision of the ionic liquids used in this work.
1
White solid. H NMR (500 MHz, CDCl
3
): δ = 7.57 (d, J = 7.5 Hz,
2
6
H), 7.48 (d, J = 8.5 Hz, 2 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.28 (m,
1
3
H), 7.14 (d, J = 8.4 Hz, 5 H), 7.03 (t, J = 7.4 Hz, 2 H) ppm.
): δ = 147.7, 147.1, 140.6, 135.1, 129.2
4 C), 128.7 (2 C), 127.7 (2 C), 126.7 (2 C), 126.6 (2 C), 124.4 (4
C), 123.9 (2 C), 122.9 (2 C) ppm. EIMS (70 eV): m/z (%) = 321
C
NMR (125.7 MHz, CDCl
(
3
[
1] a) J. F. Hartwig, Angew. Chem. Int. Ed. 1998, 37, 2046–2067;
b) A. R. Muci, S. L. Buchwald, “Practical Palladium Catalysts
for C–N and C–O Bond Formation” in Topics in Current
Chemistry (Ed.: N. Miyaura), Springer, Berlin, vol. 219, p. 133
+
[M] (100), 243 (15), 167 (10), 77 (10), 43 (10). HRMS (EI): calcd.
for C24 19N 321.1517; found 321.1508.
H
2002; c) J. Tsuji, Palladium Reagents and Catalysts, Wiley,
Chichester, 2004, p. 373; d) J. P. Corbet, G. Mignani, Chem.
Rev. 2006, 106, 2651–2710.
[2] a) F. Ullmann, Ber. Dtsch. Chem. Ges. 1903, 36, 2382–2384; b)
I. P. Beletskaya, A. V. Cheprakov, Coord. Chem. Rev. 2004, 248,
N-(4-Methoxyphenyl)-N-phenylamine (3b): The general procedure
was followed, and the reaction was heated at 75 °C (Table 3, Entry
). Yellow solid. M.p. 103–104 °C, Ref.[
23]
1
1
104–105 °C. H NMR
(500 MHz, CDCl
3
): δ = 7.26 (t, J = 8.4, 7.5 Hz, 2 H), 7.12 (d, J =
2
337–2364; c) J. Lindley, Tetrahedron 1984, 40, 1433–1456; d)
S. V. Ley, A. W. Thomas, Angew. Chem. Int. Ed. 2003, 42,
400–5449.
8
.7 Hz, 2 H), 6.86 (m, 5 H), 5.56 (br. s, 1 H), 3.84 (s, 3 H) ppm.
1
3
C NMR (125.7 MHz, CDCl
3
): δ = 155.3, 145.1, 135.7, 129.2 (2
5
C), 122.2 (2 C), 119.5 (2 C), 115.6 (2 C), 114.6, 55.5 ppm. CIMS
[3] a) J. Louie, J. F. Hartwig, Tetrahedron Lett. 1995, 36, 3609–
3612; b) A. S. Guram, R. A. Rennels, S. L. Buchwald, Angew.
Chem. Int. Ed. Engl. 1995, 34, 1348–1350.
+
(
70 eV): m/z (%) = 199 [M] (50), 184 (40), 105 (100). HRMS (CI):
calcd. for C13 13NO 199.0997; found 199.0995.
H
[
4] For a selection of recent examples, see: a) X. Xie, T. Y. Zhang,
Z. Zhang, J. Org. Chem. 2006, 71, 6522–6529; b) R. A. Singer,
M. Dore, J. E. Sieser, M. A. Berliner, Tetrahedron Lett. 2006,
47, 3727–3731; c) L. L. Hill, L. R. Moore, R. Huang, R. Crac-
iun, A. J. Vincent, D. A. Dixon, J. Chou, C. J. Woltermann,
K. H. Shaughnessy, J. Org. Chem. 2006, 71, 5117–5125; d) Q.
Shen, S. Shekhar, J. P. Stambuli, J. F. Hartwig, Angew. Chem.
Int. Ed. 2005, 44, 1371–1375; e) S. Urgaonkar, J. G. Verkade, J.
Org. Chem. 2004, 69, 9135–9142; f) C. Meyers, B. U. W. Maes,
K. T. J. Loones, G. Bal, G. L. F. Lemiere, R. A. Dommisse, J.
Org. Chem. 2004, 69, 6010–6017.
N-(4-Methoxyphenyl)-N-(4-nitrophenyl)amine (3c): The general pro-
cedure was followed, and the reaction was heated at 75 °C (Table 3,
Entry 2). Orange solid. M.p. 152–153 °C, Ref.[ 152–152.5 °C. H
24]
1
NMR (500 MHz, CDCl
3
): δ = 8.10 (d, J = 9.2 Hz, 2 H), 7.18 (d,
J = 8.9 Hz, 2 H), 6.96 (d, J = 8.9 Hz, 2 H), 6.78 (d, J = 9.2 Hz, 2
H), 6.15 (s, 1 H), 3.85 (s, 3 H) ppm. 1 C NMR (125.7 MHz,
CDCl ): δ = 157.6, 151.9, 139.2, 132.2, 126.5 (2 C), 125.6 (2 C),
15.1 (2 C), 112.6 (2 C), 55.7 ppm. CIMS (70 eV): m/z (%) = 244
3
3
1
+
[M] (35), 214 (100), 199 (60). HRMS (CI): calcd. for C13
12 2 3
H N O
244.0848; found 244.0854.
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): δ = 6.97 (d, J = 8.9 Hz, 4 H), 6.85 (d,
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(
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Published Online: February 9, 2007
44, 2217–2220.
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1423–1428