Synthesis, characterization, and reactivity of arylpalladium cyanoalkyl complexes: Selection of catalysts for the α-arylation of nitriles

Article abstract of DOI:10.1021/ja026584h

A new coupling process, the palladium-catalyzed α-arylation of nitriles, was developed by exploring the structure and reactivity of arylpalladium cyanoalkyl complexes. Complexes of 1,2-bis(diphenylphosphino)benzene (DPPBz), 1,1′-bis(di-i-propylphosphino)ferrocene (DⁱPrPF), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), and diphenylethylphosphine (PPh₂Et) were prepared. Coordination to palladium through the α-carbon was observed for DPPBz-ligated complexes and for complexes of primary and benzylic nitrile anions. However, the anion of isobutyronitrile was coordinated to palladium through the cyano-nitrogen when the complex was ligated by DⁱPrPF. The isobutyronitrile anion displaced a phosphine ligand to form a C,N-bridged dimer when generated from PPh₂Et-ligated palladium. These results suggest that the nitrile anion preferentially coordinates to palladium through the carbon atom in the absence of steric effects. Thermolysis of the arylpalladium cyanoalkyl complexes led to reductive elimination that formed α-aryl nitriles. The high yields and short reaction times observed for BINAP-ligated complexes suggested that BINAP-ligated palladium catalysts might be appropriate for the arylation of nitriles. Initial results on a palladium-catalyzed process for the direct coupling of aryl bromides and primary, benzylic, and secondary nitrile anions to form α-aryl nitriles in good yields are reported. Copyright

Full text of DOI:10.1021/ja026584h

Published on Web 07/23/2002
Synthesis, Characterization, and Reactivity of Arylpalladium Cyanoalkyl
Complexes: Selection of Catalysts for the r-Arylation of Nitriles
Darcy A. Culkin and John F. Hartwig*
Department of Chemistry, Yale UniVersity, P.O. Box 208107, New HaVen, Connecticut 06520-8107
Received April 18, 2002
Scheme 1
Cross-coupling reactions typically join an aryl or vinyl group
with a second unsaturated moiety.1 Recently our group and others
have reported palladium-catalyzed methods for the direct coupling
of aryl bromides with a variety of ketone enolates to form sp2 to
sp3 C-C bonds.2 After the development of improved catalyst
systems, the reaction is now general for a wide range of carbonyl
substrates3 and has been developed as an enantioselective process.4
In principle, one could couple the anion of a nitrile with an aryl
halide in the presence of a palladium catalyst to form products that
are versatile intermediates and have biological activity.5 A con-
ventional mechanism would include reductive elimination of R-aryl
nitrile from an arylpalladium cyanoalkyl intermediate. However,
the chemistry of R-cyanoalkyl complexes is not well developed.
Many bonding modes are available; anions of nitriles could
coordinate to a single metal through the R-carbon6 or the cyano-
nitrogen7 or bridge two metals in a µ2-C,N fashion.8 Moreover, the
electronic effect of the cyano group on the rate of reductive
elimination from even a simple cyanoalkyl complex is difficult to
predict. Nitriles are less acidic than ketones, but a cyano group is
more electron-withdrawing than an acyl group. To address these
questions, we report the synthesis and characterization of a series
of arylpalladium cyanoalkyl complexes, including examples of three
distinct binding modes. These studies paved the way to catalysts
for the coupling of nitriles with aryl halides, and initial results on
this new coupling process are reported.
Scheme 2
Arylpalladium cyanoalkyl complexes were prepared as analyti-
cally pure solids in 45-81% yield, as shown in Schemes 1 and 2.
As expected for a soft, late metal, most of the arylpalladium cyano-
alkyl complexes in Scheme 1 were C-bound (1-5, 7, 8). NMR
and IR spectroscopic techniques, in combination with X-ray crystal-
lography, revealed the coordination mode of the complexes. For
example, complex 4, ligated by 1,2-bis(diphenylphosphino)benzene
(DPPBz), was shown to be C-bound by the typical nitrile 13C NMR
resonance at δ 125.8 and nitrile IR band at 2170 cm-1. An X-ray
structure of 4 confirmed this assignment; the C-N bond length is
1.16 Å.
However, other ancillary ligands induced unusual coordination
modes. When the palladium was ligated by the larger, more donat-
ing 1,1′-bis(di-i-propylphosphino)ferrocene (DiPrPF), the anion of
isobutyronitrile coordinated to the metal through the nitrogen atom
(6). This binding mode was deduced from the doublet 13C NMR
resonance at δ 175.5 (JC-P ) 8.2 Hz), which is far downfield of
that observed for 4 and closer to the NdC resonance of keten-
imines.9 The two strong bands at 1997 and 2186 cm-1 in the IR
spectrum also resemble those for ketenimines. X-ray crystallography
secured the assignment of this rare binding mode, and the
palladium-bound NdC distance of 1.21 Å and CdC distance of
1.35 Å are consistent with the proposed double bond character.
Spectral analysis of 9 suggested a dimeric structure with the
nitrile bridging the metals by a µ2-C,N coordination mode. The 1H
NMR spectrum showed only one phosphine per palladium-bound
cyanoalkyl, and the nitrile resonance in the 13C NMR spectrum
was located at δ 138.8, which is only slightly downfield from the
chemical shift of 4. The IR spectrum displayed a broad absorption
at 2195 cm-1. The binuclear structure of 9 was decisively assigned
by X-ray crystallography.
The three different binding modes observed for the anion of
isobutyronitrile demonstrate that the nitrile anion prefers to
coordinate to palladium through the carbon atom in the absence of
steric effects. When a more sterically demanding ligand is bound
to the metal, coordination through nitrogen is observed. When a
labile phosphine is present, dissociation of ligand occurs, and the
nitrogen of the R-cyanoalkyl displaces a phosphine donor to create
a bridging cyanoalkyl complex.
Having established the distinct coordination modes, we explored
the reactivity of these complexes. Thermolysis of 1-9 at 110 °C
in the presence of added PPh3 as a trap for the Pd(0) fragment in-
duced the first reductive eliminations to form R-aryl nitriles. Reac-
tions occurred in 40-99% yield by 1H NMR spectroscopy with an
internal standard (Table 1). Yet, yields of coupled product were
notably lower and the rates of reductive elimination were signifi-
* To whom correspondence should be addressed. E-mail: john.hartwig@yale.edu.
9
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10.1021/ja026584h CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Reductive Elimination from LPd(Ar)(R)a
Diarylation of butyronitrile (entry 8) and acetonitrile (entries 9, 10)
occurred in preference to monoarylation, presumably because the
monoarylated reaction product generates the required anion more
readily and is unhindered enough to bind palladium. Reactions of
2-phenylbutyronitrile (entry 7) and butyronitrile (entry 8) conducted
with tri-tert-butylphosphine and Pd2dba3‚CHCl3 occurred in higher
yields than those conducted with BINAP and Pd(OAc)2.
Although the uncatalyzed reaction of aryl fluorides with anions
of nitriles forms tertiary benzylic nitriles, the uncatalyzed reaction
of aryl bromides and the uncatalyzed reaction of unactivated aryl
fluorides with aceto, primary, or benzylic nitrile anions does not
occur.5 Only a single example of the palladium-catalyzed arylation
of phenylacetonitrile, which occurred in moderate yield at high
temperature, has been reported.11 The synthesis of arylcyanoacetates
via palladium catalysis has also been described.12
complex
L
Ar
R
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
DPPBz
DPPBz
DPPBz
DPPBz
DiPrPF
DiPrPF
BINAP
BINAP
PPh2Et
C6H4-4-t-Bu
C6H4-4-Me
C6H4-4-Me
C6H4-4-Me
C6H4-4-t-Bu
C6H4-4-t-Bu
C6H4-4-t-Bu
C6H4-4-t-Bu
C6H4-4-Me
CH2CN
60
60
63
57
50
69
73
40
99
98
45
CH(CHMe2)CN
CHPhCN
48
CMe2CN
CHPhCN
12
<1
<1
<1
<1
<1
NdCdCMe2
CH(CHMe2)CN
CHPhCN
CMe2CN
a Yields of nitrile were determined for reactions of 0.01 mmol of complex
by 1H NMR spectroscopy in C6D6 with an internal standard.
Table 2. Palladium-Catalyzed R-Arylation of Nitriles
In summary, the effect of structure and electronic properties on
the reactivity of arylpalladium cyanoalkyl complexes showed the
potential for a new catalytic process. This new reaction provides a
convenient route to R-aryl nitriles from readily available materials
and commercially available catalysts and bases. Because these aryl-
ations occur to form quaternary centers in high yields, enantioselec-
tive couplings should be possible and will be the focus of future
studies.
Acknowledgment. We thank the NIH GM58108 for support
of this work and Johnson-Matthey for a gift of PdCl2.
Supporting Information Available: Experimental methods, spec-
tral data, and X-ray diffraction data for palladium compounds and
experimental procedures for catalytic studies (PDF). An X-ray crystal-
lographic file in CIF format. This material is available free of charge
via the Internet at http://pubs.acs.org.
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a A ) Pd(OAc)2; B ) Pd2dba3‚CHCl3. b 1:1 ratio of Pd/L for reactions
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