Formation of palladium bis (amine) complexes from reaction of amine with palladium tris(o-tolyl)phosphine mono(amine) complexes

Article abstract of DOI:10.1021/om9603169

Palladium mono(benzylamine) complexes Pd[P(o-tolyl)₃](p-C₆H₄CMe₃)[H ₂NB_n]X (X = Cl (7), Br (8), I (14)) react reversibly with benzylamine in CDCl₃ at 25 °C via P(o-tolyl)₃

Full text of DOI:10.1021/om9603169

3534
Organometallics 1996, 15, 3534-3542
F or m a tion of P a lla d iu m Bis(a m in e) Com p lexes fr om
Rea ction of Am in e w ith P a lla d iu m Tr is(o-tolyl)p h osp h in e
Mon o(a m in e) Com p lexes
Ross A. Widenhoefer and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
Received April 26, 1996X
Palladium mono(benzylamine) complexes Pd[P(o-tolyl)3](p-C6H4CMe3)[H2NBn]X (X ) Cl
(7), Br (8), I (14)) react reversibly with benzylamine in CDCl3 at 25 °C via P(o-tolyl)3
displacement to generate the corresponding bis(amine) derivatives trans-Pd(p-C6H4CMe3)[H2-
NBn]2X (X ) Cl (17), Keq ) 0.18 ( 0.02; Br (16), Keq ) 0.14 ( 0.01; I (18), Keq ) 0.10 ( 0.01).
Complexes 16-18 were isolated from reaction of the palladium aryl halide dimers {Pd[P(o-
tolyl)3](p-C6H4CMe3)(µ-X)}2 (X ) Cl (4), Br (5), I (6)) and excess benzylamine as the
corresponding mono(benzylamine) solvate Pd(p-C6H4CMe3)[H2NBn]2X‚H2NBn (X ) Br
1
(16‚H2NBn), Cl (17‚H2NBn), I (18‚H2NBn)). IR and H NMR spectroscopy of 16‚H2NBn
indicated the presence of N-H‚‚‚X (X ) N, Br, Pd) hydrogen bonds in both the solid state
and solution. The equilibrium constant for the formation of 16 and P(o-tolyl)3 from 8 and
benzylamine ranged from 0.066 ( 0.005 in CD2Cl2 to 3.6 ( 0.3 in THF-d8 and in C6D6 ranged
from 0.90 ( 0.07 at 25 °C to 0.44 ( 0.04 at 77 °C (∆G°298 K ) 0.06 ( 0.01 kcal mol-1; ∆H°298
K ) -2.8 ( 0.1 kcal mol-1; ∆S°298 K ) -9 ( 1 eu). The equilibrium constants for the formation
of the bis(amine) complexes Pd(p-C6H4CMe3)[amine]2Br from the reaction of Pd[P(o-tolyl)3]-
(p-C6H4CMe3)[amine]Br and amine decreased in the order phenethylamine ≈ cyclohexy-
lamine ≈ benzylamine ≈ (4-methylbenzyl)amine . piperidine . N-methylbenzylamine.
Sch em e 1
In tr od u ction
We have shown that mixtures of Pd2(DBA)3 or Pd-
(DBA)2 (DBA ) dibenzylideneacetone) and P(o-tol)3 (o-
tol ) o-tolyl) catalyze the conversion of aryl bromides1
or aryl iodides2 to anilines via reaction with free amine
and sodium tert-butoxide.3 In contrast to related pal-
ladium-catalyzed C-C bond-forming reactions,4 aryl
iodides required more forcing conditions and produced
lower yields of anilines than did aryl bromides. In
addition, while the cross-coupling protocol is effective
in the case of unbranched secondary amines such as
N-methylbenzylamine, both bulky secondary amines
such as diisopropylamine and primary amines such as
benzylamine produce low yields (∼0-25%) of cross-
coupled product.5
tol)3](Ar)[HNR1R2]X.7 Deprotonation and reductive elimi-
nation from the three-coordinate palladium amido com-
plex Pd[P(o-tol)3](Ar)[NR1R2]X6,8 forms the corresponding
aniline derivative ArNR1R2 and regenerates the cata-
lytically active mono(phosphine) complex.9
The Pd2(DBA)3/P(o-tol)3-catalyzed amination of aryl
halides is believed to proceed by the initial oxidative
addition of the aryl halide to the palladium mono-
(phosphine) complex Pd[P(o-tol)3] to form the palladium
halide dimer {Pd[P(o-tol)3](Ar)(µ-X)}2 (Scheme 1).6 Re-
action of the halide dimer with free amine then forms
the corresponding palladium amine monomer Pd[P(o-
In conjunction with our synthetic studies, we have
investigated the stoichiometric reactions of the pal-
ladium tris(o-tolyl)phosphine halide dimers with amines
in an effort to gain insight into the corresponding
palladium-catalyzed amination of aryl halides.10-12 For
example, we have shown that the palladium halide
dimers {Pd[P(o-tol)3](p-C6H4Me)(µ-X)}2 (X ) Cl (1), Br
(2), I (3)) react with N-benzylmethylamine to generate
the corresponding 1:1 amine adducts Pd[P(o-tol)3](p-
X Abstract published in Advance ACS Abstracts, J uly 15, 1996.
(1) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1348.
(2) Wolfe, J . P.; Buchwald, S. L. J . Org. Chem. 1996, 61, 1133.
(3) See also: (a) Louie, J .; Hartwig, J . F. Tetrahedron Lett. 1995,
36, 3609. (b) Wolfe, J . P.; Rennels, R. A.; Buchwald, S. L. Tetrahedron
1996, 20, 7525.
(4) (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (c) de Meijere, A.;
Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379.
(5) We have recently found that mixtures of Pd2(DBA)3 and BINAP
effectively cross-couple aryl bromides with primary amines: Wolfe, J .
P.; Wagaw, S.; Buchwald, S. L. J . Am. Chem. Soc., in press.
(6) Paul, F.; Patt, J .; Hartwig, J . F. J . Am. Chem. Soc. 1994, 116,
5969.
(7) Paul, F.; Patt, J .; Hartwig, J . F. Organometallics 1995, 14, 3030.
(8) (a) Loar, M. K.; Stille, J . K. J . Am. Chem. Soc. 1981, 103, 4174.
(b) Moravskiy, A.; Stille, J . K. J . Am. Chem. Soc. 1981, 103, 4182. (c)
Morrell, D. G.; Kochi, J . K. J . Am. Chem. Soc. 1975, 97, 7262. (d)
Ozawa, F.; Ito, T.; Yamamoto, A. J . Am. Chem. Soc. 1980, 102, 6457.
(e) McCarthy, T. J .; Nuzzo, R. G.; Whitesides, G. M. J . Am. Chem.
Soc. 1981, 103, 1676. (f) Komiya, S.; Albright, T. A.; Hoffmann, R.;
Kochi, J . K. J . Am. Chem. Soc. 1976, 98, 7255. (g) Komiya, S.; Albright,
T. A.; Hoffmann, R.; Kochi, J . K. J . Am. Chem. Soc. 1977, 99, 8440.
(h) Tatsumi, K.; Hoffmann, R.; Yamamoto, A.; Stille, J . K. Bull. Chem.
Soc. J pn. 1981, 54, 1857.
(9) Hartwig, J . F.; Paul, F. J . Am. Chem. Soc. 1995, 117, 5373.
S0276-7333(96)00316-0 CCC: $12.00 © 1996 American Chemical Society

Formation of Palladium Bis(amine) Complexes
Organometallics, Vol. 15, No. 16, 1996 3535
Ta ble 1. P a lla d iu m Mon o(a m in e) Com p lexes
F or m ed fr om Rea ction of P a lla d iu m Ar yl Ha lid e
Dim er s w ith Am in e
Sch em e 2
Sch em e 3
C6H4Me)[HN(Me)Bn]X (X ) Cl, Br, I) (Scheme 2).10
These mono(amine) complexes react with sodium tert-
butoxide to form mixtures of N-methyl-N-benzyl-p-
toluidine and toluene.11 We have also shown that the
thermodynamics of the formation of 1:1 palladium
amine adducts from palladium halide dimer and free
amine were dependent on both the bridging halide
ligand and the amine.12 Because primary amines
represent a particularly challenging substrate for the
Pd2(DBA)3/P(o-tol)3-catalyzed amination reaction,5 we
have continued to investigate the reactions of palladium
aryl halide dimers with primary amines. Here we
report that palladium mono(primary amine) complexes
react reversibly with excess primary amine to form
palladium bis(primary amine) complexes.
Resu lts
Syn th esis of P alladiu m Mon o(am in e) Com plexes.
The palladium tris(o-tolyl)phosphine mono(amine) com-
plexes employed in this study were synthesized by
reaction of the appropriate palladium tert-butylphenyl
halide dimer {Pd[P(o-tol)3](p-C6H4CMe3)(µ-X)}2 (X ) Cl
(4), Br (5), I (6)) with 2 equiv of the desired amine, as
has been previously described (Scheme 3, Table 1).7,10
By this procedure, the mono(amine) adducts Pd[P(o-
tol)3](p-C6H4CMe3)[H2NBn]X (X ) Cl (7), Br (8)), Pd-
[P(o-tol)3](p-C6H4CMe3)[H2NCH2CH2Ph]Br (9), Pd[P(o-
tol)3](p-C6H4CMe3)[H2NCy]Br (10), Pd[P(o-tol)3](p-C6H4-
CMe3)[HNCH2-4-C6H4Me]Br (11), Pd[P(o-tol)3](p-C6H4-
CMe3)[piperidine]Br (12), and Pd[P(o-tol)3](p-C6H4CMe3)-
[HN(Me)Bn]Br (13) were isolated in good yield. Reac-
tion of the palladium aryl iodide dimer 6 with 2 equiv
of benzylamine led to the exclusive formation of the
mono(amine) derivative Pd[P(o-tol)3](p-C6H4CMe3)[H2-
NBn]I (14), as determined by 1H and 31P NMR spec-
troscopy. However, attempts to isolate 14 from the
corresponding preparative-scale reaction produced a
mixture of products, as evidenced by the presence of
1
several tert-butyl peaks in the H NMR spectrum of the
isolated solid. Attempts to isolate or spectroscopically
identify the mono(amine) complex Pd[P(o-tol)3](p-C6H4-
CMe3)[NH3]Br (15) from treatment of a solution of 5 in
C6D6 with a 0.5 M solution of NH3 in dioxane were
unsuccessful.
Con ver sion of P a lla d iu m Mon o(a m in e) Com -
p lexes to P a lla d iu m Bis(a m in e) Com p lexes. Excess
primary amine displaced the P(o-tol)3 ligand from pal-
ladium tris(o-tolyl)phosphine mono(amine) complexes to
form the corresponding bis(amine) complexes. For
example, excess benzylamine (0.25 M) was added to a
solution of palladium aryl bromide dimer 5 (∼8 mM) in
C6D6, and the resulting solution was monitored periodi-
cally by 1H NMR spectroscopy at 25 °C. The initial
spectrum revealed quantitative conversion of 5 to the
mono(amine) complex 8, as indicated by the appearance
of a new t-Bu peak at δ 1.17 (Scheme 4). The t-Bu
resonance corresponding to 8 slowly disappeared (t1/2
) ∼3 h)13 with the formation of a 1:1 ratio of resonances
corresponding to the equivalent methyl groups of free
P(o-tol)3 at δ 2.40 and a t-Bu group assigned to the
(10) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. Organome-
tallics 1996, 15, 2745.
(11) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. Abstracts of
Papers, 210th National Meeting of the American Chemical Society,
Chicago, IL, Aug 1995; American Chemical Society: Washington, DC,
1995; INOR 70.
(12) Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996, 15,
2755.
(13) Kinetic studies have been performed: Widenhoefer, R. A.;
Zhong, H. A.; Buchwald, S. L. Manuscript in preparation.

3536 Organometallics, Vol. 15, No. 16, 1996
Widenhoefer and Buchwald
Sch em e 4
Ch a r t 1. P oten tia l Hyd r ogen -Bon d in g Mod es in
16‚H2NBn
palladium bis(benzylamine) complex 16 at δ 1.27. No
additional products or decomposition of the palladium
amine complexes was observed throughout complete
conversion of 8 to 16. Addition of P(o-tol)3 to solutions
of 16 in C6D6 regenerated 8 and free benzylamine.
The 1H NMR spectrum of 16 (∼10 mM) displayed
broad triplets at δ 3.81 (J ) 7.1 Hz) and δ 2.4 (J ) ∼7
Hz), corresponding to the benzylic protons and the
amino protons, respectively, of the benzylamine ligands.
Comparison of the intensity of these triplets to the
intensity of the single tert-butyl resonance at δ 1.27
established the 2:1 ratio of benzylamine ligands to tert-
butyl groups, while the equivalence of the benzylamine
ligands is consistent with their trans orientation. Pal-
ladium bis(amine) complexes of the form Pd(amine)2X2
(X ) halide, acetate) typically possess trans amine
ligands,14 and although cis palladium(II) bis(amine)
complexes can be generated under certain conditions,15
cis to trans isomerization is typically facile.16 Addition
of D2O to a solution of 16 in C6D6 resulted in rapid
deuterium exchange of the amino protons of the ben-
zylamine ligands, as indicated by the disappearance of
the δ 2.4 resonance and loss of coupling to the benzylic
resonance at δ 3.81 in the 1H NMR spectrum. The
solution IR spectrum of 16 (CDCl3) displayed bands at
3332 and 3274 cm-1 assigned to the antisymmetric and
symmetric N-H stretching modes of the benzylamine
ligands, respectively.17
hydrogen-bonded NH2 groups.17 The solvated bis(amine)
complex 16‚H2NBn dissolved in C6D6 to form a 1:1 ratio
of bis(amine) complex 16 and free benzylamine, as
1
determined by H NMR spectroscopy.
There are several potential hydrogen-bonding inter-
actions involving the NH2 groups in crystalline
16‚H2NBn, which may account for the observed solid-
state IR spectrum. For example, the outer-sphere
benzylamine molecule may function as a hydrogen bond
acceptor to generate an N-H‚‚‚N hydrogen bond with
a ligated benzylamine molecule (I; Chart 1). In addi-
tion, an outer-sphere or ligated benzylamine molecule
may form an N-H‚‚‚Br hydrogen bond with a palladium
bromide ligand (II). Similarly, an outer-sphere or
ligated benzylamine molecule may form an N-H‚‚‚Pd
hydrogen bond with a filled palladium d orbital (III).
Each type of hydrogen bonding (I-III) has been previ-
ously observed in platinum dichloride bis(amine) com-
plexes.17 However, our data are not sufficient to identify
the specific hydrogen-bonding modes present in 16‚H2N-
Bn.
In a preparative-scale reaction, a solution of pal-
ladium aryl bromide dimer 5 and excess benzylamine
(∼20 equiv, ∼1 M) in CH2Cl2 was stirred at room
temperature for 12 h to give a clear solution. Evapora-
tion of solvent and crystallization of the resulting yellow
oil from THF/pentane at -30 °C gave the bis(amine)
complex 16 as the mono(benzylamine) solvate Pd(p-
C6H4CMe3)[H2NBn]2Br‚H2NBn (16‚H2NBn) in 99% yield
as a white fibrous solid. Elemental analysis (C, H, N)
established the 3:1 ratio of benzylamine units to PdArBr
groups. The solid-state IR spectrum (KBr) displayed a
broad N-H stretch at 3198 cm-1 with a shoulder at
3295 cm-1, consistent with the presence of both free and
The hydrogen-bonding interactions involving the NH2
group in crystalline 16‚H2NBn also appears to persist
1
in solution. Specifically, the H NMR chemical shift of
the NH2 resonance of the benzylamine ligands of 16 in
C6D6 was dependent on benzylamine concentration,
which may indicate the formation of PdN-H‚‚‚NH2Bn
hydrogen bonds in solution.18 For example, the chemi-
cal shift of the NH2 resonance of 16 in C6D6 ([16] ) 6.7
mM) increased linearly from δ 2.29 to δ 3.0 with
increasing benzylamine concentration from 6.7 mM to
0.40 M (Figure 1). At benzylamine concentrations
greater than 0.40 M, the NH2 resonance of 16 was
obscured by the benzyl resonance of free benzylamine
at δ 3.55. The 1H NMR chemical shift of the NH2
resonance of the benzylamine ligands of 16 was also
dependent on methanol concentration, which may in-
dicate the formation of PdN-H‚‚‚OHMe bonds in solu-
tion.19 For example, the chemical shift of the NH2
resonance of 16 ([16] ) [H2NBn] ) 6.7 mM) displayed
an asymptotic approach to a limiting value of δ ∼2.75
(14) (a) Stephanson, T. A.; Morehouse, S. M.; Powell, A. R.; Heffer,
J . P.; Wilkinson, G. J . Chem. Soc. 1965, 3632. (b) Iball, J .; MacDougall,
M.; Scrimgeour, S. Acta Crystallogr. 1975, B31, 1672. (c) Goggin, P.
L.; Goodfellow, R. J .; Reed, F. J . S. J . Chem. Soc., Dalton Trans. 1972,
1298. (d) Shaplygin, I. S. Lazarev, V. B. Zh. Neorg. Khim. 1978, 23,
603. (e) Mirskova, I. S.; Sytov, G. A.; Skanazarova, I. M.; Avakyan, V.
G.; Perchenko, V. N.; Nametkin, N. S. Dokl. Akad. Nauk SSSR 1977,
237, 346. (f) Mellor, J . W. A Comprehensive Treatise on Inorganic and
Theoretical Chemistry; Longmans, Green: London, 1936; Vol. XV.
(15) Coe, J . S.; Lyons, J . R. Inorg. Chem. 1970, 9, 1775.
(16) (a) Lock, C. J . L.; Zvagulis, M. Inorg. Chem. 1981, 20, 1817. (b)
Iball, J .; Scrimgeour, S. N. Acta Crystallogr. 1977, B33, 1194. (c) Lock,
C. J . L.; Speranzini, R. A.; Zvagulis, M. Acta Crystallogr. 1980, B39,
1989. (d) Lock, C. J . L.; Zvagulis, M. Acta Crystallogr. 1980, B36, 2140.
(17) (a) Chatt, J .; Duncanson, L. A.; Venanzi, L. M. J . Inorg. Nucl.
Chem. 1958, 8, 67. (b) Chatt, J .; Duncanson, L. A.; Venanzi, L. M. J .
Chem. Soc. 1955, 4461. (c) Chatt, J .; Duncanson, L. A.; Venanzi, L. M.
J . Chem. Soc. 1956, 2712.
(18) Kollman, P. A.; Allen, L. C. Chem. Rev. 1972, 72, 283.
(19) A reviewer has suggested that the methanol concentration
dependence of the amino resonance of 16 in the 1H NMR spectrum
could also result from methanol-promoted halide dissociation.

Formation of Palladium Bis(amine) Complexes
Organometallics, Vol. 15, No. 16, 1996 3537
Sch em e 5
Ta ble 2. P a lla d iu m Bis(a m in e) Com p lexes F or m ed
F r om Rea ction of P a lla d iu m Ar yl Ha lid e Dim er s
w ith Am in e
F igu r e 1. Benzylamine and methanol concentration de-
pendence of the chemical shift of the NH2 Resonance of 16
(6.7 mM) in C6D6 at 25 °C.
with increasing methanol concentration from 0 to 2.72
M (Figure 1).
The association constant for the formation of a 1:1
hydrogen-bonded adduct can often be derived from the
dependence of the 1H NMR chemical shift of the
hydrogen bond donor on the concentration of the hy-
drogen bond acceptor via the Scatchard equation.20 For
example, the association constants for the formation of
1:1 hydrogen-bonded adducts of a low-valent transition-
metal phenoxide or alkoxide complex and a phenol have
been determined by 1H NMR spectroscopy.21 However,
determination of the association constant for the forma-
tion of 16‚H2NBn from 16 and benzylamine or for the
formation of 16‚HOMe from 16 and methanol was
precluded by the potential for multiple equilibria.22
Likewise, attempts to obtain an association constant for
the formation of 16‚H2NBn by IR spectroscopy was
precluded by the presence of intense aromatic C-H
stretching bands corresponding to free benzylamine,
which presumably obscured the hydrogen-bonded N-H
stretching bands.
The stability of 16 in C6D6 solution was enhanced by
the presence of benzylamine or methanol, possibly due
to the presence of N-H‚‚‚N or N-H‚‚‚O hydrogen bonds,
respectively. For example, while solutions of 16 (6.7
mM) in C6D6 which contained 6.7 mM benzylamine
darkened within hours at room temperature, solutions
of 16 (6.7 mM) in C6D6 which contained 0.30 M benzyl-
amine or 1 M methanol showed no signs of decomposi-
tion after 2 weeks at room temperature. The instability
of 16 in the absence of excess benzylamine precluded
a
Not isolated; detected in solution by 1H NMR spectroscopy.
isolation of unsolvated 16; attempted recrystallization
of 16‚H2NBn from a THF/pentane solution which con-
tained no added benzylamine led to extensive decom-
position and recovery of 16‚H2NBn in low yield. Like-
wise, the low solubility and the instability of 16‚H2NBn
and related derivatives (see below) in the absence of a
large excess of free amine precluded 13C NMR analysis
of these bis(amine) complexes.
Syn th esis of P a lla d iu m Bis(a m in e) Com p lexes
Rela ted to 16‚H2NBn . A series of palladium bis-
(amine) complexes were isolated from the reaction of the
appropriate palladium aryl halide dimer and excess
primary amine by procedures analogous to that em-
ployed in the synthesis of 16‚H2NBn. For example,
reaction of excess benzylamine with palladium aryl
chloride dimer 4 or the aryl iodide dimer 6 led to
isolation of the mono(benzylamine)-solvated bis(benz-
ylamine) complexes Pd(p-C6H4CMe3)[H2NBn]2Cl‚H2-
NBn (17‚H2NBn) and Pd(p-C6H4CMe3)[H2NBn]2I‚H2-
NBn (18‚H2NBn), respectively (Scheme 5, Table 2). The
spectroscopy of complexes 17 and 18 was analogous to
that observed for the bromide derivative 16. Iodide
(20) J oesten, M. D.; Schaad, L. J . Hydrogen Bonding; Marcel
Dekker: New York, 1974; p 173.
(21) (a) Kegley, S. E.; Schaverien, C. J .; Freudenberger, J . H.;
Bergman, R. G.; J . Am. Chem. Soc. 1987, 109, 6563. (b) Osakada, K.;
Kim, Y. J .; Yamamoto, A. J . Organomet. Chem. 1990, 382, 303. (c) Kim,
Y. J .; Osakada, K.; Takenaka, A.; Yamamoto, A. J . Am. Chem. Soc.
1990, 112, 1096, (d) Osakada, K.; Kim, Y. J .; Tanaka, M.; Ishiguro, S.
I.; Yamamoto, A. Inorg. Chem. 1991, 30, 404. (e) Shubina, E. S.;
Belkova, N. V.; Krylov, A. N.; Vorontsov, E. V.; Epstein, L. M.; Gusev,
D. G.; Niedermann, M.; Berke, H. J . Am. Chem. Soc. 1996, 118, 1105.
(22) (a) Deranleau, D. A. J . Am. Chem. Soc. 1969, 91, 4050. (b)
Deranleau, D. A. J . Am. Chem. Soc. 1969, 91, 4044.
(23) (a) Seligson, A. L.; Trogler, W. C. J . Am. Chem. Soc. 1991, 113,
2520. (b) The cone angle for methylbenzylamine has not been deter-
mined. A cone angle of ∼127° can be approximated by comparison to
known cone angles for the related secondary amines HN(Me)Ph (126°)
and NH(Me)-n-Pr (127°).
(24) (a) Albert, A.; Serjeant, E. P. The Determination of Ionization
Constants, 3rd ed.; Chapman and Hall: London, 1984. (b) Smith, R.
M.; Martell, A. E. Critical Stability Constants; Plenum Press: New
York, 1989; Vol. 6, 2nd supplement. (c) Perrin, D. D. Stability Constants
of Metal-Ion Complexes: Part B-Organic Ligands; IUPAC Pergamon
Press: London, 1979.

3538 Organometallics, Vol. 15, No. 16, 1996
Widenhoefer and Buchwald
the solvent to serve as a hydrogen-bond acceptor.17 The
equilibrium constant for the conversion of 8 to 16 in
C6D6 was temperature-dependent and ranged from 0.90
( 0.07 at 25 °C to 0.44 ( 0.04 at 77 °C (Table 3). A
van’t Hoff plot of the data provided the thermodynamic
parameters: ∆H° ) -2.8 ( 0.1 kcal mol-1; ∆S° ) -9 (
1 eu.
Ta ble 3. Tem p er a tu r e a n d Solven t Dep en d en ce of
Keq for th e F or m a tion of 16 a n d P (o-tol)3 fr om th e
Rea ction of 8 a n d Ben zyla m in e a t 25 °C
entry no.
solvent
temp, °C
Keq
1
2
3
4
5
6
7
8
9
C6D6
C6D6
C6D6
C6D6
25
40
55
65
77
25
25
25
25
25
0.90 ( 0.07
0.70 ( 0.06
0.57 ( 0.05
0.51 ( 0.05
0.44 ( 0.04
3.6 ( 0.3
The equilibrium constants for the conversion of mono-
(amine) to bis(amine) complexes were determined as a
function of the halide ligand (Table 4). For example,
Keq was determined in CDCl3 at 25 °C for the formation
of chloride derivative 17 from reaction of 7 and benz-
ylamine (Keq ) 0.18 ( 0.02) and for the formation of
the iodide complex 18 from the reaction of 14 and
benzylamine (Keq ) 0.10 ( 0.01) (Table 4). Similarly,
the equilibrium constants for the conversion of mono-
(amine) to bis(amine) complexes were determined as a
function of the amine (Table 4). Specifically, Keq was
determined in C6D6 at 25 °C for the formation of 19 from
the reaction of 9 and phenethylamine (1.1 ( 0.1), 20
from the reaction of 10 and cyclohexylamine (1.1 ( 0.1),
21 from the reaction of 11 and (4-methylbenzyl)amine
(0.50 ( 0.04), and 23 from the reaction of 12 and
piperidine ((18 ( 2) × 10-3).
C6D6
THF-d8
dioxane-d8
toluene-d8
CD2Cl2
CDCl3
1.8 ( 0.2
0.63 ( 0.05
0.066 ( 0.005
0.14 ( 0.01
10
derivative 18 was particularly unstable in C6D6 solution
in the absence of excess benzylamine and darkened
within minutes at room temperature.
Reaction of palladium bromide dimer 5 with excess
phenethylamine, cyclohexylamine, (4-methylbenzyl)-
amine, or ammonia led to the isolation of the corre-
sponding mono(amine)-solvated palladium bis(amine)
complexes Pd(p-C6H4CMe3)[H2NCH2CH2Ph]2Br (19‚H2-
NCH2CH2Ph), Pd(p-C6H4CMe3) [H2NCy]2Br‚H2NCy
(20‚H2NCy), Pd(p-C6H4CMe3)[H2NCH2-4-C6H4Me]2Br‚H2-
NCH2-4-C6H4Me (21‚H2NCH2-4-C6H4Me), and Pd(p-
C6H4CMe3)[NH3]2Br‚NH3 (22‚NH3), respectively. A trans
orientation of the amine ligands in complexes 19-21
was inferred due to the equivalence of the amine ligands
in the respective 1H NMR spectra and by analogy to
A solution of the mono(N-methylbenzylamine) com-
plex 13 in C6D6 which contained 0.25 M N-methylben-
zylamine displayed no evidence for the formation of the
corresponding palladium bis(amine) complex Pd(p-C6H4-
CMe3)[HN(Me)Bn]2Br (24) by 1H NMR spectroscopy; no
t-Bu resonances were observed in the region δ 1.20-
1.30, and the resonance for free P(o-tol)3 was not
observed. Making the assumption that P(o-tol)3 or tert-
butyl resonances resulting from 5% conversion of 13 to
1
related bis(amine) complexes.14 However, the H NMR
spectrum of 22 provided no information concerning the
stereochemistry of the amine ligands due to the broad-
ness of the ligated amine NH resonances. As a result,
a trans configuration of the amine ligands in 22 was
tentatively assigned. The reaction of palladium bromide
dimer 5 and excess piperidine in C6D6 formed the
corresponding bis(amine) complex Pd(p-C6H4CMe3)-
[piperidine]2Br (23), as evidenced by the appearance of
resonances corresponding to free P(o-tol)3 at δ 2.40 and
a new tert-butyl resonance at δ 1.30 in the 1H NMR
spectrum. However, the unfavorable equilibrium con-
stant for conversion of 12 to 23 precluded isolation of
23 (see below).
1
24 would be observed in the H NMR spectrum, we can
estimate an equilibrium constant for the conversion of
13 and N-methylbenzylamine to 24 and P(o-tol)3 of e4
× 10-5 at 25 °C. Our inability to satisfactorily charac-
terize the mono(amine) complex 15 precluded determi-
nation of the equilibrium constant for conversion of 15
to bis(amine) complex 22.
Discu ssion
Th er m od yn a m ics of th e In ter con ver sion of P a l-
la d iu m Mon o- a n d Bis(a m in e) Com p lexes. The
formation of palladium bis(amine) complexes from reac-
tion of amine and palladium aryl halide dimer repre-
sents a potential turnover limiting step in the corre-
sponding Pd2(DBA)3/P(o-tol)3-catalyzed amination of
aryl halides.1-3 As a result, the thermodynamics and
kinetics13 of the conversion of palladium mono(amine)
to bis(amine) complexes were investigated in greater
detail by 1H NMR spectroscopy. For example, a solution
of mono(amine) complex 8 (∼16 mM) and excess benz-
ylamine (0.115 M) in CDCl3 was monitored periodically
by 1H NMR spectroscopy at 25 °C. After 3 days, an
equilibrium 1.0:1.5 mixture of 8:16 had formed which
corresponds to an equilibrium constant of Keq ) [16]-
[P(o-tol)3]/[8][benzylamine] ) 0.14 ( 0.01 at 25 ( 1 °C
(Table 3).
The equilibrium constant for the conversion of 8 to
16 displayed a moderate solvent effect and increased
overall by a factor of 55 in the order CD2Cl2 (Keq ) 0.066
( 0.006) < CDCl3 < toluene-d8 < benzene-d6 < dioxane-
d8 < THF-d8 (Keq ) 3.6 ( 0.3) (Table 3). The large
equilibrium constant in oxygenated solvents such as
dioxane-d8 and THF-d8 may result from the ability of
Hyd r ogen Bon d in g in Tr a n sition -Meta l Am in e
Com p lexes. The NH2 groups of palladium aryl halide
bis(amine) complexes such as 16 readily form hydrogen
bonds in both the solid state and in solution. Likewise,
the proclivity of an NHx (x ) 1-3) group of a transition-
metal amine complex to serve as hydrogen bond donor
has been documented for complexes of Rh,25 Co,26 Ru,27
Fe,28 Pt, and Pd.17 In addition, transition-metal com-
plexes possessing halide,29 phenoxide, and alkoxide30
and hydroxide31 ligands also display a strong tendency
to form hydrogen bonds. Of particular relevance, Chatt
and co-workers observed the formation of PtN-H‚‚‚Cl,
(25) Thomas, K.; Osborn, J . A.; Powell, A. R.; Wilkinson, G. J . Chem.
Soc. A 1968, 1801.
(26) (a) Fujita, J .; Nakamoto, K.; Kobayashi, M. J . Chem. Soc. 1956,
3295. (b) Sakaguchi, U.; Tamaki, S.; Tomioka, K.; Yoneda, H. Inorg.
Chem. 1985, 24, 1624.
(27) Chatt, J .; Leigh, G. J .; Thankarajan, N. J . Chem. Soc. A 1971,
3168.
(28) (a) Andrews, M. A.; Kaesz, H. D. J . Am. Chem. Soc. 1979, 101,
7238. (b) Andrews, M. A.; van Buskirk, G.; Knobler, C. B.; Kaesz, H.
D. J . Am. Chem. Soc. 1979, 101, 7246.
(29) (a) Massa, W.; Babel, D. Chem. Rev. 1988, 88, 275. (b)
Richmond, T. G. Coord. Chem. Rev. 1990, 105, 221. (c) Lock, C. J . L.;
Speranzini, R. A.; Zvagulis, M. Acta Crystallogr. 1980, B36, 1789. (d)
Alsters, P. L.; Boersma, J .; Smeets, W. J . J .; Spek, A. L.; van Koten,
G. Organometallics 1993, 12, 1639.

Formation of Palladium Bis(amine) Complexes
Organometallics, Vol. 15, No. 16, 1996 3539
Ta ble 4. Am in e a n d Ha lid e Dep en d en ce of Keq for th e F or m a tion of P a lla d iu m Bis(a m in e) Com p lexes a n d
P (o-tol)3 F r om th e Rea ction of th e Cor r esp on d in g Mon o(a m in e) Com p lex a n d Am in e a t 25 °C
cone
entry no.
amine
H2NBn
H2NBn
H2NCH2CH2Ph
H2NCy
H2NCH2C6H4Me
piperidine
HN(Me)Bn
mono(amine)
bis(amine)
anglea
pKa
solvent
Keq
b
1
2
3
4
6
6
7
7
14
9
10
11
12
13
17
18
19
20
21
23
24
106
106
106
115
106
121
∼127
9.32
9.32
9.87
CDCl3
CDCl3
C6D6
C6D6
C6D6
C6D6
C6D6
0.18 ( 0.02
0.10 ( 0.01
1.1 ( 0.1
10.64
1.1 ( 0.1
0.50 ( 0.04
0.018 ( 0.002
e4 × 10-5
11.12
a
b
Cone angles from ref 23. pKa from ref 24.
PtN-H‚‚‚O(dioxane), and PtN-H‚‚‚Pt hydrogen bonds
in a series of platinum dichloride bis(amine) complexes
and platinum dichloride mono(amine) complexes
Pt(amine)(L)Cl2 (L ) neutral two-electron donor) by IR
spectroscopy.17 Significantly, they observed that the
NH2 group of a ligated primary amine was a more
effective hydrogen bond donor than was the NH group
of a ligated secondary amine. Likewise, the NHx group
of a platinum bis(amine) complex was a better hydrogen
bond donor than was the NHx group of the correspond-
ing mono(amine) mono(phosphine) complex. In accord
with these observations, hydrogen bond formation was
evident both in the solid state and in solution for
palladium bis(amine) complexes such as 16, while no
evidence for hydrogen bond formation was observed in
the corresponding mono(amine) mono(phosphine) com-
plexes 7-14.
In addition to spectroscopic studies, amine complexes
possessing either an N-H‚‚‚X (X ) Cl, Br, I) hydrogen
bond between an NHx group and a neighboring halide
ligand or an N-H‚‚‚M hydrogen bond between an NHx
group and a filled transition-metal d orbital have been
structurally characterized by X-ray crystallography. For
example, the platinum cis-dichloride bis(cycloalkyl-
amine) complexes Pt(Cl)2[H2NCH(CH2)n] (n ) 2,32 3,33
534 ] formed a three-dimensional lattice via intermo-
lecular N-H‚‚‚Cl bonds, while the iridium monohydride
mono(amine) bis(phosphine) complexes Ir(H)(CH3)-
I[NH(SiMe2CH2PR2)2] (R ) Ph, i-Pr) form inner-sphere
N-H‚‚‚I hydrogen bonds.35 Similarly, the tungsten
tricarbonyl monochloride diaminobenzene complexes
W(CO)3(Cl)[η3-o-C6H3ClCH2NH-o-C6H4NCHAr] form both
inner-sphere and intermolecular N-H‚‚‚Cl hydrogen
bonds.36 The unusual diplatinum salt [N(n-Pr)4]2
[PtCl4]‚cis-[PtCl2(NH2Me)2] formed both intermolecular
N-H‚‚‚Cl-Pt and N-H‚‚‚Pt bonds in the solid state,37
while the platinum phenylamido monohydride complex
PtH(NHPh)(PEt3)2 dimerized with close N-H‚‚‚Pt in-
termolecular contacts.38
Transition-metal amine complexes possessing N-H‚‚‚N
hydrogen bonds between the NHx group of a ligated
amine and an outer-sphere amine molecule have not
been structurally characterized. However, transition-
metal amine complexes possessing N-H‚‚‚O hydrogen
bonds between the NHx group of a ligated amine and
an oxygen atom acceptor have been structurally char-
acterized. For example, the palladium bis(phenoxide)
bis(pyrrolidine) complex Pd(OPh)2[HN(CH2)4]2 formed
a dimer in the solid state via four intramolecular PdN-
H...O(Ar)Pd hydrogen bonds.39 The corresponding bis-
(phenol) solvate Pd(OPh)2[HN(CH2)4]2‚2HOPh crystal-
lized in the form of a one-dimensional polymeric chain
via intermolecular N-H...O(phenol) bonds.40 The plati-
num dichloride monoammine mono(phosphine) complex
PtCl2(NH3)(PMe3) formed an isolable 2:1 18-crown-6
adduct, PtCl2(NH3)(PMe3)‚1/2(C12H24O6), in which all
three hydrogen atoms of the ammine ligand formed
N-H‚‚‚O hydrogen bonds with the crown ether oxygen
atoms.37 The piperidine tetracarbonyl trimethyl phos-
phite complexes M(CO)4[P(OMe)3](piperidine) (M )
Mo,41 Cr42 ) form inner-sphere N-H‚‚‚O hydrogen bonds
to a single phosphite oxygen atom.
Th er m od yn a m ics of P a lla d iu m Bis(a m in e) F or -
m a tion . Although quantitative thermodynamic data
are limited, a P-PdII bond is typically considered
stronger than the corresponding N-PdII bond. For
example, the enthalpy for cleavage of the chloride bridge
in the palladium allyl chloride dimer {[η3-CH2C(Me)-
CH2]Pd(µ-Cl)}2 with triphenylphosphine was ∼5 kcal
mol-1 greater than the corresponding bridge-cleavage
reaction employing piperidine.43 The thermodynamic
preference for a P-PdII bond over a N-PdII bond has
been attributed to the more favorable overlap of the sp2d
palladium orbital with the diffuse phosphorus sp3 hybrid
(30) (a) Kapteijn, G. M.; Dervisi, A.; Grove, D. M.; Kooijman, H.;
Lakin, M. T.; Spek, A.; van Koten, G. J . Am. Chem. Soc. 1995, 117,
10939. (b) Kim, Y. J .; Choi, J . C.; Osakada, K. J . Organomet. Chem.
1995, 491, 97. (c) Ozawa, F.; Yamagami, I.; Yamamoto, A. J . Orga-
nomet. Chem. 1994, 473, 265. (d) Simpson, R. D.; Bergman, R. G.
Organometallics 1993, 12, 781. (e) Bugno, C. D.; Pasquali, M.; Leoni,
P.; Sabatino, P.; Braga, D. Inorg. Chem. 1989, 28, 1390. (f) Seligson,
A. L.; Cowan, R. L.; Trogler, W. C. Inorg. Chem. 1991, 30, 3371. (g)
Osakada, K.; Kim, Y. J .; Tanaka, M.; Ishiguro, S. I.; Yamamoto, A.
Inorg. Chem. 1991, 30, 197. (h) Kapteijn, G. M.; Grove, D. M.; van
Koten, G.; Smeets, W. J . J .; Spek, A. L. Inorg. Chim. Acta 1993, 207,
131. (i) Osakada, K.; Ohshiro, K.; Yamamoto, A. Organometallics 1991,
10, 404. (j) Canty, A. J .; J in, H.; Skelton, B. J .; White, A. H. J .
Organomet. Chem. 1995, 503, C16. (k) Braga, D.; Grepioni, F.; Biradha,
K.; Pedireddit, V. R.; Desiraju, G. R. J . Am. Chem. Soc. 1995, 117,
3156. (l) Kapteijn, G. M.; Grove, D. M.; Kooijman, H.; Smeets, J . J .;
Spek, A. L.; van Koten, G. Inorg. Chem. 1996, 35, 526. (m) Kapteijn,
G. M.; Grove, D. M.; Kooijman, H.; Smeets, J . J .; Spek, A. L.; van Koten,
G. Inorg. Chem. 1996, 35, 534.
(36) Poss, M. J .; Arif, A. M.; Richmond, T. G. Organometallics 1988,
7, 1669.
(37) Brammer, L.; Charnock, P. L.; Goggin, P. L.; Goodfellow, R. J .;
Orpen, A. G.; Koetzle, T. F. J . Chem. Soc., Dalton Trans. 1991, 1789.
(38) Cowan, R. L.; Trogler, W. C. J . Am. Chem. Soc. 1989, 111, 4750.
(39) Alsters, P. L.; Baesjou, P. J .; J anssen, M. D.; Kooijman, H.;
Sicherer-Roetman, A.; Spek, A. L.; van Koten, G. Organometallics 1992,
11, 4124.
(31) (a) Sutherland, B. R.; Cowie, M. Organometallics 1985, 4, 1637.
(b) Sartorelli, U.; Garlashelli, L.; Bonora, G. Inorg. Chim. Acta 1972,
5, 191.
(32) Howard-Lock, H. E.; Lock, C. J . L.; Turner, G.; Zvagulis, M.
Can. J . Chem. 1981, 59, 2737.
(33) Lock, C. J . L.; Zvagulis, M. Inorg. Chem. 1981, 20, 1817.
(34) Lock, C. J . L.; Speranzini, R. A.; Zvagulis, M. Acta Crystallogr.
1980, B36, 1789.
(35) Fryzuk, M. D.; MacNeil, P. A.; Rettig, S. J . J . Am. Chem. Soc.
1987, 109, 2803.
(40) Colquhoun, H. M.; Lewis, D. F.; Stoddart, J . F.; Williams, D. J .
J . Chem. Soc., Dalton Trans. 1983, 607.
(41) Atwood, J . L.; Darensbourg, D. J . Inorg. Chem. 1977, 16, 2314.
(42) Cotton, F. A.; Darensbourg, D. J .; Fang, A.; Kolthammer, B.
W. S.; Reed, D.; Thompson, J . L. Inorg. Chem. 1981, 20, 4090.
(43) Li, M. P.; Drago, R. S.; Pribula, A. J . J . Am. Chem. Soc. 1977,
99, 6900.

3540 Organometallics, Vol. 15, No. 16, 1996
Widenhoefer and Buchwald
orbital relative to the more compact nitrogen sp3 hybrid
orbital.44 The effect of dπ-dπ back-bonding on the
stability of the M-P bond of a transition metal and a
trialkyl- or triarylphosphine is not clear.45 However,
conversion of 8 + benzylamine to 16 + P(o-tol)3 was
slightly exothermic (∆H ≈ -3 kcal mol-1), which may
result in part from the large cone angle of the P(o-tol)3
ligand (θ ) 195°)46,47 relative to benzylamine (θ )
106°).23a
The coordination or dissociation of an amine serves
as a key step in a variety of transition-metal-catalyzed
processes.48 As a result, there has been an effort to
correlate both the basicity and steric bulk of an amine
to the kinetic or thermodynamic binding affinity.23a,49
For example, we have recently shown that the binding
constants Kb (determined relative to N-benzylmethyl-
amine) for the reaction of amine with 1 to form the
palladium mono(amine) complexes Pd[P(o-tol)3](p-C6H4-
Me)(amine)Cl were dependent on both the basicity and
steric bulk of the amine.12 Specifically, for sterically
small amines with cone angles less than ∼120°, the
relative binding constant of the amine was dominated
by the basicity of the amine, while for larger amines,
the Kb value became sensitive to the steric bulk of the
amine, consistent with the presence of a steric thresh-
old.50,51 The presence of a steric threshold has been
observed in the correlation of the transition-metal
binding affinities of both phosphines50 and amines51
with the respective cone angles.
The equilibrium constants for the formation of pal-
ladium bis(amine) complexes from the corresponding
mono(amine) complex and free amine were also depend-
ent on the steric bulk of the amine (Table 3). For
example, the equilibrium constant for the formation of
16 from the reaction of 8 and benzylamine was g2 ×
104 times larger (∆∆G° g 6 kcal mol-1) than Keq for the
formation of 24 from reaction of 13 and N-methylben-
zylamine. In addition, despite limited data points, the
F igu r e 2. Plot of log Keq versus amine cone angle for the
formation of 16 from 8 and benzylamine (1), 19 from 9 and
phenethylamine (2), 20 from 10 and cyclohexylamine (3),
23 from 12 and piperidine (4), and 24 from 13 and
N-methylbenzylamine (5) in C6D6 at 25 °C.
correlation between the equilibrium constant and the
cone angle of the amine was consistent with the pres-
ence of a steric threshold. For example, a plot of log
Keq versus cone angle for the formation of 16 from 8 and
benzylamine (θ ) 106°, pKa ) 9.32), 19 from 9 and
phenethylamine (θ ) 106°, pKa ) 9.87), 20 from 10 and
cyclohexylamine (θ ) 115°, pKa ) 10.64), 23 from 12
and piperidine (θ ) 121°, pKa ) 11.12), and 24 from 13
and N-methylbenzylamine (θ ≈ 127°)24b revealed that
log Keq was independent of amine cone angles below
115° and decreased linearly with increasing cone angle
above 115° (Figure 2). Unfortunately, the limited range
of basicities for amines of comparable cone angle
precluded a detailed investigation of the relationship
between Keq and amine basicity.
The efficiency of the tin-free Pd2(DBA)3/P(o-tol)3-
catalyzed amination of aryl halides is halide-dependent;
aryl iodides required more forcing conditions and pro-
duced lower yields of anilines than did aryl bromides.1-3
We have therefore probed the influence of the halide
ligand on both the formation and reductive elimination
of palladium mono(amine) complexes in an effort to
elucidate the origin of this halide effect in the corre-
sponding catalytic reaction.10-12 For example, the equi-
librium constants for reaction of diisopropylamine with
palladium aryl halide dimers 1-3 at 25 °C in CD2Cl2
to form the corresponding amine monomers Pd[P(o-tol)3]-
(p-C6H4Me)[HN(i-Pr)2]X (X ) Cl, Br, I) were halide
dependent and decreased overall by a factor of ∼2.3 ×
103 (∆∆G° ) ∼4.6 kcal mol-1) in the order Cl > Br . I.
Similarly, the equilibrium constants for the formation
of palladium bis(amine) derivatives from mono(amine)
complexes and free amine were halide-dependent and
decreased in the order Cl > Br > I. However, the
magnitude of this halide effect was considerably smaller
than was observed in the dimer cleavage reactions. For
example, the equilibrium constant for formation of the
iodide complex 18 from 14 and benzylamine was ∼2
times smaller than Keq for the formation of the corre-
sponding chloride complex 17 from 7 and benzylamine.
(44) (a) de Graaf, W.; Boersma, J .; Smeets, W. J . J .; Spek, A. L.;
van Koten, G. Organometallics 1989, 8, 2907. (b) Wang, L.; Wang, C.;
Bau, R.; Flood, T. C. Organometallics 1996, 15, 491.
(45) Collman, J . P.; Hegedus, L. S.; Norton, J . R.; Finke, R. G.
Principles and Applications of Organotransiton Metal Chemistry;
University Science: Mill Valley, CA, 1987; p 69.
(46) Tolman, C. A. Chem. Rev. 1977, 77, 313.
(47) Farina, V.; Krishnan, B. J . Am. Chem. Soc. 1991, 113, 9585.
(48) (a) Gagne, M. R.; Stern, C. L.; Marks, T. J . J . Am. Chem. Soc.
1992, 114, 275. (b) Baralt, E.; Smith, S. J .; Hurwitz, J .; Horvath, I. T.;
Fish, R. H. J . Am. Chem. Soc. 1992, 114, 5187. (c) Gray, S. D.; Smith,
D. P.; Bruck, M. A. J . Am. Chem. Soc. 1992, 114, 5462. (d) Fish, R. H.;
Baralt, E.; Smith, S. J . Organometallics 1991, 10, 54. (e) Satterfield,
C. N. Heterogeneous Catalysis in Practice, 2nd ed.; McGraw-Hill: New
York, 1991. (f) Ball, G. E.; Cullen, W. R.; Fryzuk, M. D.; Henderson,
W. J .; J ames, B. R.; MacFarlane, K. S. Inorg. Chem. 1994, 33, 1464.
(g) Volt, J .; Pasek, J . In Catalytic Hydrogenation: Studies in Surface
Science and Catalysis; Cerverry, L., Ed.; Elsevier: Amsterdam, 1986;
Vol. 27, Chapter 4.
(49) (a) Canovese, L.; Visentin, F.; Uguagliati, P.; Di Bianca, F.;
Antonaroli, S.; Crociani, B. J . Chem. Soc., Dalton Trans. 1994, 3113.
(b) Dennenberg, R. J .; Darensbourg, D. J . Inorg. Chem. 1972, 11, 72.
(c) Canovese, L.; Visentin, F.; Uguagliati, P.; Crociani, B.; Di Bianca,
F. Inorg. Chim. Acta 1995, 235, 45. (d) Uruska, I.; Zielkiewicz, J .;
Szpakowska, M. J . Chem. Soc., Dalton Trans. 1990, 733. (e) Therien,
M. J .; Trogler, W. C. J . Am. Chem. Soc. 1987, 109, 5127. (f) Burkey,
T. J . Polyhedron 1989, 8, 2681. (g) Uruska, I.; Zielkiewicz, J .;
Szpakowska, M. J . Chem. Soc., Dalton Trans. 1990, 733. (h) Brown,
H. C. Boranes in Organic Chemistry; Cornell Univerisity Press: Ithaca,
NY, 1972. (i) Deeming, A. J .; Rothwell, I. P.; Hursthouse, M. B.; New,
L. J . Chem. Soc., Dalton Trans. 1978, 1490. (j) Odell, A. L.; Raethel,
H. A. J . Chem. Soc., Chem. Commun. 1968, 1323.
Con clu sion s
(50) (a) Liu, H. Y.; Eriks, K.; Prock, A.; Giering, W. P. Organome-
tallics 1990, 9, 1758. (b) Rahman, M. M.; Liu, H. Y.; Prock, A.; Giering,
W. P. Organometallics 1987, 6, 650.
(51) (a) Romeo, R.; Arena, G.; Scolaro, L. M. Inorg. Chem. 1992, 31,
4879. (b) Romeo, R.; Arena, G.; Scolaro, L. M.; Plutino, M. R.; Bruno,
G.; Nicolo, F. Inorg. Chem. 1994, 33, 4029.
We have shown that palladium tris(o-tolyl)phosphine
mono(primary amine) aryl halide complexes are con-
verted to the corresponding palladium bis(primary
amine) aryl halide complexes upon treatment with

Formation of Palladium Bis(amine) Complexes
Organometallics, Vol. 15, No. 16, 1996 3541
(br, 3 H), 7.32 (t, J ) 6.5 Hz, 3 H), 7.25-7.07 (m, 11 H), 6.67
(m, 4 H), 3.81 (br t, J ) 7.1 Hz, 2 H, H2NCH2Ph), 2.96 (br, 2
H, H2NCH2Ph), 2.16 [br s, 9 H, P(o-tol)3], 1.16 (s, 9 H,
C6H4CMe3). 31P{1H} NMR (CDCl3, 25 °C): δ 26.9. Anal.
Calcd (found) for C38H43BrNPPd: C, 66.48 (66.71); H, 6.31
(6.51).
P d [P (o-tol)3](p-C6H4CMe3)[H2NBn ]Br (8). Reaction of
benzylamine (30 µL, 29 mg, 0.27 mmol) and 5 (150 mg, 0.12
mmol) using a procedure analogous to that used to prepare 7
led to the isolation of 8 (95 mg, 54%) as a yellow powder. 1H
NMR (CDCl3, 50 °C): δ 7.80 (br, 3 H), 7.22 (m, J ) 6.4 Hz, 3
H), 7.07 (m, 4 H), 6.69 (s, 4 H), 3.82 (br t, J ) 8 Hz, 2 H,
H2NCH2Ph), 3.01 (br, 2 H, H2NCH2Ph), 2.15 [br s, 9 H, P(o-
tol)3], 1.17 (s, 3 H, C6H4CMe3). 31P{1H} NMR (CDCl3, 25 °C):
δ 27.2. Anal. Calcd (found) for C38H43BrNPPd: C, 62.43
(62.23); H, 5.93 (5.99).
P d [P (o-tol)3](p-C6H4CMe3)[H2NCH2CH2P h ]Br (9). Re-
action of 5 (106 mg, 0.085 mmol), and phenethylamine (20 mg,
0.17 mmol) using a procedure analogous to that used to
prepare 7 led to the isolation of 9 (118 mg, 94%) as a white
microcrystalline solid. 1H NMR (CDCl3, 50 °C): δ 7.80 (br, 3
H), 7.30 (t, J ) 6.5 Hz, 3 H), 7.15-7.06 (m, 11 H), 6.87 (m),
6.66 (m), 2.93 (br, 2 H, H2NCH2CH2Ph), 2.71 (m, 4 H, H2NCH2-
CH2Ph + H2NCH2CH2Ph), 2.14 [br s, 9 H, P(o-tol)3], 1.17 (s, 9
H, C6H4CMe3). 31P{1H} NMR (CDCl3, 25 °C): δ 28.9. Anal.
Calcd (found) for C39H45BrNPPd: C, 62.87 (62.96); H, 6.09
(6.26).
excess primary amine. These palladium bis(amine)
complexes are prone to form hydrogen bonds involving
the NH2 groups of the palladium-bound amine ligands
both in the solid state and in solution. In benzene-d6
at 25 °C, the free energy for conversion of mono(primary
amine) complexes to bis(primary amine) complexes is
<0.1 kcal mol-1. The corresponding conversion of mono-
(secondary amine) complexes to bis(secondary amine)
complexes was considerably less favorable (∆∆G° g 2.4
kcal mol-1). The greater tendency of primary amines
to form palladium bis(amine) complexes relative to
secondary amines and the failure of palladium aryl
halide bis(amine) complexes to generate detectable
quantities of aromatic amine upon treatment of sodium
tert-butoxide may contribute to the ineffectiveness of
primary amines as substrates in the corresponding Pd/
P(o-tol)3-catalyzed amination of aryl halides. We are
continuing to investigate the kinetics and mechanism
of the formation of palladium bis(amine) complexes from
palladium mono(amine) derivatives in an effort to
further evaluate this process as a turnover-limiting step
in the corresponding Pd/P(o-tol)3-catalyzed amination
of aryl halides.
Exp er im en ta l Section
P d [P (o-tol)3](p-C6H4CMe3)[H2NCy]Br (10). Reaction of
2 (100 mg, 0.08 mmol) and cyclohexylamine (20 µL, 17 mg,
0.16 mmol) using a procedure analogous to that used to
prepare 7 led to the isolation of 10 (99 mg, 85%) as a white
microcrystalline solid. 1H NMR (C6D6, 50 °C): δ 8.11 (br, 3
H), 7.05 (d, J ) 7.4 Hz), 7.01 (m), 6.92 (m), 6.77 (d, J ) 7.7
Hz), 2.55 [br, 3 H, NH2CH(CH2)5 + R-CH], 2.32 [br s, 9 H,
P(o-tol)3], 1.70 (br, 2 H, â-CH2), 1.36 (br, 2 H, â-CH2), 1.17 (s,
9 H, C6H4CMe3), 0.90 (br, 3 H, γ-CH2 + δ-CH2), 0.72 (br, 3 H,
γ-CH2 + δ-CH2). 31P{1H} NMR (CDCl3, 25 °C): δ 28.6. Anal.
Calcd (found) for C37H47BrNPPd: C, 61.46 (61.70); H, 6.55
(6.43).
P d [P (o-tol)3](p-C6H4CMe3)[H2NCH2-p-C6H4Me]Br (11).
Reaction of (4-methylbenzyl)amine (21 µL, 19 mg, 0.16 mmol)
and 5 (100 mg, 0.08 mmol) using a procedure analogous to
that used to prepare 7 led to the isolation of 11 (78 mg, 64%)
as a yellow microcrystalline solid. 1H NMR (C6D6, 50 °C): δ
7.05 (d, J ) 7.64 Hz), 6.93 (br), 6.81 (s), 6.04 (s), 3.70 (br s, 2
H, H2NCH2C6H4CH3), 2.65 (br, 2 H, H2NCH2C6H4CH3), 2.40
[br s, 9 H, P(o-tol)3], 2.03 (br s, 2 H, H2NCH2C6H4CH3), 1.18
(s, 3 H, C6H4CMe3). 31P{1H} NMR (CDCl3, 25 °C): δ 28.2.
Anal. Calcd (found) for C39H45BrNPPd: C, 62.87 (62.64); H,
6.09 (6.11).
Gen er a l Meth od s. All manipulations and reactions were
performed under an inert atmosphere of nitrogen or argon in
an inert atmosphere glovebox or by standard Schlenk tech-
niques. Preparative-scale reactions were performed in flame-
or oven-dried Schlenk tubes equipped with a stirbar, side-arm
joint, and septum. NMR experiments were performed in oven-
dried 5 mm thin-wall NMR tubes fitted with a rubber septum.
1H NMR spectra were obtained on a Varian XL-300 or Unity-
300 spectrometer and were referenced relative to the residual
proton resonance of the solvent. 31P NMR spectra were
obtained on a Varian XL-300 (121 MHz) and were referenced
relative to external H3PO4. IR spectra were recorded on a
Perkin-Elmer FTIR spectrophotometer. Elemental analyses
were performed by E+R Microanalytical Laboratories (Corona,
NY).
Diethyl ether, hexane, pentane, benzene, and benzene-d6
were distilled from purple solutions of sodium and benzophe-
none under argon or nitrogen. Toluene-d8, THF-d8, and
dioxane-d8 were distilled from Na/K alloy. Methylene chloride
and methylene chloride-d2 were distilled from CaH2; CDCl3
was distilled from P2O5. Amines (Aldrich) were either pur-
chased as anhydrous grade and used as received or were
distilled from CaH2 under Ar prior to use.
Equilibrium measurements for the conversion of mono-
(amine) to bis(amine) complexes conducted at 25 °C were
conducted at ambient laboratory temperature; periodic tem-
perature measurement indicated a variation of e1 °C through-
out approach to equilibrium. Experiments conducted at 40
°C were performed in a constant-temperature oil bath main-
tained at ( 0.5 °C or in the probe of a preheated NMR
spectrometer calibrated with an ethylene glycol thermometer
and maintained at (0.5 °C throughout data acquisition.
Experiments conducted at 55-77 °C were performed in the
probe of a preheated NMR spectrometer. Estimation of error
limits for equilibrium constants and the corresponding free
energy values was performed as previously described.12
P d [P (o-tol)3](p-C6H4CMe3)[H2NBn ]Cl (7). A solution of
benzylamine (20 µL, 20 mg, 0.2 mmol) and 4 (106 mg, 0.09
mmol) in CH2Cl2 (5 mL) was stirred at room temperature for
10 min. The resulting colorless solution was concentrated to
1 mL under vacuum and diluted with 20 mL of hexane.
Cooling the solution via concentration to 10 mL under vacuum
formed a white precipitate, which was filtered, washed with
hexane, and dried under vacuum to give 7 (118 mg, 94%) as a
white, microcrystalline solid. 1H NMR (CDCl3, 50 °C): δ 7.80
P d [P (o-tol)3](p-C6H4CMe3)[p ip er id in e]Br (12). Reaction
of 5 (100 mg, 0.08 mmol) and piperidine (25 µL, 22 mg, 0.25
mmol) using a procedure analogous to that used to prepare 7
led to the isolation of 12 (91 mg, 80%) as a white microcrys-
talline solid. 1H NMR (C6D6, 50 °C): δ 8.05 (br, 3 H), 7.05 (d,
J ) 7.33 Hz), 6.91 (m), 6.80 (d, J ) 7.41 Hz), 3.55 [br s, 1 H,
HN(CH2)5], 3.13 (br d, J ) 12.6 Hz, 2 H), 2.64 (br d, J ) 11.7
Hz, 2 H), 2.33 [br s, 9 H, P(o-tol)3], 1.18 (s, 9 H, C6H4CMe3),
1.01 (br d, J ) 11.7 Hz, 3 H), 0.80 (br, 3 H). 31P{1H} NMR
(CDCl3, 25 °C): δ 28.8 (br). Anal. Calcd (found) for C36H45
-
BrNPPd: C, 60.98 (61.09); H, 6.40 (6.49).
P d [P (o-tol)3](p-C6H4CMe3)[HN(Me)Bn ]Br (13). Reaction
of 5 (100 mg, 0.08 mmol) and methylbenzylamine (20 mg, 0.2
mmol) using a procedure analogous to that used to prepare 7
led to the isolation of 13 (118 mg, 94%) as yellow blocks. 1H
NMR (C6D6, 50 °C): δ 7.80 (br, 3 H), 7.42 (m), 7.19 (d, J ) 7.4
Hz), 7.05 (d, J ) 7.5 Hz), 6.90 (m), 6.69 (m), 4.50 (br t, J ≈ 7
Hz, 1 H, HN(Me)CH2Ph), 3.41 (br s, 1 H, HN(Me)CH2Ph), 2.96
(br, 1 H, HN(Me)CH2Ph), 2.27 [br s, 9 H, P(o-tol)3], 1.15 (s, 9
H, C6H4CMe3). Anal. Calcd (found) for C39H45BrNPPd: C,
62.87 (62.82); H, 6.09 (6.11).
P d [P (o-tol)3](p-C6H4CMe3)[H2NBn ]I (14). Benzylamine
was added in small portions (<0.5 µL) to a solution of 6 (7

3542 Organometallics, Vol. 15, No. 16, 1996
Widenhoefer and Buchwald
NCH2CH2Ph). IR (CDCl3): νN-H 3325, 3270 cm-1
. Anal.
Calcd (found) for C34H46BrN3Pd: C, 59.79 (59.61); H, 6.79
(6.86); N, 6.15 (6.13).
mg, 5 × 10-3 mmol) in CDCl3 (0.7 mL), and the mixture was
monitored by 1H NMR spectroscopy after each addition.
Addition of 1.5 µL (0.01 mmol) of benzylamine generated 14,
which was >95% pure by 1H NMR spectroscopy and was
characterized without isolation. 1H NMR (CDCl3, 50 °C): δ
7.80 (br, 3 H), 7.22 (m, J ) 6.4 Hz, 3 H), 7.07 (m, 4 H), 6.69 (s,
4 H), 3.82 (br t, J ) 8 Hz, 2 H, H2NCH2Ph), 3.01 (br, 2 H,
H2NCH2Ph), 2.15 [br s, 9 H, P(o-tol)3], 1.17 (s, 3 H, C6H4CMe3).
31P{1H} NMR (CDCl3, 25 °C): δ 27.2.
P d (p-C6H4CMe3)[H2NBn ]2Br ‚H2NBn (16‚H2NBn ). A so-
lution of 5 (250 mg, 0.20 mmol) and benzylamine (825 µL, 810
mg, 7.6 mmol) in CH2Cl2 (8 mL) was stirred overnight at room
temperature to give a colorless solution. Solvent was evapo-
rated under vacuum, and the residue was dissolved in THF
(3 mL) and diluted with pentane (10 mL). Cooling the
resulting solution to -30 °C overnight produced a precipitate
which was filtered, washed with pentane, and dried under
vacuum to give 16‚H2NBn (260 mg, 99%) as a white fibrous
solid. 1H NMR (C6D6, 25 °C): in addition to resonances
corresponding to free benzylamine (δ 7.15, 3.55, and 0.79),
resonances were observed at δ 7.13-6.85 (10 H), 3.81 (t, J )
7.0 Hz, 4 H, H2NCH2Ph), 2.4 (br t, J ≈ 7 Hz, 4 H, H2NCH2-
Ph), 1.27 (s, 9 H, C6H4CMe3). IR (KBr): 3295, 3198, 3106,
2958, 1581, 1496, 1454, 1360, 1160, 1116, 990, 817, 751, 700
cm-1. IR (CDCl3): νN-H 3333, 3275 cm-1. Anal. Calcd (found)
for C31H40BrN3Pd: C, 58.09 (57.85); H, 6.29 (6.26); N, 6.56
(6.33).
P d (p-C6H4CMe3)[H2NCy]2Br ‚H2NCy (20‚H2NCy). A so-
lution of 5 (100 mg, 0.08 mmol) and cyclohexylamine (200 µL,
173 mg, 1.8 mmol) in THF (2 mL) was stirred overnight to
give a colorless solution. Solvent was evaporated under
vacuum, and the residue was crystallized from hexane (10 mL)
at -30 °C to give 20‚H2NCy (97 mg, 89%) as white needles.
1H NMR (C6D6, 25 °C): δ 7.31 (d, J ) 8.3 Hz, 2 H), 7.23 (d, J
) 8.3 Hz, 2 H), 2.72 (tt, J ) 3.8, 10.8 Hz, 2 H, R-CH), 1.91 (d,
J ) 10.6 Hz, 4 H), 1.40 1.35, 1.28 (s, 9 H, C6H4CMe3), 0.92 (d,
J ) 12.2 Hz), 0.65 (m). IR (CDCl3): νN-H 3319, 3261 cm-1
.
Anal. Calcd (found) for C28H52BrN3Pd: C, 54.50 (54.61); H,
8.49 (8.69); N, 6.81 (6.59).
P d (p -C6H 4CMe 3)[H 2NCH 2-p -C6H 4Me ]2Br ‚H 2NCH 2-p -
C6H4Me (21‚H2NCH2-p-C6H4Me). Reaction of 5 (100 mg, 0.08
mmol) and (4-methylbenzyl)amine (300 µL, 294 mg, 2.7 mmol)
employing a procedure analogous to that used to prepare
20‚H2NCy gave 21‚H2NCH2-p-C6H4Me (97 mg, 89%) as white
needles. 1H NMR (C6D6, 25 °C): in addition to resonances
corresponding to free (4-methylbenzyl)amine (δ 7.15, 3.59, 2.14,
and 0.70), resonances were observed at δ 7.13-6.85 (aromatic,
10 H), 3.84 (t, J ) 7.05 Hz, 4 H, H2NCH2C6H4Me), 2.49 (br t,
4 H, H2NCH2C6H4Me), 2.14 (s, 3 H, H2NCH2C6H4Me), 1.28 (s,
9 H, C6H4CMe3). IR (CDCl3): νN-H 3230, 3272 cm-1
. Anal.
Calcd (found) for C34H46BrN3Pd: C, 59.79 (59.54); H, 6.79
(6.81); N, 6.15 (6.02).
P d (p-C6H4CMe3)[H2NBn ]2Cl‚H2NBn (17‚H2NBn ). Reac-
tion of 4 (95 mg, 0.08 mmol) and benzylamine (300 µL, 294
mg, 2.7 mmol) using a procedure analogous to that used to
prepare 16‚H2NBn gave 17‚H2NBn (95 mg, 97%) as a white
fibrous solid. 1H NMR (C6D6, 25 °C): in addition to resonances
corresponding to free benzylamine (δ 7.15, 3.55, and 0.79),
resonances were observed at δ 7.13-6.85 (10 H), 3.86 (t, J )
7.1 Hz, 4 H, H2NCH2Ph), 2.68 (t, J ) 7.1 Hz, 4 H, H2NCH2-
Ph), 1.27 (s, 9 H, C6H4CMe3). IR (KBr): 3302, 3186, 3059,
P d (p-C6H4CMe3)[NH3]2Br ‚NH3 (22‚NH3). A 0.5 M solu-
tion of ammonia in dioxane (5 mL, 2.5 mmol) was added to
solid 5 (100 mg, 0.08 mmol) and stirred for 5 min. The
resulting colorless solution was allowed to stand overnight at
room temperature to form a colorless precipitate, which was
filtered, washed with pentane, and dried under vacuum to give
22‚NH3 (55 mg, 92%) as white needles. 1H NMR (C6D6, 25
°C): in addition to the resonance corresponding to free NH3
(δ 0.50), resonances were observed at δ 7.07 (d, J ) 8.55 Hz,
2 H), 7.03 (d, J ) 8.55 Hz, 2 H), 2.14 (br s, 3 H, NH3), 1.25 (s,
2959, 1589, 1483, 1454, 1009, 991, 816, 751, 699 cm-1
(CDCl3): νN-H 3333, 3275 cm-1
Anal. Calcd (found) for
. IR
.
C
31H40ClN3Pd: C, 62.42 (62.46); H, 6.76 (6.93); N, 7.04 (6.94).
9 H, C6H4CMe3). IR (CDCl3): νN-H 3376, 3282 cm-1
. Anal.
P d (p-C6H4CMe3)[H2NBn ]2I‚H2NBn (18‚H2NBn ). Reac-
Calcd (found) for C10H22BrN3Pd: C, 32.41 (32.14); H, 5.98
(5.87).
tion of 6 (100 mg, 0.075 mmol) and benzylamine (300 µL, 294
mg, 2.7 mmol) employing a procedure analogous to that used
to prepare 16‚H2NBn gave 18‚H2NBn (101 mg, 99%) as yellow
needles. 1H NMR (C6D6, 25 °C): in addition to resonances
corresponding to free benzylamine (δ 7.15, 3.55, and 0.79)
resonances were observed at δ 7.13-6.85 (10 H), 3.76 (t, J )
7.3 Hz, 4 H, H2NCH2Ph), 2.28 (br t, J ) ∼7 Hz, 4 H, H2NCH2-
Ph), 1.27 (s, 9 H, C6H4CMe3). IR (KBr): 3262, 3186, 3119,
2963, 1583, 1454, 980, 816, 753, 701 cm-1. IR (CDCl3): 3329,
Th er m od yn a m ics of th e Con ver sion of 8 + H2NBn to
16 + P (o-tol)3. Benzylamine (10 µL, 0.09 mmol) was added
via syringe to an NMR tube containing a solution of 5 (7.0
mg, 0.011 mmol) and P(o-tol)3 (29.4 mg, 0.097 mmol) in C6D6
(0.70 mL). The tube was shaken, and its contents were
analyzed periodically by 1H NMR at 25 °C. The concentrations
of 8 and 16 were determined by integrating the tert-butyl
resonances for 8 (δ 1.17) and 16 (δ 1.27) and from the mass
balance. The concentration of free benzylamine was deter-
mined from the mass balance. The equilibrium constant for
the conversion of 8 to 16 was determined according to the
formula Keq ) [8][P(o-tol)3]/[16][benzylamine]. Related equi-
librium constants were determined by analogous procedures.
3271 cm-1
. Anal. Calcd (found) for C31H40IN3Pd: C, 54.12
(54.31); H, 5.86 (6.05); N, 6.11 (6.02).
P d (p -C6H 4CMe 3)[H 2NCH 2CH 2P h ]2Br ‚H 2NCH 2CH 2P h
(19‚H2NCH2CH2P h ). A solution of 5 (100 mg, 0.08 mmol) and
phenethylamine (200 µL, 193 mg, 1.6 mmol) in THF (2 mL)
was stirred overnight at room temperature to give a colorless
solution. Solvent was evaporated under vacuum, and the
residue was crystallized from Et2O/pentane (1/6) to give 19.H2-
NCH2CH2Ph (92 mg, 84%) as a white solid. 1H NMR (C6D6,
25 °C): in addition to resonances corresponding to free
phenethylamine (δ 2.68 (t, J ) 6.8 Hz), 2.45 (t, J ) 6.8 Hz),
and 0.51), resonances were observed at δ 7.11, 7.08, 7.06, 7.03,
6.81 (d, J ) 6.8 Hz), 2.71 (t, J ) 7.3 Hz, 2 H, H2NCH2CH2Ph),
2.39 (t, J ) 7.4 Hz, 2 H, H2NCH2CH2Ph), 2.71 (br, 2 H, H2-
Ack n ow led gm en t. We thank the National Science
Foundation, Dow Chemical, and Pfizer for their support
of this work. R.A.W. is an NCI Postdoctoral Trainee
supported by NIH Cancer Training Grant CI
T32CA09112. We thank Ms. H. Annita Zhong for
performing preliminary experiments.
OM9603169