Direct synthesis of primary arylamines via C-N cross-coupling of aryl bromides and triflates with amides

Article abstract of DOI:10.1016/j.tet.2009.01.033

Aryl halides and triflates are coupled with primary amides to give the corresponding arylamines in the presence of a palladium catalyst, a suitable ligand, and a base. The catalyst system performs well for a large number of different substrates at 100-150 °C without solvent, and with low catalyst levels (0.12 mol % Pd). Nicotinamide might be useful as a nitrogen source in the Pd-catalyzed amination reaction.

Full text of DOI:10.1016/j.tet.2009.01.033

Tetrahedron 65 (2009) 1951–1956
Contents lists available at ScienceDirect
Tetrahedron
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Direct synthesis of primary arylamines via C–N cross-coupling of aryl bromides
and triflates with amides
*
´
M. Romero, Y. Harrak, J. Basset, J.A. Orue, M.D. Pujol
`
Laboratori de Qu´ımica Farmace`utica (Unitat associada al CSIC), Facultat de Farmacia, Universitat de Barcelona, Av. Diagonal 643, E-08028 Barcelona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Aryl halides and triflates are coupled with primary amides to give the corresponding arylamines in the
presence of a palladium catalyst, a suitable ligand, and a base. The catalyst system performs well for
a large number of different substrates at 100–150 ꢀC without solvent, and with low catalyst levels
(0.12 mol % Pd). Nicotinamide might be useful as a nitrogen source in the Pd-catalyzed amination
reaction.
Received 3 December 2008
Accepted 7 January 2009
Available online 14 January 2009
Keywords:
Arylamination
Coupling
Ó 2009 Elsevier Ltd. All rights reserved.
Palladium catalyst
Primary amines
Nucleophilic amides
1. Introduction
a specific substrate, but often limitations are found when applying
to other substrates, or in other cases where the catalyst system or
N-Arylamines are important compounds, particularly in phar-
maceutical research and also as intermediates for organic synthe-
sis.1 For this reason significant efforts have gone into the
development of new methods for their preparation.
In spite of its apparent simplicity the preparation of primary
arylamines is some times difficult. The classical protocols for aryl
amination involve several steps and are often incompatible with
several functional groups and are also limited to determined aro-
matic compounds. In the classical reactions, the most direct for-
mation of N-aryl compounds requires copper salts as the catalyst
(Ullmann-type conditions) and usually needs drastic reaction
conditions.2–4
the ligand is excessively expensive, no commercial available or with
difficult manipulation.
Reports from several research groups on the palladium-cata-
lyzed cross-coupling of aryl halides with N-derivatives have fur-
nished interesting results but have revealed the need to find new
conditions for the preparation of primary arylamines. Several times
this aryl amination protocol does not provide direct entry to pri-
mary arylamines.
Recently, Gooben and co-workers15 present new reaction con-
ditions for the coupling of aryl chlorides with primary or secondary
amines using air- and water-stable naphtho quinone imidazolin-
2-ylidene-palladium(0) as catalyst and KOH as a base.
In the last decade, several research groups such as Buchwald and
co-workers5–8 and Hartwig and co-workers9–12 reported the
palladium-catalyzed coupling of aryl halides with several amino-
derivatives. Buchwald and co-workers described the synthesis of
N-arylamines from aryl benzenesulfonates.13,14 It is noteworthy
that significant progress in palladium-catalyzed amination
reactions has been achieved by the research groups of Buchwald
and Hartwig, showing good conditions and the tolerance for
determined substrates.
In the past decade, Buchwald and co-workers16 have been
employed commercial available benzophenone imine as ammonia
equivalent for the preparation of primary anilines. This method
needs an additional acidic hydrolysis or hydrogenolysis for yielding
the primary aniline. This work describes the utility of benzophe-
none imine for the preparation of primary amines under different
conditions according to the starting material, showing the lack of
a general protocol.
Moreover, Buchwald and Huang17 and Hartwig and co-workers18
have described separately the use of LiN(SiMe3)2/LiHMDS as a sys-
tem ammonia equivalent for the Pd-catalyzed coupling of aryl ha-
lides. Later, Hartwig and co-workers19 reported that zinc
bis(hexamethyldisilazide) is an ammonia surrogate for the amina-
tion of aryl halides better than lithium bis(trimethylsilyl)amide
(LiN(SiMe3)2), but the reaction needs of several additives. Recently,
In general, some experimental reactions proceed efficiently with
determined conditions (catalyst, ligand, base, and temperature) for
* Corresponding author. Fax: þ34 93 4035941.
E-mail address: mdpujol@ub.edu (M.D. Pujol).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.033

1952
M. Romero et al. / Tetrahedron 65 (2009) 1951–1956
Weigand and co-workers20 reported the use of amine resins as
amino group sources in palladium-catalyzed amination of aryl ha-
lides. This method served for the preparation of primary anilines
only from aryl halides containing electron-withdrawing groups.
Copper derivatives21 have been known to catalyze the amination of
bromopyridines under several conditions or the synthesis of pri-
mary arylamines using amidine hydrochlorides.22 Also the use of
ammonia as a nucleophile has been reported by several authors but
these methods for the synthesis of primary arylamines might not be
technically safe and simple (special material, high pressure and high
temperature, and limited applications).23
isonicotinamide than nicotinamide (compare entry 15 vs 17; entry
16 vs 18).
An ortho-substituent on the aryl bromides decreases the cou-
pling yields. Thus the steric hindrance has influence in both elec-
tron-rich and electron-deficient aryl halides (compare entry 20 vs
11; and 21 vs 16).
These results demonstrate that Pd-catalyzed aminations using
nicotinamide as the ammonia surrogates is a new method for the
preparation of primary anilines with interesting yields in one pot
reaction. The ease of deprotection is produced in the basic media of
the reaction. To determine the relative hydrolysis, the reaction (Table
1, entry 14) was stopped at 45 min, the compounds were separated,
and the intermediate arylamide was detected by NMR analysis.27
After the hydrolysis of the resulting arylamide with Cs2CO3 in tolu-
ene with open flask gave the p-cyanoaniline in quantitative yield
improving the hydrolysis process at high temperatures.
Triflates are not commercially available and therefore it had to
be synthesized first.28 It is important to mention that the procedure
for the preparation of aryl triflates is very efficient. The used
reaction conditions [Pd[P(o-tolyl)3]2Cl2, (BINAP), and cesium carb-
onate] for the preparation of primary amines were tested pre-
viously by us for the amination of aryl triflates,24 and now extended
to other substrates, the new results are summarized in Table 2. The
primary arylamines was obtained in moderate to excellent yields
(Table 2, entries 1–4). In the preparation of naphthylamine, aryl
bromide and aryl triflate gave comparable yield (Table 1, entry 2 vs
Table 2, entry 4). While poor-aryl bromides gave best yields than
the corresponding triflates, the electron-rich bromides were less
effective than the aryl triflate in the amination reaction (Table 1,
entry 11 vs Table 2, entry 3). In this paper we showed that the
palladium-catalyzed amination of aryl bromides or aryl triflates
methodology can be applied to the preparation of aryldiamines.
Attempts to extend our method to diaryl halides or diaryl triflates
were successful for benzene derivatives (Table 1, entry 22; Table 2,
entries 6 and 7) but we found problems for the pyridine analogues
(Table 1, entry 8). The preparation of the diamino-lactona (Table 2,
entry 7) is complicated; in this case 44% of the pure isolated diamine
was obtained, indicating that the lactone group was compatible with
this reaction conditions. We found that the coupling reaction using
nicotinamide is effective for the preparation of arylamines and the
nicotinamide can be considered as a new and efficient ammonia
equivalent not tested in previous palladium-catalyzed C–N cross-
coupling approaches. Moreover the nicotinamide is a more econom-
ical ammonia precursor than other reagents presented previously.
Reactions as in entries 15, 16 (Table 1) and 1, 6 (Table 2) were
carried out from 5 g of starting aryl bromide or triflate and the yields
were 88, 90, 80, and 53% respectively proving that this methodology
can be able for multigram scale. Only 0.12 mol % of palladium cat-
alyst was needed for the formation of the desired arylamines.
Looking at the results obtained in Tables 1 and 2, one can con-
clude that this methodology is interesting to prepare the desired
arylamines or aryldiamines from the corresponding aryl bromides
or aryl triflates. Efforts to expand the reaction scope are in progress
in our laboratory.
2. Results and discussion
This work intends to conversion of aryl bromides or triflates to
desired primary anilines using palladium catalyst. Aryl bromides
are readily available, more reactive than aryl chlorides, and more
stable than aryl iodides. The conditions used for the N-arylation of
several substrates were Pd[P(o-tolyl)3]2Cl2, chelating ligand 2,20-
bis(diphenylphosphino)-1,10-binaphthyl (BINAP), and cesium carb-
onate as the base under argon atmosphere without solvent (Fig. 1).
This protocol has been developed previously by us for the cou-
pling of aryl bromides or triflates with primary or secondary
amines.24 All the reagents can be weighed in contact with air. Some
aryl bromides and triflates were tested in our reaction conditions.
The obtained arylamines may be isolated and purified without
problems.
Primary anilines were prepared in a one-step palladium-cata-
lyzed amination reaction of aryl bromides with amides, opening
a new synthetic route to general preparation of primary anilines
(Table 1).
Other procedures reported previously, do not provide direct
entry to primary arylamines, and additional steps (protection,
cleavage) are necessary for protecting or unmasking or the am-
monia surrogate is expensive.25 Recently, Chang and co-workers
reported the use of ammonium salts in Cu-catalyzed amination of
aryl halides.26 We have found that the aryl halides react with nic-
otinamide in the general conditions indicated before, affording the
primary arylamines in a one step (Table 1, entries 2, 5, 6, 8–16, and
20–22). Other amides such as acetamide (Table 1, entries 1 and 4),
benzamide (Table 1, entries 3 and 7), isonicotinamide (Table 1,
entries 17 and 18) or formamide (Table 1, entry 19) can be used but
gave the desired amines in low yield. Coupling of 3-bromopyridine
with nicotinamide worked well, providing the 3-aminopyridine in
acceptable yield (Table 1, entry 5). Acetamide showed lower re-
activity (Table 1, entry 4).
The reactivity of 2-bromopyridine is less than the 3-bromo-
pyridine and gave a mixture of 2-aminopyridine and the in-
termediate amide (Table 1, entry 6). For 2,6-dibromopyridine,
coupling with nicotinamide occurred at the 2-position exclusively
(Table 1, entries 8 and 9). Using this procedure, unfortunately,
p-methoxybromobenzene was not converted to the desired aniline,
only the intermediate amide and poor conversion were observed
(Table 1, entry 10), but with prolonged time of reaction the yield
was increased (Table 1, entry 11) while the methylsulfonyl bro-
mobenzene give a mixture of the expected amine and the corre-
sponding diaryl amine (Table 1, entry 12). The high reactivity of the
aryl bromide in the reaction mixture led to the formation of the
double arylated amine in 21% yield (Table 1, entry 12). Results
demonstrate the expected major reactivity of the bromobenzene
containing electron-withdrawing substituents (entries 14 and 15)
in comparison with the presence of electron-donating groups
(entries 10, 11, and 13).
O
O
Ar-NH-C-R
H2O
Pd[P(o-tolyl)3]2Cl2
+
R-C-NH2
Ar-X
BINAP / Cs2CO3
SNRAr
Cs2CO3
O-H
Ar-NH-C-R
+
RCOOH
Ar-NH2
OH
The 6-amino-[1,4]-benzodioxin was obtained directly from the
corresponding electron-rich aryl bromide in moderate yield 65%
(Table 1, entry 13). Yields were low for the coupling of
Figure 1. A mechanism for the cross-coupling N-arylation from aryl halides and pri-
mary amides.

M. Romero et al. / Tetrahedron 65 (2009) 1951–1956
1953
Table 1
Palladium-catalyzed formation of primary amines from aryl halides
Entry
Ar–X
Br
R1R2NH
Time
2 h
Product
NH2
Yielda (%)
1
CH3CONH2
54
Br
Br
NH2
NH2
CONH2
2
3
4
5
2 h
16 h
2 h
2 h
75
5
N
CONH2
Br
NH2
NH2
CH3CONH2
51
83
N
N
N
Br
CONH2
N
N
N
N
31
CONH2
NH2
6
16 h
N
N
Br
Br
8327
N
N
NHOC
NH2
CONH2
CONH2
7
8
16 h
24 h
12
36
N
Br
N
NH2
Br
Br
N
N
Br
N
N
N
52
42
24
Br
Br
N
NH-CO
CONH2
Br
N
N
NH2
9
72 h
Br
N
NH-CO
Br
CONH2
CONH2
N
N
10
11
24 h
72 h
1528
OCH3
CONH
N
N
OCH3
Br
79
42
OCH3
CONH
OCH3
NH2
H3CO2S
Br
CONH2
12
2 h
N
NH
SO2CH3
21
H3CO2S
(continued on next page)
2

1954
M. Romero et al. / Tetrahedron 65 (2009) 1951–1956
Table 1 (continued )
Entry
Ar–X
R1R2NH
Time
16 h
Product
Yielda (%)
O
O
Br
Br
CONH2
O
O
NH2
NH2
13
14
65
10
N
N
NC
CONH2
45 min
NC
H
N
N
52
88
O
NC
Br
Br
CONH2
CONH2
NH2
15
16
6 h
6 h
NC
N
N
NC
NH2
NH2
90
69
O2N
O2N
NC
CONH2
Br
17
24 h
N
H
N
NC
N
1029
O
NC
CONH2
Br
Br
NH2
18
19
24 h
24 h
71
5
O2N
NC
O2N
NC
N
NH2
HCONH2
H
N
H
38
O
NC
O
NHC
N
Br
CONH2
20
21
72 h
6 h
3830
OCH3
Br
N
N
OCH3
NH2
CONH2
CONH2
56
NO2
NO2
Br
Br
H2N
NH2
22
24 h
56
N
a
Yields reported correspond to analytically pure isolated compounds (average of two or three runs). Pd[P(o-tolyl)3]2Cl2, cesium carbonate, and BINAP(ꢂ) were used in all
assays. The reactions were conducted at 150 ꢀC.
3. Experimental section
3.1. General
heterocorrelation 1H–13C (HMQC and HMBC) experiments were
recorded on a Varian VXR-500 (500 MHz). Mass spectra were
recorded on a Hewlett-Packard 5988-A. Column chromatography
was performed with silica gel (E. Merck, 70–230 mesh). Reactions
were monitored by TLC using 0.25 mm silica gel F-254 (E. Merck).
Microanalysis was determined on a Carlo Erba-1106 analyzer. All
reagents were of commercially quality or were purified before use.
Organic solvents were of analytical grade or were purified by
standard procedures. All the commercially available reagents used
were purchased from Aldrich Chemical Co. and were used without
previous purification. The catalyst was acquired from Strem
(Chemicals for Research).
Melting points were obtained on an MFB-595010M Gallenkamp
apparatus in open capillary tubes and are uncorrected. IR spectra
were obtained using an FTIR Perkin–Elmer 1600 Infrared Spectro-
photometer. Only noteworthy IR absorptions are listed (cmꢁ1). 1H
and 13C NMR spectra were recorded on a Varian Gemini-200 (200
and 50.3 MHz, respectively) or Varian Gemini-300 (300 and
75.5 MHz) Instrument using CDCl3 as solvent with tetramethylsi-
lane as internal standard or (CD3)2CO. Other 1H NMR spectra and

M. Romero et al. / Tetrahedron 65 (2009) 1951–1956
1955
Table 2
Palladium-catalyzed formation of primary amines from triflates
Entry
Ar–X
R1R2NH
CONH2
Time
16 h
Product
Yielda (%)
80
1
O2N
NC
OTf
OTf
OTf
O2N
NC
NH2
NH2
NH2
N
N
N
N
CONH2
CONH2
CONH2
2
3
4
16 h
72 h
16 h
83
52
76
H3CO
H3CO
OTf
NH2
CONH2
OTf
NH2
5
6
16 h
16 h
65
53
N
CONH2
CONH2
TfO
OTf
H2N
NH2
N
N
O
O
O
O
7
16 h
44
OTf
NH2
TfO
H2N
a
Yields reported correspond to analytically pure isolated compounds (average of two or three runs). Pd[P(o-tolyl)3]2Cl2, cesium carbonate, and BINAP(ꢂ) were used in all
assays. The reactions were conducted at 150 ꢀC.
3.2. Aryl triflates. General procedure
was heated at 100–150 ꢀC (after the substrate and all reagents have
been added without any period of incubation) with stirring until
the starting material has been completely consumed as analyzed by
TLC. The mixture was then allowed to cool to room temperature
with the flask opened, water was added (15 mL) and was taking up
in dichloromethane (15 mL), filtered, and concentrated. The crude
product was then purified further by flash chromatography on silica
gel, eluting with mixtures of hexane/ethyl acetate. Yields reported
correspond to analytically pure isolated compounds.
The starting triflates were prepared by treatment of the corre-
sponding phenol (1 mmol) with triflate anhydride (1.2 mmol) in
dichloromethane (10 mL)inthepresenceoftriethylamine(1.2 mmol)
at 0 ꢀC. The resulting mixture was stirred at this temperature for
90 min. The reactionwas performed under an argon atmosphere. The
solvent was removed and the crude of reaction was directly purified
by silica gel column chromatography (hexane/ethyl acetate).
The spectroscopic data of the known compounds is in full
agreement with that obtained from an authentic sample purchased
from Aldrich Chemicals Co. Combustion analyses were obtained for
all new compounds, and for compounds which had been previously
reported with limited analysis.
3.2.1. 3,3-Bis(4-trifluoromethylsulfonyloxyphenyl)-1(3H)-
isobenzofuranone (Table 2, entry 7)
IR (KBr)
(200 MHz, acetone-d6)
n
(cmꢁ1): 1560 (C]C),1425 (S]O),1210 (Ar–O). 1H NMR
d
(ppm): 7.29 (d, J¼8.2 Hz, 4H, ortho-phe-
nyl), 7.43 (d, J¼8.2 Hz, 4H, meta-phenyl), 7.52 (d, J¼8 Hz, H-4), 7.61
(t, J¼8 Hz, 1H, H-5), 7.78 (t, J¼8 Hz, 1H, H-6), 8.00 (d, J¼8 Hz, 1H, H-
3.3.1. N-(6-Bromopyridin-2-yl)nicotinamide (Table 1, entries
8 and 9)
7). 13C NMR (50.3 MHz, acetone-d6)
d (ppm): 100.2 (C, C-3), 116.8
(CH, C-30, C-50 (ꢃ2)), 118.6 (C, CF3 (ꢃ2)), 127.2 (CH, C-6), 128.1 (CH,
C-4), 129.3 (C, C-7a), 130.2 (CH, C-20, C-60 (ꢃ2)), 132.1 (CH, C-7),
134.2 (CH, C-5), 138.0 (C, C-10 (ꢃ2)), 153.2 (C, C-40 (ꢃ2)), 158.3 (C, C-
60), 150.1 (CH, C-6), 167.4 (C, CO). Anal. Calcd for C22H12F6O8S2: C
45.38%; H 2.09%; F 19.58%. Found: C 45.67%; H 2.34%; F 19.86%.
IR (KBr)
(200 MHz, acetone-d6)
n
(cmꢁ1): 3000 (NH), 2912 (C–H), 1674 (C]O). 1H NMR
d
(ppm): 7.45 (d, J¼8 Hz, 1H, H-30), 7.58 (m,
1H, H-5), 7.81 (t, J¼8 Hz, H-40), 8.36 (d, J¼8 Hz, 1H, H-50), 8.46 (m,
1H, H-3), 8.81 (dd, J¼1, 6 Hz, 1H, H-6), 9.21 (d, J¼1 Hz, 1H, H-2). 13C
NMR (50.3 MHz, acetone-d6) d
(ppm): 110.4 (CH, C-30), 118.6 (CH, C-
50), 124.2 (CH, C-5), 131.6 (C, C-3), 138.0 (CH, C-4), 140.2 (CH, C-40),
144.3 (C, C-60), 150.1 (CH, C-6), 154.8 (CH, C-2), 159.0 (C, C-20), 166.4
(C, CO). Anal. Calcd for C11H8BrON3: C 47.51%; H 2.90%; N 15.11%.
Found: C 47.86%; H 2.78%; N 14.78%.
3.3. Amination of aryl halides (Tables 1 and 2). General
procedure
A flask was charged with aryl halide or aryl triflate (1 mmol),
amide (2 mmol), cesium carbonate (2 mmol), Pd[P(o-tolyl)3]2Cl2
(0.12 mol % Pd), and BINAP (0.075 mmol) under argon without ad-
dition of solvent (just a drop of toluene was added only in excep-
tional cases). The flask was hermetically closed, and the mixture
3.3.2. N-(4-Cyanophenyl) nicotinamide (Table 1, entry 14)
IR (KBr)
n
(cmꢁ1): 3165 (NH), 2928 (C–H), 2230 (CN), 1654
(C]CO). 1H NMR (200 MHz, CDCl3)
d (ppm): 7.52 (m, 1H, H-5), 7.78
(d, J¼8.8 Hz, 2H, H-20, and H-60), 8.06 (d, J¼8.8 Hz, 2H, H-30, H-50),

1956
M. Romero et al. / Tetrahedron 65 (2009) 1951–1956
6. Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 1997, 62, 1264–1267.
7. Wolfe, J. P.; Rennels, R. A.; Buchwald, S. L. Tetrahedron 1996, 52, 7525–7546.
8. (a) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144–1157; (b) Yin, J.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043–6048; (c) Ikawa, T.; Barder, T.
E.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 13001–13007.
9. Mann, G.; Hartwig, J. F.; Driver, M. S.; Ferna´ndez-Rivas, C. J. Am. Chem. Soc. 1998,
120, 827–828.
8.32 (d, J¼7 Hz,1H, H-4), 8.80 (d, J¼5 Hz,1H, H-6), 9.20 (d, J¼2.4 Hz,
1H, H-2). 13C NMR (50.3 MHz, CDCl3) (ppm): 108.3 (C, C-40), 120.8
(C, CN), 122.4 (CH, C-20, C-60), 125.4 (CH, C-5), 132.4 (C, C-3), 134.9
(CH, C-30, C-50), 137.6 (CH, C-4), 145.5 (C, C-10), 151.1 (CH, C-6), 154.4
(CH, C-2), 166.7 (C, CO). Anal. Calcd for C13H9ON3: C 69.95%; H
4.06%; N 18.82%. Found: C 70.22%; H 4.42%; N 18.46%.
d
10. Hartwig, J. F. Synlett 1996, 329–340.
11. Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 7217–7218.
12. Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046–2067.
13. (a) Ahman, J.; Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6363–6366; (b) Huang,
X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.; Buchwald, S. L. J. Am. Chem.
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Lett. 1997, 38, 6367–6370.
15. Gooben, L. J.; Paetzold, J.; Briel, O.; Rivas-Nass, A.; Karch, R.; Kayser, B. Synlett
2005, 275–278.
3.3.3. 3,3-Bis(4-aminophenyl)-1(3H)-isobenzofuranone (Table 2,
entry 7)
IR (KBr)
n
(cmꢁ1): 3262 (OH), 2922 (C–H), 1600 (C]C), 1261 (Ar–
O),1080(C–O).1HNMR(300 MHz,CDCl3)
d
(ppm):6.74(d, J¼8 Hz,4H,
ortho-amine), 7.02 (d, J¼8 Hz, 4H, meta-amine), 7.46 (m, 2H, Ar), 7.62
(d, J¼7.6 Hz,1H, H-4), 7.82 (d, J¼7.2 Hz, 1H, H-7). 13C NMR (75.5 MHz,
16. Wagaw, S.; Yang, B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
10251–10252.
CDCl3)
d
(ppm): 90.2 (C, C-3),115.3 (CH, ortho-amine(ꢃ4)),119.8 (C, C-
10 (ꢃ2)),120.9 (CH, C-4),121.4 (CH, C-6),128.2 (CH, meta-amine (ꢃ2)),
128.7 (CH, C-7), 130.9 (C, C-7a), 131.6 (CH, C-5), 140.5 (C, C-3a), 144.2
(C, C-40),165.8 (C, CO). Anal. Calcd for C20H18O2N2: C 75.45%; H 5.70%;
N 8.80%. Found: C 75.21%; H 5.93%; N 8.42%.
17. Buchwald, S. L.; Huang, X. Org. Lett. 2001, 3, 3417–3419.
18. Lee, S.; Jorgensen, M.; Hartwig, J. F. Org. Lett. 2001, 3, 2729–2732.
19. Lee, D.-Y.; Hartwig, J. F. Org. Lett. 2005, 7, 1169–1172.
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Acknowledgements
Financial support for this work was provided by the Ministerio
´
de Ciencia y Tecnologıa (CTQ2007-60614/BQU), and the Departa-
0
´
ment d Universitats, Recerca i Societat de la Informacio de la Gen-
eralitat de Catalunya, Spain (2005-SGR-00180). One of us (J.B.)
acknowledges the Generalitat de Catalunya for the doctoral
fellowship.
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