Alkylpalladium n-heterocyclic carbene complexes: Synthesis, reactivity, and catalytic properties

Article abstract of DOI:10.1021/om800455h

The dimers [trans-[(neopentyl)Pd(μ-Cl)(rBu)]₂, 2, and (cis-[(neopentyl)Pd(μ-Cl)(IPr)]₂,3 (I^tBu = 1,3-bis-tert-butylimidazol-2-ylidene, IPr = l,3-bis-2,6-diidopropylimidazol-2- ylidene), have been synthesized from [Pd(neopentyl)(Cl)(l,5-COD)], and their reactivity toward a variety of nucleophiles has been evaluated. In particular, this study revealed that 2 can be readily cleaved by primary and secondary amines, affording stable transamination products, which are surprisingly resistant to deprotonation. Dimer 3 was subsequently used as a catalyst in a series of Buchwald-Hartwig animation reactions of aryl chlorides.

Full text of DOI:10.1021/om800455h

Organometallics 2008, 27, 6411–6418
6411
Articles
Alkylpalladium N-Heterocyclic Carbene Complexes: Synthesis,
Reactivity, and Catalytic Properties
†
†,‡,§
§
,§
Oriana Esposito, Pedro M. P. Gois,
Alexandra K. de K. Lewis, Stephen Caddick,*
,† †
F. Geoffrey N. Cloke,* and Peter B. Hitchcock
Department of Chemistry and Biochemistry, School of Life Sciences, UniVersity of Sussex,
Falmer, Brighton BN1 9QJ, U.K., CQFM, Departamento de Engenharia Qu ´ı mica e Biologia, Complexo I,
Instituto Superior T e´ cnico, AVenida RoVisco Pais 1, 1049-001 Lisboa, Portugal, and Department of
Chemistry, UniVersity College London, 20 Gordon Street, London WC1H OAJ, U.K.
ReceiVed May 19, 2008
t
t
The dimers [trans-[(neopentyl)Pd(µ-Cl)(I Bu)]
2
, 2, and (cis-[(neopentyl)Pd(µ-Cl)(IPr)] , 3 (I Bu ) 1,3-
2
bis-tert-butylimidazol-2-ylidene, IPr ) 1,3-bis-2,6-diidopropylimidazol-2-ylidene), have been synthesized
from [Pd(neopentyl)(Cl)(1,5-COD)], and their reactivity toward a variety of nucleophiles has been
evaluated. In particular, this study revealed that 2 can be readily cleaved by primary and secondary
amines, affording stable transamination products, which are surprisingly resistant to deprotonation. Dimer
3
was subsequently used as a catalyst in a series of Buchwald-Hartwig amination reactions of aryl
chlorides.
Introduction
The generation of well-defined Pd(II)-NHC precatalysts is
an area of considerable activity. These complexes display
improved air- and moisture-stability and contain the desired (1:
Metal-catalyzed cross-coupling methodologies are extensively
used in organic chemistry for the formation of carbon-carbon
1) ratio of NHC ligand:metal. The existence of easily displace-
1
and carbon-nitrogen bonds. Even though different metals have
able ligands in the coordination sphere allows the generation,
been used to mediate this process, the efficiency of palladium
complexes has remained unsurpassed, and advances in pal-
ladium-catalyzed transformations are intrinsically related to the
development of new ligands. Indeed electron-rich σ-donor
ligands, such as bulky alkyl phosphines and N-heterocyclic
0
in solution, of the putative monoligated Pd -NHC active species.
Nolan has explored this concept using (NHC)Pd(R-allyl)Cl
(3) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 2457. (a) Miyaura, N.
Top. Curr. Chem. 2002, 219, 11. (b) Suzuki, A. J. Organomet. Chem. 1999,
576, 147. (c) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 15, 2419.
2
carbenes (NHCs), have considerably expanded the scope of
(
4) (a) Negishi, E. I. Acc. Chem. Res. 1982, 15, 340. (b) O’Brien, C. J.;
aryl halide cross-coupling reactions to include aryl chlorides
Kantchev, E. A. B.; Chass, G. A.; Hadei, N.; Hopkinson, A. C.; Organ,
M. G.; Setiadi, D. H.; Tang, T.-H.; Fang, D.-C. Tetrahedron 2005, 61, 9723.
(c) Organ, M. G.; Avola, S.; Dubovyk, I.; Hadei, N.; Assen, E.; Kantchev,
B.; O’Brien, C. J.; Valente, C. Chem.-Eur. J. 2006, 12, 4749. (d) Negishi,
E.; King, A. O.; Okukado, N. J. Org. Chem. 1977, 42, 1821. (e) King,
A. O.; Okukado, N.; Negishi, E. J. Chem. Soc., Chem. Commun. 1977,
3
4
5
6
as standard substrates in Suzuki, Negishi, Heck, Kumada,
7
or Buchwald-Hartwig amination reactions. The use of alkyl
halides in the same transformations has remained, until recently,
8
much more challenging.
6
83.
(
5) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
*
Corresponding author. E-mail: s.caddick@ucl.ac.uk; f.g.cloke@
(6) (a) Organopalladium Chemistry for Organic Synthesism; Wiley-
sussex.ac.uk.
Interscience: New York, 2002; Vol 311. (b) Tamao, K.; Sumitani, K.;
Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374. (c) Wolfe, J. P.; Wagaw,
S.; Macroux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805. (d)
Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852. (e) Hartwig, J. F. In Modern
Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, 2000.
(7) (a) Caddick, S.; Cloke, F. G. N.; Hitchcock, P. B.; Leonard, J.; Lewis,
A. K.; de, K.; McKerrecher, D.; Titcomb, L. R. Organometallics 2002, 21,
4318. (b) Arentsen, K.; Caddick, S.; Cloke, F. G. N. Tetrahedron 2005,
61, 9710.
(8) (a) Ishiyamap, T.; Abe, S.; Miyaura, N.; Suzuki, A. Chem. Lett. 1992,
691. (b) Netherton, M. R.; Dai, C.; Neusch u¨ tz, K.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 10099. (c) Kirchoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem.
2002, 114, 2025. (d) Arentsen, K.; Caddick, S.; Cloke, F. G. N.; Herring,
A. P.; Hitchcock, P. B. Tetrahedron Lett. 2004, 45, 3511. (e) Zhou, J.; Fu,
G. C. J. Am. Chem. Soc. 2003, 125, 12527. (f) Eckhardt, M.; Fu, G. C.
J. Am. Chem. Soc. 2003, 125, 13642. (g) Tang, H. F.; Menzel, K.; Fu,
G. C. Angew. Chem., Int. Ed. 2003, 41, 5079. (h) Zhou, J.; Fu, G. C. J. Am.
Chem. Soc. 2004, 126, 1340. (i) Zhou, J.; Fu, G. C. J. Am. Chem. Soc.
2004, 126, 1340. (j) Firmansjah, L.; Fu, G. C. J. Am. Chem. Soc. 2007,
129, 11340. (k) Valente, C.; Baglione, S.; Candito, D.; O’Brien, C. J.; Organ,
M. J. Chem. Commun. 2008, 735.
†
University of Sussex.
Instituto Superior T e´ cnico.
University College London.
‡
§
(
1) (a) Diedrich, F., Stang, P. J. Metal-Catalysed Cross-Coupling
Reactions; Wiley-VCH: Weinheim, 1998. (b) Tsuji, J. Palladium Reagents
and Catalysts; Wiley: Chichester, 1995. (c) Corbet, J.-P.; Mignani, G. Chem.
ReV. 2006, 106, 2651. For a recent review see: (d) Kantchev, E. A. B.;
O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed. 2007, 46, 2768.
(
2) For the synthesis of NHCs see: (a) Arduengo, A. J.; Harlow, R. L.;
Kline, M. J. Am. Chem. Soc. 1991, 113, 361. For reviews on aryl chloride
cross-coupling using NHCs see: (b) Herrmann, W. A. Angew. Chem., Int.
Ed. 2002, 41, 1290, and references therein. (c) Weskamp, T.; B o¨ hm,
V. P.W.; Herrmann, W. A. J. Organomet. Chem. 2000, 600, 12. (d) Hillier,
A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.; Nolan, S. P. J.
Organomet. Chem. 2002, 653, 69, and references therein. (e) Littke, A. F.;
Fu, G. C. J. Am. Chem. Soc. 1999, 41, 4176. (f) Hahn, F. E.; Jahnke, M. C.
Angew. Chem., Int. Ed. 2008, 47, 3122. (g) Gois, P. M. P.; Trindade, A. F.;
Veiros, L. F.; Andre, V.; Duarte, M. T.; Afonso, C. A. M.; Caddick, S.;
Cloke, F. G. N. Angew. Chem., Int. Ed. 2007, 46, 5750. (h) Diez-Gonzalez,
S.; Nolan, S. P. Coord. Chem. ReV. 2007, 251, 847.
1
0.1021/om800455h CCC: $40.75  2008 American Chemical Society
Publication on Web 11/13/2008

6
412 Organometallics, Vol. 27, No. 24, 2008
Scheme 1. Synthesis of Alkylpalladium N-Heterocyclic Carbene Complexes 2 and 3
Esposito et al.
9
complexes, which proved to be extremely efficient catalysts
1
0
in Suzuki-Miyaura and Buchwald-Hartwig reactions.
Recently, we became interested in the development of new
alkylpalladium N-heterocyclic carbene complexes, not least
because their coordination sphere has the potential to generate,
0
in solution, highly active catalytic Pd species. Furthermore,
these alkylpalladium N-heterocyclic carbene complexes may
well also provide significant insight toward understanding the
1
1
challenging cross-coupling reactions using alkyl halides, in
particular the still undeveloped alkyl-amination reaction. Herein
we report the preparation of two alkylpalladium N-heterocyclic
2
carbene complexes of the type [Pd(alkyl)(µ-Cl)(NHC)] , their
reactions with amines, phosphines, and NHCs, and their ability
to catalyze a series of Buchwald-Hartwig amination reactions
of aryl chloride; parts of this work have been briefly com-
1
2
municated.
Figure 1. Molecular structure of 1. Selected bond distances (Å)
and bond angles (deg): Pd-C(1) 2.155(8), Pd-C(6) 2.457(9),
Pd-Cl 2.332(2), Pd-C(9) 2.070(9); C(9)-Pd-Cl 91.4(3),
M(1)-Pd-Cl 170.8(3), M(1)-Pd-M(2) 83.7(3), C(9)-Pd-M(2)
175.1(3). M(1) and M(2) are the midpoints of the C(1)-C(2)
and C(5)-C(6) bonds.
Discussion
In line with our ongoing efforts toward the isolation of
alkyl halide oxidative addition (OA) and transamination
products of Pd-NHC complexes, further investigations have
been carried out on compounds 1, 2, and 3, the synthesis of
1
2
which was detailed in our previous work and is summarized
crystals of 1 obtained from a concentrated solution of pentane,
kept at -20 °C for 3 days. The molecular structure of 1 is shown
in Figure 1, together with selected bond lengths and angles,
and 1 exhibits the expected square-planar geometry around the
palladium center. The Pd-neopentyl bond length (Pd-C(9))
of 2.070(9) Å in 1 is comparable to that found (2.051 Å) for
in Scheme 1.
The novel [Pd(neopentyl)(Cl)(1,5-COD)], 1, resulting from
2
the stoichiometric alkylation of [Cl Pd(COD)], was prepared
by a procedure analogous to that employed for the synthesis of
1
3
[
Pd(benzyl)(Cl)(1,5-COD)] and used in the preparation of
1
4
complexes 2 and 3, via displacement of the 1,5-COD ligand
with the NHC. X-ray diffraction analysis was conducted on
the benzyl ligand in [Pd(benzyl)(Cl)(1,5-COD)]. Addition of
t
1 equiv of I Bu (1,3-bis-tert-butylimidazol-2-ylidene) to 1
t
afforded exclusively the desired dimeric complex trans-[Pd(I
Bu)(neopentyl)(Cl)]
IPr (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) cis-
Pd(IPr)(neopentyl)(Cl)] (3) was obtained in 80% yield. Unlike
-
(
9) Caddick, S.; Cloke, F. G. N.; Clentsmith, G. K. B.; Hitchcock, P. B.;
McKerrecher, D.; Titcomb, L. R.; Williams, M. R. V. J. Organomet. Chem.
001, 617, 635.
10) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.;
Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101.
11) Valente, C.; Baglione, S.; Candito, D.; O’Brian, C. J.; Organ, M. G.
Chem. Commun. 2008, 735.
12) Esposito, O.; Lewis, A. K. de K.; Hitchcock, P. B.; Caddick, S.;
Cloke, F. G. N. Chem. Commun. 2007, 11, 1157.
13) Gutierrez, E.; Nicasio, M. C.; Paneque, M.; Ruiz, C.; Salazar, V.
J. Organomet. Chem. 1997, 549, 167.
14) Stockland, R. A., Jr.; Anderson, G. K.; Rath, N. P.; Braddock-
Wilking, J.; Ellegood, J. C. Can. J. Chem. 1996, 74, 1990.
2
, 2, and following a similar procedure using
2
[
2
(
complex 2, the neopentyl substituents in 3 do not adopt the trans
geometry but prefer the cis orientation in the solid state, as
confirmed by the X-ray structures of 2 and 3 previously
(
(
1
2
communicated.
(
The reactivity of dimer 2 toward the addition of a further
t
equivalent of I Bu, ITMe (1,3,4,5-tetramethylimidazol-2-ylidene)
(
(
(
15) Marshall, W. J.; Grushin, V. V. Organometallics 2003, 22, 1591.
16) (a) Cavallo, L.; Correa, A.; Costabile, C.; Jacobsen, H. J. Orga-
nomet. Chem. 2005, 690, 5407. (b) Dorta, R.; Stevens, E. D.; Scott, N. M.;
Costabile, C.; Cavallo, L.; Hoff, C. D.; Nolan, S. P. J. Am. Chem. Soc.
(17) (a) Clement, N. D.; Cavell, K. J. Angew. Chem., Int. Ed. 2004, 43,
3845. (b) McGuinness, D. S.; Saendig, N.; Yates, B. F.; Cavell, K. J. J. Am.
Chem. Soc. 2001, 123, 4029. (c) Graham, D. C.; Cavell, K. J.; Yates, B. F.
Dalton Trans. 2005, 1093. (d) Cavell, K. J.; McGuinness, D. S. Coord.
Chem. ReV. 2004, 248, 671.
2
005, 127, 2485.

Alkylpalladium N-Heterocyclic Carbene Complexes
Organometallics, Vol. 27, No. 24, 2008 6413
Scheme 2. Reactivity of Dimers 2 and 3 toward Nucleophiles
Figure 2. Molecular structure of 5. Selected bond distances (Å)
and angles (deg): Pd-(C1) 2.4554(7), Pd-C(12) 2.090(3), Pd-P
2
.3211(8), Pd-Cl 2.4554(7) Å. C(1)-Pd-C(12) 90.92(11),
C(1)-Pd-P 175.49(7), C(12)-Pd-P 92.36(8), C(1)-Pd-Cl
7.04(7), C(12)-Pd-Cl 174.01(8), P-Pd-Cl 89.38(2).
8
presence of an aryl group in 6, as opposed to the alkyl
substituent in 5, promotes the reductive elimination pathway
and formation of the corresponding arylated imidazolium salt,
15
6 6
as reported by Marshall et al. At 50 °C in C D , the neopentyl
or PPh
3
(Scheme 2, reactions A, B, and C) was described in
analogue 5 did not form the expected alkylated imidazolium
salt, instead exhibiting clear signals in the H NMR spectrum
1
2
1
our previous communication. The elimination of neopentyl
chloride in reaction A in Scheme 2 is particularly noteworthy,
as the reductive elimination of an alkyl halide from a palla-
dium(II) moiety has, to the best of our knowledge, not been
previously reported; Hartwig et al. have previously found that
associated with the free carbene and a dimeric (or, less likely,
a monomeric) phosphine complex still bearing a neopentyl
group. The unusual reductive elimination of neopentyl chloride
from 4 under the same conditions is therefore most probably
the result of the presence of the ITMe ligand, both bulkier and
Pd[P(o-tolyl)
3
](aryl)halide dimers reductively eliminate aryl
t
17
halides in the presence of the strongly donating P( Bu)
3
ligand.
3
a better σ donor than the PPh ligand in 5.
In general, the reductive elimination of alkyl halides is an
uncommon process since the oxidative addition (inverse reac-
tion) is thermodynamically favored. However, in the particular
case of the oxidative addition of neopentyl chloride to 2, the
reaction is thermodynamically impeded even at high tempera-
The reluctance of 4 and 5 to eliminate the neopentyl
alkylimidazolium salt (Scheme 3) raises an interesting point for
discussion. It is known that the reductive elimination of
alkylimidazolium salt and precipitation of palladium(0) metal
represents one of the potentially serious drawbacks of the
application of NHC ligands in catalytic reactions involving alkyl
halides as substrates. This deactivation process has been studied
by Cavell and co-workers and reported in a series of publica-
12
tures, as previously reported; therefore, the reductive elimina-
tion in the presence of the bulky, strongly electron donating
t
I Bu may be, to some extent, facilitated.
Further to the work described in our earlier communication,
12
17
tions, in which the authors highlighted the fact that cationic
the molecular structure of the phosphine complex 5 has been
determined and is shown in Figure 2, together with selected
bond lengths and angles. The mixed-ligand complex 5 exhibits
a square-planar geometry around the palladium center, where
the carbene ligand lies trans to the phosphine, on a plane
perpendicular to the mean plane defined by Pd-C12-C1-Cl.
palladium(II) species undergo alkyl-carbene reductive elimina-
tion at a much higher rate and at lower temperature than the
corresponding neutral species. In fact, Pd(ITMe) (Me)Cl shows
2
1
8
slight decomposition only at 120 °C, in line with the lack of
alkyl-carbene reductive elimination in 4 and 5. Similar behavior
t
was displayed by the Pd(I Bu) (tolyl)chloride complex previ-
2
Comparison with the analogous Pd(PPh
complex 6 (Scheme 3), isolated by Marshall and Grushin,
reveals shorter palladium-phosphine (2.307(1) Å), Pd-Cl
2.404(1) Å), and palladium-carbene bond distances (2.057(2)
3
)(IPr)(aryl)chloride
ously reported from this laboratory: at high temperature (90 °C)
1
5
t
1
free I Bu was observed by H NMR spectroscopy, but no
arylimidazolium salt deriving from reductive elimination was
1
9
(
detected.
Å) in 6. The difference in bond lengths is probably due to the
inferior σ-donating ability of the aryl group in 6, compared to
the neopentyl group of 5, which makes the palladium center in
Further studies were also conducted on the related compound
3
3
(
to allow comparison between the two dimeric species 2 and
t
. Indeed, treatment of dimer 3 with IPr, I Bu, and ITMe
6
less electron rich. This increases the σ-bonding character of
reactions D, E, and F, Scheme 2) highlighted the ability of IPr
the palladium-phosphine bond in the latter, making this bond
shorter than in 5. In addition, the weaker trans effect induced
by the aryl group may be responsible for the observed shorter
t
(
and, to a lesser extent, I Bu) to promote reductive elimination
of neopentyl chloride (reactions D and E, Scheme 2). Addition
of 5 equiv of IPr to 3 (reaction D, Scheme 2) led to quantitative
formation of an intermediate species in 30 min, which was
t
palladium-chloride in 6, while the increased bulk of I Bu
compared to IPr (as measured by their relative %VBur (buried
believed to be (IPr)
2
Pd(neopentyl)chloride on the basis of the
1
6
volume) in the DFT studies by Cavallo et al. ), along with the
presence of a sterically demanding neopentyl group, makes the
palladium-carbene bond longer in 5 than in 6.
1
H NMR spectrum. Subsequent full conversion to the known
(
18) McGuinness, D. S.; Green, M. J.; Cavell, K. J.; Skelton, B. W.;
White, A. H. J. Organomet. Chem. 1998, 565, 165.
19) Lewis, A. K. de K.; Caddick, S.; Cloke, F. G. N.; Billingham, N. C.;
Hitchcock, P. B.; Leonard, J. J. Am. Chem. Soc. 2003, 125, 10066.
Different decomposition pathways were observed for the
heteroleptic palladium complexes 4 and 5 and are shown in
(
1
5
Scheme 3, with that of 6 included for comparison. The

6
414 Organometallics, Vol. 27, No. 24, 2008
Scheme 3. Stability Evaluation of Complexes 4 and 5
Esposito et al.
Scheme 4. Preparation of Transamination Products 7 and 8
Scheme 5. Catalytic Cycle for Alkyl-Amine Cross-Coupling
Reactions Mediated by Palladium Catalysts
2
0
palladium(0) complex, Pd(IPr)
2
,
and neopentyl chloride oc-
t
curred in 24 h. In contrast, reaction of 3 with I Bu revealed a
more stable (IPr)Pd(I Bu)(neopentyl)chloride species, which
reductively eliminates neopentyl chloride to form (IPr)Pd(I Bu)
in only 3:1 ratio ((IPr)Pd(I Bu)(neopentyl)chloride:(IPr)Pd(I -
Bu)), as shown in reaction E of Scheme 2. Finally, the reaction
of 3 with 5 equiv of ITMe (reaction F, Scheme 2) resulted in
the displacement of the bulkier IPr to afford, in a 1:1 ratio
t
t
21
t
t
(
Pd(ITMe)
2
(neopentyl)chloride:(IPr)Pd(ITMe)(neopentyl)chlo-
(neopentyl)chloride
ride), the less sterically hindered Pd(ITMe)
2
Scheme 6. Surprising Stability of Transamination Product 7
complex, which was found to be stable toward reductive
elimination of neopentyl chloride at RT.
Dimer 2 is also readily cleaved by secondary (morpholine)
t
and primary (hexylamine) amines, affording the [Pd(I Bu)-
(
amine)(neopentyl)chloride] complexes, 7 and 8 (Scheme 4),
respectively, which represent the transamination intermediates
in a putative catalytic cycle for a palladium-catalyzed alkyl-
2
2
amination reaction (Scheme 5). The structure of 7 has been
determined and previously communicated.
1
2
or any alkyl-amine cross-coupling product. A likely explanation
7
and 8 were found to be thermally stable at 50 °C; however
a
for this behavior is that the pK of the amine -NH is not
when 7 was heated at 80 °C (Scheme 6), dissociation of free
amine and formation of the (presumably dimeric) C-H activated
product 9 and neopentane were observed by NMR spectroscopy.
significantly lowered to allow deprotonation, due to the increased
electron density on Pd arising from the donating effects of the
t
alkyl substituent and the I Bu ligand. These results indicate that
Complex 2 undergoes a similar C-H activation process, also
alkyl-amination reactions may be complicated not only by
ꢀ-hydride elimination but also by the formation of surprisingly
stable transamination products.
t
observed in the reaction of Pd(I Bu)
2
and neopentyl bromide at
1
2
7
5 °C, as previously reported.
Despite the cis-geometry between the neopentyl and mor-
Despite the stability shown by alkylpalladium complexes 2
and 3, they were evaluated as potential catalysts for the
Buchwald-Hartwig amination reactions. Complexes 2 and 3
were therefore tested in a series of preliminary reactions using
different aryl chlorides, and indeed both catalysts afforded the
desired cross-coupling products in high conversion even at room
temperature (Table 1, entries 1-6). On the basis of these
promising reactions, the catalytic system was optimized using
chloroanisole and morpholine (Scheme 7). Among the condi-
tions tested, dimer 3 proved to be the most efficient catalyst,
allowing the cross-coupling reaction to occur at room temper-
1
2
pholine groups, attempted deprotonation of the coordinated
amines in either 7 or 8 by a variety of bases typically used in
t
aryl-amination cross-coupling reactions (KO Bu, NaOCEt
3
,
LHMDS, and NaH) failed to yield the palladium amide complex
(
20) Arentsen, K.; Caddick, S.; Cloke, F. G. N.; Herring, A. P.;
Hitchcock, P. B. Tetrahedron Lett. 2004, 45, 3511.
21) Titcomb, L. R.; Caddick, S.; Cloke, F. G. N.; Wilson, D. J.;
McKerrecher, D. Chem. Commun. 2001, 1388.
22) Green, J. C.; Herbert, B. J.; Lonsdale, R. J. J. Organomet. Chem.
005, 690, 6054.
(
(
2

Alkylpalladium N-Heterocyclic Carbene Complexes
Organometallics, Vol. 27, No. 24, 2008 6415
1
Scheme 7. Buchwald-Hartwig Amination Reaction Using
red. Analysis of the H NMR spectra identified a set of peaks
Complexes 2 and 3
3
belonging to a OCEt moiety, along with another set of peaks
t
assigned to a palladium I Bu-ligated complex, whose integration
gave a 1:1 ratio (OCEt :I Bu). However, the absence of the
3
t
distinctive peaks belonging to 3-ethyl(neopentyloxy)pentane, and
the presence of peaks assignable to 2,2,5,5-tetramethylhexane,
leads us to suggest the alternative activation mechanism
presented in Scheme 11.
Table 1
Cleavage of the Pd-neopentyl bonds in the intermediate
catalyst
(mol %) solvent
temperature time yield
species 20 reductively elimimates 2,2,5,5-tetramethylhexane
(
entry
R
base
(°C)
(min) (%)
1
observed in the H NMR study, Vide supra) and affords the
1
2
3
4
5
6
7
8
9
COMe
3 (4.5) DME
COOMe 3 (4.5) toluene NaOCEt
NaOCEt
3
3
3
RT
50
80
80
90
90
90
80
80
RT
RT
1200
60
20 100
40 100
90
90
90
60
60
60
60
85
90
alkoxy-bridged dimer 21. Palladium(I) complexes of this type,
but with phosphine ligands and bromide or iodide bridge, have
been found to be efficient precatalysts in aryl-amination reactions
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
3 (4.5) benzene NaOCEt
2 (4.5) benzene LHMDS
2 (2.0) toluene LHMDS
34
27
37
97
99
98
84
23
t
by Hartwig; hence, there is a possibility that analogous species
2 (2.0) toluene KO Bu
2 (2.0) toluene NaOCEt
3 (2.0) toluene LHMDS
3 (2.0) toluene LHMDS
3 (2.0) THF
3 (1.0) THF
3
are involved in the activation of 2. Ozerov et al. proposed a
homolytic cleavage of the Pd-(n-C
8
H17) bond in 22 to generate
the Pd-Pd bond in the resulting dimeric species, 23 (Scheme
10
1
LHMDS
LHMDS
2
4
1
2); the latter theory was supported by the detection of the
1
corresponding alkyl-alkyl product (n-C16H34) via GC-MS
Scheme 8. Scope of Optimized Buchwald-Hartwig
analysis of the reaction solution.
Amination Reactions Using Complex 3
Similarly, formation and subsequent dimerization of the
neopentyl radical via homolysis of the Pd-neopentyl bond in
2
0 (Scheme 11) would yield 2,2,5,5-tetramethylhexane, which
1
was indeed detected in the reaction solution by H NMR.
In conclusion, several alkylpalladium N-heterocyclic carbene
complexes have been synthesized. The chloride-bridged dimers
ature in 1 h (Table 1, entry 10). Despite the efficiency displayed
by the different bases and solvents tested, the system LHMDS/
THF was chosen to continue this study, as it allows a more
practical synthetic protocol with no requirement to use a
glovebox. In fact, a reaction was carried out outside the
glovebox, using a solution of LHMDS in THF and, after 1 h at
room temperature, the product was isolated in 84% with a
catalyst loading of only 1 mol % (Table 1, entry 11).
Once optimized, the catalytic system was evaluated using
several aryl halides and different amines (Scheme 8). Both
bromo and chloro aryl compounds are suitable substrates in this
protocol, affording the expected arylamines in high yields (Table
2
and 3 can be readily cleaved by a variety of nucleophiles,
including primary and secondary amines, which results in the
isolation of surprisingly stable transamination products. These
results highlight the fact that alkyl-amine cross-coupling reac-
tions may be complicated not only by ꢀ-hydride elimination
but also by the formation of stable transamination product.
Complexes 2 and, in particular, 3 were also shown to be
effective precatalysts for a series of Buchwald-Hartwig ami-
nation reactions of aryl chlorides. Based on H NMR studies, a
potential mechanism is proposed for the activation process of
the precatalyst 2 in the latter.
1
2
). However, in several examples it was observed that steric
effects can result in yield erosion (Table 2, entry 9). Regarding
the range of amines used, the cyclic secondary amines displayed
unsurpassed reactivity when compared with acyclic amines,
which afforded a satisfying yield of cross-coupling products only
at 40 °C (Table 2, entries 10 and 11).
Experimental Section
All glassware was oven-dried prior to use. Air-sensitive com-
pounds were manipulated using standard Schlenk line techniques
or in an inert atmosphere provided by an MBraun glovebox.
Solvents were purified by predrying over sodium wire (except for
chloroform), followed by heating at reflux over a suitable drying
agent in a solvent still under an atmosphere of dinitrogen. The
collected solvent was degassed and stored in an ampule under argon.
NMR solvents were purified by refluxing over a suitable drying
agent, then vacuum transferred to an ampule and stored under
dinitrogen in a glovebox.
Intriguingly, di-n-butylamine afforded a rather disappointing
4
2% yield of product under the standard protocol conditions
(
Table 2, entry 12), although by replacing the LHMDS base
t
for KO Bu, a much more efficient cross-coupling reaction was
achieved, and 98% of arylated amine was isolated after 1 h at
4
0 °C (Scheme 9).
A possible explanation for this observation may reside in the
25
neopentyl lithium, ItBu, and IPr2a were syn-
26
Pd(COD)Cl
2
,
steric constraints imposed by the amine volume, thus making
deprotonation more difficult; another possibility is that the base
may be ligated to the catalytically active species. The latter
hypothesis suggests two possible mechanisms for the activation
process of the precatalyst 2. In the first, the activation of the
precatalysts, 2 and 3, proceeds through the mechanism depicted
in Scheme 10: the three-coordinate palladium(alkoxide) inter-
mediate reductively eliminates 3-ethyl(neopentyloxy)pentane,
concurrently generating in solution the singly ligated, 12-electron
thesized according to literature procedures. Morpholine and hexy-
lamine (used in the reactions of Scheme 4) were purchased from
Aldrich and dried over activated 3 Å molecular sieves, degassed,
and vacuum transferred into ampules equipped with greaseless
stopcocks. The aryl halides and amines used in the Buchwald-
Hartwig amination reactions were distilled prior to use.
Synthesis of [Pd(1,5-COD)(neopentyl)(Cl)], 1. Pd(COD)Cl2
2
(0.300 g; 1.05 mmol) was suspended in 20 mL of Et O and
0
t
Pd -I Bu active catalyst species.
NMR experiments were run to acquire evidence to support
the mechanism proposed in Scheme 10. The dimer 2 was reacted
(
23) (a) Hoper, M. W.; Utsunomiya, M.; Hartwig, J. F. J. Org. Chem.
2003, 68, 2861. (b) Hartwig, J. F. Synlett 2006, 9, 1283.
24) Fafard, C. M.; Adhikari, D.; Foxman, B. M.; Mindiola, D. J.;
Ozerov, O. V. J. Am. Chem. Soc. 2007, 129, 10318.
25) Itoh, K.; Fukui, M.; Ishii, Y. J. Organomet. Chem. 1977, 129, 259.
(26) Beringer, F. M.; Nathan, R. A. J. Org. Chem. 1970, 35, 2095.
(
with an excess of NaOCEt
3 6
in d -benezene at RT, and instantly
(
the color of the solution changed from bright green to deep

6
416 Organometallics, Vol. 27, No. 24, 2008
Esposito et al.
Table 2. Optimized Buchwald-Hartwig Amination Reactions Using Complex 3
t
Scheme 9. Influence of Base in the Buchwald-Hartwig
Synthesis of trans-[(I Bu)Pd(neopentyl)(Cl)]
2
, 2. To a solution
Amination Reaction.
of [Pd(1,5-COD)(neopentyl)(Cl)], 1 (0.175 g; 0.5 mmol), in 15
mL of THF cooled to 0 °C was added a solution of I Bu (0.090
t
g, 1 equiv) in 5 mL of THF via cannula, and the reaction stirred
t
+
-
at 0 °C for 30 min. A very fine gray solid (I BuH Cl )
precipitated, which was allowed to settle, and the reaction
mixture was filtered by cannula to afford a dark orange solution.
The solvent was removed under reduced pressure, and the solid
cooled to -75 °C in a acetone/IMS/dry ice bath. A solution of
neopentyl lithium (0.090 g; 1 equiv) in 5 mL of Et
2
O was added
residue washed with pentane (2 × 10 mL) and Et
mL) and dried under vacuum, yielding 2 as a white powder. A
further batch of product was obtained by concentrating the Et
2
O (1 × 15
to the cold Pd(COD)Cl
every 5 min until fully transferred in about 1 /
2
suspension via cannula in small aliquots
1
2
h. The dark
O
reaction mixture was stirred at -75 °C for 1 h and allowed to
gradually warm to room temperature and stirred for further 3 h.
The reaction mixture was filtered through flamed-dried Celite,
and the orange-yellow filtrate dried under vacuum to afford 1
in 48% yield (0.175 g; 0.5 mmol). The product was recrystallized
2
and pentane washings until precipitation was observed; the
mixture was left at room temperature for 12 h to achieve
complete precipitation of 2, which was isolated by decantation
and dried under vacuum. 2 was obtained in overall 75% yield
(
0.375 mmol; 0.147 g). Crystals suitable for X-ray diffraction
were grown from Et O at -20 °C.
1H NMR (d
-benzene): δ 6.51 (s; 2H); 1.99 (s; 18H); 1.86 (s;
2H); 1.37 (s; 9H). C{ H} NMR (d
(Pd-C(carbene)); 118.7 (NCHdCHN); 59.2 (C(CH
(C(CH
from pentane at -20 °C.
1
2
H NMR (d
1
-chloroform): δ 5.89 (q; 2H; CH
CHdCHCH , J(H-H) 12 Hz); 2.58 (m;
H); 2.43 (m; 4H); 2.22 (s; 2H); 1.12 (s; 9H). C{ H} NMR (d
), 33.4
2 2
CHdCHCH , J(H-H)
1
4
5 Hz); 5.15 (q; 2H; CH
2
2
6
1
3
1
13
1
-benzene): δ 170.4
6
-
6
benzene): δ 125.1 (CHdCH), 99.9 (CHdCH), 35.8 (C(CH
3
)
3
3
)(t-Butyl)); 34.5
+
(
CH
Anal. Calcd for C13
H: 7.07. Crystal data: see Supporting Information.
3
), 30.6 (CH
2
), 27.0 (CH
2
-CH
2
). MS (ES): m/z 285 (M - Cl).
3
)(neopentyl)); 32.8 (CH3(neopentyl)); 32.3 (CH3(t-Butyl)); 31.0
+
t
H23ClPd: C: 46.61, H: 7.17. Found: C: 46.50,
(CH2(neopentyl)). MS (EI): m/z 502 (M - Cl, CH
2
(CCH
3
)
3
and I Bu),
465 (M+ - 2Cl, CH
(CCH
)
3
and I Bu), 322 (M - 2Cl,
t
+
2
3

Alkylpalladium N-Heterocyclic Carbene Complexes
Organometallics, Vol. 27, No. 24, 2008 6417
Scheme 10. Possible Mechanism Proposed for the Activation Process of the Precatalyst 2
Scheme 11. Proposed Mechanism for the Activation Process of the Precatalyst 2.
t
Scheme 12. Proposed Homolytic Cleavage of the
Pd-(n-C 17) Bond in 12
Synthesis of [Pd(I Bu)(ITMe)(neopentyl)(Cl)], 4. To a mixture
8
H
of 2 (0.050 g; 0.06 mmol) and ITMe (4 equiv; 0.030 g) was added
C D (0.6 mL). The H NMR, recorded few minute after the starting
6 6
1
of the reaction, showed that only the desired product was present
in solution. The solution was transferred to a small Schlenck and
the solvent removed under vacuum. The resultant white powder
was washed with pentane (3 × 1 mL) and dried under vacuum to
leave analytically pure 4 in 80% yield.
1
H NMR (d -benzene): δ 6.73 (s; 2H); 3.82 (s; 6H); 2.07 (s;
6
13 1
1
8H); 1.76 (s; 6H); 0.96 (s; 9H). C{ H} NMR (d
6
-benzene): δ
Table 3
drying agent
184.7 (Pd-C(carbene)); 181.0 (Pd-C(carbene)); 124.0 (CdC); 118.1
(
CH
2
dCH
2
); 58.8 (C(CH
3
)
(t-Butyl)); 35.4 (C(CH
3
)3(neopentyl)); 34.4
solvent
THF
toluene
pentane
diethyl ether
chloroform
stored over
(
8
CH2(neopentyl)); 33.6 (CH3(t-Butyl)); 32.9 (CH3(neopentyl)), 26.4 (N-CH
.8 (CH CdCCH ). Anal. Calcd for C23H N
3 3 41 4
3
);
Cl: C: 53.40, H: 7.93,
N:10.83. Found: C; 53.56, H: 8.09, N: 10.77.
potassium
sodium
potassium
sodium/potassium alloy
calcium hydride
4 Å molecular sieves
potassium mirror
potassium mirror
potassium mirror
4 Å molecular sieves
t
3
Synthesis of [Pd(I Bu)(PPh )(neopentyl)(Cl)], 5. THF (15 mL)
was added to a mixture of 2 (0.120 g; 0.15 mmol) and triph-
enylphosphine (4 equiv; 0.160 g) and the yellow reaction solution
stirred at room temperature for 2 h, resulting in a color change
from yellow to orange. The solvent was removed under vacuum,
and the orange residue washed with pentane (3 × 5 mL) and dried
under vacuum, to leave analytically pure 5 in 75% yield (0.150 g;
t
2
CH
2
(CCH
3
)
3
and I Bu). Anal. Calcd for C16
H
31
N
2
ClPd: C: 48.87,
H: 7.89, N: 7.12. Found: C: 48.73, H: 7.78, N: 7.07.
Synthesis of cis-[ Pd(IPr)(neopentyl)(Cl)] , 3. The synthesis
2
of 3 was conducted by following the same experimental
procedure as that for 2, with the exception that, following the
addition of IPr (0.145 g, 1 equiv), no precipitate was observed.
The reaction solution was stirred at RT and the solvent removed
under vacuum, affording a yellow oil. Pentane (15 mL) was
added and few seconds later a white solid precipitated. The solid
was isolated by decanting the solution via cannula, washing the
precipitate with cold pentane (3 × 5 mL), and drying under
vacuum. The product was obtained as a white-gray powder in
0
.23 mmol). Crystals suitable for X-ray analysis were grown from
toluene at -20 °C.
1
H NMR (d
6
-benzene): δ 8.00-7.94 (m; 5H); 7.16-7.03 (m:
31 1
10H); 6.67 (s; 2H); 1.96 (s; 18H); 1.52 (s; 2H); 0.73 (s; 9H). P{ H}
NMR: δ 27.37 ppm. C{ H} NMR (d -benzene): δ 176.0
(Pd-C(carbene)); 135.9 (CH(aryl)), 135.7 (CH(aryl)), 134.0 (CH(aryl)),
133.5 (CH(aryl)), 129.7 (CH(aryl)), 128.7 (CH(aryl)), 128.7 (C(aryl)), 128.5
1
3
1
6
8
0% yield. Crystals suitable for X-ray diffraction were grown
from Et O at -20 °C.
H NMR (d
d; 4H; J(H-H) ) 16 Hz); 7.13 (s; 2H); 2.66 (septet; 4H; J(H-H)
(C(aryl)), 119.6 (HCdCH); 59.9 (C(CH
3
)(t-Butyl)); 34.7 (CH3(neopentyl)),
33.1 (CH2(neopentyl)); 32.8 (CH3(t-Butyl)); 32.5 (CH3(neopentyl)). MS (ES):
2
1
+
+
1
-chloroform): δ 7.52 (t; 2H; J(H-H) ) 8 Hz); 7.36
3
m/z 655 (M ), 399 (M - PPh ). Crystal data: see Supporting
(
1
)
Information.
t
2 Hz); 2.29 (s; 2H); 1.44 (d; 12H; J(H-H) ) 8 Hz); 1.17 (d; 12H;
Synthesis of [Pd(I Bu)(neopentyl)(amine)chloride] Complexes,
7 and 8. 2 (0.08 g; 0.18 mmol) was dissolved in toluene (10 mL).
The amine (morpholine 3.0 equiv, 27.0 µL or hexylamine 3.0 equiv,
38.0 µL) was introduced via syringe, and the reaction solution stirred
at room temperature for 1 h. After that time the solvent and the
excess amine were removed under reduced pressure. The residue
was washed with pentane and the product dried under vacuum to
afford, respectively, 84% (0.145 g) and 75% (0.132 g) yields of
1
3
1
J
1
1
(H-H) ) 8 Hz); 0.73 (s; 9H). C{ H} NMR (d
1
-chloroform): δ
87.8 (Pd-C(carbene)); 146.5 (C(aryl)); 134.6 (C(aryl)); 130.7 (CH(aryl));
25.6 (CH(aryl)); 124.6 (NCHdCHN); 31.8 (CH(CH
); 29.0 (CH(CH ); 26.6 (CH(CH
3.6 (C(CH) ). MS (ES): 996 (M - aryl and CH(CH
aryl, CH(CH
ClPd: C: 64.12, H: 7.84, N: 4.67. Found: C: 64.25, H:
3 2
) ); 31.2
(C(CH
)
3 3
3
)
2
3 2
) ); 26.1 (CH2(neopentyl));
+
), 960 (M+
2
-
3
3 2
)
+
3 2
) and Cl), 600 (M (monomer)). Anal. Calcd for
32 47 2
C H N
7
.74, N: 4.51.
the palladium-amine adducts 7 and 8.
1
General Procedure for the Reactions Shown in Scheme 2. 2
7. H NMR (d
1
-chloroform): δ 7.12 (s; 2H); 3.83 (br d; 2H;
or 3 (0.03 mmol) was weighed in a glovebox and placed in a
Young’s tap NMR tube. Four equivalents of NHC or PPh , as
indicated in Scheme 3, was added, followed by d -benzene (0.6
mL). The reactions were monitored by H NMR on a regular basis.
J
(H-H)) 12 Hz); 3.74 (br s; 1H); 3.46 (br q; 4H; J(H-H) ) 16 Hz);
3
2.91 (br d; 2H; J(H-H) ) 12 Hz); 2.01 (s; 18H); 1.00 (s; 2H); 0.79
(s; 9H). C{ H} NMR (d
(NCHdCHN); 77.2 (CH2(morpholine)); 68.4 (C(CH )(t-Butyl)); 59.0
1
3
1
6
1
-chloroform): δ 167.5 (C(carbene)); 119.4
1
3

6
418 Organometallics, Vol. 27, No. 24, 2008
Esposito et al.
(
(
C(CH
3
)
3(neopentyl)); 48.1 (CH2(morpholine)); 34.5 (CH2(neopentyl)); 32.4
aryl halide (0.351 mmol) were than sequentially added through the
septum. The reaction mixture was then stirred at room temperature
unless otherwise indicated. When the reaction reached completion
(the disappearance of aryl halide was monitored by TLC), the
volatiles were evaporated and the product was purified by flash
chromatography on silica gel.
CH3(t-Butyl)); 32.1 (CH3(neopentyl)). Anal. Calcd for C20
40 3
H N OClPd:
C: 50.0, H: 8.33, N: 8.75. Found: C: 49.90, H: 8.24; N: 8.86.
1
8
. H NMR (d
1 2
-chloroform): δ 7.14 (s; 2H); 2.30 (br t; 2H; NH ;
J
(H-H) ) 12 Hz); 1.98 (s; 18H); 1.46 (br q; 2H; J(H-H) ) 8 Hz);
1
3
1
1
.32 (s; 2H); 1.25 (m; 6H); 0.87 (m; 3H); 0.85 (s; 9H). C{ H}
-chloroform): δ 171.3 (Pd-C(carbene)); 119.4 (NCHdCHN);
9.3 (C(CH (t-Butyl)); 44.3 (C(CH
CH3(neopentyl)); 32.4 (CH3(t-Butyl)); 31.9 (CH
NMR (d
5
(
1
3
)
3
)3(neopentyl)); 34.8 (CH2(neopentyl)); 33.3
Acknowledgment. We thank EPSRC and Funda c¸ a˜ o para
a Ci eˆ ncia e Tecnologia (POCI 2010) and FEDER (SFRH/
BPD/18624/2004, PTDC/QUI/66695/2006) for financial
support.
2
); 30.9 (CH
). MS (ES): m/z 397 (M+ - hexylamine). Anal. Calcd
PdCl: C: 53.45, H: 8.90, N: 8.50. Found: C: 53.34, H:
.10, N: 8.66.
General Procedure for the Buchwald-Hartwig Cross-Cou-
2
); 23.0 (CH
2
);
1
4.4 (CH
3
44 3
for C22H N
9
Supporting Information Available: Details of structure deter-
mination for 1 and 5 and NMR data for Buchwald-Hartwig
amination products in Table 2. This material is available free of
charge via the Internet at http://pubs.acs.org.
plings (Scheme 8, Table 2). In a glovebox, to a round-bottom flask
equipped with a magnetic stir bar was added the palladium
precatalyst (2 mol %) and the base (0.456 mmol, 1.3 equiv), after
which the flask was closed with a septum and taken out off the
glovebox. Dry THF (0.5 mL), amine (0.421 mmol, 1.2 equiv), and
OM800455H