Understanding the coupling of heteroaromatic substrates: Synthesis, structures, and reductive eliminations of heteroarylpalladium amido complexes

Article abstract of DOI:10.1021/om030257g

Palladium furyl- and thiophenyl complexes have been studied to uncover the origin of the difference in reactivity between coupling of five-membered heterocyclic halides and coupling of aryl halides and six-membered heteroaryl halides. A range of DPPF-ligated furanylpalladium and thiophenylpalladium halide and amido complexes were synthesized, and several examples were structurally characterized. The heteroatom in the 2-heteroaryl groups did not coordinate palladium to generate η²-heteroaryl complexes. The furyl- and thiophenylpalladium complexes underwent reductive elimination of heteroarylamines in yields that were much different for related 2- and 3-isomers. The yields of reductive elimination from these isomeric complexes paralleled the yields from catalytic aminations of 2- and 3-halofurans and 2- and 3-halothiophenes. This correlation suggests that the scope of the amination of five-membered heteroaryl halides is controlled by the reductive elimination step. The yields of reductive elimination correlated with the distribution of electron density at different positions of furans and thiophenes, and this correlation between electron density at different positions of the heteroarenes explains why yields are higher for reductive elimination from 2-furyl and 3-thiophenyl complexes than they are from 3-furyl and 2-thiophenyl complexes.

Full text of DOI:10.1021/om030257g

3394
Organometallics 2003, 22, 3394-3403
Un d er sta n d in g th e Cou p lin g of Heter oa r om a tic
Su bstr a tes: Syn th esis, Str u ctu r es, a n d Red u ctive
Elim in a tion s of Heter oa r ylp a lla d iu m Am id o Com p lexes
Mark W. Hooper and J ohn F. Hartwig*
Department of Chemistry, P.O. Box 208107, Yale University,
New Haven, Connecticut 06520-8107
Received April 8, 2003
Palladium furyl- and thiophenyl complexes have been studied to uncover the origin of the
difference in reactivity between coupling of five-membered heterocyclic halides and coupling
of aryl halides and six-membered heteroaryl halides. A range of DPPF-ligated furanylpal-
ladium and thiophenylpalladium halide and amido complexes were synthesized, and several
examples were structurally characterized. The heteroatom in the 2-heteroaryl groups did
not coordinate palladium to generate η2-heteroaryl complexes. The furyl- and thiophenylpal-
ladium complexes underwent reductive elimination of heteroarylamines in yields that were
much different for related 2- and 3-isomers. The yields of reductive elimination from these
isomeric complexes paralleled the yields from catalytic aminations of 2- and 3-halofurans
and 2- and 3-halothiophenes. This correlation suggests that the scope of the amination of
five-membered heteroaryl halides is controlled by the reductive elimination step. The yields
of reductive elimination correlated with the distribution of electron density at different
positions of furans and thiophenes, and this correlation between electron density at different
positions of the heteroarenes explains why yields are higher for reductive elimination from
2-furyl and 3-thiophenyl complexes than they are from 3-furyl and 2-thiophenyl complexes.
In tr od u ction
stricted to substrates containing strongly electron-
withdrawing substituents, such as nitro or acyl groups.8
To address this limitation in scope of uncatalyzed
reactions, palladium-catalyzed amination9-13 of hetero-
cyclic halides has been reported.14-28 Yet, yields of the
Many, if not most, palladium-catalyzed cross-coupling
reactions conducted in the context of pharmaceutical
synthesis contain heteroaromatic groups.1-3 Yet, mecha-
nistic data on the palladium-catalyzed coupling of
heteroaryl reactants are limited.4 Therefore, mechanis-
tic studies with heteroaryl substrates would provide
useful information to understand and predict the scope
of coupling reactions that are conducted in common
synthetic applications. The absence of this mechanistic
data applies to recently developed carbon-heteroatom
coupling processes, as well as more classic C-C coupling
chemistry.
(8) Prim, D.; Kirsch, G. Tetrahedron 1999, 55, 6511.
(9) Hartwig, J . F. Angew. Chem., Int. Ed. 1998, 37, 2046.
(10) Hartwig, J . F. In Modern Amination Methods; Ricci, A., Ed.;
Wiley-VCH: Weinheim, 2000.
(11) Hartwig, J . F. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E. I., Ed.; J ohn Wiley and Sons: New York,
2002; p 1051.
(12) Yang, B. H.; Buchwald, S. L. J . Organomet. Chem. 1999, 576,
125-146.
(13) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131-
209.
(14) Hooper, M. W.; Utsunomiya, M.; Hartwig, J . F. J . Org. Chem.
2003, 68, 2861-2873.
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J . L.; Murcia, M.; Ramos, J . A.; Viso, A. Tetrahedron 2000, 56, 3245-
3253.
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Wald, S. A.; Senanayake, C. H. Tetrahedron Lett. 1997, 38, 5607-
5610.
Five-membered heteroarylamines are substructures
of biologically active compounds and novel electronic
materials.5-7 Many of the classical routes to five-
membered heteroarylamines are limited in scope or
occur at high temperatures. Direct, nucleophilic ami-
nation of the more electron-rich five-membered het-
eroaryl halides containing a single heteroatom is re-
(18) Tanoury, G. J .; Senanayake, C. H.; Hett, R.; Kuhn, A. M.;
Kessler, D. W.; Wald, S. A. Tetrahedron Lett. 1998, 39, 6845-6848.
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2001, 42, 1475-1477.
* Corresponding author. E-mail: john.hartwig@yale.edu.
(1) Bradley, D. A.; Godfrey, A. G.; Schmid, C. R. Tetrahedron Lett.
1999, 40, 5155-5159.
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L.; Murcia, M. Bioorg. Med. Chem. Lett. 1999, 9, 2339-2342.
(3) Yin, J .; Zhao, M. M.; Huffman, M. A.; McNamara, J . M. Org.
Lett. 2002, 4, 3481-3484.
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10.1021/om030257g CCC: $25.00 © 2003 American Chemical Society
Publication on Web 07/22/2003

Coupling of Heteroaromatic Substrates
Organometallics, Vol. 22, No. 17, 2003 3395
Sch em e 1
shows the synthesis of DPPF-ligated heteroarylpalla-
dium bromide complexes. Both DPPF- and PtBu3-ligated
arylpalladium halide complexes are likely intermediates
in the reactions of heteroaryl bromides with amines
catalyzed by complexes generated from Pd(dba)2 and
these phosphines.14 Arylpalladium complexes ligated by
PtBu3 are unstable,35,36 and we have been unable to
generate thiophenyl or furanylpalladium complexes
ligated by PtBu3. However, heteroarylpalladium halide
and amido complexes ligated by DPPF were stable
enough to isolate. These DPPF complexes possess the
same two reactive ligands as the more reactive tri-tert-
butyl phosphine-ligated heteroarylpalladium amido com-
pounds, and they possess the same dative ligand as the
DPPF-ligated arylpalladium amido complexes we in-
vestigated previously.37
heteroaryl halide amination process vary with the
substitution pattern and the position of the halogen. In
particular, yields from reactions of 2-halofurans were
higher than those from reactions of 2-halothiophenes,
but yields from reactions of 3-halothiophenes were
higher than those from reactions of 3-halofurans.14
These trends in reactivity were difficult to rationalize
with existing data. A few bisphosphine-ligated furanyl-
and thiophenylpalladium(II) halide complexes have
been reported, but these complexes encompass only
2-substituted derivatives.29-33 No 3-furanyl- or 3-thio-
phenylpalladium complexes that would begin to reveal
how the different electronic properties of the 2- and
3-positions of these heterocycles1,34 influence reactivity
are known. The 2-furanyl- and 2-thiophenylpalladium
halides have generated products from homocoupling,30
but reductive elimination of heteroaryl products from
an isolated furanyl- or thiophenylpalladium complex has
not been observed directly.
To address this absence of mechanistic data on
heterocyclic systems, we have begun to evaluate how
to extrapolate mechanistic information on coupling of
aryl halides to coupling of heteroaryl halides. As a first
case study, we have focused on the factors that control
the amination of deactivated five-membered heteroaryl
halides. We report the synthesis, structures, and reac-
tions of furyl and thiophenylpalladium halide and amido
complexes ligated by bis-diphenylphosphinoferrocene
(DPPF). The yields of heteroarylamine product cor-
related with electronic properties of the heteroaromatic
systems in a manner that explain the reversal in
reactivity of 2- and 3-halo thiophenes versus 2- and
3-halofurans. The data generated from this study should
aid in the understanding of other palladium-catalyzed
reactions of heteroaryl substrates.
DPPF-ligated arylpalladium halide complexes were
previously prepared from the reaction of DPPF with
isolated tris(ortho-tolyl)phosphine-ligated arylpalladium
halide dimers.37 However, (P(o-tol)3)2PdBr2 was the
major isolated product from reactions of Pd(P(o-tol)3)2
with 2- or 3-bromofuran or -thiophene. This product was
obtained previously from oxidative addition of electron-
rich aryl bromides to Pd[P(o-tol)3]2.38
Thus, one method to prepare the desired DPPF-
ligated arylpalladium halide complexes 1a -f involved
reaction of the heteroaryl bromides with Pd[P(o-tol)3]2
and subsequent reaction of the unstable heteroarylpal-
ladium halide in situ with DPPF. Alternatively, the
thiophenyl complexes were prepared from Pd(dba)2,
DPPF, and the heteroaryl bromide. Complexes 1c and
1d were generated cleanly by this reaction at 100 °C
for 4-12 h, as determined by 31P NMR spectroscopy,
and complex 1c was isolated in 70% yield by this
procedure. Reactions of the less stable bromofurans
were conducted by the milder route starting with Pd-
[P(o-tol)3]2. Complexes 1a -f were nearly insoluble in
benzene and toluene after isolation, but were soluble
enough in dichloromethane to obtain spectroscopic data.
To confirm that the heteroarylpalladium halide com-
plexes were kinetically and chemically competent to be
intermediates in the catalytic process, we compared the
rates and yields for reactions catalyzed by a 1:1 com-
bination of Pd(dba)2 and DPPF to those for reactions
catalyzed by isolated 2-thiophenylpalladium bromide 1c.
Consistent with the intermediacy of the heteroarylpal-
ladium bromides in the catalytic process, the two
reactions occurred with yields that were indistinguish-
able. The amounts of amidine formed as side product
(vide infra) were also similar. In addition, the rate of
reaction catalyzed by isolated 1c was slightly faster than
the rate of reaction catalyzed by Pd(dba)2 and DPPF.
Resu lts
Syn th esis of DP P F -Liga ted Heter oa r ylp a lla d i-
u m Br om id e a n d Am id e Com p lexes. Scheme 1
(26) De Riccardis, F.; Bonala, R. R.; J ohnson, F. J . Am. Chem. Soc.
1999, 121, 10453-10460.
(27) De Riccardis, F.; J ohnson, F. Org. Lett. 2000, 2, 293-295.
(28) Lakshman, M. K.; Keeler, J . C.; Hilmer, J . H.; Martin, J . Q. J .
Am. Chem. Soc. 1999, 121, 6090-6091.
The heteroarylpalladium halide complexes 1a -f were
converted to the corresponding deep purple, crystalline
amido complexes 2a -f by reaction with KN(p-tolyl)2
(Scheme 2). Complexes 2a -f were stable at room
temperature. Complexes 1a -f were also converted to
the red heteroarylpalladium N-methylanilides 3a -f by
(29) Xie, Y.; Wu, B.-M.; Xue, F.; Ng, S.-C.; Mak, T. C. W.; Hor, T. S.
A. Organometallics 1998, 17, 3988.
(30) Xie, Y.; Tan, G. K.; Yan, Y. K.; Vittal, J . J .; Ng, S.-C.; Hor, T.
S. A. J . Chem. Soc., Dalton Trans. 1999, 5, 773.
(31) Amatore, C.; Carre, E.; J utand, A.; Tanaka, H.; Ren, Q.; Torii,
S. Chem. Eur. J . 1996, 2, 957.
(32) Morita, D. K.; Stille, J . K.; Norton, J . R. J . Am. Chem. Soc. 1995,
117, 8576.
(33) Chia, L.-Y.; McWhinnie, W. R. J . Organomet. Chem. 1980, 188,
121.
(34) J ones, G. B.; Chapman, B. J . In Comprehensive Heterocyclic
Chemistry II; Katritzky, R., Rees, C. W., Scriven, E. F. V., Ed.;
Pergamon: New York, 1996; Vol. 2, p 3.
(35) Roy, A. H.; Hartwig, J . F. J . Am. Chem. Soc. 2001, 123, 1232.
(36) Stambuli, J . P.; Bu¨hl, M.; Hartwig, J . F. J . Am Chem. Soc. 2002,
124, 9346-9347.
(37) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1997, 119, 8232.
(38) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. Organome-
tallics 1995, 15, 2745.

3396 Organometallics, Vol. 22, No. 17, 2003
Hooper and Hartwig
F igu r e 2. ORTEP drawing of (DPPF)Pd(3-furyl)[N(C6H4-
4-Me)2] (2b) with 30% probability ellipsoids. Hydrogen
atoms are omitted for clarity.
F igu r e 1. ORTEP drawing of (DPPF)Pd(2-furyl)[N(C6H4-
4-Me)2] (2a ) with 30% probability ellipsoids. Hydrogen
atoms are omitted for clarity.
Sch em e 2
reaction with KNMePh. These complexes were less
stable than 2a -f. All the heteroarylpalladium amido
complexes were soluble in benzene and toluene. The
heteroarylpalladium halides were also cleanly converted
to the corresponding DPPF-ligated heteroarylpalladium
anilides, but the high reactivity of these derivatives
prevented isolation. For example, reaction of (DPPF)-
Pd[2-(5-CH3)C4H3S](Br) (1e) with a combination of H2-
NPh and NaOtBu formed a product, 4, which displayed
two new doublets in the 31P NMR spectrum and a new
F igu r e 3. ORTEP drawing of (DPPF)Pd(2-thiophenyl)-
[N(C6H4-4-Me)2] (2c) with 30% probability ellipsoids. Hy-
drogen atoms are omitted for clarity.
were present in 75% and 25% occupancies. 3-Thiophenyl
complex 2d was disordered between two analogous
conformers that were present in 55% and 45% occupan-
cies.
1
methyl and four new ferrocenyl signals in the H NMR
spectrum. These data indicate that the desired hetero-
arylpalladium anilide is formed. However, this complex
decomposed at room temperature and was not isolated
in pure form. Reaction of 1e with hexylamine or piper-
idine in the presence of NaOtBu did not form an amido
complex that could be detected by 1H NMR spectroscopy.
No evidence for a secondary interaction between the
heteroatom of the heteroaryl group and the palladium
was observed for the 2-furanyl or the 2-thiophenyl
complexes; the Pd-X (X ) O, S) distances were greater
than 2.99 Å. The identity of the heteroatom did,
however, affect the Pd-C bond distances. The Pd-C
bond in the 2-furanyl complex is shorter than that in
the 2-thiophenyl complex by 0.04 Å, and the Pd-C bond
in the 3-furanyl complex is shorter than that in the
3-thiophenyl complex by 0.01 Å. The Pd-C bonds of the
heteroaryl complexes are shorter than the Pd-C bond
in the arylpalladium ditolylamido complex reported
previously (2.000-2.047 vs 2.048 Å).37 The Pd-N bonds
of the heteroarylpalladium diarylamido complexes are
also shorter than that of the arylpalladium ditolylamido
complex (2.084-2.090 vs 2.097 Å).37
Str u ctu r a l An a lysis of (DP P F )P d (h eter oa r yl)-
[N(p-tolyl)2] Com p lexes 2a -d . Structures of 2- and
3-furanyl diarylamido complexes and 2- and 3-thiophen-
yl diarylamido complexes were obtained by X-ray dif-
fraction. ORTEP diagrams are provided in Figures 1-4.
Crystal data are provided in Table 1, and selected bond
distances and angles are provided in Tables 2 and 3.
The thiophenyl group in the 2-thiophenyl complex 2c
was disordered between two conformers related by a
180° rotation about the Pd-C bond. The two conformers

Coupling of Heteroaromatic Substrates
Organometallics, Vol. 22, No. 17, 2003 3397
Ta ble 1. Da ta Collection a n d Refin em en t P a r a m eter s for X-r a y Str u ctu r es of
(DP P F )P d (X-fu r a n yl)[N(p-CH3C6H4)2] (2a , X ) 2; 2b, X ) 3) a n d (DP P F )P d (X-th iop h en yl)[N(p-CH3C6H4)2]
(2c, X ) 2; 2d , X ) 3)
2a
2b
2c
2d
empirical formula
fw
C
52H45NOP2FePd‚1.75C6H6
C
63H63NOP2FePd
C59H53NP2SFePd
1032.33
C59H53NP2SFePd
1032.33
1060.83
1074.39
cryst color, habit
cryst syst
red, needle
monoclinic
red, plate
triclinic
dark red, column
monoclinic
dark red, plate
monoclinic
lattice params
a ) 11.5842(4) Å
b ) 39.513(1) Å
c ) 12.3266(4) Å
R ) 111.763(2) o
a ) 11.2535(10) Å
b ) 15.0540(10) Å
c ) 16.5496(10) Å
R ) 109.615(3) o
â ) 97.804(3)°
γ ) 92.340(3)°
2605.3(3) Å3
P1h (#2)
a ) 11.1159(4)Å
b ) 21.836(1) Å
c ) 20.646(1) Å
R ) 104.485(2) o
a ) 11.1442(2) Å
b ) 21.8246(5) Å
c ) 20.7322(4) Å
R ) 104.870(1) o
volume
space group
Z value
5240.1(3) Å3
P21/a (#14)
4
4852.1(3) Å3
P21/c (#14)
4
4873.6(2) Å3
P21/c (#14)
4
2
diffractometer
radiation
Nonius KappaCCD
Mo KR (λ ) 0.71069 Å) graphite monochromated
temperature
residuals: R; Rw
goodness of fit indicator
-90.0 °C
0.052; 0.048
1.79
-90.0 °C
0.033; 0.037
1.43
-90.0 °C
0.043; 0.039
1.42
-90.0 °C
0.037; 0.040
2.04
Ta ble 3. Selected In tr a m olecu la r Bon d An gles
(d eg) of DP P F -Liga ted F u r yl a n d Th iop h en yl
Ditolyla m id es 2a -d
atom atom atom
angle
atom atom atom
angle
2a
2c
P(1) Pd(1) P(2)
99.50(10) P(1) Pd(1) P(2) 101.26(5)
P(1) Pd(1) C(1) 173.7(1)
P(2) Pd(1) C(1) 84.0(1)
C(5) N(1) C(12) 119.8(4)
P(1) Pd(1) N(1) 87.0(1)
P(2) Pd(1) N(1) 171.6(1)
P(1) Pd(1) C(1) 172.5(3)
P(2) Pd(1) C(1) 86.6(3)
C(5) N(1) C(12) 124.1(9)
P(1) Pd(1) N(1) 88.7(2)
P(2) Pd(1) N(1) 171.9(2)
N(1) Pd(1) C(1)
85.3(4)
N(1) Pd(1) C(1)
87.9(2)
2b
2d
P(1) Pd(1) P(2) 101.30(5)
P(1) Pd(1) C(1) 84.5(1)
P(2) Pd(1) C(1) 174.1(1)
P(1) Pd(1) N(1) 171.44(11) C(5) N(1) C(12) 120.1(3)
P(1) Pd(1) P(2) 101.53(3)
P(1) Pd(1) C(1) 172.92(9)
P(2) Pd(1) C(1)
84.09(9)
P(2) Pd(1) N(1)
N(1) Pd(1) C(1)
C(5) N(1) C(12) 119.9(4)
87.13(11) P(1) Pd(1) N(1)
87.2(2) P(2) Pd(1) N(1) 170.55(8)
N(1) Pd(1) C(1) 86.8(1)
87.75(8)
F igu r e 4. ORTEP drawing of (DPPF)Pd(3-thiophenyl)-
[N(C6H4-4-Me)2] (2d ) with 30% probability ellipsoids. Hy-
drogen atoms are omitted for clarity.
Sch em e 3
Ta ble 2. Selected In tr a m olecu la r Bon d Dista n ces
(Å) of DP P F -Liga ted F u r yl a n d Th iop h en yl
Ditolyla m id es 2a -d
atom
atom
distance
atom
atom
distance
2a
2c
Pd(1)
Pd(1)
Pd(1)
Pd(1)
P(1)
N(1)
P(2)
C(1)
2b
2.379(3)
2.090(7)
2.278(3)
2.00(1)
Pd(1)
Pd(1)
Pd(1)
Pd(1)
P(1)
N(1)
P(2)
C(1)
2d
2.365(1)
2.085(4)
2.291(1)
2.037(4)
Pd(1)
Pd(1)
Pd(1)
Pd(1)
P(1)
N(1)
P(2)
C(1)
2.289(1)
2.090(4)
2.3796(13)
2.035(5)
Pd(1)
Pd(1)
Pd(1)
Pd(1)
P(1)
N(1)
P(2)
C(1)
2.3742(9)
2.084(3)
2.2853(9)
2.046(3)
Table 4 summarizes the yields of heteroarylamines
formed by reductive elimination from complexes 2a -f
and 3a -f and from catalytic amination of the heteroaryl
bromides in the presence of Pd(dba)2 and DPPF as
catalyst and NaO-tBu as base (see Experimental Section
for procedures). The 2-furyl complexes formed the two
heteroarylamines in higher yields than did the corre-
sponding 3-furyl complexes (54% and 71% yield vs 3%
and 0% yield). This trend was reversed for reaction of
the thiophenyl complexes. The 3-thiophenylpalladium
amides consistently formed the two heteroarylamines
in higher yields than did the two 2-thiophenylpalladium
complexes (39% and 59% yield vs 26% and 32% yield).
Red u ctive Elim in a tion fr om (DP P F )P d (h eter o-
a r yl)(a m id o) Com p lexes 2a -f a n d 3a -f. The isolated
(DPPF)Pd(heteroaryl)(amido) complexes 2 and 3 were
heated in benzene-d6 to evaluate the yields for reductive
elimination of heteroarylamines (Scheme 3). Reactions
were conducted in the presence of PPh3 to generate
stable Pd(0) products. A ligand to trap the unstable,
initially formed Pd(0) complex was required to observe
high yields of arylamine by reductive elimination from
arylpalladium amido complexes.37

3398 Organometallics, Vol. 22, No. 17, 2003
Hooper and Hartwig
Ta ble 4. Com p a r ison of Yield s fr om Red u ctive Elim in a tion a n d Yield s fr om Ca ta lytic Rea ction s In volvin g
DP P F -Liga ted P a lla d iu m Com p lexes
a
b
Yields determined by NMR. Yields determined by GC for reactions catalyzed by 2% Pd(dba)2 and 2% DPPF in toluene at 100 °C for
12 h.
The data in Table 4 reveal the parallel trends in yields
resulting from stoichiometric reductive elimination from
isomeric heteroarylpalladium amides and resulting from
catalytic amination of the different heteroaryl halides.
The yields were higher for formation of 2-furylamines
than for formation of 3-furylamines, but the yields were
higher for formation of 3-thiophenylamines than for
formation of 2-thiophenylamines.
Sch em e 4
We also evaluated whether the anilide complex
(DPPF)Pd(2-(5-CH3)C4H3S)(NHPh), 4, which was un-
stable at room temperature, formed heteroaryl aryl-
amine from reductive elimination. Studies on reductive
elimination from arylpalladium amido complexes showed
that the anilides underwent reductive elimination of
diarylamine in high yields at room temperature.37
Warming of the heteroarylpalladium anilido complex at
60 °C for 30 min in the presence of PPh3 formed
(DPPF)2Pd(0) and (PPh3)4Pd(0). However, no heteroaryl
arylamine product was formed. The absence of coupled
product from this stoichiometric reaction is consistent
with the low yield of coupled product from the reaction
of aniline with the five-membered heteroaryl halides in
the presence of palladium catalysts containing either
DPPF or PtBu3 as ligand.
The yields of products from reductive elimination
depend not only on the rate of reductive elimination but
on the rate of competing reactions. To identify reactions
that compete with reductive elimination, we determined
the yields of all major organic products formed from
heating the heteroarylpalladium amido complexes. These
experiments were conducted with the 5-methyl-2-
thiophenylpalladium N-methylanilide 3e because the
substituted thiophenyl products could be identified more
readily by NMR spectroscopy and GC than the parent
thiophenyl side products. The products were identified
by a combination of 1H NMR spectroscopy, GC/mass
spectroscopy, and independent synthesis. Scheme 4
summarizes the yields of the various organic products
formed from heating of 3e in benzene-d6 with added
PPh3. The major side products were amine from proto-
nolysis, amidine from â-hydrogen elimination and imine
disproportionation, and bithiophene from a homo-
coupling process. These products, along with the het-
eroarylamine from reductive elimination, accounted for
91% of the heteroaryl groups and 86% of the amido
groups of the starting complex.
Discu ssion
Con n ection s betw een Heter oa r yl Ha lid e Su b-
stitu tion P a tter n a n d Red u ctive Elim in a tion . The
isomeric furyl and thiophenyl complexes have signifi-
cantly different electronic properties, and the yields of
the catalytic reactions can be understood, in part, by
the relationship between electronics and reductive
elimination rates. Carbon-nitrogen bond-forming re-
ductive elimination of arylamines is faster from com-
plexes with more electron-donating amido groups and
less electron-donating aryl groups.37 Thus, the com-
plexes with more electron-donating heteroaryl groups
on palladium should undergo slower reductive elimina-
tion. We did not measure the rates for reaction of each
heteroaryl compound. However, slower reductive elimi-
nation would allow side reactions to occur and could
reduce the yields of the desired heteroarylamine prod-
ucts.
Figure 5 shows the Mulliken charge distributions on
furans and thiophenes, as determined by RHF calcula-
tions with a 6-31G* basis set. Similar calculations have
been performed previously at various levels,34,39 but not
in an identical manner for the two systems. These
calculations show that the 3-position of furan is much

Coupling of Heteroaromatic Substrates
Organometallics, Vol. 22, No. 17, 2003 3399
Sch em e 5. π-Com p lexes in th e Red u ctive
Elim in a tion fr om Ar yl- a n d Heter oa r ylp a lla d iu m
Am id es
F igu r e 5. Natural charges of furan and thiophene ob-
tained by a 6-31G* RHF calculation.
more electron rich than the 2-position. In contrast, the
calculations showed that the 2-position of thiophene is
more electron-rich. Thus, reductive elimination from
complexes containing 3-furanyl and 2-thiophenyl groups
should be less favorable than reductive elimination from
complexes containing 2-furanyl and 3-thiophenyl groups.
This prediction is consistent with the yields of reductive
elimination product from heating of complexes 2a -d
and 3a -d .
Str u ctu r a l Effects on th e Rea ction Ra tes a n d
Yield s. The position of the donor atom and the pattern
of substitution of the heterocycles could be envisioned
to influence the reductive elimination from isolated
thiophenyl- and furanylpalladium amido complexes by
mechanisms other than electronic effects. First, the
heteroatom could coordinate to palladium in the ground
or transition state structures. However, structures of
the amido complexes determined by X-ray diffraction
showed M-S and M-O bond lengths that are beyond
bonding distance.
dopalladium complexes formed from 2-bromo-3-meth-
ylthiophene underwent reductive elimination in lower
yields, and 2-bromo-3-methylthiophene coupled with
amines in lower yields than the equivalent unsubsitu-
tuted thiophene.
The combination of the heteroatom position and the
presence of substituents contiguous to the metal on the
heteroaryl group did influence the yields of reductive
elimination, however. This effect on reductive elimina-
tion was distinct from that of ortho substituents located
on an aromatic ring. A detailed study of structural
effects on the reductive elimination of sulfides has
suggested that arylpalladium thiolate complexes first
generate an arylsulfide complex that is coordinated
through the arene π-system.40 Similar arene π-complex-
es have been suggested by computational studies to be
intermediates in the oxidative addition of aryl halides
to Pd(0).41 Thus, the stability of such π-arene intermedi-
ates should influence the rates for reductive elimination.
Stable η2, π-complexes of thiophenes are coordinated
through CdC bonds between the 2- and 3-carbons.42,43
As shown in Scheme 5, the 3-methyl-2-amidopalladium
thiophenyl π-complex and the 4-methyl-3-amidopalla-
dium thiophenyl π-complex have different structures
and, therefore, different stabilities. The intermediate
thiophenyl π-complex in the top reaction of Scheme 5
will be the least stable of the three π-complexes because
it is coordinated through a C-S bond. The middle
intermediate will be more stable, but will experience
large steric effects because the palladium is coordinated
to a fully substituted thiophene CdC bond. The bottom
intermediate, which would be formed from reductive
elimination of a 4-methyl-3-amidopalladium thiophenyl
complex, is the most stable and should, therefore, have
the lowest energy transition state to form it by reductive
elimination. In accord with this argument, the ami-
Con clu sion s
To begin to understand the factors that control
reductive eliminations and the scope of coupling reac-
tions with electron-rich heteroaryl halides, we prepared
a range of DPPF-ligated furanylpalladium and thio-
phenylpalladium amido complexes. The observed trends
in reductive elimination can be explained by the distri-
bution of electron density within the heteroaryl systems.
Heteroarylpalladium amido complexes in which the
palladium was attached to the less electron-rich position
of the heteroaryl groups underwent reductive elimina-
tion faster and in higher yields than did complexes in
which the palladium was attached to the more electron-
rich position. Because the position that is more electron-
rich and less electron-rich is reversed in thiophenes and
furans, the yields of reductive elimination for isomeric
thiophenes and furans are different. Coordination of the
heteroatom in 2-thiophenyl and 2-furanyl complexes
does not appear to influence the yields and scope of the
reductive elimination. However, the presence of the
heteroatom does alter the effect of substituents proximal
to the metal center. In contrast to the general accelerat-
ing effect of an ortho substituent on the rate and yields
of reductive elimination of arylamines, -sulfides, and
-ethers, a pseudo-ortho substituent decreases the yields
of reductive elimination from 2-thiophenyl complexes.
Exp er im en ta l Section
(39) Lazzaroni, R.; Boutique, J . P.; Riga, J .; Verbist, J . J .; Fripiat,
J . G.; Delhalle, J . J . Chem. Soc., Perkin Trans. 2 1985, 97-102.
(40) Mann, G.; Baran˜ano, D.; Hartwig, J . F.; Rheingold, A. L.; Guzei,
I. A. J . Am. Chem. Soc. 1998, 120, 9205.
(41) Sundermann, A.; Uzan, O.; Martin, J . M. L. Chem. Eur. J . 2001,
7, 1703.
Gen er a l Meth od s. Unless otherwise noted, all reactions
and manipulations were performed in an inert atmosphere
glovebox. All 31P{1H} NMR chemical shifts are reported in
parts per million relative to an 85% H3PO4 external standard.
Shifts downfield of the standard are reported as positive.
Benzene, toluene, and pentane solvents were distilled from
(42) Spera, M. L.; Harman, W. D. Organometallics 1995, 14, 1559-
1561.
(43) Rauchfuss, T. B. Prog. Inorg. Chem. 1991, 39, 259.

3400 Organometallics, Vol. 22, No. 17, 2003
Hooper and Hartwig
sodium/ benzophenone prior to use. 3-Bromofuran was distilled
prior to use. 2-Bromofuran,44 2-bromo-5-methylfuran, 44 2-bromo-
5-methylthiophene,44 and 3-bromo-N-methylindole45 were all
prepared according to literature procedures. All other chemi-
cals were used as received from commercial suppliers.
Gen er a l P r oced u r e for th e P r ep a r a tion of (DP P F )P d -
(Heter oa r yl)Br Com p lexes, 1a -f. In a drybox, Pd(P(o-
tolyl)3)2 (0.71 mmol) was weighed directly into a screw-capped
vial. A stir bar was added, followed by 10 mL of benzene. The
heteroaryl bromide (2.84 mmol, 4 equiv) was added and stirred
for 10 min. DPPF (391 mg, 0.71 mmol) was dissolved in 10
mL of benzene and added dropwise over 2 min. The reaction
was monitored by removing an aliquot, adding 0.5 mL of CH2-
Cl2 to ensure homogeneity, and obtaining a 31P NMR spectrum.
Upon completion of the reaction, the yellow precipitate was
filtered, washed with 5 mL of benzene, then 2 × 5 mL of
pentane, and dried in vacuo.
(DP P F )P d (2-C4H3O)(Br ), 1a . The above general procedure
was followed using Pd(P(o-tolyl)3)2 (500 mg, 0.71 mmol),
2-bromofuran (418 mg, 251 µL, 2.8 mmol), and DPPF (391 mg,
0.71 mmol) in 20 mL of benzene to give 476 mg (83%) of
(DPPF)Pd(2-C4H3O)(Br) as a yellow solid: 1H NMR (400 MHz,
CD2Cl2) δ 7.99 (m, 4H), 7.51 (m, 10H), 7.40 (m, 2H), 7.26 (m,
4H), 7.10 (bs, 1H), 5.94 (bs, 1H), 5.65 (bs, 1H), 4.61 (bs, 2H),
4.46 (bs, 2H), 4.21 (m, 2H), 3.83 (bs, 2H); 13C{1H} NMR (101
MHz, CD2Cl2) δ 154.73 (dd, J CP ) 164.3, 9.8 Hz), 146.56 (d,
J CP ) 5.6 Hz), 136.14 (d, J CP ) 11.9 Hz), 134.76 (d, J CP ) 12.2
Hz), 133.62(d, J CP ) 51.7 Hz), 133.53 (d, J CP ) 45.8 Hz), 131.24,
131.23, 128.85 (d, J CP ) 9.9 Hz), 128.79 (d, J CP ) 11.1 Hz),
115.13 (dd, J CP ) 5.5 Hz, 13.4 Hz), 111.78 (d, J CP ) 6.1 Hz),
77.40 (dd, J CP ) 58.3, 7.9 Hz), 76.77 (d, J CP ) 11.1 Hz), 75.32
(d, J CP ) 8.7 Hz), 75.05 (dd, J CP ) 45.0, 3.3 Hz), 74.32 (d,
J CP ) 7.3 Hz), 73.49 (d, J CP ) 5.3 Hz); 31P{1H} NMR (202 MHz,
CD2Cl2) δ 28.36 (d, J PP ) 21.3 Hz), 13.17 (d, J PP ) 21.7 Hz).
Anal. Calcd for C38H31BrFeOP2Pd: C, 56.58; H, 3.88. Found:
C, 56.82; H, 3.60.
(m), 128.60 (d, J CP ) 10.0 Hz), 128.44 (d, J CP ) 11.1 Hz), 127.04
(d, J CP ) 11.3 Hz), 77.22 (dd, J CP ) 51.3, 8.3 Hz), 76.70 (d,
J CP ) 11.3 Hz), 74.92 (d, J CP ) 8.5 Hz), 74.85 (dd, J CP ) 33.0,
2.3 Hz), 74.21 (d, J CP ) 7.5 Hz), 73.18 (d, J CP ) 5.3 Hz); 31P{1H}
(202 MHz, CD2Cl2) NMR δ 30.77 (d, J PP ) 21.0 Hz), 12.68 (d,
J PP ) 20.8 Hz). Anal. Calcd for C38H31BrFeSP2Pd: C, 55.48;
H, 3.77; S, 3.89. Found: C, 55.50; H, 3.98; S, 3.62.
(DP P F )P d (3-C4H3S)(Br ), 1d . The above general procedure
was followed using Pd(P(o-tolyl)3)2 (500 mg, 0.71 mmol),
3-bromothiophene (457 mg, 262 µL, 2.8 mmol), and DPPF (391
mg, 0.71 mmol) in 20 mL of benzene to give 374 mg (64%) of
(DPPF)Pd(3-C4H3S)(Br) as a yellow solid: 1H NMR (400 MHz,
CD2Cl2) δ 8.02 (m, 4H), 7.51 (m, 6H), 7.44 (dd, J HH ) 7.9 Hz,
J HP ) 12.1 Hz, 4H), 7.36 (m, 2H), 7.20 (t of d, J HH ) 7.8 Hz,
J HP ) 2.2 Hz, 4H), 6.76 (quin, J ) 2.3 Hz, 1H), 6.48 (m, 1H),
6.24 (m, 1H), 4.63 (m, 2H), 4.47 (m, 2H), 4.18 (m, 2H), 3.77 (q,
J ) 1.8 Hz, 2H); 13C{1H} NMR (101 MHz, CD2Cl2) 144.88 (dd,
J CP ) 130.8, 7.2 Hz), 135.91 (d, J CP ) 12.0 Hz), 134.41 (d,
J CP ) 11.9 Hz), 133.72 (d, J CP ) 37.0 Hz), 133.49 (d, J CP
)
56.4 Hz), 133.31 (m), 130.85, 130.84, 128.57 (d, J CP ) 9.8 Hz),
128.51 (d, J CP ) 11.1 Hz), 122.20 (d, J CP ) 11.8 Hz), 119.35
(m), 77.48 (dd, J CP ) 51.3, 7.9 Hz), 76.46 (d, J CP ) 11.3 Hz),
75.15 (dd, J CP ) 39.5, 3.0 Hz), 74.84 (d, J CP ) 8.6 Hz), 74.01
(d, J CP ) 7.4 Hz), 73.04 (d, J CP ) 5.0 Hz); 31P{1H} NMR (162
MHz, CD2Cl2) δ 30.07 (d, J PP ) 26.0 Hz), 11.33 (d, J PP ) 25.9
Hz).
(DP P F )P d (2-(5-CH3)C4H3S)(Br ), 1e. The above general
procedure was followed using Pd(P(o-tolyl)3)2 (500 mg, 0.71
mmol), 2-bromo-5-methylthiophene (496 mg, 315 µL, 2.8
mmol), and DPPF (391 mg, 0.71 mmol) in 20 mL of benzene
to give 297 mg (50%) of (DPPF)Pd(2-(5-CH3)C4H3S)(Br) as a
yellow solid: 1H NMR (400 MHz, CD2Cl2) δ 8.00 (m, 4H), 7.53-
7.46 (m, 10H), 7.39 (m, 2H), 7.21 (t of d, J HH ) 8.0 Hz, J HP
)
2.4 Hz, 4H), 6.19 (bs, 1H), 5.89 (m, 1H), 4.64 (m, 2H), 4.47
(bs, 2H), 4.18 (m, 2H), 3.75 (m, 2H), 2.18 (s, 3H); 13C{1H} NMR
(126 MHz, CD2Cl2) δ 144.23 (m), 142.70 (dd, J CP ) 150.9, 10.6
Hz) 135.96 (d, J CP ) 11.7 Hz), 134.65 (d, J CP ) 12.0 Hz), 133.53
(d, J CP ) 38.8 Hz), 132.14 (d, J CP ) 57.1 Hz), 130.94 (m), 130.89
(m), 129.45 (m), 128.60 (d, J CP ) 9.7 Hz), 128.39 (d, J CP ) 10.9
Hz), 126.21 (d, J CP ) 10.2 Hz), 77.42 (dd, J CP ) 50.2, 8.0 Hz),
76.66 (d, J CP ) 11.1 Hz), 74.95 (dd, J CP ) 43.2, 3.8 Hz), 74.92
(d, J CP ) 8.5 Hz), 74.13 (d, J CP ) 7.4 Hz), 73.14 (d, J CP ) 5.1
(DP P F )P d (3-C4H3O)(Br ), 1b. The above general procedure
was followed using Pd(P(o-tolyl)3)2 (500 mg, 0.71 mmol),
3-bromofuran (418 mg, 256 µL, 2.8 mmol), and DPPF (391 mg,
0.71 mmol) in 20 mL of benzene to give 482 mg (84%) of
(DPPF)Pd(3-C4H3O)(Br) as a yellow solid: 1H NMR (400 MHz,
CD2Cl2) δ 7.99 (m, 4H), 7.51 (m, 10H), 7.40 (m, 2H), 7.26 (m,
4H), 6.90 (bs, 1H), 6.20 (m, 1H), 5.72 (m, 1H), 4.58 (q, J ) 1.9
Hz, 2H), 4.44 (m, 2H), 4.19 (m, 2H), 3.83 (q, J ) 1.8 Hz, 2H);
13C{1H} NMR (101 MHz, CD2Cl2) δ 140.64 (d, J CP ) 8.1 Hz),
139.66 (m), 136.18 (d, J CP ) 11.9 Hz), 134.86 (d, J CP ) 11.9
Hz), 134.04 (d, J CP ) 25.2 Hz), 134.56 (d, J CP ) 43.3 Hz), 131.29
Hz), 15.68; 31P{1H} NMR (162 MHz, CD2Cl2) δ 30.18 (d, J PP
22.2 Hz), 12.32 (d, J PP ) 22.2 Hz). Anal. Calcd for C39H33
BrFeSP2Pd: C, 55.99; H, 3.98. Found: C, 55.83; H, 4.05.
)
-
(DP P F )P d (2-(3-CH3)C4H3S)(Br ), 1f. The above general
procedure was followed using Pd(P(o-tolyl)3)2 (500 mg, 0.71
mmol), 2-bromo-3-methylthiophene (496 mg, 311 µL, 2.8
mmol), and DPPF (391 mg, 0.71 mmol) in 20 mL of benzene
to give 315 mg (53%) of (DPPF)Pd(2-(3-CH3)C4H3S)(Br) as a
yellow solid: 1H NMR (500 MHz, CD2Cl2) δ 8.06 (m, 2H), 7.98
(m, 2H), 7.81 (m, 2H), 7.56 (m, 2H), 7.49 (m, 4H), 7.31 (t of d,
J HH ) 7.8 Hz, J HP ) 2.4 Hz, 2H), 7.22 (m, 2H), 7.01 (m, 5H),
6.32 (dd, J HH ) 4.8 Hz, J HP ) 2.2 Hz, 1H), 4.88 (m, 1H), 4.58
(m, 1H), 4.47 (bs, 1H), 4.44 (m, 1H), 4.17 (m, 2H), 3.75 (m,
1H), 3.58 (m, 1H), 1.91 (s, 3H); 13C{1H} NMR (126 MHz, CD2-
Cl2) 140.97 (dd, J CP ) 146.8, 8.6 Hz), 137.25 (m), 136.63 (d,
(d, J CP ) 2.5 Hz), 131.15 (d, J CP ) 2.4 Hz), 128.83 (d, J CP
5.2 Hz), 128.73 (d, J CP ) 6.4 Hz), 124.21 (dd, J CP ) 138.2, 10.3
Hz), 116.83 (m), 77.83 (dd, J CP ) 49.9, 8.0 Hz), 76.65 (d, J CP
)
)
11.0 Hz), 75.26 (dd, J CP ) 40.6, 3.4 Hz), 75.20 (d, J CP ) 8.7
Hz), 74.26 (d, J CP ) 7.1 Hz), 73.46 (d, J CP ) 4.8 Hz); 31P{1H}
NMR (162 MHz, CD2Cl2) δ 30.18 (d, J CP ) 21.8 Hz), 11.98 (d,
J CP ) 21.7 Hz).
(DP P F )P d (2-C4H3S)(Br ), 1c. The above general procedure
was followed using Pd(P(o-tolyl)3)2 (500 mg, 0.71 mmol),
2-bromothiophene (457 mg, 273 µL, 2.8 mmol), and DPPF (391
mg, 0.71 mmol) in 20 mL of benzene to give 509 mg (87%) of
(DPPF)Pd(2-C4H3S)(Br) as a yellow solid: 1H NMR (500 MHz,
CD2Cl2) δ 8.02 (m, 4H), 7.52 (m, 6H), 7.46 (dd, J HH ) 7.2 Hz,
J HP ) 12.1 Hz, 4H), 7.37 (m, 2H), 7.20 (t of d, J HH ) 7.9 Hz,
J CP ) 12.3 Hz), 136.36 (d, J CP ) 13.3 Hz), 135.67 (d, J CP
)
10.9 Hz), 134.86 (d, J CP ) 62.6 Hz), 134.48 (d, J CP ) 41.6 Hz),
133.33 (d, J CP ) 104.8 Hz), 133.17 (d, J CP ) 10.8 Hz), 132.51
(d, J CP ) 55.2 Hz), 132.22 (m), 131.47 (m), 130.91 (m), 130.59
(d, J CP ) 11.2 Hz), 130.24 (m), 129.38 (m), 128.97 (d, J CP
)
J HP ) 2.4 Hz, 4H), 7.06 (m, 1H), 6.56 (m, 1H), 6.17 (dd, J HH
)
9.8 Hz), 128.94 (d, J CP ) 11.2 Hz), 128.72 (d, J CP ) 9.6 Hz),
127.89 (d, J CP ) 10.7 Hz), 78.00 (d, J CP ) 16.9 Hz), 77.36 (dd,
J HP ) 3.9 Hz, 1H), 4.66 (q, J ) 1.9 Hz, 2H), 4.49 (m, 2H), 4.19
(m, 2H), 3.74 (q, J ) 1.7 Hz, 2H); 13C{1H} NMR (101 MHz,
CD2Cl2) δ 146.79 (dd, J CP ) 150.3, 10.5 Hz), 135.92 (d, J CP
J CP ) 51.0, 7.4 Hz), 76.08 (d, J CP ) 6.3 Hz), 75.34 (dd, J CP
)
)
42.1, 3.6 Hz), 75.27, 75.22 (m), 75.21 (d, J CP ) 6.7 Hz), 74.21
(d, J CP ) 5.9 Hz), 73.74 (d, J CP ) 6.0 Hz), 72.39 (d, J CP ) 4.4
11.8 Hz), 134.50 (d, J CP ) 11.8 Hz), 133.39 (d, J CP ) 40.1 Hz),
133.13 (d, J CP ) 57.4 Hz), 130.99, 130.97, 129.46 (m), 129.17
Hz), 18.96; 31P{1H} NMR (162 MHz, CD2Cl2) δ 30.50 (d, J CP
)
-
22.5 Hz), 11.79 (d, J CP ) 22.3 Hz). Anal. Calcd for C39H33
(44) Keegstra, M. A.; Klomp, A. J . A.; Brandsma, L. Synth. Commun.
1990, 20, 3371.
(45) Bocchi, V.; Palla, G. Synlett 1982, 1096.
BrFeSP2Pd‚CD2Cl2: C, 51.95; H, 3.57. Found: C, 51.58; H,
3.69.

Coupling of Heteroaromatic Substrates
Organometallics, Vol. 22, No. 17, 2003 3401
P r ep a r a tion of 1d fr om P d (d ba )2, DP P F , a n d 2-Br o-
m oth iop h en e. Into a vial were placed 55.4 mg (0.100 mmol)
of DPPF and 52.4 mg (0.100 mmol) of Pd(dba)2. Into a second
vial were placed 82 mg (0.50 mmol) of 2-bromothiophene and
1 mL of toluene. The toluene solution was added to the mixture
of metal and ligand, and the vial was sealed with a screw cap.
The resulting solution was heated at 100 °C for 1 h, after which
time a yellow solid had crystallized. The toluene was removed
by pipet, and the resulting solid was washed with pentane.
The mother liquor and pentane washes were combined, and
after 2 h additional solid had formed. The solvent was removed
from this solid, and the solid was washed with pentane. The
two crops were combined to total 58 mg (70%) of yellow
product, which was identical by 1H and 31P NMR spectroscopy
to samples prepared by the above procedure.
mg, 0.12 mmol) and KN(p-CH3C6H4)2 (42.3 mg, 0.18 mmol) in
5 mL of toluene to give 81 mg (72%) of (DPPF)Pd(2-C4H3S)-
[N(p-CH3C6H4)2] as purple crystals: 1H NMR (400 MHz, C6D6)
δ 7.84 (m, 4H), 7.72 (m, 4H), 7.43 (d, J ) 8.3 Hz, 4H), 7.09-
7.02 (m, 6H), 6.92 (m, 7H), 6.91 (d, J ) 8.3 Hz, 4H), 6.62 (m,
1H), 6.37 (m, 1H), 4.63 (m, 2H), 4.00 (m, 2H), 3.95 (m, 2H),
3.65 (m, 2H), 2.25 (s, 6H); 13C{1H} NMR (126 MHz, CD2Cl2) δ
152.69, 149.85 (dd, J CP ) 145.15, 14.4 Hz), 135.47 (d, J CP
)
12.5 Hz), 135.20 (d, J CP ) 11.6 Hz), 135.02 (d, J CP ) 40.32
Hz), 132.90 (d, J CP ) 50.9 Hz), 131.69 (m), 131.09 (m), 130.81
(m), 128.84, 128.79 (d, J CP ) 11.5 Hz), 128.17 (d, J CP ) 9.6
Hz), 127.34 (d, J CP ) 4.7 Hz), 125.40 (d, J CP ) 10.6 Hz), 124.09,
121.60 (d, J CP ) 2.1 Hz), 78.86 (dd, J CP ) 49.9, 6.7 Hz), 76.78
(d, J CP ) 11.7 Hz), 75.63 (d, J CP ) 8.7 Hz), 74.59 (d, J CP ) 6.5
Hz), 74.27 (dd, J CP ) 39.4, 2.9 Hz), 72.97 (d, J CP ) 5.8 Hz),
20.98; 31P{1H} NMR (162 MHz, C6D6) δ 23.86 (d, J PP ) 33.8
Hz), 20.37 (d, J PP ) 34.0 Hz). Anal. Calcd for C52H45FeNP2-
PdS‚C7H8: C, 68.66; H, 5.18; N, 1.36. Found: C, 68.79; H, 5.20;
N, 1.25. See below for X-ray structural determination.
Gen er a l P r oced u r e for th e P r ep a r a tion of (DP P F )P d -
(Heter oa r yl)[N(p-CH3C6H4)2] Com p lexes, 2a -f. In a dry-
box, (DPPF)Pd(HetAr)Br (0.12 mmol) and KN(p-CH3C6H4)2
(0.18 mmol) were weighed directly into a screw-capped vial.
A stir bar was added followed by 5 mL of toluene, and the
mixture was stirred. The reaction was monitored by removing
an aliquot and obtaining a 31P NMR spectrum. Upon comple-
tion of the reaction, the mixture was filtered through Celite,
concentrated in vacuo to approximately 2 mL, layered with
10 mL of pentane, and placed at -40 °C for 24 h. The
supernatant was removed, and the resulting purple crystals
were washed with 3 × 5 mL of pentane and dried in vacuo.
(DP P F )P d (2-C4H3O)[N(p-CH3C6H4)2], 2a . The above gen-
eral procedure was followed using (DPPF)Pd(2-C4H3O)Br (100
mg, 0.12 mmol) and KN(p-CH3C6H4)2 (42.3 mg, 0.18 mmol) in
5 mL of toluene to give 78 mg (70%) of (DPPF)Pd(2-C4H3O)-
[N(p-CH3C6H4)2] as purple crystals: 1H NMR (400 MHz, C6D6)
δ 8.08 (m, 4H), 7.60 (d, J ) 8.2 Hz, 4H), 7.57 (m, 4H), 7.13-
6.81 (m, 13H), 6.94 (d, J ) 8.1 Hz, 4H), 6.37 (d, J ) 3.1 Hz,
1H), 5.97 (m, 1H), 4.70 (m, 2H), 4.01 (m, 2H), 3.68 (m, 2H),
3.61 (bs, 2H), 2.26 (s, 6H); 13C{1H} NMR (126 MHz, CD2Cl2) δ
164.38 (dd, J CP ) 161.5, 9.7 Hz), 152.95, 143.19 (d, J CP ) 6.8
Hz), 135.20 (d, J CP ) 14.4 Hz), 135.13 (d, J CP ) 12.5 Hz), 135.01
(d, J CP ) 33.4 Hz), 133.88 (d, J CP ) 50.7 Hz), 130.98, 130.72,
128.96, 128.76 (d, J CP ) 10.7 Hz), 128.16 (d, J CP ) 9.9 Hz),
123.82, 121.27, 116.30 (d, J CP ) 12.9 Hz), 110.20 (d, J CP ) 5.2
Hz), 79.36 (dd, J CP ) 49.1, 6.7 Hz), 77.08 (d, J CP ) 11.8 Hz),
75.73 (d, J CP ) 8.6 Hz), 74.64 (dd, J CP ) 40.2, 1.9 Hz), 74.58
(d, J CP ) 6.4 Hz), 72.64 (d, J CP ) 5.7 Hz), 20.97; 31P{1H} NMR
(DP P F )P d (3-C4H3S)[N(p-CH3C6H4)2], 2d . The above gen-
eral procedure was followed using (DPPF)Pd(3-C4H3S)Br (100
mg, 0.12 mmol) and KN(p-CH3C6H4)2 (42.3 mg, 0.18 mmol) in
5 mL of toluene to give 53 mg (47%) of (DPPF)Pd(3-C4H3S)-
[N(p-CH3C6H4)2] as purple crystals: 1H NMR (400 MHz, C6D6)
δ 7.80-7.70 (m, 8H), 7.37 (d, J ) 8.3 Hz, 4H), 7.03 (m, 6H),
6.97 (m, 6H), 6.90 (d, J ) 8.2 Hz, 4H), 6.78 (m, 1H), 6.65 (m,
1H), 6.25 (m, 1H), 4.57 (m, 2H), 4.05 (m, 2H), 3.99 (m, 2H),
3.68 (m, 2H), 2.25 (s, 6H); 13C{1H} NMR (126 MHz, CD2Cl2) δ
153.08, 147.93 (dd, J CP ) 125.8, 11.6 Hz), 135.59 (d, J CP ) 12.7
Hz), 135.33 (d, J CP ) 37.3 Hz), 134.96 (d, J CP ) 11.6 Hz), 134.59
(m), 133.08 (d, J CP ) 51.4 Hz), 130.89 (m), 130.71 (m), 128.89,
128.70 (d, J CP ) 10.2 Hz), 128.20 (d, J CP ) 9.5 Hz), 123.92,
121.65 (m), 121.55 (m), 119.68 (d, J CP ) 11.0 Hz), 78.96 (dd,
J CP ) 43.9, 7.2 Hz), 76.39 (d, J CP ) 11.3 Hz), 75.45 (d, J CP
)
9.2 Hz), 74.39 (d, J CP ) 6.4 Hz), 73.95 (dd, J CP ) 37.4, 2.9 Hz),
74.02 (d, J CP ) 5.9 Hz), 20.99; 31P{1H} NMR (162 MHz, C6D6)
δ 23.45 (d, J PP ) 33.7 Hz), 17.39 (d, J PP ) 33.7 Hz). Anal. Calcd
for C52H45FeNP2PdS: C, 66.45; H, 4.83; N, 1.49. Found: C,
66.57; H, 4.62; N, 1.36. See below for X-ray structural deter-
mination.
(DP P F )P d (2-(5-CH 3)C4H 3S)[N(p -CH 3C6H 4)2], 2e. The
above general procedure was followed using (DPPF)Pd(2-(5-
CH3)C4H3S)Br (100 mg, 0.12 mmol) and KN(p-CH3C6H4)2 (42.3
mg, 0.18 mmol) in 5 mL of toluene to give 90 mg (79%) of
(DPPF)Pd(2-(5-CH3)C4H3S)[N(p-CH3C6H4)2] as purple crystals:
(162 MHz, C6D6) δ 27.10 (d, J PP ) 32.1 Hz), 22.83 (d, J PP
)
1H NMR (400 MHz, C6D6) δ 7.90 (ddd, J HH ) 6.6 Hz, J HP
)
32.2 Hz). Anal. Calcd for C52H45FeNOP2Pd: C, 67.60; H, 4.91;
N, 1.51. Found: C, 67.26; H, 4.71; N, 1.46. See below for X-ray
structural determination.
11.1, 1.6 Hz, 4H), 7.72 (m, 4H), 7.46 (d, J ) 8.3 Hz, 4H), 7.14-
6.90 (m, 12H), 6.91 (d, J ) 8.2 Hz, 4H), 6.27 (m, 1H), 6.09 (m,
1H), 4.62 (q, J ) 1.8 Hz, 2H), 4.01 (m, 2H), 3.96 (q, J ) 1.8
Hz, 2H), 3.67 (m, 2H), 2.25 (s, 6H), 2.07 (s, 3H); 13C{1H} NMR
(126 MHz, CD2Cl2) 156.78, 146.45 (dd, J CP ) 145.0, 13.9 Hz),
141.93 (d, J CP ) 4.5 Hz), 135.48 (d, J CP ) 12.5 Hz), 135.29 (d,
(DP P F )P d (3-C4H3O)[N(p-CH3C6H4)2], 2b. The above gen-
eral procedure was followed using (DPPF)Pd(3-C4H3O)Br (100
mg, 0.12 mmol) and KN(p-CH3C6H4)2 (42.3 mg, 0.18 mmol) in
5 mL of toluene to give 84 mg (76%) of (DPPF)Pd(3-C4H3O)-
[N(p-CH3C6H4)2] as purple crystals: 1H NMR (400 MHz, C6D6)
δ 7.90 (m, 4H), 7.69 (m, 4H), 7.46 (d, J ) 8.3 Hz, 4H), 7.09-
6.87 (m, 13H), 6.92 (d, J ) 8.2 Hz, 4H), 6.36 (m, 1H), 6.14 (m,
1H), 4.64 (m, 2H), 4.04 (m, 2H), 3.87 (m, 2H), 3.62 (m, 2H),
2.26 (s, 6H); 13C{1H} NMR (101 MHz, CD2Cl2) δ 152.57, 141.90
(m), 138.25 (d, J CP ) 7.7 Hz), 135.17 (d, J CP ) 12.9 Hz), 134.93
J CP ) 11.6 Hz), 135.16 (d, J CP ) 39.7 Hz), 132.99 (d, J CP
)
51.2 Hz), 131.81 (dd, J CP ) 5.7, 5.7 Hz), 130.97 (d, J CP ) 2.0
Hz), 130.76 (d, J CP ) 1.8 Hz), 128.83, 128.74 (d, J CP ) 10.6
Hz), 128.16 (d, J CP ) 9.7 Hz), 124.51 (d, J CP ) 9.7 Hz), 123.98,
121.66 (d, J CP ) 2.3 Hz), 78.88 (dd, J CP ) 46.0, 6.7 Hz), 76.69
(d, J CP ) 11.5 Hz), 75.64 (d, J CP ) 8.7 Hz), 74.54 (d, J CP ) 6.3
Hz), 74.27 (dd, J CP ) 38.6, 2.9 Hz), 72.96 (d, J CP ) 5.8 Hz),
(d, J CP ) 11.8 Hz), 134.91 (d, J CP ) 39.5 Hz), 132.99 (d, J CP
)
21.00, 15.65; 31P{1H} NMR (162 MHz, C6D6) δ 24.03 (d, J PP
)
51.0 Hz), 130.97 (m), 130.49 (m), 128.70, 128.64 (d, J CP ) 8.6
Hz), 127.93 (d, J CP ) 9.5 Hz), 125.17 (dd, J CP ) 134.8, 13.6
Hz), 123.58, 120.98 (d, J CP ) 2.0 Hz), 117.77 (d, J CP ) 3.3 Hz),
79.57 (dd, J CP ) 46.2, 7.4 Hz), 76.63 (d, J CP ) 11.8 Hz), 75.26
(d, J CP ) 8.8 Hz), 74.44 (dd, J CP ) 38.6, 3.1 Hz), 74.23 (d,
J CP ) 6.2 Hz), 72.51 (d, J CP ) 5.6 Hz), 20.76; 31P{1H} NMR
33.7 Hz), 20.09 (d, J PP ) 33.7 Hz). Anal. Calcd for C53H47FeNP2-
PdS: C, 66.71; H, 4.96; N, 1.47. Found: C, 66.48; H, 5.01; N,
1.30.
(DP P F)P d(2-(3-CH3)C4H3S)[N(p-CH3C6H4)2], 2f. The above
general procedure was followed using (DPPF)Pd(2-(3-CH3)-
C4H3S)Br (100 mg, 0.12 mmol) and KN(p-CH3C6H4)2 (42.3 mg,
0.18 mmol) in 5 mL of toluene to give 61 mg (54%) of (DPPF)-
Pd(2-(3-CH3)C4H3S)[N(p-CH3C6H4)2] as purple crystals: 1H
NMR (400 MHz, C6D6) 8.43 (m, 4H), 7.46 (dd, J HH ) 8.2 Hz,
J HP ) 8.8 Hz, 2H), 7.38 (d, J ) 8.2 Hz, 2H), 7.29-7.13 (m,
(162 MHz, C6D6) δ 25.79 (d, J PP ) 31.6 Hz), 21.32 (d, J PP
)
31.7 Hz). Anal. Calcd for C52H45FeNOP2Pd: C, 67.60; H, 4.91;
N, 1.51. Found: C, 67.55; H, 4.81; N, 1.43. See below for X-ray
structural determination.
(DP P F )P d (2-C4H3S)[N(p-CH3C6H4)2], 2c. The above gen-
eral procedure was followed using (DPPF)Pd(2-C4H3S)Br (100
4H), 7.06-7.01 (m, 4H), 6.97-6.83 (m, 13H), 6.49 (dd, J HH
)

3402 Organometallics, Vol. 22, No. 17, 2003
Hooper and Hartwig
4.8 Hz, J HP ) 1.7 Hz, 1H), 5.14 (s, 1H), 4.78 (s, 1H), 3.95 (s,
1H), 3.85 (s, 1H), 3.83 (s, 1H), 3.81 (s, 1H), 3.70 (s, 1H), 3.53
(s, 1H), 2.32 (s, 3H), 2.18 (s, 3H), 1.49 (s, 3H); 13C{1H} NMR
(101 MHz, CD2Cl2) δ 151.64, 151.42, 143.77 (dd, J CP ) 140.1,
16.0 Hz), 137.35 (m), 135.92 (d, J CP ) 14.4 Hz), 135.56 (d,
Hz, 1H), 4.33 (m, 2H), 4.27 (s, 1H), 4.22 (s, 1H), 3.92 (m, 1H),
3.86 (m, 1H), 3.80 (s, 1H), 3.77 (s, 1H), 2.56 (d, J HP ) 4.5 Hz,
3H); 31P{1H} NMR (202 MHz, C6D6) δ 23.99 (d, J PP ) 36.5 Hz),
12.70 (d, J PP ) 36.8 Hz).
(DP P F )P d (2-(5-CH3)C4H3S)(NMeP h ), 3e. The above gen-
eral procedure was followed using (DPPF)Pd(2-(5-CH3)C4H3S)-
Br (100 mg, 0.12 mmol) and KNMePh (19.4 mg, 0.14 mmol)
in 5 mL of toluene to give 62 mg (60%) of (DPPF)Pd(2-(5-CH3)-
C4H3S)(NMePh) as a red solid: 1H NMR (C6D6, 400 MHz) δ
7.91 (m, 2H), 7.84 (m, 4H), 7.61 (m, 2H), 7.20 (t, J ) 7.8 Hz,
2H), 7.13-6.94 (m, 14H), 6.52 (t, J ) 7.1 Hz, 1H), 6.37 (m,
2H), 4.35 (q, J ) 1.8 Hz, 2H), 4.17 (q, J ) 1.8 Hz, 2H), 3.90
(m, 1H), 3.86 (m, 1H), 3.77 (m, 1H), 3.75 (m, 1H), 2.72 (d,
J HP ) 4.8 Hz, 3H), 2.10 (s, 3H); 31P{1H} NMR (162 MHz, C6D6)
δ 22.57 (d, J PP ) 37.5 Hz), 14.28 (d, J PP ) 37.3 Hz).
J CP ) 13.1 Hz), 132.84 (d, J CP ) 39.7 Hz), 132.67 (d, J CP
)
49.9 Hz), 132.40 (d, J CP ) 38.5 Hz), 131.57 (d, J CP ) 10.0 Hz),
131.19 (d, J CP ) 9.6 Hz), 130.15, 129.92, 129.70 (d, J CP ) 53.9
Hz), 128.24, 127.60, 127.17, 126.79 (d, J CP ) 10.2 Hz), 126.69,
126.54 (d, J CP ) 12.1 Hz), 125.25 (d, J CP ) 9.7 Hz), 125.08 (d,
J CP ) 9.9 Hz), 125.09 (m), 123.77, 123.08, 120.67, 118.62,
116.12 (d, J CP ) 5.5 Hz), 75.44 (dd, J CP ) 41.8, 6.4 Hz), 75.22
(d, J CP ) 22.4 Hz), 74.12 (d, J CP ) 16.2 Hz), 73.38 (d, J CP
8.7 Hz), 72.82, 72.78 (d, J CP ) 7.7 Hz), 71.99, 71.10 (dd, J CP
)
)
37.0, 2.6 Hz), 71.04 (m), 69.74 (d, J CP ) 3.9 Hz), 18.74, 18.65,
15.44 (m); 31P{1H} NMR (162 MHz, C6D6) δ 18.66 (d, J PP
34.1 Hz), 14.20 (d, J PP ) 34.0 Hz).
)
(DP P F )P d (2-(3-CH3)C4H3S)(NMeP h ), 3f. The above gen-
eral procedure was followed using (DPPF)Pd(2-(3-CH3)C4H3S)-
Br (100 mg, 0.12 mmol) and KNMePh (19.4 mg, 0.14 mmol)
in 5 mL of toluene to give 50 mg (49%) of (DPPF)Pd(2-(3-CH3)-
Gen er a l P r oced u r e for th e P r ep a r a tion of (DP P F )P d -
(Hetor oa r yl)(NMeP h ) Com p lexes, 3a -f. In a drybox, (DP-
PF)Pd(HetAr)Br (0.12 mmol) and KNMePh (0.14 mmol) were
weighed directly into a screw-capped vial. A stir bar was added
followed by 5 mL of toluene. The mixture was stirred for 10
min. The reaction was monitored by removing an aliquot and
obtaining a 31P NMR spectrum. Upon completion of the
reaction, the mixture was filtered through Celite, concentrated
in vacuo to approximately 2 mL, layered with 10 mL of
pentane, and placed at -40 °C for 24 h. The supernatant was
removed, and the resulting red precipitate was washed with
3 × 5 mL of pentane and dried in vacuo. The complexes were
1
C4H3S)(NMePh) as a red solid: 2 conformers; selected H NMR
(C6D6, 400 MHz) δ 2.85 (d, J HP ) 4.8 Hz, 3H, NMeaPh), 2.68
(d, J HP ) 5.0 Hz, 3H, NMebPh), 2.15 (s, 3H, 3-Mea-thiophene),
2.03 (s, 3H, 3-Meb-thiophene); 31P{1H} NMR (162 MHz, C6D6)
δ 22.11 (d, J PP ) 37.3 Hz, P1b), 21.40 (d, J PP ) 37.1 Hz, P1a),
12.14 (d, J PP ) 36.7 Hz, P2b), 8.84 (d, J PP ) 36.9 Hz, P2a).
P r oced u r e for in -Situ Gen er a tion of (DP P F )P d (2-(5-
CH3)C4H3S)(NHP h ), 4. In a drybox, (DPPF)Pd(2-(5-CH3)-
C4H3S)Br (25 mg, 0.03 mmol), NaOtBu (3.4 mg, 0.035 mmol),
and H2NPh (4.2 µL, 0.035 mmol) were weighed directly into a
small vial. Then 0.5 mL of benzene-d6 was added, and the
resulting suspension was transferred to a screw-capped NMR
tube. The reaction was monitored by obtaining 1H and 31P
NMR spectrum. The yellow suspension was converted to a
bright orange solution with clean formation of the amido
complex. This complex decomposed at room temperature over
1 h. (DPPF)Pd(2-(5-CH3)C4H3S)(NHPh): 1H NMR (C6D6, 500
MHz) δ 7.87 (m, 2H), 7.46 (m, 4H), 7.15-6.74 (m, 17H), 6.50
(m, 2H), 6.12 (m, 14H), 4.22 (m, 2H), 3.78 (m, 2H), 3.70 (m,
2H), 3.55 (m, 2H), 1.90 (s, 3H). 31P{1H} NMR (162 MHz, C6D6)
δ 24.86 (d, J PP ) 37.1 Hz), 9.90 (d, J PP ) 37.1 Hz).
1
obtained in approximately 90-95% purity by H and 31P{1H}
NMR spectroscopy.
(DP P F )P d (2-C4H3O)(NMeP h ), 3a . The above general
procedure was followed using (DPPF)Pd(2-C4H3O)Br (100 mg,
0.12 mmol) and KNMePh (19.4 mg, 0.14 mmol) in 5 mL of
toluene to give 42 mg (42%) of (DPPF)Pd(2-C4H3O)(NMePh)
as a red solid: 1H NMR (500 MHz, C6D6) δ 7.99 (dd, J HP
)
11.3 Hz, J HH ) 7.1 Hz, 2H), 7.84-7.77 (m, 6H), 7.68 (m, 2H),
7.25 (t, J ) 7.9 Hz, 2H), 7.14-6.90 (m, 13H), 6.55 (t, J ) 7.2
Hz, 1H), 6.25 (d, J ) 3.1 Hz, 1H), 6.04 (m, 1H), 4.56 (s, 1H),
4.45 (s, 1H), 3.96 (m, 2H), 3.90 (m, 2H), 3.71 (s, 1H), 3.69 (s,
1H), 2.78 (d, J HP ) 4.6 Hz, 3H); 31P{1H} NMR (202 MHz, C6D6)
δ 25.47 (d, J PP ) 36.7 Hz), 18.97 (d, J PP ) 36.2 Hz).
(DP P F )P d (3-C4H3O)(NMeP h ), 3b. The above general
procedure was followed using (DPPF)Pd(3-C4H3O)Br (100 mg,
0.12 mmol) and KNMePh (19.4 mg, 0.14 mmol) in 5 mL of
toluene to give 55 mg (55%) of (DPPF)Pd(3-C4H3O)(NMePh)
as a red solid: 1H NMR (400 MHz, C6D6) δ 7.90 (m, 4H), 7.69
(m, 4H), 7.27 (t, J ) 7.7 Hz, 2H), 7.07-6.95 (m, 15H), 6.57 (t,
J ) 7.0 Hz, 1H), 6.47 (s, 1H), 6.29 (m, 1H), 4.58 (s, 1H), 4.22
(s, 1H), 4.16 (s, 1H), 4.01 (s, 1H), 3.96 (s, 1H), 3.88 (s, 1H),
3.73 (s, 1H), 3.70 (s, 1H), 2.54 (d, J HP ) 4.6 Hz, 3H); 31P{1H}
NMR (C6D6, 162 MHz) δ 24.69 (d, J PP ) 35.4 Hz), 16.26 (d,
J PP ) 35.6 Hz).
(DP P F )P d (2-C4H3S)(NMeP h ), 3c. The above general pro-
cedure was followed using (DPPF)Pd(2-C4H3S)Br (100 mg, 0.12
mmol) and KNMePh (19.4 mg, 0.14 mmol) in 5 mL of toluene
to give 63 mg (61%) of (DPPF)Pd(2-C4H3S)(NMePh) as a red
solid: 1H NMR (400 MHz, C6D6) δ 7.87-7.80 (m, 6H), 7.60 (m,
2H), 7.22 (t, J ) 7.5 Hz, 2H), 7.09-6.95 (m, 15H), 6.84 (m,
1H), 6.66 (dd, J HP ) 3.8 Hz, J HH ) 3.1 Hz, 1H), 6.55 (t, J ) 7.0
Hz, 1H), 4.38 (s, 1H), 4.33 (s, 1H), 4.21 (s, 1H), 4.17 (m, 1H),
3.90 (m, 1H), 3.85 (s, 1H), 3.76 (m, 2H), 2.65 (d, J HP ) 4.9 Hz,
3H); 31P{1H} NMR (162 MHz, C6D6) δ 22.74 (d, J PP ) 38.1 Hz),
14.29 (d, J PP ) 38.1 Hz).
(DP P F )P d (3-C4H3S)(NMeP h ), 3d . The above general pro-
cedure was followed using (DPPF)Pd(3-C4H3S)Br (100 mg, 0.12
mmol) and KNMePh (19.4 mg, 0.14 mmol) in 5 mL of toluene
to give 52 mg (51%) of (DPPF)Pd(3-C4H3S)(NMePh) as a red
solid: 1H NMR (400 MHz, C6D6) δ 7.92-7.81 (m, 6H), 7.44 (m,
2H), 7.23 (t, J ) 7.5 Hz, 2H), 7.08-6.91 (m, 15H), 6.75 (m,
1H), 6.55 (t, J ) 7.2 Hz, 1H), 6.45 (dd, J HP ) 3.4 Hz, J HH ) 2.1
P r oced u r e for Am in a tion of Heter oa r om a tic Ha lid es
Ca ta lyzed by P d (d ba )2 a n d DP P F or Isola ted 1d (Da ta
for Ta ble 4). In a drybox, aryl bromide (0.5-2.5 mmol), amine
(0.5-2.5 mmol), and NaOtBu (0.55-2.75 mmol) were placed
directly into a screw-capped vial. A stir bar and 0.5-2.5 mL
of toluene or 1 mL of C6D6 for comparisons of reactivity of Pd-
(dba)2 and DPPF to 1d were added. In a separate vial was
placed 2 mol % Pd(dba)2 (0.01-0.05 mmol) and 2 mol % DPPF
(0.01-0.05 mmol) or 2 mol % of 1d . These solids were
suspended or dissolved (for 1d ) in 0.5-2.5 mL of toluene. The
catalyst suspension or solution was then added to the reac-
tants. The vial was sealed with a screw cap containing a
Teflon-lined septum, and the mixture was stirred for 4-16 h
at 100 °C outside the drybox. After this time, the mixture was
poured into pentane (15 mL), filtered, and concentrated in
vacuo. The crude product was adsorbed onto neutral alumina
and purified by flash chromatography eluting with 5% diethyl
ether in hexanes. Naphthalene and trimethoxybenzene were
used as internal standards when obtaining yields by GC. The
yields from reactions in the presence of 1d and in the presence
of Pd(dba)2 and DPPF were determined by integration of the
product resonances to those of trimethoxybenzene internal
standard.
2-(Di-p-tolyla m in o)fu r a n (In d ep en d en t Syn th esis for
Da ta in Ta ble 4). The above general procedure with 2-bro-
mofuran (184 mg, 110 µL, 1.3 mmol), 1.0 equiv of di-p-
tolylamine (246 mg, 1.3 mmol), 1.1 equiv of NaOtBu (132 mg,
1.4 mmol), 2 mol % Pd(dba)2, and 2 mol % tri-tert-butylphos-
phine in 2.5 mL of toluene gave 160 mg (49%) of 2-(di-p-
tolylamino)furan as a white solid: 1H NMR (400 MHz, C6D6)
δ 7.14 (bs, 1H), 7.05 (d, J ) 8.5 Hz, 4H), 6.87 (d, J ) 8.5 Hz,

Coupling of Heteroaromatic Substrates
Organometallics, Vol. 22, No. 17, 2003 3403
4H), 6.06 (m, 1H), 5.76 (m, 1H), 2.04 (s, 6H); 13C{1H} NMR
(101 MHz, CD2Cl2) δ 154.50, 144.89, 138.18, 132.82, 130.48,
122.84, 111.83, 100.26, 21.08; MS (EI) 263 (M+), 234, 220, 91,
65. Anal. Calcd for C18H17NO: C, 82.13; H, 6.46; N, 5.32.
Found: C, 81.92; H, 6.47; N, 5.24.
2-(Di-p-tolyla m in o)-5-m eth ylth iop h en e (In d ep en d en t
Syn th esis for Da ta in Ta ble 4). The above general procedure
with 2-bromo-5-methylthiophene (177 mg, 111 µL, 1.0 mmol),
1.0 equiv of di-p-tolylamine (197 mg, 1.0 mmol), 1.1 equiv of
NaOtBu (106 mg, 1.1 mmol), 2 mol % Pd(dba)2, and 2 mol %
tri-tert-butylphosphine in 2 mL of toluene gave give 221 mg
(75%) of 2-(di-p-tolylamino)-5-methylthiophene as a white
solid: 1H NMR (400 MHz, C6D6) δ 7.30 (d, J ) 8.5 Hz, 4H),
7.01 (d, J ) 8.2 Hz, 4H), 6.61 (d, J ) 3.6 Hz, 1H), 6.42 (m,
1H), 2.18 (s, 9H); 13C{1H} NMR (101 MHz, CDCl3) δ 149.61,
146.25, 135.32, 132.32, 130.04, 123.79, 122.43, 121.70, 21.16,
16.32; MS (EI) 293 (M+), 187, 170, 91, 65. Anal. Calcd for
3-(Di-p-tolyla m in o)fu r a n (In d ep en d en t Syn th esis for
Da ta in Ta ble 4). The above general procedure with 3-bro-
mofuran (184 mg, 113 µL, 1.3 mmol), 1.0 equiv of di-p-
tolylamine (246 mg, 1.3 mmol), 1.1 equiv of NaOtBu (132 mg,
1.4 mmol), 2 mol % Pd(dba)2, and 2 mol % tri-tert-butylphos-
phine in 2.5 mL of toluene gave 231 mg (70%) of 3-(di-p-
1
tolylamino)furan as a white solid: H NMR (400 MHz, C6D6)
δ 7.21 (d, J ) 8.5 Hz, 4H), 7.07 (dd, J 1 ) 1.8, 1.8 Hz, 1H), 7.01
(m, 1H), 7.00 (d, J ) 8.3 Hz, 4H), 6.30 (m, 1H), 2.20 (s, 6H);
13C{1H} NMR (101 MHz, CD2Cl2) δ 143.98, 140.79, 133.91,
132.76, 130.07, 128.19, 121.18, 106.87, 18.80; MS (EI) 263
(M+), 234, 218, 204, 91, 65. Anal. Calcd for C18H17NO: C,
82.13; H, 6.46; N, 5.32. Found: C, 81.97; H, 6.48; N, 5.32.
2-(Di-p-tolyla m in o)th iop h en e (In d ep en d en t Syn th esis
for Da ta in Ta ble 4). Method A of the above general proce-
dure with 2-bromothiophene (204 mg, 122 µL, 1.3 mmol), 1.0
equiv of di-p-tolylamine (246 mg, 1.3 mmol), 1.1 equiv of
NaOtBu (132 mg, 1.4 mmol), 2 mol % Pd(dba)2, and 2 mol %
tri-tert-butylphosphine in 2.5 mL of toluene gave 188 mg (54%)
of 2-(di-p-tolylamino)thiophene as a white solid: 1H NMR (400
MHz, C6D6) δ 7.24 (d, J ) 8.5 Hz, 4H), 6.98 (d, J ) 8.2 Hz,
4H), 6.71 (bs, 1H), 6.70 (m, 1H), 6.65 (m, 1H), 2.17 (s, 6H);
13C{1H} NMR (101 MHz, CD2Cl2) δ 153.43, 146.94, 132.77,
130.49, 126.46, 123.41, 120.72, 120.30, 21.10; MS (EI) 279
(M+), 173, 147, 91, 65. Anal. Calcd for C18H17NS: C, 77.38;
H, 6.13; N, 5.01; S, 11.47. Found: C, 77.46; H, 6.28; N, 4.97;
S, 11.61.
3-(Di-p-tolyla m in o)th iop h en e (In d ep en d en t Syn th esis
for Da ta in Ta ble 4). The above general procedure with
3-bromothiophene (204 mg, 117 µL, 1.3 mmol), 1.0 equiv of
di-p-tolylamine (246 mg, 1.3 mmol), 1.1 equiv of NaOtBu (132
mg, 1.4 mmol), 2 mol % Pd(dba)2, and 2 mol % tri-tert-
butylphosphine in 2.5 mL of toluene gave 307 mg (88%) of
3-(di-p-tolylamino)thiophene as a white solid: 1H NMR (400
MHz, C6D6) δ 7.18 (d, J ) 8.4 Hz, 4H), 6.99 (d, J ) 8.5 Hz,
4H), 6.92 (m, 1H), 6.88 (m, 1H), 6.54 (m, 1H), 2.20 (s, 6H);
13C{1H} NMR (101 MHz, CD2Cl2) δ 148.11, 146.66, 132.60,
130.52, 125.37, 125.15, 124.21, 111.71, 21.14; MS (EI) 279
(M+), 231, 91, 65. Anal. Calcd for C18H17NS: C, 77.38; H, 6.13;
N, 5.01; S, 11.47. Found: C, 77.26; H, 6.19; N, 5.08; S, 11.43.
C
19H19NS: C, 77.77; H, 6.53; N, 4.77; S, 10.93. Found: C,
77.51; H, 6.47; N, 4.81; S, 10.78.
2-(Di-p-tolyla m in o)-3-m eth ylth iop h en e (In d ep en d en t
Syn th esis for Da ta in Ta ble 4). The above general procedure
with 2-bromo-3-methylthiophene (177 mg, 108 µL, 1.0 mmol),
1.0 equiv of di-p-tolylamine (197 mg, 1.0 mmol), 1.1 equiv of
NaOtBu (106 mg, 1.1 mmol), 2 mol % Pd(dba)2, and 2 mol %
tri-tert-butylphosphine in 2 mL of toluene gave 215 mg (73%)
1
of 2-(di-p-tolylamino)-3-methylthiophene as a white solid: H
NMR (400 MHz, C6D6) δ 7.19 (d, J ) 8.5 Hz, 4H), 6.99 (d, J )
8.1 Hz, 4H), 6.78 (d, J ) 5.6 Hz, 1H), 6.65 (d, J ) 5.6 Hz, 1H),
2.18 (s, 6H), 2.00 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
145.53, 132.53, 131.85, 130.08, 129.51, 129.16, 128.70, 121.67,
21.17, 16.35; MS (EI) 293 (M+), 187, 91, 65. Anal. Calcd for
C
19H19NS: C, 77.77; H, 6.53; N, 4.77. Found: C, 77.50; H, 6.40;
N, 4.61.
Ack n ow led gm en t. We thank the NIH (GM-55382)
for support of this work, J ohnson-Matthey for a gift of
palladium, and Merck Research Laboratories for unre-
stricted support. We are grateful to Tim Boller for
conducting a calculation of the charge distribution in
furan and thiophene.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and full tabular data for the determinations of the
structures of 2a -d by X-ray diffraction. This material is
available free of charge via the Internet at http://pubs.acs.org.
OM030257G