Room-temperature palladium-catalyzed amination of aryl bromides and chlorides and extended scope of aromatic C-N bond formation with a commercial ligand

Article abstract of DOI:10.1021/jo990408i

The reactions of aryl bromides with amines occurs at room temperature when using Pd(0) and P(t-Bu)₃ in a 1:1 ratio, and the reactions of aryl chlorides occur at room temperature or 70 °C. The arylation of indoles and the new arylation of carbamates also occur when using P(t-Bu)₃ as ligand.

Full text of DOI:10.1021/jo990408i

J . Org. Chem. 1999, 64, 5575-5580
5575
Room -Tem p er a tu r e P a lla d iu m -Ca ta lyzed Am in a tion of Ar yl
Br om id es a n d Ch lor id es a n d Exten d ed Scop e of Ar om a tic C-N
Bon d F or m a tion w ith a Com m er cia l Liga n d
J ohn F. Hartwig,* Motoi Kawatsura, Sheila I. Hauck, Kevin H. Shaughnessy, and
Luis M. Alcazar-Roman
Department of Chemistry, Yale University P.O. Box 208107, New Haven, Connecticut 06520-8107
Received March 8, 1999
The reactions of aryl bromides with amines occurs at room temperature when using Pd(0) and
P(t-Bu) in a 1:1 ratio, and the reactions of aryl chlorides occur at room temperature or 70 °C. The
3
arylation of indoles and the new arylation of carbamates also occur when using P(t-Bu) as ligand.
3
The palladium-catalyzed amination of aryl halides1
-6
and increased scope of the aromatic C-N bond formation.
(
eq 2) has become an important method for the synthesis
of arylamines found in pharmaceuticals, materials with
Workers at Tosoh Co. reported that P(t-Bu) provided
3
7
,8
high turnover numbers for the formation of arylpipera-
9
-21
23
important electronic properties,
and ligands for early
zines with excess ligand at 120 °C. Our group has
metal catalysts.22 Because of the importance of this
synthetic method, there has been extensive effort to find
shown that a sterically hindered alkylphosphine prepared
in one step allows for room-temperature amination of aryl
halides and that another commercially available, steri-
cally hindered alkylphosphine allows for the reaction of
aryl chlorides with primary alkylamines under mild
conditions.25 Buchwald’s group has recently reported that
a P,N ligand containing a biphenyl backbone, which is
prepared in three steps, generates a catalyst that leads
to examples of room-temperature amination chemistry
with aryl bromides and room-temperature Suzuki chem-
istry.26
2
3,24
catalysts that provide high turnover numbers,
fast
reaction rates,2
5,26
high functional group compatibility,
27
(
1) Hartwig, J . F. Angew. Chem., Int. Ed. Engl. 1998, 37, 2046-
2
067.
(
(
218.
(
2) Louie, J .; Hartwig, J . F. Tetrahedron Lett. 1995, 36, 3609-3612.
3) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1996, 118, 7217-
7
4) Wolfe, J . P.; Wagaw, S.; Marcoux, J .-F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805-818.
5) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1348-1350.
6) Wolfe, J . P.; Wagaw, S.; Buchwald, S. L. J . Am. Chem. Soc. 1996,
18, 7215-7216.
7) Hong, Y. P.; Tanoury, G. J .; Wilkinson, H. S.; Bakale, R. P.; Wald,
S. A.; Senanayake, C. H. Tetrahedron Lett. 1997, 38, 5663-5666.
8) Hong, Y.; Senanayake, C. H.; Xiang, T.; Vandenbossche, C. P.;
Tanoury, G. J .; Bakale, R. P.; Wald, S. A. Tetrahedron Lett. 1998, 39,
(
(
1
(
(
3
121-3124.
9) Goodson, F. E.; Hartwig, J . F. Macromolecules 1998, 31, 1700-
703.
(
1
In this paper, we show that conditions can be found
for the amination of aryl bromides with arylamines and
with secondary alkylamines at room temperature using
(
10) Louie, J .; Hartwig, J . F. Macromolecules 1998, 31, 6737-6739.
(11) Bellmann, E.; Shaheen, S.; Thayumanavan, S.; Barlow, S.;
Grubbs, R.; Marder, S.; Kippelen, B.; Peyghambarian, N. Chem. Mater.
1
1
1
998, 10, 1668-76.
12) Thayumanavan, S.; Barlow, S.; Marder, S. R. Chem. Mater.
997, 9, 3231-3235.
13) Kanbara, T.; Honma, A.; Hasegawa, K. Chem. Lett. 1996, 1135-
136.
14) Kanbara, T.; Izumi, K.; Nakadani, Y.; Narise, T.; Hasegawa,
K. Chem. Lett. 1997, 1185-1186.
15) Kanbara, T.; Izumi, K.; Narise, T.; Hasegawa, K. Polym. J .
998, 30, 66.
3
commercially available P(t-Bu) . Moreover, this ligand
(
allows for similar aminations to be conducted with
unactivated aryl chlorides at 70 °C and in one case room
temperature. In addition, aryl halides react with tert-
butylcarbamate to provide Boc-protected anilines in the
(
(
(
3 2
presence of P(t-Bu) and Pd(dba) , and they react with
1
azoles such as indole and pyrrole under mild conditions
to provide N-arylazoles in high yield. Thus, many of the
examples of mild amination reported previously with new
ligands can be conducted with the simple commercially
(
(
16) Kanbara, T.; Imayasu, T.; Hasegawa, K. Chem. Lett. 1998, 709.
17) Kanbara, T.; Oshima, M.; Hasegawa, K. J . Polym. Sci. Pol.
Chem. 1998, 36, 2155.
18) 3041Kanbara, T.; Oshima, M.; Imayasu, T.; Hasegawa, K.
Macromolecules 1998, 31, 8725-8730.
19) Singer, R. A.; Sadighi, J . P.; Buchwald, S. L. J . Am. Chem. Soc.
998, 120, 213-214.
20) Sadighi, J . P.; Singer, R. A.; Buchwald, S. L. J . Am. Chem. Soc.
998, 120, 4960-4976.
21) Spetseris, N.; Ward, R. E.; Meyer, T. Y. Macromolecules 1998,
1, 3158-3161.
22) Greco, G. E.; Popa, A. I.; Schrock, R. R. Organometallics 1998,
7, 5591.
(
(
3
available P(t-Bu) if certain procedures are followed. Our
1
1
3
1
3
3
7
1
adoption of these procedures, which simply use a 1:1 ratio
of ligand to palladium in most cases, stemmed from
preliminary kinetic studies on the amination of p-tolyl
bromide with N-methylbenzylamine using preformed Pd-
(
(
(
3 2
[P(t-Bu) ] as catalyst. We found that this reaction
(23) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998,
occurred rapidly at room temperature, in contrast to the
elevated temperatures necessary for the reaction using
a 4:1 ratio of P(t-Bu) and Pd(OAc) .
3 2
9, 617-620.
(24) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998,
9, 2367-2370.
25) Hamann, B. C.; Hartwig, J . F. J . Am. Chem. Soc. 1998, 120,
369-7370.
26) Old, D. W.; Wolfe, J . P.; Buchwald, S. L. J . Am. Chem. Soc.
998, 120, 9722.
(
(
(27) Wolfe, J . P.; Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6359-
6362.
1
0.1021/jo990408i CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/07/1999

5
576 J . Org. Chem., Vol. 64, No. 15, 1999
Hartwig et al.
Ta ble 1. Room -Tem p er a tu r e Rea ction s of Ar yl Br om id es
from haloanilines. Reactions with secondary alkyl amines
were the slowest, but the use of 1-2 mol % catalyst
allowed room-temperature reactions to occur with unac-
tivated aryl bromides within 6 h. Reaction between
primary alkylamines and unhindered aryl halides was
the one class of reaction that was not amenable to this
room-temperature chemistry.
w ith Am in es Ca ta lyzed by P d (0)/P (t-Bu )3
Systems with enolizable hydrogens, nitro groups, or
labile esters are incompatible with the strongly basic
NaO-t-Bu. Thus, Buchwald and Wolfe previously re-
2 3 3 4
ported conditions using Cs CO or K PO for the amina-
tion of activated aryl bromides with BINAP as ligand and
conditions involving the use of the commercially available
but expensive ligand of Kumada and Hayashi for the
reaction of unactivated aryl halides with secondary
2
6,27
2 3 3 4
amines in the presence of Cs CO or K PO base.
Equation 3 shows that this class of reaction can be
conducted under similar conditions when using 0.8 equiv
of P(t-Bu) /Pd(dba) as catalyst.
3 2
a
Reactions run with 1 mmol of aryl halide in 1-2 mL of toluene
solvent at room temperature. Pd(dba)2 was used in combination
with 0.8 equiv of ligand/Pd. Isolated yields are an average of at
least two runs. Pd(OAc)2 was used in place of Pd(dba)2.
b
Finally, the use of aryl chlorides rather than bromides
or iodides in cross-coupling chemistry has been actively
c
2
6,28-42
pursued because of the low cost of these reagents.
P(t-Bu) complexes of palladium have allowed for the
palladium-catalyzed arylation of ketones and malonates
Resu lts a n d Discu ssion
3
Room -Tem p er a tu r e Am in a tion of Ar yl Br om id es
a n d Mild Am in a tion of Ar yl Ch lor id es. The room-
temperature amination of aryl bromides with arylamines
and secondary alkylamines is summarized in eq 2, and
specific examples are provided in Table 1. In most cases,
at room temperature2
6,43
and for Suzuki and Heck
chemistry to be conducted with chlorides at mild tem-
peratures.3
5,36
Our optimized conditions for aromatic
amination allow for the formation of dialkylanilines,
diarylamines, or triarylamines from aryl chlorides at 70
°
C with 1-5 mol % catalyst in yields that are similar to
those observed at room temperature with bromides. The
reaction of activated aryl chlorides with secondary amines
occurred at room temperature. Remarkably, the reaction
(
28) Ben-David, Y.; Portnoy, M.; Milstein, D. J . Am. Chem. Soc.
1989, 111, 8742-3.
29) Ben-David, Y.; Portnoy, M.; Milstein, D. J . Chem. Soc., Chem.
Commun. 1989, 1816-1817.
30) Ben-David, Y.; Portnoy, M.; Gozin, M.; Milstein, D. Organome-
the use of Pd(dba)
of Pd(OAc) . However, in the singular case of reacting
ortho-substituted aryl bromides with secondary amines,
reactions initiated with Pd(OAc) were faster. In all cases,
the room-temperature chemistry was achieved by using
.8 equiv of ligand/ Pd(dba) . The use of 4 equiv of ligand,
2
led to faster reactions than the use
(
2
(
tallics 1992, 11, 1995-1996.
2
(
(
31) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94, 1047-1062.
32) Beller, M.; Reirmeier, T. H.; Reisinger, C.; Herrman, W. A.
0
2
Tetrahedron Lett. 1997, 38, 2073-2074.
or even 2 equiv in most cases, led to reactions that
occurred only at elevated temperatures.
(33) Shen, W. Tetrahedron Lett. 1997, 38, 5575-5578.
(
(
34) Perry, R. J .; Wilson, B. D. J . Org. Chem. 1996, 61, 7482-7485.
35) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. Engl. 1998, 37,
When 0.8 equiv of ligand was used, 1-2 mol % of
catalyst led to complete conversion of the aryl bromide
within hours. Reactions with diarylamines were the
fastest, occurring within 15 min in some cases. Reactions
of aniline with aryl bromides also occurred within hours
at room temperature. In this case, small amounts of
triarylamine were observed. Thus, catalysts bearing this
ligand are remarkably efficient for the synthesis of
diarylamines, but they are not suitable for the formation
of polyanilines that would be free of cross-links directly
3387-3388.
(
36) Littke, A. F.; Fu, G. C. J . Org. Chem. 1999, 64, 10-11.
37) Lipshutz, B. H.; Blomgren, P. A.; Kim, S. K. Tetrahedron Lett.
(
1
999, 40, 197-200.
(38) Indolese, A. F. Tetrahedron Lett. 1997, 38, 3513-3516.
(39) Brenner, E.; Fort, Y. Tetrahedron Lett. 1998, 39, 5359-5362.
(40) Riermeier, T. H.; Zapf, A.; Beller, M. Top. Catal. 1997, 4, 301.
(41) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int.
Ed. Engl. 1998, 37, 481-483.
42) Wolfe, J . P.; Buchwald, S. L. J . Am. Chem. Soc. 1997, 119,
054-6058.
43) Kawatsura, M.; Hartwig, J . F. J . Am. Chem. Soc. 1999, 121,
1473-1478.
(
6
(

Palladium-Catalyzed Amination of Aryl Bromides and Chlorides
J . Org. Chem., Vol. 64, No. 15, 1999 5577
Ta ble 2. Rea ction s of Ar yl Ch lor id es w ith Am in es
Ta ble 3. Rea ction s of Ar yl Ha lid es w ith Azoles
Ca ta lyzed by P d (0)/P (t-Bu )3
Ca ta lyzed by P d (0)/P (t-Bu )3
a
Reactions run with 1 mmol of aryl halide in 1-2 mL of toluene
solvent. Pd(dba)2 was used in combination with 0.8 equiv of ligand/
Pd. Isolated yields are an average of at least two runs.
b
of aniline with even the unactivated phenyl chloride oc-
curred at room temperature and was complete in 1 day
when 5 mol % of palladium was used. As for aryl bro-
a
Reactions were run with 1 mmol of azole in 1-2 mL of toluene
solvent at 100 °C. Pd(dba)2 was used in combination with 0.8-1.0
equiv of ligand/Pd. Isolated yields are an average of at least two
b
mides, reaction of primary alkylamines with unhindered
aryl chlorides was the one class of reaction that was not
amenable to chemistry with this ligand system. This
reaction is currently best conducted with ligands devel-
oped at Novartis using procedures reported by our group
previously.25
runs.
Ta ble 4. Rea ction s of Ar yl Ha lid es w ith ter t-Bu tyl
Ca r ba m a te Ca ta lyzed by P d (0)/2P (t-Bu )3
Exten d ed Scop e of C-N Bon d F or m a tion . The
reductive elimination to form arylamines, ethers, and
sulfides is sensitive to the nucleophilicity of the hetero-
atom bound to palladium.4
4-47
For example, the reductive
4
8
elimination of N-arylazoles is slow, and the reductive
elimination of N-arylcarbamates has not been observed.
However, we recently observed directly that sterically
hindered alkylphosphines accelerated reductive elimina-
tion of aryl ethers.49 Thus, it seemed likely that optimized
3
conditions with P(t-Bu) as ligand might increase the
scope of aromatic C-N bond formation to examples that
are hampered by slow reductive elimination. This poten-
tial was realized as shown in eqs 5 and 6 and Tables 3
and 4.
a
Reactions run with 1 mmol of aryl halide and 1.5 mmol tert-
butyl carbamate in 3 mL of toluene solvent at 100 °C. Pd(dba)2
was used in combination with 2.0 equiv of ligand/Pd. bIsolated
yields are an average of at least two runs.
of Pd(OAc)
2
and DPPF we reported previously.48 The
reaction between indole or pyrrole and unhindered aryl
halides, either activated or unactivated, occurred at 100
°
2 3
C after 12 h. The use of Cs CO as base, rather than
NaO-t-Bu, was crucial to the success of this reaction.
Perhaps a high concentration of azolyl anion leads to
4
8
palladium ate complexes as we described previously.
When reacted with simple indoles, hindered aryl halides
such as 2-bromotoluene generated two isomeric products
and one product from the addition of two aryl groups.
We assigned these materials to the products of arylation
at the nitrogen, at the C3-position and both sites. Thus,
reaction of 2-bromotoluene with 3-methylindole occurred
cleanly to give the N-arylation product in high yield.
The catalyst system involving P(t-Bu)
for much milder arylation of azoles than the combination
3
as ligand allows
Finally, an optimized catalyst system allows for the
use of a convenient ammonia equivalent, tert-butylcar-
bamate, to form Boc-protected anilines from aryl halides.
In this case, the use of NaOPh as base was crucial to the
success of this reaction. We reported the synthesis of
(
(
44) Hartwig, J . F. Acc. Chem. Res. 1998, 31, 852-860.
45) Bara n˜ ano, D.; Hartwig, J . F. J . Am. Chem. Soc. 1995, 117,
2
8
1
1
937-2938.
46) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1997, 119,
232-8245.
47) Widenhoefer, R. A.; Buchwald, S. L. J . Am. Chem. Soc. 1998,
20, 6504.
48) Mann, G.; Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1998,
20, 827-828.
(
(
(
(49) Mann, G.; Hartwig, J . F. J . Am. Chem. Soc. 1999, 121,
3715-6.

5
578 J . Org. Chem., Vol. 64, No. 15, 1999
Hartwig et al.
palladium phenoxide intermediates in the formation of
aryl ethers,49 and it was the clean reaction of these
mol % tri-tert-butylphosphine in 1.0 mL of toluene. After 1 h,
the reaction mixture was adsorbed onto silica gel and chro-
matographed using 5% ethyl acetate/hexanes to give 236 mg
compounds with carbamates50 that led to our use of this
(
C
91%) of triphenylamine as a white solid: 1H NMR (500 MHz,
2 3
base. Reactions that employed Cs CO or NaO-t-Bu as
1
3
6
D
6
) δ 7.17-6.99 (m, 12 H), 6.82 (t, J ) 7.2 Hz, 3H); C NMR
base for the coupling of tert-butylcarbamate with aryl
bromides gave low conversions. In contrast to the C-N
bond formations described above, the use of a 2:1 ratio
of ligand/palladium was optimal, presumably because the
rate for oxidative addition is less important than other
steps of the cycle in dictating the kinetics of this process.
For these reactions, toluene proved to be the most
effective solvent.
(
125 MHz, C
N-(2-Tolyl)d ip h en yla m in e. The above general procedure
was followed using 2-bromotoluene (188 mg, 1.10 mmol) and
diphenylamine (169 mg, 1.00 mmol) with 1 mol % Pd(dba)
6 6
D
) δ 148.4, 129.5, 124.6, 122.9.
54
2
and 0.8 mol % tri-tert-butylphosphine in 1.5 mL of toluene.
After 4 h, the reaction mixture was adsorbed onto silica gel
and chromatographed with 2.5% ethyl acetate/hexanes to give
2
47 mg (95%) of N-(2-tolyl)diphenylamine as a colorless oil that
1
crystallized to a white solid: H NMR (500 MHz, C
6
D
6
) δ 7.05-
.96 (m, 12 H), 6.78 (tt, J ) 7.25, 1.30 Hz, 2H), 1.99 (s, 3H);
3
6
1
Con clu sion s
C NMR (125 MHz, C
29.4, 127.7, 126.1, 122.0, 121.8, 18.7.
N-(4-Cya n op h en yl)d ip h en yla m in e. The above general
6 6
D ) δ 148.0, 146.0, 136.6, 132.0, 129.9,
1
In general, we have shown that the use of P(t-Bu)
3
as
54
ligand in a 0.8:1 ratio with Pd(dba) allows for all the
2
procedure was followed using 4-bromobenzonitrile (188 mg,
1.03 mmol) and diphenylamine (169 mg, 1.00 mmol) with 1
mol % Pd(dba) and 0.8 mol % tri-tert-butylphosphine in 1.5
2
room temperature aminations reported previously with
new ligands and for an increase in the scope of nitrogen
substrates that react with aryl halides. The reason for
the rate acceleration with low ligand/palladium ratios is
complex and under investigation. It is likely that the
reaction rates are inverse first order in phosphine and a
ratio that is less than 2:1 ensures a low concentration of
free phosphine. The original observation that led to this
study, the room-temperature amination when using
mL of toluene. After 1 h, the reaction mixture was adsorbed
onto silica gel and chromatographed with 50% toluene/hexanes
to give 263 mg (97%) of N-(4-cyanophenyl)diphenylamine as
a white solid: 1H NMR (500 MHz, C
6 6
D
) δ 6.97 (t, J ) 8 Hz,
4
H), 6.92 (d, J ) 8.9 Hz, 2H), 6.86-6.83 (m, 6H), 6.56 (d, J )
1
3
8.7 Hz, 2H); C NMR (125 MHz, C D ) δ 151.3, 146.6, 133.2,
6
6
129.9, 126.1, 124.9, 120.5, 119.4, 104.0.
The above general procedure was followed using 4-chlo-
robenzonitrile (138 mg, 1.00 mmol) and diphenylamine (169
mg, 1.00 mmol) with 1 mol % Pd(dba) and 0.8 mol % tri-tert-
2
3 2
preformed Pd[P(t-Bu) ] , suggests that a 2:1 ratio would
be optimal. However, loss of palladium during the reac-
tion as either insoluble material or as complexes contain-
ing only one phosphine ligand will generate free phos-
phine and will lead to rate decreases. Perhaps this
explains the benefits of a ratio that is substantially less
butylphosphine in 2.0 mL of toluene. After 5.5 h, the reaction
mixture was adsorbed onto silica gel and chromatographed
with 50% toluene/hexanes to give 242 mg (90%) of N-(4-
cyanophenyl)diphenylamine as a white solid.
Tr i(4-m eth oxyp h en yl)a m in e.55 The above general proce-
dure was followed using 4-bromoanisole (187 mg, 1.00 mmol)
and di(4-methoxyphenyl)amine (229 mg, 1.00 mmol) with 1
2
than 2:1. Pd(dba) does not catalyze these reactions.
2
mol % Pd(dba) and 0.8 mol % tri-tert-butylphosphine in 1.5
Exp er im en ta l Section
mL of toluene. After 1 h, the reaction mixture was adsorbed
onto silica gel and chromatographed with 5% ethyl acetate/
hexanes to give 321 mg (96%) of tri(4-methoxyphenyl)amine
Gen er a l Meth od s. All reactions were assembled in the
drybox in sealed reaction vessels and were reacted either at
room temperature or were heated in an oil bath. Toluene
solvent was distilled from sodium/benzophenone ketyl. Dieth-
ylene glycol dimethyl ether was purchased in anhydrous grade
from Aldrich and was used in the drybox. Palladium bis-
as a white solid: 1H NMR (500 MHz, C
D ) δ 7.08 (d, J ) 10
6 6
13
Hz, 6 H), 6.73 (d, J ) 10 Hz, 6H), 3.31 (s, 9H); C NMR (125
MHz, C ) δ 155.7, 142.6, 125.3, 115.0, 55.0.
6
D
6
5
3
N,N,N′,N′-Tet r a p h en yl-1,4-p h en ylen ed ia m in e. The
above general procedure was followed using 1,4-dibromoben-
zene (130 mg, 0.55 mmol) and diphenylamine (169 mg, 1.00
(
dibenzylideneacetone) was prepared according to literature
5
2
procedures, and the palladium content was determined by
elemental analysis. Sodium tert-butoxide and cesium carbonate
were purchased from Aldrich and were used in a drybox.
Sodium phenoxide was prepared by deprotonation of phenol
with sodium hydride in THF followed by precipitation with
pentane. All amines were used as received and were not
degassed prior to use.
Gen er a l P r od ecu r e for th e Rea ction of Am in es w ith
Ar yl Ha lid es. In a drybox, aryl halide (1.00-1.10 mmol),
2 2
amine (1.00 mmol), Pd(dba) or Pd(OAc) (0.01-0.02 mmol),
2
mmol) with 1 mol % Pd(dba) and 0.8 mol % tri-tert-butylphos-
phine in 1.5 mL of toluene. After 1 h, the reaction mixture
was adsorbed onto silica gel and chromatographed using 30%
toluene/hexanes to give 200 mg (97%) of N,N,N′,N′-tetraphen-
yl-1,4-phenylenediamine as a white solid. This solid was
1
recrystallized from ethy acetate to afford 168 mg (81%):
NMR (500 MHz, C
Hz, 8H), 6.95 (s, 4H), 6.81 (t, J ) 7.2 Hz, 4H); C NMR (125
MHz, C
H
6
D ) δ 7.10 (d, J ) 7.5 Hz, 8H), 7.03 (t, J )
6
13
8
6
6
D ) δ 148.4, 143.4, 129.6, 125.8, 124.2, 122.8.
Dip h en yla m in e. The above general procedure was followed
tri-tert-butylphosphine (1.6-3.2 mg, 0.008-0.016 mmol, 0.8
eq/Pd), and sodium tert-butoxide (144 mg, 1.50 mmol) were
weighed directly into a screw cap vial. A stir bar was added
followed by 1.0-2.0 mL of toluene to give a purple mixture.
The vial was removed from the drybox, and the mixture was
stirred at room temperature. The reaction was monitored by
thin-layer chromatography or GC. After complete consumption
of starting materials, the resulting thick brown suspension was
adsorbed onto silica gel and purified by flash chromatography.
using bromobenzene (157 mg, 1.00 mmol) and aniline (93 mg,
1
2
.00 mmol) with 1 mol % Pd(dba) and 0.8 mol % tri-tert-
butylphosphine in 1.5 mL of toluene. After 1 h, the reaction
mixture was adsorbed onto silica gel and chromatographed
with 5% ethyl acetate/hexanes to give 145 mg (86%) of
1
diphenylamine as a gray solid: H NMR (500 MHz, C
7
6
D
6
) δ
1
3
.11-7.08 (m, 4H), 6.85-6.80 (m, 6H), 4.97 (br s, 1H); C NMR
(125 MHz, C
6 6
D ) δ 143.6, 129.5, 121.1, 118.2. In addition, 21
5
3
mg (8%) of triphenylamine was isolated.
Tr ip h en yla m in e. The above general procedure was fol-
The above general procedure was followed using chloroben-
zene (135 mg, 1.20 mmol) and aniline (93 mg, 1.00 mmol) with
lowed using bromobenzene (171 mg, 1.10 mmol) and diphen-
ylamine (169 mg, 1.00 mmol) with 1 mol % Pd(dba) and 0.8
2
5
2
mol % Pd(dba) and 4 mol % tri-tert-butylphosphine in 2.0
mL of toluene. After 25 h, the reaction mixture was adsorbed
(
(
(
50) Hartwig, J . F. Unpublished results.
51) This ligand is commercially available from Strem.
52) Ukai, T.; Kawazura, H.; Ishii, Y.; Bounet, J . J .; Ibers, J . A. J .
(54) Nelson, R. F.; Adams, R. N. J . Am. Chem. Soc. 1968, 90, 3925-
3930.
(55) Walters, R. I. J . Am. Chem. Soc. 1955, 77, 5999-6002.
Organomet. Chem. 1974, 65, 253.
53) Paine, A. J . J . Am. Chem. Soc. 1987, 109, 1496-1502.
(

Palladium-Catalyzed Amination of Aryl Bromides and Chlorides
J . Org. Chem., Vol. 64, No. 15, 1999 5579
onto silica gel and chromatographed with 2.5% ethyl acetate/
hexanes to give 126 mg (75%) of diphenylamine as an off-white
The above general procedure was followed using 4-chloro-
toluene (126 mg, 1.00 mmol) and dibutylamine (129 mg, 1.00
solid.
N-(4-Meth oxyp h en yl)d ip h en yla m in e.53 The above gen-
eral procedure was followed using 4-chloroanisole (127 mg,
.00 mmol) and diphenylamine (169 mg, 1.00 mmol) with 5
mol % Pd(dba) and 4 mol % tri-tert-butylphosphine in 2.0 mL
2
mmol) with 1 mol % Pd(dba) and 0.8 mol % tri-tert-butylphos-
phine in 1.0 mL of toluene. After 4 h at 70 °C, the reaction
mixture was adsorbed onto silica gel and chromatographed
with 2% ethyl acetate/hexanes to give 196 mg (90%) of N,N-
dibutyl-p-toluidine.
1
2
of toluene. After 16 h at 70 °C, the reaction mixture was
adsorbed onto silica gel and chromatographed with 2% ethyl
N,N-Dibu tyl-p-tolu id in e Usin g Cs CO3 or K P O a s
Ba se. The above general procedure was followed using 4-bro-
motoluene (171 mg, 1.00 mmol) and dibutylamine (162 mg,
2
3
4
acetate/hexanes to give 267 mg (97%) of N-(4-methoxyphenyl)-
1
diphenylamine as a white solid: H NMR (500 MHz, C
6
D
6
) δ
1.25 mmol) with 5 mol % Pd(dba) , 4 mol % tri-tert-butylphos-
2
7
.10-6.99 (m, 10 H), 6.81 (t, J ) 7 Hz, 2H), 6.66 (d, J ) 8.8
Hz, 2H), 3.28 (s, 3H); C NMR (125 MHz, C
41.2, 129.4, 127.7, 123.4, 122.2, 115.2, 54.94.
N-(2-Met h ylp h en yl)m or p h olin e. The above general
phine, and cesium carbonate (489 mg, 1.50 mmol) or K PO
3
4
1
3
6
D
6
) δ 156.8, 148.8,
(318 mg, 1.50 mmol) in 1.0 mL of diglyme. After 12 h at 100
°C, the reaction mixture was adsorbed onto silica gel and
chromatographed with 2% ethyl acetate/hexanes to give 179
mg (82%) of N,N-dibutyl-p-toluidine.
N,N-Dibu tyl-o-tolu id in e.59 The above general procedure
was followed using 2-bromotoluene (171 mg, 1.00 mmol) and
1
5
6
procedure was followed using 2-bromotoluene (171 mg, 1.10
mmol) and morpholine (87 mg, 1.00 mmol) with 1 mol % Pd-
2
(OAc) and 0.8 mol % tri-tert-butylphosphine in 1.0 mL of
toluene. After 6 h, the reaction mixture was adsorbed onto
dibutylamine (129 mg, 1.00 mmol) with 2 mol % Pd(OAc)
2
and
.6 mol % tri-tert-butylphosphine in 1.0 mL of toluene. After
h, the reaction mixture was adsorbed onto silica gel and
silica gel and chromatographed using 5% ethyl acetate/hexanes
1
6
1
to give 179 mg (>99%) of N-(2-methylphenyl)morpholine:
NMR (500 MHz, CDCl
7.4 Hz, 1H), 7.03 (d, J ) 7.4 Hz, 1H), 7.01 (d, J ) 7.4 Hz,
H
3
) δ 7.20 (d J ) 7.4 Hz, 1H), 7.18 (d, J
chromatographed with 2% ethyl acetate/hexanes to give 181
)
1
mg (83%) of N,N-dibutyl-o-toluidine: H NMR (500 MHz,
CDCl
1
3
1
H), 3.86 (t, J ) 4.5 Hz, 4H), 2.92 (t, J ) 4.5 Hz, 4H), 2.33 (s,
3
) δ 7.18 (t, J ) 7.8 Hz, 1H), 7.13 (d, J ) 7.8 Hz, 1H),
.08 (d, J ) 7.8 Hz, 1H), 6.97 (t, J ) 7.8 Hz, 1H), 2.91 (t, J )
13
H); C NMR (125 MHz, CDCl
23.5, 119.0, 67.5, 52.4, 17.8.
N-(4-Meth oxyp h en yl)-N-m eth yla n ilin e. The above gen-
eral procedure was followed using 4-bromoanisole (187 mg,
.00 mmol) and N-methylaniline (107 mg, 1.00 mmol) with 1
mol % Pd(dba) and 0.8 mol % tri-tert-butylphosphine in 1.0
3
) δ 151.4, 132.7, 131.2, 126.7,
7
7
.5 Hz, 4H), 2.30 (s, 3H), 1.41-1.37 (m, 4H), 1.27 (sept, J )
4
2
13
7.3 Hz, 4H), 0.87 (t, J ) 7.3 Hz, 6H); C NMR (125 MHz,
CDCl ) δ 150.7, 135.0, 130.9, 126.0, 123.1, 122.3, 53.9, 29.6,
3
1
20.5, 18.3, 14.0.
2
Gen er a l P r oced u r e for Rea ction of Azoles w ith Ar yl
mL of toluene. After 6 h, the reaction mixture was adsorbed
onto silica gel and chromatographed with 5% ethyl acetate/
Ha lid es. In a drybox, aryl halide (1.00-1.20 mmol), azole (1.00
mmol), Pd(dba) (17-23 mg, 0.03-0.04 mmol, 3-4 mol %), tri-
2
hexanes to give 218 mg (>99%) of N-(4-methoxyphenyl)-N-
tert-butylphosphine (4.8-8.1 mg, 0.024-0.040 mmol, 0.8-1.0
equiv/Pd), and cesium carbonate (489-554 mg, 1.50-1.70
mmol) were weighed directly into a 1 dram screw cap vial. A
stir bar was added followed by 1.0-2.0 mL of toluene. The
vial was removed from the drybox, and the mixture was stirred
as rapidly as possible with a magnetic stir plate at 100 °C.
The reaction was monitored by GC, and after the consumption
of starting materials, the reaction mixture was adsorbed onto
silica gel and purified by chromatography.
1
methylaniline: H NMR (500 MHz, CDCl
3
) δ 7.21 (dd, J )
8
2
3
1
.9, 7.0 Hz, 2H), 7.12 (d, J ) 8.8 Hz, 2H), 6.91 (d, J ) 8.8 Hz,
H), 6.81 (d, J ) 8.4 Hz, 2H), 6.80 (t, J ) 7.0 Hz, 1H), 3.83 (s,
H), 3.28 (s, 3H); 13C NMR (125 MHz, CDCl
) δ 156.3, 149.8,
42.4, 128.9, 126.1, 118.5, 115.9, 114.8, 55.5, 40.4.
3
5
7
N-(4-Cya n op h en yl)-N-m eth yla n ilin e. The above gen-
eral procedure was followed using 4-bromobenzonitrile (187
mg, 1.00 mmol) and N-methylaniline (107 mg, 1.00 mmol) with
1
mol % Pd(dba)
2
and 0.8 mol % tri-tert-butylphosphine in 1.0
N-(4-F lu or op h en yl)-5-m eth oxyin d ole.60 The above gen-
eral procedure was followed using 4-flouorobromobenzene (210
mg, 1.20 mmol), 5-methoxyindole (147 mg, 1.00 mmol), 4 mol
mL of toluene. After 6 h, the reaction mixture was adsorbed
onto silica gel and chromatographed with 10% ethyl acetate/
hexanes to give 201 mg (97%) of N-(4-cyanophenyl)-N-methy-
%
2
Pd(dba) , 4 mol % tri-tert-butylphosphine, and cesium car-
1
laniline: H NMR (500 MHz, CDCl
3
) δ 7.45-7.42 (m, 4H), 7.27
bonate (1.70 mmol) in 1.0 mL of toluene. After 12 h at 100 °C,
the reaction mixture was adsorbed onto silica gel and chro-
matographed with 5% ethyl acetate/hexanes to give 212 mg
(
t, J ) 7.5 Hz, 1H), 7.21 (d, J ) 8.3 Hz, 2H), 6.73 (d, J ) 9.0
13
Hz, 2H), 3.36 (s, 3H); C NMR (125 MHz, CDCl
46.8, 133.1, 130.1, 126.4, 126.2, 120.2, 114.0, 99.4, 40.1.
The above general procedure was followed using 4-chlo-
robenzonitrile (137 mg, 1.00 mmol) and N-methylaniline (107
mg, 1.00 mmol) with 1 mol % Pd(dba) and 0.8 mol % tri-tert-
3
) δ 152.0,
1
(
88%) of N-(4-fluorophenyl)-5-methoxyindole. Recrystallization
from 5% ethyl acetate/hexanes gave 174 mg (72%) of pure
product: 1H NMR (300 MHz, CDCl
) δ 7.49-7.39 (m, 3H), 7.28
d, J ) 3.2 Hz, 1H), 7.22 (t, J ) 8.6 Hz, 1H), 7.18 (d, J ) 2.3
3
2
(
butylphosphine in 1.0 mL of toluene. After 12 h, the reaction
mixture was adsorbed onto silica gel and chromatographed
with 10% ethyl acetate/hexanes to give 191 mg (92%) of N-(4-
cyanophenyl)-N-methylaniline.
Hz, 1H), 6.93 (dd, J ) 9.0, 1.6 Hz, 1H), 6.64 (d, J ) 3.1 Hz,
13
1
2
3
H), 3.90 (s, 3H); C NMR (76 Mz, CDCl ) δ 160.9 (d, J )
44.0 Hz)154.4, 136.0, 131.3, 129.7, 128.4, 125.76 (d, J ) 8.5
Hz), 116.38 (d, J ) 23 Hz), 112.6, 11.0, 103.2, 102.7, 55.76.
5
8
N,N-Dibu tyl-p-tolu id in e. The above general procedure
N-(2-Meth ylp h en yl)-3-m eth ylin d ole. The above general
procedure was followed using 2-bromotoluene (205 mg, 1.20
was followed using 4-bromotoluene (171 mg, 1.00 mmol) and
dibutylamine (129 mg, 1.00 mmol) with 1 mol % Pd(dba)
0
4
2
and
.8 mol % tri-tert-butylphosphine in 1.0 mL of toluene. After
h, the reaction mixture was adsorbed onto silica gel and
mmol), 3-methylindole (131 mg, 1.00 mmol), 3 mol % Pd(dba)
2
,
2
.4 mol % tri-tert-butylphosphine, and cesium carbonate (1.70
mmol) in 1.0 mL of toluene. After 12 h at 100 °C, the reaction
mixture was adsorbed onto silica gel and chromatographed
with 5% ethyl acetate/hexanes to give 195 mg (88%) of N-(2-
chromatographed with 2% ethyl acetate/hexanes to give 207
1
mg (95%) of N,N-dibutyl-p-toluidine: H NMR (500 MHz,
CDCl
3
) δ 7.01 (d, J ) 8.7 Hz, 2H), 6.58 (d, J ) 8.7 Hz, 2H),
methylphenyl)-3-methylindole: 1H NMR (300 MHz, CDCl
) δ
3
3
.23 (t, J ) 7.6 Hz, 4H), 2.24 (s, 3H), 1.58-1.52 (m, 4H), 1.34
7
(
.76 (m, 1H), 7.46 (m, 2H), 7.40 (m, 2H), 7.28 (m, 2H), 7.15
1
3
(sept, J ) 7.4 Hz, 4H), 0.95 (t, J ) 7.4 Hz, 6H); C NMR (125
m, 1H), 7.06 (s, 1H), 2.53 (s, 3H), 2.21 (s, 3H); 1 C NMR (76
MHz, CDCl ) δ 138.4, 137.1, 135.7, 131.1, 128.6, 128.1, 127.8,
26.6, 126.2, 121.9, 119.3, 118.9, 111.6, 110.4, 17.7, 9.6.
HRMS(EI): m/z calcd for C16 15N 221.1204, obsd 221.1202.
3
MHz, CDCl ) δ 146.4, 129.7, 124.5, 112.5, 51.1, 29.6, 20.5, 20.2,
3
3
1
4.0.
1
H
(
56) Barluenga, J .; Aznar, F.; Fernandez, M. Chem. Eur. J . 1997,
, 1629-1637.
57) Marcoux, J .-F.; Wagaw, S.; Buchwald, S. L. J . Org. Chem. 1997,
2, 1568-1569.
58) Watanabe, Y.; Tsuji, Y.; Ige, H.; Ohsugi, Y.; Ohta, T. J . Org.
Chem. 1985, 50, 1365-1370.
3
6
(
(59) Watanabe, Y.; Suzuki, N.; Tsuji, Y.; Shim, S. C.; Mitsudo, T.
Bull. Chem. Soc. J pn. 1982, 55, 1116-1120.
(60) Perregaard, J .; Arnt, J .; Bogeso, K. P.; Hyttel, J .; S a´ nchez, C.
J . Med. Chem. 1992, 35, 1092-1101.
(

5
580 J . Org. Chem., Vol. 64, No. 15, 1999
Hartwig et al.
N-(4-Meth oxyp h en yl)in d ole.61 The above general proce-
flash chromatographed eluting with 1:1 CH
mL) and then 70:30 CH Cl /hexanes. A pale yellow oil that
crystallized upon standing was isolated (177 mg, 85%). Re-
2 2
Cl /hexanes (150
dure was followed using bromoanisole (138 µL, 1.10 mmol) and
indole (119 mg, 1.02 mmol) with 3 mol % Pd(dba) , 3 mol %
tri-tert-butylphosphine, and cesium carbonate (1.70 mmol) in
mL of toluene. After 6 h at 100 °C, the reaction mixture was
2
2
2
crystallization from hexanes gave colorless needles: mp 92-
1
2
92.5 °C (lit.63 mp 91-93 °C); H NMR (500 MHz, CDCl
3
) δ 7.24
adsorbed onto silica gel and flash chromatographed with 5%
ethyl acetate/hexanes to give 163 mg (72%) of product as a
(br d, 8.3 Hz, 2H), 7.10 (d, J ) 8.2 Hz, 2H), 6.41 (br s, 1H),
2.30 (s, 3H), 1.52 (s, 9H); 13C NMR (125 MHz, CDCl
) δ 152.9,
135.7, 132.5, 129.4, 118.7, 80.3, 28.3, 20.7; FTIR (KBr disk)
3
1
colorless oil that was pure by H NMR. Recrystallization from
6
1
-1
ethanol gave a white, crystalline solid: mp 59.5-60.5 °C (lit.
3356, 1699, 1529, 1240, 1157 cm
The above general procedure was followed using 4-chloro-
toluene (118 µL, 1.00 mmol), 4 mol % Pd(dba) , and 8 mol %
.
1
mp 57-58 °C); H NMR (500 MHz, CDCl
Hz, 1H), 7.52 (d, J ) 7.93 Hz, 1H), 7.45 (d, J ) 7.80 Hz, 2H),
.32 (d, J ) 3.4 Hz, 2H), 7.26 (t, J ) 6.90 Hz, 1H), 7.21 (t, J
7.40 Hz, 1H), 7.08 (d, J ) 8.01 Hz, 2H), 6.71 (d, J ) 3.11
3
) δ 7.74 (d, J ) 7.84
2
7
)
tri-tert-butylphosphine. After 24 h, tert-butyl N-(4-tolyl)car-
bamate was isolated as described above to give 122 mg (59%
yield) of product.
1
3
Hz, 2H), 3.91 (s, 3H); C NMR (125 MHz, CDCl
3
) δ 158.2,
1
1
36.3, 132.8, 128.9, 128.2, 125.9, 122.1, 121.0, 120.0, 114.7,
t-Bu tyl N-(2-Tolyl)ca r ba m a te.64 The above general pro-
cedure was followed using 2-bromotoluene (120 µL, 1.00 mmol).
After 2 h, the toluene was removed under reduced pressure
and the residue loaded on silica gel. The crude material was
10.3, 102.8, 55.5.
N-(4-Meth ylp h en yl)p yr r ole.62 The above general proce-
dure was followed using bromotoluene (135 µL, 1.10 mmol)
and pyrrole (69 µL, 1.00 mmol) with 3 mol % Pd(dba) , 3 mol
tri-tert-butylphosphine, and cesium carbonate (1.70 mmol)
2 2
flash chromatographed eluting with 1:1 CH Cl /hexanes. A
2
%
pale yellow oil that crystallized upon standing was isolated
(178 mg, 86%). Recrystallization from hexanes gave colorless
in 2.0 mL of toluene. After being heated at 100 °C for 6 h, the
reaction mixture was loaded on silica gel and flash chromato-
graphed with 2.5% ethyl acetate/hexanes to give 135 mg (86%)
of product as a pinkish solid that was pure by 1H NMR.
Recrystallization from ethanol gave a colorless, crystalline
6
4
1
needles: mp 82-83 °C (lit. mp 82 °C); H NMR (500 MHz,
CDCl ) δ 7.81 (br s, 1H), 7.20 (t, J ) 7.4 Hz, 1H), 7.15 (d, J )
7.4 Hz, 1H), 6.99 (t, J ) 8.3 Hz, 1H), 6.27 (br s, 1H), 2.26 (s,
3H), 1.54 (s, 9H); 13C NMR (125 MHz, CDCl
) δ 153.1, 136.4,
130.3, 127.3, 126.8, 123.7, 121.1, 80.4, 28.3, 17.6; FTIR (KBr
3
3
6
2
1
solid: mp 81.5-83 °C (lit. mp 82-83 °C); H NMR (500 MHz,
-
1
CDCl
3
) δ 7.30 (d, J ) 8.15 Hz, 2H), 7.23 (d, J ) 8.44 Hz, 2H),
.08 (brs, 2H), 6.36 (brs, 2H), 2.40 (s, 3H); C NMR (125 MHz,
disk) 3261, 1696, 1510, 1371, 1155 cm .
1
3
7
t-Bu tyl N-(4-Cya n op h en yl)ca r ba m a te. The above gen-
eral procedure was followed using 4-bromobenzonitrile (186
mg, 1.02 mmol). After 1.5 h, the reaction was diluted with
CDCl ) δ 138.5, 135.3, 130.0, 120.5, 119.4, 110.0, 20.8.
3
5
9
N-(4-Meth ylp h en yl)in d ole. The above general procedure
was followed using 4-chlorotoluene (126 mg, 1.00 mmol), indole
117 mg, 1.00 mmol), 4 mol % Pd(dba) , 4 mol % tri-tert-
2
butylphosphine, and cesium carbonate (1.50 equiv) in 1.0 mL
of toluene. After 12 h at 100 °C, the reaction mixture was
adsorbed onto silica gel and chromatographed with 10% ethyl
CH
phenol, which coelutes with the product. The organic layer was
dried over MgSO and the solvent removed under reduced
pressure. The residue was flash chromatographed eluting with
70:30 CH Cl /hexanes (200 mL) and then CH Cl . A pale yellow
solid was isolated (193 mg, 87%). Recrystallization from
toluene/hexanes gave colorless needles: mp 120-120.5 °C;
NMR (500 MHz, CDCl ) δ 7.57 (d, J ) 8.6 Hz, 2H), 7.48 (d, J
) 8.6 Hz, 2H), 6.74 (br s, 1H), 1.53 (s, 9H); C NMR (125 MHz,
CDCl ) δ 151.9, 142.6, 133.2, 119, 118.1, 105.8, 81.7, 28.2; FTIR
2 2
Cl and extracted with 10% NaOH solution to remove
(
4
2
2
2
2
acetate/hexanes to give 137 mg (66%) of N-(4-methylphenyl)-
1
1
H
indole: H NMR (500 MHz, CDCl
3
) δ 7.70 (d, J ) 7.8 Hz, 1H),
7
(
(
.54 (d, J ) 8.2 Hz, 1H), 7.40 (d, J ) 7.8 Hz, 2H), 7.34-7.33
3
1
3
m, 3H), 7.23 (t, J ) 7.8 Hz, 1H), 7.18 (t, J ) 7.8 Hz, 1H), 6.68
1
3
d, J ) 2.4 Hz, 1H), 2.46 (s, 3H); C NMR (125 MHz, CDCl
3
)
3
-
1
δ 137.4, 136.4, 136.1, 130.2, 129.3, 128.2, 124.4, 122.3, 121.2,
(KBr disk) 3368, 2226, 1692, 1510, 1239, 1151 cm . Anal.
Calcd for C12 : C, 66.05; H, 6.47; N, 12.83. Found: C,
5.80; H, 6.43; N, 12.77.
ter t-Bu tyl N-(4-Meth oxyp h en yl)ca r ba m a te.6 The above
general procedure was followed using 4-bromoanisole (123 µL,
.98 mmol), 4 mol % Pd(dba) , and 8 mol % tri-tert-butylphos-
phine. Upon completion of the reaction, the reaction was
diluted with CH Cl and extracted with 10% NaOH solution
to remove phenol which coelutes with the product. The organic
layer was dried over MgSO and the solvent removed under
reduced pressure. The residue was flash chromatographed
eluting with 70:30 CH Cl /hexanes. A pale yellow, waxy solid
was isolated (145 mg, 66%). Recrystallization from hexanes
1
20.3, 110.6, 103.3, 21.1.
14 2 2
H N O
6
Gen er a l P r oced u r e for Ca r ba m a te Ar yla tion . In a
5
drybox, a small round-bottom flask was charged with Pd(dba)
14.4 mg, 0.025 mmol, 2.5 mol %), t-Bu P (10.1 mg, 0.050
mmol), sodium phenoxide (174 mg, 1.50 mmol), aryl halide
1.00 mmol), and tert-butyl carbamate (176 mg, 1.50 mmol).
2
(
3
0
2
(
Toluene (3 mL) was added to give a thick suspension. The flask
was sealed with a septum, removed from the drybox, and
placed in an oil bath preheated to 100 °C. The reaction was
vigorously stirred until the aryl halide was completely con-
sumed as judged by GC analysis. The reaction was then
worked up as described below. The pure product was obtained
by flash chromatography.
t-Bu tyl N-(4-Tolyl)ca r ba m a te.63 The above general pro-
cedure was followed using 4-bromotoluene (123 µL, 1.00 mmol).
After 2 h, the toluene was removed under reduced pressure
and the residue loaded on silica gel. The crude material was
2
2
4
2
2
6
5
gave colorless needles: mp 92.5-93 °C (lit. mp 92-94 °C);
1
H NMR(500 MHz, CDCl
Hz, 2H), 6.36 (br s, 1H), 3.79 (s, 3H), 1.52 (s, 9H); C NMR
125 MHz, CDCl ) δ 155.5, 153.1, 131.4, 120.4, 114.0, 80.1,
5.4, 28.3; FTIR (KBr disk) 3365, 1694, 1522, 1246, 1161 cm
3
) δ 7.28 (br s, 2H), 6.84 (d, J ) 9.4
13
(
5
3
-1
.
J O990408I
(
61) Tokmakov, G. P.; Grandberg, I. I. Tetrahedron 1995, 51, 2091-
2
3
098.
(
(
(64) Muchowski, J . F.; Venuti, M. C. J . Org. Chem. 1980, 45, 4798-
4801.
(65) Kondo, T.; Hiraishi, N.; Morisaki, Y.; Wada, K.; Watanabe, Y.;
62) J ones, R. A. Aust. J . Chem. 1966, 19, 289-296.
63) Stanley, R. L.; Tarbell, D. S. J . Org. Chem. 1977, 42, 3686-
690.
Mitsudo, T. Organometallics 1998, 17, 2131-2134.