Influences on the relative rates for C-N bond-forming reductive elimination and β-hydrogen elimination of amides. A case study on the origins of competing reduction in the palladium-catalyzed amination of aryl halides

Article abstract of DOI:10.1021/ja954121o

Typical decomposition by β-hydrogen elimination has limited the productive catalytic organometallic chemistry of late transition metal amido complexes. However, one reaction that has been shown to involve a late metal amido complex with β-hydrogens and elude extensive β-hydrogen elimination is the palladium-catalyzed animation of aryl bromides to give arylamines. The primary side products formed in these catalytic aminations are arenes, the products of aryl halide reduction. It would seem reasonable that both arylamine and arene products result from competitive reductive elimination of amine and β-hydrogen elimination from a common amido aryl intermediate. Our results do substantiate competitive β-hydrogen elimination and reductive elimination involving an amido group, but also reveal a second pathway to reduction that occurs when employing Pd(II) precursors. This second pathway for aryl halide reduction was shown principally by the observations that (1) stoichiometric reactions of aryl halide complexes or catalytic reactions employing [P(o-tolyl)₃]₂Pd(0) showed less arene side product than did catalytic reactions employing Pd(II) precursors, (2) increasing amounts of Pd(II) catalyst gave increasing amounts of arene product, and (3) reactions catalyzed by Pd(II) precursors showed amine:arene ratios at early reaction times that were lower than ratios after complete reaction. In addition to data concerning arene formation during Pd(II) reduction, we report data that demonstrate how electronic and steric factors control the relative rates for amine vs arene formation. The relative amounts of reduction product and amination product depend on the size of the phosphine and substitution pattern of the amide ligands. Systematic variation of phosphine size demonstrated that increasing the size of this ligand gave increasing amounts of arylamine product, increasing size of the amido group gave increasing amounts of arylamine product, while decreased nucleophilicity of the amide gave decreased amounts of arylamine product. Further, the presence of electron withdrawing groups on the palladium-bound aryl ring accelerated the reductive elimination reaction, relative to β-hydrogen elimination, and this result is consistent with previously observed acceleration of carbon-heteroatom bond-forming reductive eliminations with isolable palladium complexes.

Full text of DOI:10.1021/ja954121o

3626
J. Am. Chem. Soc. 1996, 118, 3626-3633
Influences on the Relative Rates for C-N Bond-Forming
Reductive Elimination and â-Hydrogen Elimination of Amides.
A Case Study on the Origins of Competing Reduction in the
Palladium-Catalyzed Amination of Aryl Halides
John F. Hartwig,* Steven Richards, David Baran˜ano, and Fre´de´ric Paul
Contribution from the Department of Chemistry, Yale UniVersity, P.O. Box 208107,
New HaVen, Connecticut 06520-8107
ReceiVed December 7, 1995X
Abstract: Typical decomposition by â-hydrogen elimination has limited the productive catalytic organometallic
chemistry of late transition metal amido complexes. However, one reaction that has been shown to involve a late
metal amido complex with â-hydrogens and elude extensive â-hydrogen elimination is the palladium-catalyzed
amination of aryl bromides to give arylamines. The primary side products formed in these catalytic aminations are
arenes, the products of aryl halide reduction. It would seem reasonable that both arylamine and arene products
result from competitive reductive elimination of amine and â-hydrogen elimination from a common amido aryl
intermediate. Our results do substantiate competitive â-hydrogen elimination and reductive elimination involving
an amido group, but also reveal a second pathway to reduction that occurs when employing Pd(II) precursors. This
second pathway for aryl halide reduction was shown principally by the observations that (1) stoichiometric reactions
of aryl halide complexes or catalytic reactions employing [P(o-tolyl)3]2Pd(0) showed less arene side product than
did catalytic reactions employing Pd(II) precursors, (2) increasing amounts of Pd(II) catalyst gave increasing amounts
of arene product, and (3) reactions catalyzed by Pd(II) precursors showed amine:arene ratios at early reaction times
that were lower than ratios after complete reaction. In addition to data concerning arene formation during Pd(II)
reduction, we report data that demonstrate how electronic and steric factors control the relative rates for amine vs
arene formation. The relative amounts of reduction product and amination product depend on the size of the phosphine
and substitution pattern of the amide ligands. Systematic variation of phosphine size demonstrated that increasing
the size of this ligand gave increasing amounts of arylamine product, increasing size of the amido group gave increasing
amounts of arylamine product, while decreased nucleophilicity of the amide gave decreased amounts of arylamine
product. Further, the presence of electron withdrawing groups on the palladium-bound aryl ring accelerated the
reductive elimination reaction, relative to â-hydrogen elimination, and this result is consistent with previously observed
acceleration of carbon-heteroatom bond-forming reductive eliminations with isolable palladium complexes.
Introduction
Scheme 1
The reaction of an amide sourceseither a tin amide, a boron
amide with base, or an amine in the presence of baseswith
aryl bromides catalyzed by tri-o-tolylphosphine palladium
complexes leads to the formation of arylamines as shown in eq
1.1-9 The dominant reaction that competes with amination is
of an amido aryl intermediate by either reversible, endothermic6
transfer of the amide from the tin reagent11 or coordination of
an amine to the aryl halide complex and deprotonation of the
amine N-H.7
The formation of a palladium dialkylamido complex is
unusual, and productive catalytic chemistry of such intermediates
is rare. Indeed the dialkylamido complex involved in the
catalytic amination chemistry is unstable at room temperature.
Experiments directed at generating the complex at low temper-
atures by methods that were independent of the catalytic
reactions showed that such complexes provided arylamine
products below room temperature.10 Further, it is remarkable
that this intermediate would undergo the rare reductive elimina-
tion of amine, since â-hydrogen elimination of alkylamido
reduction of the aryl halide to the corresponding arene. We
have recently provided strong evidence for a reaction pathway10
in Scheme 1 that involves oxidative addition of aryl halide to
a monophosphine Pd(0) complex,5 and subsequent generation
X Abstract published in AdVance ACS Abstracts, April 1, 1996.
(1) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927-928.
(2) Kosugi, M.; Kameyama, M.; Sano, H.; Migita, T. Nippon Kagaku
Kaishi 1985, 3, 547-551.
(3) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969.
(4) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030.
(5) Hartwig, J. F.; Paul, F. J. Am. Chem. Soc. 1995, 117, 5373.
(6) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 4708.
(7) Louie, J.; Hartwig, J. F. Tetrahedron Lett, 1995, 36, 3609.
(8) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901.
(9) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1348-1350.
(10) Louie, J.; Paul, F.; Hartwig, J. F. Submitted for publication.
(11) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11598.
0002-7863/96/1518-3626$12.00/0 © 1996 American Chemical Society

Palladium-Catalyzed Amination of Aryl Halides
J. Am. Chem. Soc., Vol. 118, No. 15, 1996 3627
complexes has been thought to be a rapid route to their
decomposition.12,13
The most concise mechanism that accounts for both arylamine
and arene products includes a palladium-amido intermediate
that would competitively form amine by C-N bond-forming
reductive elimination and arene after initial â-hydrogen elimina-
tion. Few data are known concerning factors that would control
the relative rates for C-N bond-forming reductive elimination
of amines and for â-hydrogen elimination from transition metal
amides. Only a handful of papers report reductive elimination
of amines.6,14,15 Although imine insertions into hydrides, the
reverse of â-hydrogen elimination from amides, are presumably
crucial to imine hydrogenation reactions,16 little is known about
factors that control either direction of this transformation.17
Since the selectivity of reactive intermediates typically
controls product composition in both catalytic and stoichiometric
processes, information on factors controlling the chemistry of
the organometallic palladium-amide reactive intermediate
would be important for understanding the capability of late metal
amido complexes to serve as intermediates in productive
catalytic chemistry despite, or as a result of, their instability. In
this paper, we provide strong evidence for a reaction mechanism
that accounts for amine and arene product formation by reaction
of an amido group with a palladium aryl halide complex, and
our results are consistent with divergent reactivity of a palladium
amido complex. However, we also provide strong evidence for
a separate reaction pathway that forms arenes during the early
stages of reactions initiated by Pd(II) catalyst precursors. We
have drawn these conclusions by analyzing product ratios
formed during stoichiometric reactions involving either Pd(0)
complexes or Pd(II) aryl halide complexes and catalytic reac-
tions involving either Pd(0) complexes, Pd(II) aryl halide
complexes, Pd(II) dichloride catalyst precursors, and Pd(II)
diacetate catalytst precursors. Further, we have delineated the
steric and electronic effects on product selectivity in both
stoichiometric and catalytic reactions to reveal their effects on
the relative rates for â-hydrogen elimination and reductive
elimination. As a side light, these studies have also revealed
several advantages of the tri-o-tolylphosphine ligand for such
catalytic chemistry.
to trap the Pd(0) as L2Pd gave the dialkylaniline products in
greater than 85% yields. No p-BuC6H4-t-Bu was formed that
could result from transfer of the alkyl rather than the amido
group.
Amido tin reagents were employed as the source of the amide
group, since their reaction is likely to be milder than generating
the amide by reaction of amine in the presence of base. Further,
reactions with tin reagents allowed for comparisons to be made
between reactions involving different Pd-phosphine systems.
Phosphines smaller than tri-o-tolylphosphine are not displaced
by secondary amines, precluding catalytic activity in the tin-
free system.7,9
In addition to stoichiometric experiments, catalytic reactions
(eq 1) between p-BrC6H4-t-Bu and tin amides were conducted
using either 1, [(o-tolyl)3P]2Pd (2),4 Pd(OAc)2 with 3 equiv of
P(o-tolyl)3 (3: catalyst mixture), or [(o-tolyl)3P]2PdCl2 (4)1 as
catalyst, and the ratios of arene and arylamine products were
again determined by GC. Unless otherwise state, 5 mol %
catalyst was employed and reactions were conducted with 0.13
mmol of aryl bromide, 1.5 equiv of tin amide, and 0.5 mL of
benzene solvent. In all cases, arene and arylamine were the
only products observed in substantial quantities. Other products
were formed in less than 5% yields. Again, no p-BuC6H4-t-Bu
was formed that could result from transfer of the alkyl rather
than the amido group.
The ratios of amine to arene products formed from the
catalytic and stoichiometric experiments involving complexes
of the P(o-tolyl)3 ligand are provided in Table 1. The stoichio-
metric reations gave amine:arene product ratios of 11:1 for tin
dimethylamide and 15:1 for tin diethylamide. Ratios of amine:
arene that were comparable to those formed during stoichio-
metric reactions of 1 were observed during reactions of the aryl
bromide with tin amide catalyzed by either Pd(0) complex 2 or
aryl bromide complex 1.10 Reactions catalyzed by 1 or 2 gave
ratios between 9:1 and 10:1 in favor of amine product. In the
case of 1 or 2, varying the amount of catalyst from 0.5 mol %
to 5 mol % had no measurable effect on selectivity. Further,
product ratios remained constant throughout the course of the
reaction.
Results and Discussion
I. Comparison of Product Selectivities between Stoichio-
metric and Catalytic Reactions. The aryl halide complexes
{[(o-tolyl)3P]Pd(p-C6H4-t-Bu)(Br)}2 clearly lie on the palladium-
catalyzed amination reaction pathway in either their monomeric
or dimeric forms.3,10 Thus, stoichiometric reactions of tin
amides with these compounds allow observation of the products
resulting from amide generation and amide reactivity during a
single turnover of the catalysis. In order to understand the
selectivity of the amido intermediate, reaction of the aryl halide
complex {[(o-tolyl)3P]Pd(p-C6H4-t-Bu)(Br)}2 (1)4 with tin amides
(eq 2) was conducted and the ratio of tert-butylbenzene vs N,N-
dialkylaniline product was determined by gas chromatography
after correcting for response factors. The stoichiometric reaction
of 1 at 80 °C in benzene in the presence of 6 equiv of (o-tolyl)3P
Reactions involving Pd(II) catalyst precursors 3 and 4 gave
more arene product than those catalyzed by 1 and 2. For
example, reactions catalyzed by the mixture 3 gave a 5:1 ratio
of amine to arene, while the Pd(II) complex 4 gave a 6:1 ratio.
The amount of reduction product was greater for reactions that
used a higher mole percent of Pd(II) catalyst precursors. For
example, the use of 0.5 mol % 4 in reactions of Me3SnNMe2
led to greater than 90% conversion of aryl bromide and gave a
10:1, rather than 6:1, ratio of amine to arene. The use of 25
mol % catalyst gave a 4:1 ratio of amine to arene. Similar
results were observed with Bu3SnNEt2. The ratio of 9:1 with
5 mol % catalyst was reduced to 5:1 in reactions employing 25
mol % catalyst.
As one might expect from this result, the observed ratios of
amine to arene products varied with time when employing the
Pd(II) precursors, and improved over the course of the reaction.
For example, the reaction of p-BrC6H4-t-Bu with Bu3SnNMe2
catalyzed by 5 mol % 4 showed a 4:1 ratio of amine to arene
after roughly 50% conversion. The reaction was stopped at this
point since all of the insoluble dichloride catalyst had reacted
to provide soluble materials. A product ratio near the 9:1
selectivity for the Pd(0) complex would be required for the
remainder of the reaction in order to obtain a final ratio of 6:1.
(12) Fryzuk, M. D.; Montgomery, C. D. Coord. Chem. ReV. 1989, 95,
1-40.
(13) Bryndza, H.; Tam, W. Chem. ReV. 1988, 88, 1163-1188.
(14) Villanueva, L. A.; Abboud, K. A.; Boncella, J. M. Organometallics
1994, 13, 3921.
(15) Koo, K.; Hillhouse, G. L. Organometallics 1995, 14, 4421.
(16) For a recent review see: James, B. R. Chem. Ind. 1995, 62, 167-
180.
(17) A direct observation of imine insertion that produces an amide
complex potentially similar to those in catalytic systems is the following:
Fryzuk, M. D.; Piers, W. E. Organometallics 1990, 9, 986-98.

3628 J. Am. Chem. Soc., Vol. 118, No. 15, 1996
Hartwig et al.
Table 1. Ratios of Amine:Arene under Different Stoichiometric
and Catalytic Conditions for Reactions Involving the Aryl Group
p-C6H4-t-Bu
Table 2. Electronic Effects on Amination vs Reduction Selectivity
for reactions Involving Bu3SnNMe2
stoichiometric
amine:arene
catalytic L2PdCl2
amine:arene
tin amide
expt no.
aryl group
Pd
complex
Bu3SnX,
X )
ratio of
amine:arene
1
2
3
C6H4C(O)Me
C6H4-t-Bu
C6H4-p-NMe2
30:1
9:1
5:1
15:1
6:1
3:1
expt no.
description
1
2
2
3
4
5
6
7
8
stoichiometric
stoichiomeric
stoichiometric
catalytic
catalytic
catalytic
catalytic
catalytic
catalytic
catalytic
1
1
1
NMe2
NMe2-d6
NEt2
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
NEt2
11:1
25:1
15:1
10:1
9:1
5:1
6:1
4:1
9:1
9:1
5:1
1 (5%)
2 (5%)
3 (5%)
4 (5%)
4 (25%)
4 (0.5%)
4 (5%)
4 (25%)
arises from â-hydrogen elimination from the amido group we
conducted reactions with Bu3SnN(CD3)2. Two predictions can
be made for reactions involving this substrate. First, arene
product would contain a single deuterium. Second, the ratio
of amine:arene would increase since the â-hydrogen elimination
would be slower for N(CD3)2 as a result of a primary isotope
effect. The experimental data were consistent with these
predictions. The labeled reagent was prepared using LiN(CD3)2,
generated from commercially available (CD3)2NH2Cl.
9
10
catalytic
NEt2
Scheme 2
As expected for stoichiometric reactions, the arene product
consisted of predominantly deuterated material. For example,
reaction of 1 with Bu3SnN(CD3)2 under identical conditions to
the stoichiometric reaction of Bu3SnNMe2 gave arene and amine
products, with the arene showing 70% monodeuterated ma-
terial.18 The amount of deuterium incorporation was unaffected
by using protiated or deuterated solvent. Further, the ratio of
amine:arene was altered as a result of using deuterated amide.
The ratio of amine:arene was 25:1 rather than 11:1, as was
observed with protiated amide. Assuming that the rate of
reductive elimination of amine is identical for deuterated and
protiated amides, the value of kH/kD is on the order of 2 for the
â-hydrogen elimination process, and this value is consistent with
a primary isotope effect. Of course, this value is approximate
since the arene is not completely deuterated and the reductive
elimination may show a significant secondary isotope effect
resulting from the six deuteria on the amide group. The
deuterated amide reagent was also employed in reactions
catalyzed by 4. In this case, the arene product was roughly
50% protiated and 50% deuterated. Thus, the additional arene
product formed when using Pd(II) catalysts may be formed by
a process other than that involving amide â-hydrogen elmination.
Alternatively, generation of small amounts of HCl in the
reduction process may lead to scrambling with trace amounts
of water. Again, protons or deuterons from solvent were not
incorporated into the arene product; arene product formed during
reactions conducted in benzene-d6 showed identical isotope
patterns to those formed during reactions in protiated benzene.
In the catalytic reactions, the majority of arene is formed during
reduction of Pd(II) to Pd(0), and the ratio of amine:arene was
not altered enough to allow quantitative conclusions in this more
complex catalytic case.
Although these data are approximate, the required selectivity
is clearly similar if not identical to the 9:1 selectivity observed
with 1 or 2 or with 0.5 mol % of 4.
These data are consistent with at least two independent
reaction pathways to form arene as depicted simply in Scheme
2. The arene product does not arise from competitive transfer
of a butyl and an amido group, because no p-BuC6H4-t-Bu is
formed as reaction product. Carbon-carbon bond-forming
reductive elimination is known to be faster than â-hydrogen
elimination with these systems, since alkyl groups can be
employed in coupling reactions with aryl halides. Thus, any
arene formed by butyl group transfer must be accompanied by
p-BuC6H4-t-Bu. Instead, one pathway for arene formation
appears to involve the aryl bromide complexes, is a direct result
of the catalytic cycle, and produces both amine and arene
product. Competitive reductive elimination and â-hydrogen
elimination is the simplest mechanism that accounts for both
amine and arene products during the stoichiometric reaction.
Steric and electronic effects on the product selectivity presented
below are further consistent with such competitive reactions that
most likely diverge at a common amido intermediate.
However, a second pathway occurs during the reduction
process and leads to additional formation of arene. This
conclusion is clearly indicated by (1) the similarity between
selectivities observed for stoichiometric reactions involving 1
and for catalytic reactions involving either 1 or 2, (2) the
increased amount of arene formed in catalytic reactions involv-
ing either 3 or 4, (3) the increased amount of arene product
with increasing amounts of Pd(II) catalyst, and (4) similar
selectivity with variable amounts of Pd(0) catalyst. More subtly,
the increasing ratio of amine:arene over the course of time with
reactions catalyzed by Pd(II), but not Pd(0), indicates that
additional arene is formed early in the reaction, presumably
when the Pd(II) precursor is being reduced to Pd(0). It is unclear
how the arene is produced as a result of Pd(II) reduction, but
one possibility is the formation of arene by reaction of a portion
of the aryl halide complex with HCl that may form as a
byproduct of palladium reduction.
III. Effect of Palladium-Bound Aryl Group Electronic
Properties. Table 2 shows the effect of aryl group electronic
properties on the ratio of amine:arene. Reaction of Bu3SnNMe2
with {Pd[P(o-tolyl)3][C6H4-p-C(O)Me](Br)}2 gave significantly
higher ratios of amine:arene than did reactions with {Pd[P(o-
tolyl)3](p-C6H4-t-Bu)(Br)}2, while reaction of {Pd[P(o-tolyl)3]-
(C6H4-p-NMe2)(Br)}2 gave significantly lower ratios of amine:
arene. Once again, the reactions of p-BrC6H4C(O)Me and
p-BrC6H4NMe2 catalyzed by 4 showed lower amine to arene
ratios than the stoichiometric reactions of the corresponding aryl
(18) The amine product is fully d6. It is, therefore, unlikely that the
residual protiated arene results from preliminary scrambling of the amide
â-hydrogens. Alternatively, the hydrogen of the arene may result from
scrambling of the intermediate palladium hydride, a small amount of
competing transfer of the butyl group, reaction with a small amount of tin
hydride, or reversible metallation of the phosphine. In any case, these are
clearly minor pathways.
II. Source of Hydrogen on the Arene Reduction Product.
In order to demonstrate conclusively that the reduction product

Palladium-Catalyzed Amination of Aryl Halides
J. Am. Chem. Soc., Vol. 118, No. 15, 1996 3629
Table 3. Effect of Amino Group on Amination vs Reduction
Selectivity for Reactions Involving the Aryl Group p-C6H4-t-Bu
Table 4. Effect of Phosphine Size on Product Selectivity for
Reactions Involving Bu3SnNMe2
stoichiometric
catalytic
catalytic
amido
group
stoichiometric
amine:arene
expt
{LnPd(C6H4-t-Bu)(Br)}m Pd(OAc) + 3L L2PdCl2
expt no.
no. phosphine
n, m; Amine:Arene
amine:arene amine:arene
1
2
3
NMe2
NEt2
NMePh
11:1
15:1
5:1
1
2
3
4
P(o-tolyl)3
P(o-tolyl)2Ph
P(o-tolyl)Ph2
PPh3
n ) 1, m ) 2; 9:1
n ) 2, m ) 1; 8:1
n ) 2, m ) 1; 3:1
n ) 2, m ) 1; 1:1.2
5:1
3:1
1:1.2
-
6:1
4:1
2:1
-
halide complexes. However, the relative effects of aryl
substitution were the same for stoichiometric reactions with
analogs of 1 and for catalytic reactions involving 4.
tolyl)3. Solutions of isolated aryl halide complexes containing
the P(o-tolyl)2Ph ligand displayed an equilibrium in solution
between two species. One complex displayed a resonance at
δ 21.9 and the other one at δ 25.4 in the 31P{1H} NMR
spectrum. A resonance for free P(o-tolyl)2Ph that was equal in
intensity to the resonance at δ 25.4 was also observed.
Treatment of the solution with additional free phosphine
provided solutions displaying 31P{1H} NMR spectra with a
single resonance at δ 21 accompanying the signal for free
phosphine. We, therefore, assign the resonance at δ 21 to the
monomeric aryl bromide complex 5 with two phosphine ligands
and the resonance at δ 25.4 to a dimeric species {Pd[P(o-
tolyl)2Ph](p-C6H4-t-Bu)(Br)}2 with a structure analogous to that
for {Pd[P(o-tolyl)3](Ar)(Br)}2, which we have reported previ-
ously.4 Solid product obtained from the exchange reactions
analyzed satisfactorily for the monomeric bis-phosphine com-
plex and an X-ray diffraction study was performed on the
analogous four-coordinate, monomeric p-tolyl analog {Pd[P(o-
tolyl)2Ph]2(p-C6H4-t-Bu)(Br)} (5′) (Vide infra).
These results are consistent with a previous result from our
group concerning electronic effects on the rates for reductive
eliminations that form carbon-heteroatom bonds.19 We have
shown that the rates of carbon-heteroatom bond-forming
reductive eliminations involving aryl groups are accelerated by
the presence of electron withdrawing groups attached to the
palladium-bound aromatic system. Although little is known
about â-hydrogen elimination of amido groups, it is reasonable
to expect that the properties of the palladium-bound aryl group
would have less effect on this reaction than on reductive
elimination, since the â-hydrogen elimination step does
not directly involve the aryl system. Thus, the change in
amination:reduction ratios as a function of arene electronics is
consistent with acceleration of the reductive elimination and
substantiates the proposal of competitive reductive elimination
and â-hydrogen elimination by divergent reactivity with a
common intermediate.
IV. Effect of Amide Group on Selectivity. We investigated
the effect of amide size, amide electronic properties, and the
prsence of primary vs secondary C-H bonds in the amide
â-position by comparing selectivities of Bu3SnNMe2 with
Bu3SnNEt2 and Bu3SnNMePh. These results are presented in
Table 3. Larger tin amides such as Bu3SnN(i-Bu)2 reacted very
slowly with 1, suggesting that the amido group was too large
to undergo transmetalation. In both catalytic and stoichiometric
reactions, the ratio of amine:arene was slightly greater for
reaction with Bu3SnNEt2 than for the reaction with Bu3SnNMe2.
In contrast, stoichiometric reaction of the larger, but less
nucleophilic Bu3SnNMePh with 1 gave a 5:1 ratio of amine:
arene, markedly reduced from ratios obtained from SnNMe2.
The data for NMe2 vs NEt2 are consistent with slightly slower
â-hydrogen elimination involving secondary hydrogens than that
involving primary hydrogens and/or faster reductive elimination
with the slightly larger diethylamido group. The lower amine:
arene ratio with NMePh is clearly consistent with the electronic
effects in the previous section. The aromatic ring acts as an
electrophile, the amide as a nucleophile, and reductive elimina-
tion is faster with more nucleophilic amides. Alternatively,
â-hydrogen elimination may be faster with aryl-substituted
amides because a conjugated imine would be formed. In either
case, these results again support divergent reactivity with a
common intermediate.
V. Phosphine Steric Effects on Catalytic and Stoichio-
metric Reactions. In order to determine the selectivities for
complexes containing phosphines with systematically varied
steric requirements, aryl halide complexes of P(o-tolyl)2Ph, {Pd-
[P(o-tolyl)2Ph]2(p-C6H4-t-Bu)(Br)} (5), and of P(o-tolyl)Ph2,
{Pd[P(o-tolyl)Ph2]2(p-C6H4-t-Bu)(Br)} (6), were prepared. The
simplest method we found for preparing these compounds was
exchange of the smaller phosphines for P(o-tolyl)3 in 1.
Reaction of the dimeric aryl halide complex {Pd[P(o-tolyl)3]-
(p-C6H4-t-Bu)(Br)}2 or {Pd[P(o-tolyl)3](C6H4-p-Me)(Br)}2 with
P(o-tolyl)2Ph or P(o-tolyl)Ph2 quantitatively displaced P(o-
The ratios of amine:arene obtained from stoichiometric and
catalytic amination reactions catalyzed by palladium complexes
of phosphine ligands with systematically varied steric require-
ments are given in Table 4. It should be noted that reaction
rates and total yields of amine and arene decreased significantly
with decreasing phosphine size. Yields of amine in stoichio-
metric and catalytic reactions were on the order of 60% for P(o-
tolyl)2Ph, 30% for P(o-tolyl)Ph2, and less than 10% for PPh3.
LnPd(0) complexes were the dominant metal-containing product.
Besides the arene and amine products, multiple organic side
products were observed by 1H NMR spectroscopy and GC, but
were not identified. Nevertheless, the four ligands show the
same characteristic of higher amination:reduction ratios for
stoichiometric reactions than for catalytic reactions. Again,
these results are consistent with a pathway for reduction that is
separate from the pathway that forms arylamine.
Experiments with the different phosphines demonstrated that
amination:reduction ratios decreased with decreasing ligand size.
These results were observed for both stoichiometric and catalytic
reactions. The ratios for stoichiometric reactions of the aryl
bromide complexes containing P(o-tolyl)3 and P(o-tolyl)2Ph
were measurably different, but increases in reduction product
were more dramatic as the ligand was changed from P(o-
tolyl)2Ph to P(o-tolyl)Ph2.
The combination of data from catalytic and stoichiometric
reactions revealed a second factor that led to increasing amounts
of reduction product with the mixed aryl phosphines. Reactions
involving complexes that contained a mixture of o-tolyl and
phenyl groups rapidly gave phosphines resulting from scram-
bling of the phosphine aryl groups. Thus, reactions involving
complexes of P(o-tolyl)2Ph produced P(o-tolyl)Ph2 and P(o-
tolyl)3. Surprisingly, little scrambling with the palladium-bound
aryl group occurred.19-22 Exchange of aryl groups between
(20) Morita, D. K.; Stille, J. K.; Norton, J. R. J. Am. Chem. Soc. 1995,
117, 8576.
(21) Wallow, T. I.; Novak, B. M. J. Org. Chem. 1994, 59, 5034.
(22) Kong, K.-C.; Cheng, C.-H. J. Am. Chem. Soc. 1991, 113, 6313.
(19) Baran˜ano, D.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 2937.

3630 J. Am. Chem. Soc., Vol. 118, No. 15, 1996
Hartwig et al.
phosphines was clearly faster than exchange between the
palladium-bound and phosphine aryl groups. Since the smaller
ligands coordinate in preference to the larger ligands, the
observed selectivities should approach those of the smaller
ligands as the reactions proceed. Of course, this effect will be
more pronounced for the catalytic reactions than the stoichio-
metric reactions, since the stoichiometric reactions gave less
ligand group scrambling. In a similar fashion, reactions
containing P(o-tolyl)Ph2 produced P(o-tolyl)2Ph and PPh3.
One can rationalize the generally favorable selectivity for
reductive elimination over â-hydrogen elimination from com-
plexes bearing larger ligands in terms of changes in coordination
number for the two competing reactions. A reaction that
decreases the coordination number should be favored over one
that increases or maintains the same coordination number when
larger ligands are present. Reductive elimination reduces the
metal coordination number. â-Hydrogen elimination either
maintains the same coordination number or increases it before
subsequent reactions, such as reductive elimination, occur that
ultimately decrease coordination number. It is reasonable to
expect that a single amide ligand would generate a hydride and
coordinated imine since it is believed that â-hydrogen elimina-
tion from alkyl groups gives rise to a hydride and a coordinated
alkene.23 Further, Blum and Milstein have recently provided
mechanistic data on â-hydrogen elimination with an iridium
methoxide complex and their data suggest that a hydride and a
coordinated aldehyde initially forms during this process.24 An
alternative pathway for the â-hydrogen elimination in our
studies, direct transfer of a â-hydrogen from the tin amide to
palladium, would also increase or maintain the coordination
number of the aryl halide complex. Thus, one would expect
that the amine:arene ratio resulting from competitive reductive
elimination and â-hydrogen elimination would increase with
increasing size of the phosphine ligand, as we have observed
experimentally.
Figure 1. ORTEP Drawing of 5′.
Scheme 3
Scheme 4
VI. X-ray Structural Studies of Ligand Conformations.
We have previously reported X-ray diffraction data for a dimeric
tri-o-tolylphosphine palladium aryl bromide complex and for
the monomeric two-coordinate Pd(0) complex 2.4 The structure
of the aryl halide complex showed two o-tolyl methyl groups
pointing toward the metal center and the third o-tolyl methyl
group pointing toward the region of space between the three
aryl groups. In contrast, all three o-tolyl groups within the
phosphines of 2 were pointed toward the metal. It would,
therefore, be possible that the P(o-tolyl)2Ph ligand could create
a similar steric environment to P(o-tolyl)3 if both o-tolyl groups
pointed toward the metal or a smaller steric environment than
P(o-tolyl)3 if one tolyl group pointed toward the metal and the
other between the three aryl groups. Solution NMR spectro-
scopic data presented above suggested that P(o-tolyl)2Ph was
smaller than P(o-tolyl)3 since monomeric, rather than dimeric,
complexes predominated in solution.
The P(o-tolyl)2Ph-ligated p-tolyl bromide complex 5′ provided
single crystals suitable for an X-ray diffraction study after
addition of pentane to the toluene reaction solution. An ORTEP
drawing of 5′ is given in Figure 1. Crystal and data collection
parameters are given in Table 5, and bond distances and angles
are given in Tables 6 and 7. Compound 5′ crystallized in space
group P2/n, and the structure was solved by Patterson methods.
Consistent with the solution data, P(o-tolyl)2Ph was shown
in the solid state to be smaller than P(o-tolyl)3, since one methyl
group pointed at the metal and the other pointed toward the
space between the three aryl groups. Both phosphine groups
showed this conformation. In fact, the molecule lay on a
crystallographic 2-fold axis containing the bromide, the pal-
ladium center, and the palladium-bound tolyl group. The
molecule showed nearly perfect 90° angles in the pseudo-square-
planar geometry. The Pd-P (2.354(3) Å) distance was measur-
ably longer than that in {Pd[P(o-tolyl)3](C6H4-p-Bu)(Br)}2
(2.288(3) Å). This difference in distance must result from the
trans effect of phosphine in 5′ vs bridging bromide in the p-Bu
analogs of 1, since the trend opposes that expected for steric
effects. Consistent with the distances controlled by trans effects
rather than steric effects, the Pd-C distances in the two
compounds are essentially identical. Both aryl groups are trans
to a bromide, although one is a bridging and one a terminal
bromide.
VII. Potential Divergent Pathways for Formation of
Amine and Arene. Although formation of amine and arene
from the same amido intermediate during stoichiometric reac-
tions and catalytic reactions involving 1 or 2, as shown in
Scheme 3, is the most concise explanation for both products, it
(23) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles
and Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, 1987.
(24) Blum, O.; Milstein, D. J. Am. Chem. Soc. 1995, 117, 4582.

Palladium-Catalyzed Amination of Aryl Halides
J. Am. Chem. Soc., Vol. 118, No. 15, 1996 3631
Table 5. Experimental Details
Table 6. Intramolecular Distances Involving the Non-Hydrogen
Atomsa
A. Crystal Data
atom-atom
distance
atom-atom
distance
empirical formula
C23.5H21PBr0.5Pd0.5
formula weight
crystal color/habit
crystal dimensions (mm)
crystal system
no. of reflcns used for unit cell
determination (2θ range)
lattice parameters
427.55
Pd1-Br1
Pd1-P1
2.516(2)
2.354(3)
1.36(2)
1.37(2)
1.39(2)
1.38(2)
1.36(2)
1.35(2)
1.37(2)
1.43(2)
1.44(2)
1.25(2)
1.44(2)
1.31(2)
1.40(2)
C9-C10
C10-C11
Pd1-C21
P1-C1
1.38(2)
1.41(2)
2.04(1)
1.83(1)
1.85(1)
1.83(1)
1.37(1)
1.39(1)
1.40(2)
1.32(2)
1.35(2)
1.40(2)
1.46(2)
1.38(1)
1.52(2)
pale yellow prism
0.10 X 0.15 X 0.17
monoclinic
C11-C12
C12-C13
C14-C15
C14-C19
C15-C16
C16-C17
C17-C18
C18-C19
C19-C20
C21-C22
C6-C7
17 (8.8-18.0°)
P1-C8
P1-C14
C1-C2
a ) 12.506(2) Å
b ) 12.572(2) Å
c ) 12.825(2) Å
â ) 97.35(1)°
V ) 1999.8(9) Å3
P2/n (No. 13)
4
C1-C6
C2-C3
C3-C4
C4-C5
C5-C6
space group
Z value
Dcalc
F000
ν(MoKR)
C22-C23
C23-C24
C24-C25
C8-C9
C8-C13
1.420 g/cm3
870
a Distances are in angstroms. Estimated standard deviations in the
least significant figure are given in parentheses.
15.56 cm-1
B. Intensity Measurements
Enraf-Nonius CAD-4
Table 7. Intramolecular Bond Angles Involving the
Non-Hydrogen Atoms
diffractometer
radiation
temperature
attenuator
Mo KR (λ ) 0.71069 Å)
23 °C
atom-atom-atom
angle
atom-atom-atom
angle
Zr foil (factor ) 20.4)
2.8°
2.0-2.5mm hor./2.0mm vert.
21 cm
Br1-Pd1-P1
C8-C9-C10
C9-C10-C11
C10-C11-C12
C11-C12-C13
Pd1-P1-C1
Pd1-P1-C8
Pd1-P1-C14
C1-P1-C8
89.92(9)
125(1)
115(1)
122(1)
119(2)
114.1(4)
117.5(4)
112.3(3)
101.8(5)
105.8(5)
103.9(6)
116.5(9)
124.9(9)
118(1)
121(1)
120(1)
119(2)
117(2)
126(1)
118(1)
116(2)
122.2(9)
C9-C8-C13
Br1-Pd1-C21
P1-Pd1-P1
118(1)
180.00
179.8(2)
90.08(9)
121(1)
119.3(9)
122(1)
119(1)
123(1)
118(1)
124(1)
118(1)
119(1)
125(1)
117(1)
121.3(9)
123(1)
118(1)
128(1)
115(1)
124(1)
118(1)
take-off angle
detector aperture
crystal-to-detector distance
scan type
P1-Pd1-C21
C8-C13-C12
P1-C14-C15
P1-C14-C19
C15-C14-C19
C14-C15-C16
C15-C16-C17
C16-C17-C18
C17-C18-C19
C14-C19-C18
C14-C19-C20
C18-C19-C20
Pd1-C21-C22
C4-C5-C6
ω-2θ
scan rate
scan width
2θmax
1.0 - 16.5°/min (in omega)
(0.94 + 0.61 tanθ)°
52.6°
no. of reflcns meas
unique
total 4436
4249 (Rint ) 0.073)
Lorentz-polarization absorption
(trans 0.90-1.00)
C1-P1-C14
C8-P1-C14
P1-C1-C2
corrections
P1-C1-C6
C. Structure Solution and Refinement
C2-C1-C6
structure solution
refinement
Patterson method
C1-C2-C3
full-matrix least-squares
C2-C3-C4
2
2
function minimized least-squares
∑w(|Fo| - |Fc|)2 4Fo /σ2(Fo )
C3-C4-C5
weights
p-factor
C22-C21-C22
C21-C22-C23
C22-C23-C24
C23-C24-C23
C23-C24-C25
C1-C6-C5
0.03
C1-C6-C7
anomalous dispersion
no. of observations (I > 3.00σ(I))
no. of variables
all non-hydrogen atoms
1777
232
C5-C6-C7
P1-C8-C9
P1-C8-C13
reflcn/parameter ratio
residuals
goodness of fit indicator
max shift/error in final cycle
max peak in final diff map
min peak in final diff map
7.66
a Angles are in degrees. Estimated standard deviations in the least
significant figure are given in parentheses.
R, Rw: 0.057, 0.062
1.81
0.00
1.00 e-/Å3
-0.53 e-/Å3
pathway competes with reductive elimination of amine from
the palladium amido complex. Our studies reveal the factors
that accelerate or decelerate the relative rates for reductive
elimination vs â-hydrogen elimination.
is possible that arene is produced by a â-hydrogen elimination
process that does not involve transfer of the amide from tin to
palladium. Specifically, the arene can form by a â-hydrogen
elimination pathway that competes with amide formation and
involves direct transfer of the â-hydrogen from the amido group
to palladium as shown in Scheme 4. Since a combination of
transmetalation and reductive elimination, not simply trans-
metalation, determines the reaction rate of the aryl halide
complex, we have not been able to find a way to distinguish
between competitive reactivity of the amido intermediate and
direct transfer of the â-hydrogen by a path that is separate from
the one involving the palladium amide. Of course, the labeling
study simply demonstrates the origin of the hydrogen necessary
for the reduction and does not discriminate between the
mechanisms in Schemes 3 and 4. However, none of our data
contradict the simplest mechanism, competitive reductive
elimination and â-hydrogen elimination from the same amido
intermediate. Moreover, the arene clearly forms by a â-hydro-
gen elimination pathway involving the amido group, and this
VIII. Conclusions. The factors that control product selec-
tivity in metal-catalyzed chemistry are often subtle, and those
controlling amine vs arene selectivity in the palladium-catalyzed
amination of aryl halides are no exception. Our results have
shown that the dominant reaction pathway is a combination of
aryl halide oxidative addition, production of an aryl amido
species from the aryl halide complex, and reductive elimination
of arylamine that competes, albeit effectively, with â-hydrogen
elimination. The results of this paper show that a second
pathway exists for formation of additional arene product for
reactions run with Pd(II) catalyst precursors. The increasing
amounts of arene observed for reactions conducted with
increasing quantities of Pd(II) catalyst suggest strongly that some
arene is formed either directly or indirectly from reduction to
Pd(0) from Pd(II). The similarity of amine:arene product ratios
formed from stoichiometric reactions to those formed from
catalytic reactions involving either the tri-o-tolylphosphine Pd(0)
phosphine complex or the Pd(II) aryl bromide intermediate

3632 J. Am. Chem. Soc., Vol. 118, No. 15, 1996
Hartwig et al.
Pd[P(o-tolyl)Ph2]2(p-C6H4-t-Bu)(Br). The aryl bromide complex
{Pd[P(o-tolyl)3](p-C6H4-t-Bu)(Br)}2 (182 mg, 0.146 mmol) was sus-
pended in 5 mL of ether and to this suspension was added 2.2 equiv
(89 mg, 0.321 mmol) of P(o-tolyl)Ph2. The suspension was stirred for
1 h, after which time the solid product was isolated by filtration and
was washed several times with ether. This procedure gave 255 mg
(72%) of product as a white powder that was pure by NMR
spectroscopy. Samples that were analytically pure were obtained by
dissolving the compound in a large amount of toluene followed by
precipitation with pentane. 1H NMR (300 MHz, C6D6) δ 7.58 (q, J )
5.3 Hz, 8H), 7.05 (m, 6H), 6.93 (m, 12H), 6.48 (d, J ) 8.2 Hz, 2H),
3.09 (s, 6H), 1.16 (s, 9H); 31P{1H} NMR δ 17.9. Anal. Calcd for
C48H47BrP2Pd: C, 66.10; H, 5.43. Found: C, 65.93; H, 5.52.
General Procedure for Stoichiometric Reactions. The appropriate
aryl bromide complex (0.008 mmol, ca. 5 mg) and 15 mg of phosphine
were dissolved in 0.5 mL of benzene. This solution was added to a
vial that contained 10 mg (0.03 mmol) of tin amide. The sample was
placed in a vial equipped with a Teflon-lined septum and was heated
at 90 °C. Samples for GC analysis were removed by syringe.
General Procedure for Catalytic Reactions. The appropriate
catalyst or catalyst precursor (0.004 mmol, ca. 3 mg) and 5 mg of
phosphine were dissolved in 0.5 mL of benzene. This solution was
added to a vial that contained 55 mg (0.16 mmol) of tin amide and 28
mg (0.13 mmol) of aryl bromide. The sample was placed in a vial
equipped with a Teflon-lined septum and was heated at 90 °C. Samples
for GC analysis were removed by syringe.
X-ray Diffraction Study of 5′. Crystals of 5′ were obtained by
adding pentane to the reaction solution and rapidly mixing. A pale
yellow prism having approximate dimensions of 0.10 × 0.15 × 0.17
mm was mounted on a glass fiber. All measurements were made on
an Enraf-Nonius CAD-4 diffractometer with graphite monochromated
Mo KR radiation.
Cell constants and orientation matrix for data collection were
obtained from a least-squares refinement using the setting angles of
17 carefully centered reflections in the range 8.80 < 2θ < 18.05°
corresponding to a monoclinic cell. Based on the systematic absences
of h0l (h + 1 ) 2n + 1), packing considerations, a statistical analysis
of intensity distribution, and the successful solution and refinement of
the structure, the space group was determined to be P2/n (No. 13). In
this space group, the molecule is situated on a crystallographic 2-fold
axis. Refinement of the molecule in the space group Pn (No. 7) was
also attempted, but was not successful.
confirm this conclusion. However, some arene appears to be
formed by a â-hydrogen elimination that competes with
reductive elimination. This arene is not formed as a result of
competing alkyl and amido group transfer, since no p-BuC6H4-
t-Bu is formed that would also result from alkyl group transfer.
The rates for reductive elimination and â-hydrogen elimination
are modulated by the combination of steric and electronic factors
summarized in Schemes 3 and 4. Reactions catalyzed by
complexes containing phosphines with increasing steic demands,
involving amides with increasing nucleophilicity and steric
demands, and involving palladium-bound aryl groups with
decreasing electron density led to higher ratios of arylamine to
arene product.
Experimental Section
General. Unless otherwise specified, all reagents were purchased
from commercial suppliers and used without further purification.
n-Pentane (tech grade) was distilled under nitrogen from purple sodium/
benzophenone ketyl made soluble by addition of tetraglyme to the still.
Diethyl ether, THF, benzene, and toluene were distilled from sodium
benzophenone ketyl under nitrogen. Deuterated solvents for use in
NMR experiments were dried as their protiated analogs, but were
vacuum transferred from the drying agent. {Pd[P(o-Tol)3]2Cl2},
{Pd[P(o-Tol)2Ph]2Cl2}, {Pd[P(o-Tol)Ph2]2Cl2}, and [Pd(PPh3)2Cl2] were
prepared by standard addition of phosphine to (CH3CN)2PdCl2 formed
by refluxing PdCl2 in CH3CN. Pd[P(o-Tol)3]2,4 {Pd[P(o-tolyl)3][p-C6H4-
t-Bu](Br)}2, {Pd[P(o-tolyl)3](C6H4-p-Me)(Br)}2,4 and P(o-tolyl)2Ph25
were prepared by literature methods. {Pd[P(o-tolyl)3](C6H4-p-NMe2)-
(Br)}2 and {Pd[P(o-tolyl)3](C6H4-p-C(O)Me)(Br)}2 were prepared and
isolated in a fashion identical to {Pd[P(o-tolyl)3][p-C6H4-t-Bu](Br)}2.
Unless otherwise noted, all manipulations were carried out in an
inert atmosphere glovebox or by using standard Schlenk or vacuum
line techniques. 1H NMR spectra were obtained on a GE QE 300 MHz
or Ω 300 MHz Fourier Transform spectrometer. 31P NMR spectra were
obtained on the Ω 300 operating a 121.65 MHz. 1H NMR spectra
were recorded relative to residual protiated solvent and 31P{1H}
chemical shifts are reported in units of parts per million realtive to
85% H3PO4. A positive value of the chemical shift denotes a resonance
downfield from the reference. Samples for elemental analysis were
submitted to Atlantic Microlab, Inc. GC analyses were conducted on a
Hewlett Packard 5890 instrument connected to a 3395 integrator.
Response factors were determined by injection of samples containing
known quantities of authentic materials.
Pd[P(o-tolyl)2Ph]2[p-C6H4-t-Bu](Br). The aryl bromide complex
[Pd[P(o-tolyl)3][C6H4-p-(t-Bu)](Br)}2 (250 mg, 0.201 mmol) was
suspended in 5 mL of ether and to this suspension was added 2.2 equiv
(129 mg, 0.442 mmol) of P(o-tolyl)2Ph. The solution was stirred for
1 h, after which time the solid product was isolated by filtration and
was washed several times with ether. This procedure gave 340 mg
(84%) of product as a pale yellow powder that analyzed satisfactorily
for the monomeric bis-phosphine complex. 1H NMR (300 MHz, C6D6,
2 equiv of P(o-tolyl)2Ph added) δ 8.29 (broad s, 4H), 7.26 (broad s,
4H), 6.90-7.15 (m, 16H), 6.79 (t, J ) 7.3 Hz, 4H), 6.24 (d, J ) 7.6
Hz, 2H), 2.41 (s, 12 H), 1.10 (s, 9H); 31P{1H} NMR δ 21.9.
Anal. Calcd for C50H51BrP2Pd: C, 66.71; H, 5.71. Found: C, 67.26;
H, 5.80.
The data were collected at a temperature of 23 ( 1 °C using the
ω-2θ scan technique to a maximum 2θ value of 52.6°. Scans of (0.94
+ 0.61 tan θ)° were made at speeds ranging from 1.0 to 16.5 deg/min
(in Ω). Moving-crystal moving-counter-background measurements
were made by scanning an additional 25% above and below the scan
range. The counter aperture consisted of a variable horizontal slit with
a width ranging from 2.0 to 2.5 mm and a vertical slit set to 2.0 mm.
The diameter of the incident beam collimator was 0.8 mm and the
crystal to detector distance was 21 cm. For intense reflections an
attenuator was automatrically inserted in front of the detector.
Of the 4436 reflections which were collected, 4249 were unique
(Rint
) 0.073). The intensities of three representative reflections which
were measured after every 60 min of X-ray exposure time remained
constant throughout data collection, indicating crystal and electronic
stability (no decay correction was applied). The linear absorption
coefficient for Mo KR was 15.6 cm-1
.
An empirical absorption
correction based on azimuthal scans of several reflections was applied,
which resulted in transmission factors ranging from 0.90 to 1.00. The
data were corrected for Lorentz and polarization effects.
Pd[P(o-tolyl)2Ph]2(C6H4-p-Me)(Br). The aryl bromide complex
{Pd[P(o-tolyl)3][C6H4-p-Me](Br)}2 (132 mg, 0.106 mmol) was dissolved
in 5 mL of toluene and to this solution was added 2.2 equiv (68 mg,
0.233 mmol) of P(o-tolyl)2Ph. The solution was allowed to stand for
1 h, after which time 15 mL of pentane was added and the solution
was mixed. Over the course of 24 h, 181 mg (36%) of product formed
pale yellow crystals suitable for X-ray diffraction that were pure as
determined by NMR spectroscopy. 1H NMR (300 MHz, C6D6, 2 equiv
of P(o-tolyl)2Ph added) δ 8.16 (broad s, 4H), 7.28 (broad s, 4H), 6.95-
7.1 (m, 8H), 6.92 (m, 8H), 6.80 (m, 4H), 6.24 (d, J ) 7.6 Hz, 2H),
2.45 (broad s, 12 H), 1.95 (s, 3H); 31P{1H} NMR δ 21.9.
The structure was solved by the Patterson method, which revealed
the location of the Pd and Br atoms. The remaining atoms were located
in subsequent electron density maps. The non-hydrogen atoms were
refined anisotropically. The hydrogen atoms were included in calcu-
lated positions. The hydrogen atoms were omitted from the C25 methyl
group since it was located on the crystallographic 2-fold axis. The
final cycle of full-marix least-squares refinement was based on 1777
observed reflections (I > 3.00σ(I)) and 232 variable parameters and
(26) Cromer, D. T.; Waber, J. T. In International Tables for X-ray
Crystallography; The Kynoch Press: Birmingham, 1974; Vol. IV.
(25) Segall, Y.; Granoth, I. J. Am. Chem. Soc. 1978, 100, 5130.

Palladium-Catalyzed Amination of Aryl Halides
J. Am. Chem. Soc., Vol. 118, No. 15, 1996 3633
converged (the largest parameter shift was 0.00 times its esd) with
unweighted and weighted agreement factors of
Acknowledgment. We are grateful for an NSF Young
Investigator Award, a Dreyfus Foundation New Faculty Award,
a Union Carbide Innovative Recognition Award, a DuPont
Young Faculty Award, and a Yale University Junior Faculty
Fellowship that supported this work. We are also grateful to
Johnson Matthey/Alpha/Aesar for a generous loan of palladium
dichloride.
R )
||Fo| - |Fc||/ |Fo| ) 0.057
∑
∑
Rw ) [( w(|Fo| - |Fc|)2/ |Fo|)]1/2 ) 0.062
∑
∑
The standard deviation of an observation of unit weight was 1.81.
The weighting scheme was based on counting statistics and included a
factor (p ) 0.03) to downweight the intense reflections. Plots of
∑w(|Fo| - |Fc|)2 versus |Fo|, reflection order in data collection, sinθ/l,
and various classes of indices showed no unusual trends. The maximum
and minimum peaks on the final difference Fourier map corresponded
to 1.00 and -0.53 e-/Å3. Neutral atom scattering factors were taken
from Cromer and Waber.25 Anomalous dispersion effects were included
in Fcalc; the values for ∆f′ and ∆f′′ were also those of Cromer and
Waber. All calculations were performed using the TEXSAN crystal-
lographic software package of Molecular Structure Corp.
Supporting Information Available: Positional parameters
and B(eq), U values, Cartesian coordinates, and torsion or
conformational angles for 5′ (6 pages). This material is
contained in many libraries on microfiche, immediately follows
this article in the microfilm version of the journal, can be ordered
from the ACS, and can be downloaded from the Internet; see
any current masthead page for ordering information and internet
access instructions.
JA954121O