The first example of simple oxidative addition of an aryl chloride to a discrete palladium N-heterocyclic carbene amination precatalyst

Article abstract of DOI:10.1021/om020552l

The oxidative addition of an aryl chloride to a discrete palladium n-heteocyclic carbene amination precatalyst, was discussed. It was found that the oxidative addition of 4-chlorotoluene to Pd(0) resulted in the formation of not a four-coordinate complex but rather the arylated imidazolium salt. The identity of imidazolium salt was confirmed by x-ray crystallography.

Full text of DOI:10.1021/om020552l

4318
Organometallics 2002, 21, 4318-4319
Th e F ir st Exa m p le of Sim p le Oxid a tive Ad d ition of a n
Ar yl Ch lor id e to a Discr ete P a lla d iu m N-Heter ocyclic
Ca r ben e Am in a tion P r eca ta lyst
Stephen Caddick,*,† F. Geoffrey N. Cloke,*,† Peter B. Hitchcock,† J ohn Leonard,‡
Alexandra K. de K. Lewis,† Darren McKerrecher,‡ and Lisa R. Titcomb†
The Chemistry Laboratory, CPES, University of Sussex, Falmer, Brighton BN1 9QJ , U.K., and
AstraZeneca Pharmaceuticals, Mereside, Macclesfield, Cheshire SK10 4TF, U.K.
Received J uly 10, 2002
Summary: Reaction of 4-chlorotoluene with the amina-
tion precatalyst [Pd(cyclo-C{N(2,6-iPr2-C6H3)CH2}2)2]
leads to reductive elimination of the arylated imidazo-
lium salt, whereas the analogous reaction with [Pd(cyclo-
C{NtBuCH}2)2] affords the structurally characterized
oxidative-addition product trans-[Pd(cyclo-C{NtBuCH}2)2-
(4-Me-C6H4)Cl].
It has become apparent that the ligating properties
of N-heterocyclic carbenes (NHCs) exhibit considerable
similarities to those of phosphines and offer an effective
ligand environment for transition-metal-mediated or-
ganic transformations. A number of reports have suc-
cessfully demonstrated that a range of such carbene
ligands can be incorporated into Pd(II) complexes and
offer an alternative class of precatalysts, with improved
stability (and potential turnover capacity), for C-C
coupling reactions.1 In particular, recent work by Nolan2
and Hartwig3 has demonstrated the use of imidazo-
linium and imidazolium salts for the in situ generation
of catalytically active species from Pd2dba3 for amina-
tion couplings using aryl chlorides. Both reports suggest
formation of a Pd(0) carbene complex via deprotonation
of the imidazolium salt to generate carbene followed by
subsequent displacement of dba ligands. Hartwig has
suggested a mechanism for amination catalyzed by
2-coordinate Pd(0) phosphine species (generated in situ
from Pd2(dba)3 and e.g. PtBu3), in which the key step is
dissociation of phosphine from PdL2 to generate a PdL
fragment, which then undergoes turnover-limiting oxi-
dative addition (OA) of aryl halide (Figure 1).3,4
F igu r e 1. Proposed mechanism for amination.
F igu r e 2. Isolated amination precatalysts.
we have been exploring the ability of the isolated
2-coordinate NHC complexes of Pd(0) 1 and 2 (Figure
2) to effect amination of aryl chlorides.5 1, in particular,
is highly effective for a range of amine couplings with
4-chlorotoluene.
In this paper we report studies on the OA reaction of
an aryl chloride with 1 and 2,6 which, in the case of 2,
results in isolation of the first example of a stable OA
product from a well-defined NHC amination precatalyst.
Attempted OA of 4-chlorotoluene to 1 resulted in the
formation of not a four-coordinate complex but rather
the arylated imidazolium salt 3 (see Scheme 1), together
with the deposition of palladium metal.
The identity of 3 has been confirmed by X-ray crystal-
lography, but the structure will not be reported here.
The formation of 3 parallels the report by Cavell on
reductive elimination from trans-[Pd(carbene)2(Ph)I],7
in which elimination of such an imidazolium salt is
proposed as an important decomposition pathway in
palladium-carbene-mediated couplings.8
This mechanism is also very likely to be applicable
to the case where L is an NHC ligand. In contrast to
the in situ approach to presumably generate Pd(NHC)2,
* To whom correspondence should be addressed. E-mail: F.G.N.C.,
f.g.cloke@sussex.ac.uk; S.C., s.caddick@sussex.ac.uk.
† University of Sussex.
‡ AstraZeneca Pharmaceuticals.
(1) Herrmann, W. A.; Elison, M.; Fischer, J .; Ko¨cher, C.; Artus, G.
R. J . Angew. Chem., Int. Ed. Engl. 1995, 34, 2371. Herrmann, W. A.;
Ko¨cher, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2162. Herrmann,
W. A.; Reisinger, C. P.; Spiegler, M. J . Organomet. Chem. 1998, 557,
93. Herrmann, W. A.; Bo¨hm, V. P. W.; Reisinger, C. P. J . Organomet.
Chem. 1999, 576, 23. Wescamp, T.; Bo¨hm, V. P. W.; Herrmann, W. A.
J . Organomet. Chem. 1999, 585, 348. McGuiness, D. S.; Green, M. J .;
Cavell, K. J .; Skelton, B. W.; White, A. H. J . Organomet. Chem. 1998,
565, 165. McGuiness, D. S.; Cavell, K. J .; Skelton, B. W.; White, A. H.
Organometallics 1999, 18, 1596.
(5) Titcomb, L. R.; Caddick, S.; Cloke, F. G. N.; Wilson, D. J . F.;
McKerrecher, D. Chem. Commun. 2001, 1388. See also: Muci, A. R.;
Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
(6) DFT calculations on OA of an aryl bromide to Pd(NHC)2 have
been reported: Albert, K.; Gisdakis, P.; Ro¨sch, N. Organometallics
1998, 17, 1608.
(2) Huang, J .; Grasa, G.; Nolan, S. P. Org. Lett. 1999, 1, 1307.
(3) Stauffer, S. R.; Lee, S. W.; Stambuli, J . P.; Hauck, S. I.; Hartwig,
J . F. Org. Lett. 2000, 2, 1423.
(4) Louie, J .; Paul, F.; Hartwig, J . F. Organometallics 1996, 15, 2794.
Hartwig, J . F. Angew. Chem., Int. Ed. 1998, 37, 2047.
(7) McGuiness, D. S.; Cavell, K. J .; Skelton, B. W.; White, A. H.
Organometallics 1999, 18, 1596.
10.1021/om020552l CCC: $22.00 © 2002 American Chemical Society
Publication on Web 09/11/2002

Communications
Sch em e 1. Rea ction s of 1 a n d 2 w ith
Organometallics, Vol. 21, No. 21, 2002 4319
4-Ch lor otolu en e
F igu r e 3. Molecular structure of 4 (thermal ellipsoids at
the 50% probability level). Selected bond distances (Å) and
angles (deg): Pd-C1 ) 2.094(4), Pd-C12 ) 2.091(4), Pd-
C23 ) 2.065(4), Pd-Cl ) 2.445(1), C1-N1 ) 1.376(5), C1-
N2 ) 1.376(5), N1-C2 ) 1.376(5), N2-C3 ) 1.379(5), C2-
C3 ) 1.335(6), C12-N3 ) 1.378(5), C12-N4 ) 1.373(5),
N3-C13 ) 1.383(5), N4-C14 ) 1.388(5), C13-C14 )
1.323(6); Cl-Pd-C1 ) 88.30(11), C1-Pd-C23 ) 91.63(15),
C23-Pd-C12 ) 90.01(15), C12-Pd-Cl ) 90.05(10).
In contrast, the reaction between 2 and 4-chlorotolu-
ene proceeded slowly at room temperature, to comple-
tion after 1 h at 90 °C, to afford the OA product 4
essentially quantitatively by NMR (see Scheme 1).
Reaction of 4 with morpholine and potassium tert-
butoxide in dioxane at 100 °C afforded the arylated
amine in >95% yield, a result identical with that
previously obtained for the same coupling using 2.5
Single crystals of 4 suitable for X-ray diffraction were
grown from benzene at room temperature, and the
molecular structure together with selected bond dis-
tances and angles is shown in Figure 3.9
The geometry around palladium in 4 is virtually
perfectly square planar with the carbene ligands mutu-
ally trans. Despite the smaller radius of Pd(II) relative
to Pd(0), the palladium-carbene bond lengths in 4
(identical within esds at 2.094(4) and 2.091(4) Å) are
slightly longer than that found in the parent Pd(0)
complex 2 (2.041(6) Å),10 a reflection of the steric
congestion in the 4-coordinate Pd(II) complex. Similarly,
in 2 the carbene rings are mutually orthogonal,10
whereas in 4 they are coplanar in order to sterically
accommodate the additional two ligands, with the Cl-
Pd-aryl (C23) vector being orthogonal to the carbene
ring plane. The Pd-aryl (C23) distance (2.065(4) Å) lies
within the range found for related Pd(II) complexes;11
however, the aryl ring lies in the coordination plane in
4, atypical for square-planar arylmetal complexes, in
which the aryl ring is usually orthogonal to the square
plane. CaChe modeling studies on 4 showed the or-
thogonal arrangement to be ca. 10 kJ mol-1 higher in
energy than the coplanar case, presumably due to the
resultant close contact (3.0 Å) between the ortho carbons
of the aryl ring and the carbene tert-butyl methyl
groups. The distances and angles within the carbene
rings in 4 are essentially identical (within esds) with
those in 2.
The trans geometry of the carbene ligands in 4 is
worthy of comment and suggests (a) concerted OA of
4-chlorotoluene to 2 (perhaps unlikely on steric grounds)
and collapse of the resultant tetrahedral intermediate,
(b) a nonconcerted OA of 4-chlorotoluene to 2, or (c) prior
dissociation of one carbene ligand from 2 (cf. Figure 1)
followed by concerted OA of 4-chlorotoluene and final
reattachment of carbene. Detailed kinetic studies are
in progress to establish the mechanism of this funda-
mental step in amination mediated by complexes of
types 1 and 2.
Ack n ow led gm en t. We are grateful to AstraZeneca
and the EPSRC for support of this project. We also
thank the BBSRC, AICR, GSK, Novartis, and Pfizer for
support of our program. We thank Dr. Tony Avent, Dr.
Ali Abdul Sada, and the EPSRC Mass Spectrometry
Service for technical assistance.
Su p p or tin g In for m a tion Ava ila ble: Text giving details
of experimental procedures and characterization data for
complexes 3 and 4 and tables giving X-ray data for 4. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(8) McGuinness, D. S.; Saendig, N.; Yates, B. F.; Cavell, K. J . J .
Am. Chem. Soc. 2001, 123, 4029.
(9) Crystal data for 4:
C29H47ClN4Pd‚2C6D6, Mr ) 749.77, mono-
OM020552L
clinic, a ) 12.5279(6) Å, b ) 13.7541(3) Å, c ) 23.2188(11) Å, R ) 90°,
â ) 97.785(2)°, γ ) 90°, U ) 3964.0(3) Å3, T ) 173(2) K, space group
P21/n (No. 14), Z ) 4, λ(Mo KR) ) 0.710 73 Å, 20 601 reflections
measured, 6950 unique (Rint ) 0.057). The final wR2 value was 0.112
(all data).
(10) Arnold, P. L.; Cloke, F. G. N.; Geldbach, T.; Hitchcock, P. B.
Organometallics 1999, 18, 3228.
(11) Vicente, J .; Abad, J . A.; Frankland, A. D.; Ramirez de Arellano,
M. C. Chem. Eur. J . 1999, 5, 3066. Flemming, J . P.; Pilon, M. C.;
Borbulevitch, O. Y.; Antipin, M. Y.; Grushin, V. V. Inorg. Chim. Acta
1998, 280, 87. Spee, M. P. R.; Ader, B.; Steenwinkel, P.; Kooijman, H.;
Spek A. L.; van Koten, G. J . Organomet. Chem. 2000, 598, 24.