PdII complexes possessing a seven-membered N-heterocyclic carbene ligand

Article abstract of DOI:10.1002/anie.200501522

(Chemical Equation Presented) Carbenes with a twist: A seven-membered N-heterocyclic carbene (NHC) ligand is prepared from an amidinium precursor, derived from 2,2′-dinitrobiphenyl, and yields the NHC-Pd^II complex [PdCl(allyl)-(NHC)] (see scheme). This carbene framework exhibits a tortional twist that results in axial symmetry. This ligand class can be readily modified and is attractive for future application in asymmetric catalysis.

Full text of DOI:10.1002/anie.200501522

Angewandte
Chemie
Organometallic Chemistry
DOI: 10.1002/anie.200501522
Pdii Complexes Possessing a Seven-Membered
N-Heterocyclic Carbene Ligand**
Christopher C. Scarborough, Michael J. W. Grady,
Ilia A. Guzei, Bhavesh A. Gandhi, Emilio E. Bunel,
and Shannon S. Stahl*
Since the discovery of stable N-heterocyclic carbenes
(NHCs),[1] these complexes have found widespread use in
catalysis, in which they serve both as nucleophilic catalysts[2]
and as ligands in metal-mediated reactions.[3] Carbenes
derived from five-membered heterocycles represent the
most common class of these molecules (1–3, Scheme 1);[1–3]
however, four-[4] and six-membered[5] analogues have also
been reported (4 and 5). Most of these structures possess a
Scheme 1. Typical heterocyclic frameworks of NHCs.
[*] C. C. Scarborough, M. J. W. Grady, Dr. I. A. Guzei, B. A. Gandhi,
Prof. S. S. Stahl
Department of Chemistry
University of Wisconsin—Madison
1101 University Avenue, Madison, WI 53706 (USA)
Fax: (+1)608-262-6143
E-mail: stahl@chem.wisc.edu
Dr. E. E. Bunel
Amgen Inc.
1 Amgen Center Drive
Thousand Oaks, CA 91320 (USA)
[**] This work was supported by the National Institutes of Health
(RO1 GM67173-01) and the Dreyfus Foundation (Teacher–Scholar
Award).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Communications
[10]
nearly planar heterocyclic framework, and this feature places
triethylorthoformate with NH4BF4 produces the C2-sym-
constraints on the spatial arrangement of the NHC substitu-
ents. To relax this constraint, we targeted a new class of NHCs
with a seven-membered heterocyclic frame-
metric amidinium tetrafluoroborate salt 8, which was charac-
terized by single-crystal X-ray diffraction analysis
(Figure 1).[11]
work 6 that would undergo a torsional twist to
alleviate ring strain. Structures of this type have
been analyzed previously by computational
methods,[6] but synthetic examples have not
been prepared. We describe herein the facile
synthesis of two Pdii complexes that possess the
first member of this newclass of carbene
ligands, in which R = 2-adamantyl (2-ad).
Our initial synthetic efforts targeted analogues of 6 with
bulky aryl substituents (e.g., R = mesityl, 2,6-diisopropyl-
phenyl), which are commonly found in stable NHCs. 2,2’-
Diaminobiphenyl (7a) was obtained in quantitative yield by
reduction of 2,2’-dinitrobiphenyl, and mesitylation of 7a
proceeded effectively under previously reported conditions
(Scheme 2).[7] Subsequent condensation to afford the amidi-
Figure 1. Molecular structure of the amidinium salt 8. Hydrogen
atoms and the BF4À counterion are omitted for clarity. Thermal ellip-
soids are shown at 50% probability. Selected bond lengths [Š] and
angles [8]: C(7)-N(1) 1.319(2), N(1)-C(1) 1.456(3), C(1)–C(6) 1.393(3),
C(6)-C(6A) 1.472(4), C(1)-C(2) 1.388(3), C(2)-C(3) 1.385(3), C(3)-C(4)
1.384(3), C(4)-C(5) 1.401(3), C(55)-C(6) 1.401(3); N(1)-C(7)-N(1A)
124.2(3), C(7)-N(1)-C(8) 118.52(19), C(7)-N(1)-C(1) 117.21(18), C(1)-
N(1)-C(8) 120.89(16).
The amidinium salt 8 represents an attractive NHC
precursor, and our initial studies focused on the preparation
of NHC-coordinated Pdii complexes. Deprotonation of 8 with
potassium tert-butoxide in
a THF solution of [{PdCl-
(allyl)}2][12–14] generated the NHC–PdCl(allyl) complex 9 in
high yield (Scheme 4). This complex is air stable and can be
purified by flash column chromatography on silica gel under
Scheme 2. Attempted synthesis of an arylated seven-membered NHC.
Mes=mesitylene, binap=1,1’-binaphthalene-2,2’-diylbis(diphenylphos-
phine).
nium salt, however, was unsuccessful when a
variety of known protocols was used. The origin
of this failure is not certain, but we reasoned that it
may result from the weak basicity of the diaryl
amines, and therefore N-alkylated derivatives
might be more successful.
Preparation of N-substituted derivatives of 7a
with sterically encumbered primary and secondary
alkyl groups proceeds smoothly (R = neopentyl, 2-
adamantyl; Scheme 3).[8] For example, condensa-
tion of 7a with 2-adamantanone followed by
Scheme 4. Synthesis of NHC-coordinated Pdii complexes.
1
reduction of the imine with lithium aluminum hydride
ambient conditions. The H NMR spectrum of 9 reveals the
presence of two diastereomeric allyl rotamers in solution in a
1.4:1 ratio.[15] Single-crystal X-ray diffraction studies[11]
confirmed the identity of 9 (Figure 2); a mixture of
diastereomers is also present in the solid state, with the
allyl group disordered over two positions in a 2.7:1 ratio.
Protonolysis of the allyl ligand[12] of 9 with HCl
produces [{PdCl2(NHC)}2] (10) in quantitative yield
(Scheme 4). Only one isomer of this dimeric compound
is detected in solution by 1H NMR spectroscopic analysis.
Single-crystal X-ray diffraction studies reveal the presence
of a heterochiral dimer (Figure 3).[11]
produces 7c in quantitative yield.[9] Heating 7c in neat
Scheme 3. Synthesis of a seven-membered biphenyl amidinium salt.
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hexamethyldisilazide, potassium tert-butox-
ide, sodium methoxide, and sodium hydride.
1H NMR spectroscopic data reveals that
alkoxide bases, which are the most effective
reagents for the in situ preparation of
NHC–Pd complexes form NHC–alcohol
adducts 11a and 11b. Attempts to isolate
the free carbene from such compounds by
vacuum thermolysis[16] or trapping the
released alcohol (in the case of the meth-
anol adduct) in a Dean–Stark apparatus
equipped with 4-Š molecular sieves and
benzene at reflux were unsuccessful and only yielded slightly
decomposed starting material in each case. These adducts do
not react further in the presence of [{PdCl(allyl)}2] to form the
NHC–PdCl(allyl) complex 9. These results suggest that the
preparation of 9 occurs by an in situ deprotonation of 8 by
KOtBu and competitive trapping of the free carbene by
[{PdCl(allyl)}2] in solution.
Figure 2. Solid-state molecular structure of 9. Only the preferred orien-
tation of the allyl group is shown. Hydrogen atoms and the solvent are
omitted for clarity. Thermal ellipsoids are shown at 30% probability.
Rzepa and co-workers analyzed a series of 8p-electron
heterocycles, including seven-membered NHCs, by DFT
computational methods.[6] These studies highlight the attenu-
ation of antiaromatic character when such heterocyclic rings
undergo a torsional twist. This conformational change enables
partial Möbius aromatic stabilization[17] in addition to relief of
the ring strain intrinsic to seven-membered rings. These
calculations also suggest that coordination of these ligands to
metal complexes results in higher inversion barriers between
the two enantiomeric conformations.
In conclusion, we have prepared the first examples of
metal complexes with a seven-membered N-heterocyclic
carbene ligand that exhibits a tortional twist resulting in
C2 symmetry. This architecture can be readily altered with
different substituents at the nitrogen atom and modifications
to the biaryl backbone. Future studies will focus on the
preparation of conformationally stable and enantiomerically
resolved analogues, and their utility in asymmetric catalysis
will be investigated.
Figure 3. Molecular structure of 10. Hydrogen atoms and solvent mol-
ecules are omitted for clarity. Thermal ellipsoids are shown at 30%
probability.
The amidinium salt 8 and the NHC ligands in 9 and 10
exhibit axial symmetry arising from the torsional twist of the
seven-membered ring. The torsional angle a between the two
phenyl rings in 8 (C(1)-C(6)-C(6A)-C(1A)) is 46.1(4)8, which
is similar to this angle in 9 and 10 (41.9(5) and 46.4(8)8,
respectively). Another relevant metric is the torsional angle
Experimental Section
All manipulations were performed in an inert nitrogen atmosphere
unless otherwise specified. Dry, oxygen-free solvents were employed.
1H and 13C NMR spectra were recorded on either a Bruker Homer-
300, Bruker Athena-300, Varian Mercury-300, or Varian Inova-500
NMR spectrometer. 1H NMR chemical shifts are reported in ppm
relative to Me4Si as the external standard, and the 13C NMR chemical
shifts are reported in ppm relative to CHCl3. Please refer to the
Supporting Information for the spectral data of all the compounds.
7a: Compound 7a was synthesized by the adaptation of a
literature procedure:[18] 2,2’-Dinitrobiphenyl (102.0 g, 417.5 mmol)
and 10% Pd/C (16.4 g) were combined with EtOAc (300 mL) in a
hydrogenation vessel. The vessel was pressurized to 40 psi H2 for 3.5 h
(when H2 was no longer being consumed). The slurry was filtered
through a plug of celite. Rotary evaporation followed by drying on a
vacuum line gave the pure product as a light yellow–orange powder in
100% yield.
À
between the two N C(2-ad) bonds, which reflects the spacial
disposition of the adamantyl groups directed into the metal
coordination sphere. This angle b in 8 (namely, M = H+) is
56.2(5)8 and expands to 72.3(8) and 79.7(1.3)8 in the
Pdii complexes 9 and 10, respectively. The larger size of the
Pdii center relative to a proton probably accounts for this
increase. Overall, these torsional parameters highlight the
utility of the seven-membered heterocycle to induce out-of-
plane deviations in the orientation of the NHC substituents.
Moreover, the C2 symmetry of these structures supports their
potential utility as templates for the preparation of non-
fluxional, enantiomerically resolved analogues for use in
asymmetric catalysis.
7c: 2,2’-Diaminobiphenyl (7a; 614 mg, 3.33 mmol) and 2-ada-
mantanone (1 g, 6.65 mmol) were combined with para-toluenesul-
fonic acid (1% (per amine functionality)) in a Dean–Stark apparatus.
The reagents were dissolved in toluene (ca. 200 mL) and refluxed for
Thus far, attempts to isolate and characterize the free
carbene have been unsuccessful. Numerous bases have been
applied in these studies, including mesityl lithium, potassium
Angew. Chem. Int. Ed. 2005, 44, 5269 –5272
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Communications
72 h. The solvent was removed, and lithium aluminum hydride
G. P. A. Yap, D. S. Richeson, J. Am. Chem. Soc. 2003, 125,
13314 – 13315.
[6] a) C. J. Kastrup, S. V. Oldfield, H. S. Rzepa, J. Chem. Soc. Dalton
Trans. 2002, 2421 – 2422; b) C. J. Kastrup, S. P. Oldfield, H. S.
Rzepa, Chem. Commun. 2002, 642 – 643.
[7] M. T. Reetz, H. Oka, R. Goddard, Synthesis 2003, 1809 – 1814.
[8] The neopentyl-substituted derivative of NHC 6 is less stable than
the 2-adamantyl derivative; full presentation of the synthesis and
properties of this carbene and its metal complexes will be
described in a forthcoming full paper.
[9] Full characterization data of the reported compounds are
provided in the Supporting Information.
[10] a) S. Saba, A. Brescia, M. K. Kaloustian, Tetrahedron Lett. 1991,
32, 5031 – 5034; b) R. W. Alder, M. E. Blake, S. Bufali, C. P.
Butts, A. G. Orpen, J. Schütz, S. J. Williams, J. Chem. Soc. Perkin
Trans. 1 2001, 1586 – 1593.
[11] CCDC-272584–272586 (8–10, respectively) contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from the Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[12] D. R. Jensen, M. S. Sigman, Org. Lett. 2003, 5, 63 – 65.
[13] NHC–PdCl(allyl) complexes were first synthesized by Nolan
and co-workers by combination of free carbene and [{PdCl-
(allyl)}2]; see: a) M. S. Viciu, R. F. Germaneau, O. Navarro-
Fernandez, E. D. Stevens, S. P. Nolan, Organometallics 2002, 21,
5470 – 5472; b) M. S. Viciu, O. Navarro, R. F. Germaneau, R. A.
Kelly III, W. Sommer, N. Marion, E. D. Stevens, L. Cavallo, S. P.
Nolan, Organometallics 2004, 23, 1629 – 1635.
[14] Nolan and co-workers have shown that such complexes are able
to function as cross-coupling catalysts; for the first example, see:
M. S. Viciu, R. F. Germaneau, S. P. Nolan, Org. Lett. 2002, 4,
4053 – 4056.
[15] Similar observations have been made for other chiral NHC–
PdCl(allyl) complexes: S. Roland, M. Audouin, P. Mangeney,
Organometallics 2004, 23, 3075 – 3078.
[16] D. Enders, K. Breuer, G. Raabe, J. Runsink, J. H. Teles, J.-P.
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Angew. Chem. Int. Ed. Engl. 1995, 34, 1021 – 1023.
[17] a) E. Heilbronner, Tetrahedron Lett. 1964, 5, 1923 – 1928;
b) H. E. Zimmerman, Acc. Chem. Res. 1971, 4, 272 – 280.
[18] K. M. Gillespie, C. J. Sanders, P. OꢀShaughnessy, I. Westmore-
land, C. P. Thickitt, P. Scott, J. Org. Chem. 2002, 67, 3450 – 3458.
(122 mg, 3.22 mmol) was added followed by THF (ca. 200 mL). The
reaction flask was heated to 508C for 2 h followed by a careful
quenching with water (ca. 100 mL) and sat. NH4BF4 (10 mL). The
resulting slurry was filtered through a plug of celite, and the plug
washed with CH2Cl2. The aqueous layer was washed once with
CH2Cl2 (ca. 100 mL). The organic layers were combined, dried over
MgSO4, filtered, and the solvent was removed, thus yielding pure 7c
in 100% yield.
(Æ)-8:
2,2’-Bis(2-adamantylamino)biphenyl
(7c;
5.76 g,
12.7 mmol) and NH4BF4 (1.3 g, 12.7 mmol) were combined under
nitrogen in a 500-mL round-bottomed flask and triethyl orthoformate
(c.a. 200 mL) was added. The reaction was heated to 1008C for 16 h,
after which time the product precipitated as a white powder. The
reaction mixture was allowed to cool to room temperature and
filtered. The solid was washed with diethyl ether followed by pentane
to give the amidinium salt (Æ )-8 in 65% yield as a light fluffy white
powder without further purification. Crystals suitable for X-ray
analysis were achieved by vapor diffusion of n-pentane onto a
solution of (Æ )-8 in CHCl3.
(Æ)-9: Aminidinium salt (Æ )-8 (200 mg, 0.363 mmol) and [{PdCl-
(allyl)}2] (78 mg, 0.213 mmol) were combined with KOtBu (1.2 equiv)
under nitrogen. The reaction mixture was stirred in THF for 12 h,
filtered through celite, and purified by column chromatography under
ambient conditions (SiO2, diethyl ether/hexanes 1:1) to give the
NHC–PdCl(allyl) complex (Æ )-9 in 93% yield as a light yellow–tan
solid. Crystals suitable for X-ray analysis were obtained by layering n-
heptane onto a À208C ethereal solution of (Æ )-9 followed by
diffusion overnight at À208C. (Æ )-9 crystallized as a mixture of
diastereomers in a ratio of 73:27.
10: A 50-mL round-bottomed flask was charged with (Æ )-9
(100 mg, 0.16 mmol) and ethereal HCl (2.0 mL, 2.0m). The color of
the reaction mixture instantly changed to bright yellow–orange.
Diethyl ether (8.0 mL) was added, and the resultant suspension was
stirred for 1 h. Volatiles were removed in vacuo, which left pure 10 as
a bright yellow–orange powder in quantitative yield. Recrystallization
was carried out by dissolving 10 in a small amount of toluene and
adding excess n-pentane to cause precipitation (87% yield). Crystals
suitable for X-ray analysis were achieved by vapor diffusion of n-
pentane onto a solution of 10 in CH2Cl2.
Received: May 3, 2005
Published online: July 20, 2005
Keywords: carbene ligands · N-heterocyclic carbenes ·
.
organometallic chemistry · palladium
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