From pyrroles to isoindolines: Synthesis of a γ-diimine ligand for applications in palladium coordination chemistry and catalysis

Article abstract of DOI:10.1021/om800080e

The γ-diimine 1,2-(2,6-ⁱPr₂-C₆H ₃NC)₂-C₆H₄ (2) was synthesized by the reaction of phthalaldehyde with 2,6-diisopropylaniline. Depending on reaction conditions, 2 can cyclize to form the corresponding iminoisoindoline or isoindolinone. Unlike analogous α- and β-diimine complexes, reaction of the γ-diimine 2 with (MeCN)₂PdCl₂ results in a dinuclear complex, [(γ-diimine)PdCl(μ-Cl)]₂ (5), where the ligand does not coordinate to the Pd(II) center in a chelating fashion but instead adopts a monodentate coordination mode. On the other hand, reaction of 2 with Pd(OAc)₂ results in C-H activation and formation of the trinuclear Pd₃(OAc)₄-based palladacycle {1,2-(2,6- ⁱPr₂-C₆H₃NC)₂-C ₆H₃]Pd(μ-OAc)₂}₂Pd (6). The resulting palladium complexes were tested as precatalysts in Heck and Suzuki coupling reactions.

Full text of DOI:10.1021/om800080e

Organometallics 2008, 27, 2337–2345
2337
From Pyrroles to Isoindolines: Synthesis of a γ-Diimine Ligand for
Applications in Palladium Coordination Chemistry and Catalysis
Jackson M. Chitanda,† Demyan E. Prokopchuk,† J. Wilson Quail,‡ and Stephen R. Foley*,†
Department of Chemistry, UniVersity of Saskatchewan, 110 Science Place, S7N 5C9 Saskatoon,
Saskatchewan, Canada, and Saskatchewan Structural Sciences Centre, 110 Science Place,
S7N 5C9 Saskatoon, Saskatchewan, Canada
ReceiVed January 29, 2008
The γ-diimine 1,2-(2,6-iPr2-C6H3NC)2-C6H4 (2) was synthesized by the reaction of phthalaldehyde
with 2,6-diisopropylaniline. Depending on reaction conditions, 2 can cyclize to form the corresponding
iminoisoindoline or isoindolinone. Unlike analogous R- and ꢀ-diimine complexes, reaction of the γ-diimine
2 with (MeCN)2PdCl2 results in a dinuclear complex, [(γ-diimine)PdCl(µ-Cl)]2 (5), where the ligand
does not coordinate to the Pd(II) center in a chelating fashion but instead adopts a monodentate coordination
mode. On the other hand, reaction of 2 with Pd(OAc)2 results in C-H activation and formation of the
trinuclear Pd3(OAc)4-based palladacycle {1,2-(2,6-iPr2-C6H3NC)2-C6H3]Pd(µ-OAc)2}2Pd (6). The resulting
palladium complexes were tested as precatalysts in Heck and Suzuki coupling reactions.
Introduction
R-Diimines based on 1,4-diazabutadienes of the general
formula RNdCR′CR′dNR have received considerable attention
in recent years due to their application as ligands in a wide
variety of catalytic reactions. It was initial reports by Brookhart
Figure 1
in the field of olefin polymerization and olefin/CO copolymer-
ization using Ni(II) and Pd(II) complexes that have initiated
Scheme 1
the widespread interest in applications of these diimines as
ligands.1,2 Group 10 complexes with diazabutadiene ligands
showed activities higher than those of the classical Ziegler
catalysts and exhibited a greatly reduced susceptibility to
poisoning by polar functionalities.3 Pd(II) complexes of diimines
is a simple condensation reaction of primary amines or anilines
with diketones or dialdehydes, thereby producing a wide range
of R- and ꢀ-diimines (Figure 1).
In 1997, ꢀ-diimine ligands analogous to Brookhart’s R-di-
imines were synthesized and their reactivity was explored in
the formation of group 10 complexes.5 ꢀ-Diimines are usually
best interpreted as ꢀ-diketimines, due to the acidic nature of
the methylene protons (Scheme 1), and have been successfully
employed as monoanionic ligands in a wide variety of reactions.6
have also been reported to be active catalysts for the Suzuki,
Heck, Sonogashira, and Hiyama coupling reactions.4
This class of ligand has become increasingly popular, due to
its ease of synthesis and outstanding steric and electronic
tunability. The most common synthetic route to diimine ligands
* To whom correspondence should be addressed. E-mail:
Stephen.foley@usask.ca.
† University of Saskatchewan.
‡ Saskatchewan Structural Sciences Centre.
ꢀ-diimine variations in which the acidic protons have been
(1) (a) Johnson, L. K.; Killian, C. M.; Brookhart, M. J. Am. Chem. Soc.
1995, 117, 6414. (b) Johnson, L. K.; Mecking, S.; Brookhart, M. J. Am.
Chem. Soc. 1996, 118, 267. (c) Mecking, S.; Johnson, L. K.; Wang, L.;
Brookhart, M. J. Am. Chem. Soc. 1998, 120, 888. (d) McLain, S. J.;
Feldman, J.; McCord, E. F.; Gardner, K. H.; Teasley, M. F.; Coughlin,
E. B.; Sweetman, K. J.; Johnson, L. K.; Brookhart, M. Macromolecules
1998, 31, 6705. (e) Gottfried, A. C.; Brookhart, M. Macromolecules 2001,
34, 1140. (f) Shultz, L. H.; Tempel, D. J.; Brookhart, M. J. Am. Chem.
Soc. 2001, 123, 11539. (g) Leatherman, M. D.; Svejda, S. A.; Johnson,
L. K.; Brookhart, M. J. Am. Chem. Soc. 2003, 125, 3068. (h) Popeney, C.;
Guan, Z. Organometallics 2005, 24, 1145. (i) Mino, T.; Shirae, Y.; Saito,
T.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2006, 71, 9499. (j) Popeney,
C. S.; Camacho, D. H.; Guan, Z. J. Am. Chem. Soc. 2007, 129, 10062. (k)
Meinhard, D.; Wegner, M.; Kipiani, G.; Hearley, A.; Reuter, P.; Fischer,
S.; Marti, O.; Rieger, B. J. Am. Chem. Soc. 2007, 129, 9182. (l) Okada, T.;
Park, S.; Takeuchi, D.; Osakada, K. Angew. Chem., Int. Ed. 2007, 46, 6141.
(m) Borkar, S.; Yennawar, H.; Sen, A. Organometallics 2007, 26, 4711.
(n) McCord, E. F.; McLain, S. J.; Nelson, L. T. J.; Ittel, S. D.; Tempel, D.;
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410.
substituted by alkyl groups to form stable neutral ligands have
(4) (a) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3,
1077. (b) Grasa, G. A.; Singh, R.; Stevens, E. D.; Nolan, S. P. J. Organomet.
Chem. 2003, 687, 269. (c) Iyer, S.; Kulkarni, G. M.; Ramesh, C. Tetrahedron
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T. J. Org. Chem. 2006, 71, 9499.
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Calabrese, J. C.; Arthur, S. D. Organometallics 1997, 16, 1514.
(6) (a) For applications of ꢀ-diimines in group 10 chemistry, see:
Bourget-Merle, L.; Lappert, M. F.; Severn, J. R. Chem. ReV. 2002, 102,
3031. (b) Cope-Eatough, E. K.; Mair, F. S.; Pritchard, R. G.; Warren, J. E.;
Woods, R. J. Polyhedron 2003, 22, 1447. (c) Domin, D.; Benito-Garagorri,
D.; Mereiter, K.; Froehlich, J.; Kirchner, K. Organometallics 2005, 24, 3957.
(d) Landolsi, K.; Richard, P.; Bouachir, F. J. Organomet. Chem. 2005, 690,
513. (e) Zhang, J.; Ke, Z.; Bao, F.; Long, J.; Gao, H.; Zhu, F.; Wu, Q. J.
Mol. Catal. A: Chem. 2006, 249, 31. (f) Domin, D.; Benito-Garagorri, D.;
Mereiter, K.; Hametner, C.; Froehlich, J.; Kirchner, K. J. Organomet. Chem.
2007, 692, 1048. (g) Zou, H.; Hu, S.; Huang, H.; Zhu, F.; Wu, Q. Eur.
Polym. J. 2007, 43, 3882. (h) Belhaj Mbarek Elmkacher, N.; Guerfel, T.;
Tkatchenko, I.; Bouachir, F. Polyhedron 2008, 27, 893.
(2) Ittel, S. D.; Johnson, L. K.; Brookhart, M. Chem. ReV. 2000, 100,
1169.
(3) Gibson, V. C.; Spitzmesser, S. K. Chem. ReV. 2003, 103, 283.
10.1021/om800080e CCC: $40.75
2008 American Chemical Society
Publication on Web 04/18/2008

2338 Organometallics, Vol. 27, No. 10, 2008
Chitanda et al.
Scheme 2
Scheme 3
Scheme 4
recently been reported.6c,f,7 The corresponding Pd(II) complexes
were found to be active precatalysts for C-C coupling
reactions.6c
There is one report in the patent literature concerning the
synthesis of a cobalt complex of A, which polymerizes ethylene
in the presence of methylaluminoxane.2,8 This represents the
only report of a γ-diimine in the published literature. Analogous
γ-diimines have, however, been proposed as intermediates in
the synthesis of iminoisoindolines and isoindolinones.9 We
initially envisioned that the synthesis of γ-diimine compounds
might be a general reaction leading to a new class of diimine
ligands; however, intramolecular cyclization reactions have to
date inhibited this notion. Herein we report the synthesis of a
γ-diimine ligand and subsequent formation of Pd(II) complexes.
Depending on the reaction conditions, cyclization of the
γ-diimine can be induced to form either the corresponding
iminoisoindoline or the isoindolinone. The resulting (γ-di-
imine)PdII complexes were tested as precatalysts for Suzuki and
Heck coupling reactions.
In our hands, all attempts to synthesize γ-diimine A were
unsuccessful, yielding only the previously reported iminoisoin-
doline 1-(phenylimino)-2-phenylisoindoline, according to Scheme
3.9a It appears unlikely that the γ-diimine A was ever actually
isolated, as it would be prone to rapid intramolecular cyclization
to the corresponding iminoisoindoline. Increasing the steric bulk
on the nitrogen positions via condensation with a bulky primary
amine should, however, retard or inhibit intramolecular cycliza-
tion, allowing for isolation of a γ-diimine. Thus, a γ-diimine
was prepared through the reaction of phthalaldehyde with 2,6-
diisopropylaniline in methanol to yield the corresponding
phthalaldimine 1,2-(2,6-iPr2-C6H3NC)2-C6H4 (2) as a yellow
precipitate in 66% yield (Scheme 4). The remaining products
in the filtrate consisted only of the isoindolinone 3 (30% yield)
and 2,6-diisopropylaniline. 1H NMR of 2 in CDCl3 showed one
singlet downfield at δ 8.78 integrating for two protons for the
imine HCdN, while 13C NMR showed one signal at δ 161.8
for the imine indicative of a C2V-symmetric species in solution
at room temperature. FT-IR spectroscopy showed a single CdN
Results and Discussion
Synthesis of a γ-Diimine. Attempts to synthesize a γ-diimine
ligand from a simple diketone such as 2,5-hexanedione and 2,6-
diisopropylaniline in acidified methanol yielded only the pyrrole
1 via a Paal-Knorr synthesis as the sole product, regardless of
stoichiometry (Scheme 2). The same pyrrole was recently
synthesized employing metal triflates as catalysts.10
Use of a constrained dialdehyde such as phthalaldehyde
should inhibit pyrrole formation, possibly allowing for isolation
of the desired γ-diimine. As mentioned earlier, reactions of
phthalaldehyde with primary amines have been known for
several decades and usually result in formation of the corre-
sponding iminoisoindoline or isoindolinone, depending on
reaction conditions. While γ-diimines have been postulated as
intermediates in the formation of iminoisoindolines or isoin-
dolinones, only γ-diimine A has ever been isolated.8,9
stretch at 1633 cm-1
.
The solid-state structure of 2 has been determined by X-ray
diffraction (Table 1 and Figure 2). Unlike the proposed solution
structure, the solid-state structure of 2 has Cs symmetry and
crystallizes preferentially as rotamer b (Scheme 5), where one
imine is rotated into a cisoidal orientation and the other imine
adopts a transoidal orientation. The solution data indicates,
however, that the barrier to rotation between the three possible
rotational conformers depicted in Scheme 5 is low at room
temperature, resulting in fast interconversion between the
rotamers and an average structure with C2V symmetry. While
variable-temperature 1H NMR spectra support the fluxional
behavior of 2, as seen in Figure 3, even at 183 K the static
limit for rotational isomerization had not been reached and
discrete rotational isomers were not observed. At 296 K one
doublet at δ 1.08 for the methyl groups is observed, along with
(7) Cope-Eatough, E. K.; Mair, F. S.; Pritchard, R. G.; Warren, J. E.;
Woods, R. J. Polyhedron 2003, 22, 1447.
(8) Doi, Y.; Fujita, T. JP Patent 10298225 to Mitsui Chemicals Inc.,
Japan, priority date April 25, 1997.
(9) (a) Takahashi, I.; Miyamoto, R.; Nishiuchi, K.; Hatanaka, M.;
Yamano, A.; Sakushima, A.; Hosoi, S. Heterocycles 2004, 63, 1267. (b)
Takahashi, I.; Tsuzuki, M.; Yokota, H.; Kitajima, H.; Isa, K. Heterocycles
1994, 37, 933. (c) Takahashi, I.; Hatanaka, M. Heterocycles 1997, 12, 2475.
(d) Takahashi, K.; Nishiuchi, K.; Miyamoto, R.; Hatanaka, M.; Uchida,
H.; Isa, K.; Sakushima, A.; Hosoi, S. Lett. Org. Chem. 2005, 2, 40. (e)
DoMinh, T.; Johnson, A. L.; Jones, J. E.; Senise, P. P. J. Org. Chem. 1977,
42, 4217. (f) Grigg, R.; Gunaratne, H. Q. N.; Sridharan, V. Chem. Commun.
1985, 1183.
1
a sharp singlet at δ 8.78 for the imine protons. The H NMR
spectra at 183 K showed the methyl groups as two discrete broad
resonances, while the signal for the imine protons exhibited line
broadening.
Interestingly, if 2 is not isolated as a precipitate from the
methanolic solution, it further reacts by redissolving back into
(10) Chen, J.; Wu, H.; Zheng, Z.; Jin, C.; Zhang, X.; Su, W. Tetrahedron
Lett. 2006, 47, 5383.

From Pyrroles to Isoindolines
Organometallics, Vol. 27, No. 10, 2008 2339
Table 1. Crystal Data and Refinement Parameters for Compounds 2-6
2
3
4-DCl · CDCl3
5 · 2CHCl3
6 · 2CH2Cl2
formula
formula wt
color
cryst syst
space group
a, Å
C32H40N2
452.66
yellow
orthorhombic
Fdd2
15.3632(15)
41.9140(9)
8.5520(9)
90
90
90
8
1.092
173(2)
C20 H23 NO
293.39
colorless
monoclinic
C2/c
18.3891(6)
14.9010(5)
12.2811(4)
90
94.906(2)
90
C33H40D2Cl4N2
608.49
colorless
monoclinic
P21/m
10.983(2)
14.196(3)
11.017(2)
90
106.04(3)
90
C66H82Cl10N4 Pd2
1498.70
orange
monoclinic
P21/c
12.5210(3)
10.1820(2)
27.5197(6)
90
94.7006(8)
90
2
1.423
173(2)
C74H94Cl4N4O8Pd3
1628.53
orange
orthorhombic
Pnn2
13.101(3)
29.389(6)
10.898(2)
90
90
90
2
1.289
173(2)
b, Å
c, Å
R, deg
ꢀ, deg
γ, deg
Z
8
2
F
calcd, Mg/m3
temp, K
1.162
173(2)
1.224
173(2)
F(000)
1968
1264
644
1536
1672
θ range, deg
3.65-25.02
R1 ) 0.0848,
wR2 ) 0.1899
R1 ) 0.0973,
wR2 ) 0.1981
3.52-26.37
R1 ) 0.0478,
wR2 ) 0.1090
R1 ) 0.0743,
wR2 ) 0.1242
2.40-27.48
R1 ) 0.0642,
wR2 ) 0.1563
R1 ) 0.0815,
wR2 ) 0.1658
2.29-27.48
R1 ) 0.0510,
wR2 ) 0.0809
R1 ) 0.0949,
wR2 ) 0.0954
2.80-25.35
R1 ) 0.0444,
wR2 ) 0.1106
R1 ) 0.0544,
wR2 ) 0.1167
final R (I >2σ(I))
R (all data)
Scheme 5
(Scheme 4). Presumably the reaction is catalyzed by trace DCl
present in the solvent. Observation of 2 by H NMR spectros-
1
copy in CDCl3 showed that, over the course of 12 h at 60 °C,
50% of the γ-diimine underwent cyclization to form the
corresponding iminoisoindoline 4. Heating for an additional 12 h
resulted in quantitative cyclization of 2 to the iminoisoindoline
(Figure 5). 1H NMR spectra of 4 in CDCl3 showed a
characteristic singlet at δ 4.69 for the two methylene protons.
Prolonged exposure of iminoisoindoline 4 to CDCl3 resulted
in precipitation of the DCl salt of iminoisoindoline (4-DCl) as
X-ray-quality crystals. The solid-state structure of 4-DCl was
subsequently determined by X-ray diffraction (Table 1 and
Figure 6). The iminoisoindoline bicyclic ring is lying on a mirror
plane. The two diisopropylphenyl moieties are bisected by the
mirror plane and are thus perpendicular to the primary isoin-
doline ring.
solution to form the corresponding isoindolinone 3 and 1 equiv
of 2,6-diisopropylaniline. Thus, the yield of 2 decreases, favoring
formation of isoindolinone 3 at longer reaction times. Isoin-
dolinone 3 can be directly synthesized by reaction of phthala-
ldehyde with 1 equiv of 2,6-diisopropylaniline at ambient
temperature in 75% yield. γ-Diimine 2, however, is stable in
nonpolar organic solvents in the absence of protic acids for
1
prolonged periods. H NMR of the isoindolinone 3 in CDCl3
showed a characteristic singlet at δ 4.56 for the two methylene
protons. The solid-state structure of 3 has been determined by
X-ray diffraction and is depicted in Figure 4 (Table 1). The
structure of 3 has been previously communicated.11
Slow cyclization of γ-diimine 2 to form the corresponding
iminoisoindoline 4 in quantitative yield is observed in CDCl3
Figure 2. ORTEP plot of γ-diimine 2 at the 50% probability level.
The hydrogen atoms have been omitted for clarity. Selected bond
lengths (Å) and angles (deg): N(1)-C(13) ) 1.250(15), N(1)-C(1)
) 1.395(10), N(1A)-C(13A) ) 1.280(13), N(1A)-C(1A) )
1.424(11); C(13)-N(1)-C(1) ) 118.6(9), C(13A)-N(1A)-C(1A)
) 120.1(9), N(1)-C(13)-C(14) ) 125.8(9), N(1A)-C(13A)-C(19)
) 120.4(9).
Figure 3. Variable-temperature 1H NMR (CD2Cl2) study of
γ-diimine 2 focusing on the methyl signals of the isopropyl groups
(residual ether is observed immediately downfield of methyl
resonances).

2340 Organometallics, Vol. 27, No. 10, 2008
Chitanda et al.
Reaction of γ-diimine 2 with Pd(OAc)2 in ether at ambient
temperature for 16 h affords the air-stable five-membered
palladacyclic species 6 as an orange solid (Scheme 6). In contrast
to the reaction with (MeCN)2PdCl2 or [(cyclooctene)PdCl2]2,
where no C-H activation of the ligand is observed, ortho
cyclopalladation readily occurs when Pd(OAc)2 is employed as
the Pd(II) source. 1H NMR of 6 showed two distinct singlets at
δ 9.50 and 8.09 for the coordinated and uncoordinated imine
protons (HCdN), respectively, as well as four bridging acetate
ligands. The identity of the complex was further established by
X-ray diffraction studies. Most interestingly, the complex
possesses a rare Pd3(OAc)4 core, which results in an S-shaped
complex (Figures 8 and 9). To our knowledge, this is the fifth
example of a structurally characterized Pd3(OAc)4-containing
complex.13 The Pd-C distance of 1.949(6) Å is consistent with
those in the previously reported Pd3(OAc)4-based complexes,
as is the Pd-Pd distance of 2.9721(6) Å.
Catalysis. Cross-coupling reactions are powerful synthetic
strategies to build carbon-carbon and carbon-heteroatom
bonds.14 Palladium -catalyzed Heck and Suzuki coupling
reactions are among the most efficient methods to construct
C-C bonds.15 The development of coupling reactions for aryl
chlorides has been a major research area in recent years, as aryl
chlorides tend to be cheaper and much more widely available
than the analogous bromides or iodides but are, however, much
more difficult to activate.16 Along these lines, several powerful
systems have been developed for the activation of not only para-
substituted aryl chlorides16,17 but also hindered substrates such
as ortho-substituted aryl halides, as shown by Buchwald’s
group,18 and even alkyl halides, as reported by Fu’s group.19
While palladacycles have been around since 1965,20 the first
examples of palladacycles as precatalysts in the Heck and Suzuki
Figure 4. ORTEP plot of isoindolinone 3 at the 50% probability
level. The hydrogen atoms have been omitted for clarity. Selected
bond lengths (Å) and angles (deg): O(1)-C(1) ) 1.223(2),
N(1)-C(1) ) 1.362(2), N(1)-C(9) ) 1.362(19), N(1)-C(8) )
1.362(19); C(1)-N(1)-C(9) ) 125.86(12), C(9)-N(1)-C(8) )
120.62(12), O(1)-C(1)-N(1) ) 125.96(14).
(γ-diimine)PdII Complexes. Reaction of the γ-diimine ligand
2 with (CH3CN)2PdCl2 in benzene afforded the dinuclear (γ-
diimine)PdII complex [(γ-diimine)PdCl(µ-Cl)]2 (5) as an orange
solid in 47% yield (Scheme 6). The reaction also proceeded with
[(cyclooctene)PdCl2]2 as the PdCl2 source; however, no reaction
was observed if (cyclooctadiene)PdCl2 was employed. Complex
5 was air-stable both in noncoordinating solvents and in the solid
state. The γ-diimine did not coordinate in a chelating mode but
instead acted as a monodentate ligand with one imine remaining
uncoordinated, as evidenced by 1H, 13C NMR, and IR spectroscopic
studies. It is worthwhile to note that a reported (diphosphaal-
kene)PdII analogue showed the diphosphaalkene ligand coordinat-
(13) (a) Friedlein, F. K.; Kromm, K.; Hampel, F.; Gladysz, J. A. Chem.
Eur. J. 2006, 12, 5267. (b) Giri, R.; Liang, J.; Lei, J.; Li, J.; Wang, D.;
Chen, X.; Naggar, I. C.; Guo, C.; Foxman, B. M.; Yu, J. Angew. Chem.,
Int. Ed. 2005, 44, 7420. (c) Moyano, A.; Rosol, M.; Moreno, R. M.; Lopez,
C.; Maestro, M. A. Angew. Chem., Int. Ed. 2005, 44, 1865. (d) Ukhin,
L. Y.; Dolgopolova, N. A.; Kuz’mina, L. G.; Struchkov, Y. T. J. Organomet.
Chem. 1981, 210, 263.
ing in a bidentate fashion, forming a seven-membered ring.12 1
H
NMR of 5 in CDCl3 showed two characteristic singlets appearing
downfield at δ 8.25 and 8.17, indicating that the two imine (HCdN)
protons were no longer equivalent.
(14) (a) de Meijere, A., Diederich, F., Eds. Metal-Catalyzed Cross-
Coupling Reactions; Wiley-VCH: Weinheim, Germany, 2004; Vol. 2,. (b)
Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009. (c) Wolfe,
J. P.; Wang, S.; Marcoux, J. F.; Buchwald, S. L. Acc. Chem. Res. 1998,
31, 805. (d) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046.
(15) (a) Suzuki, A. J. Orgmet. Chem. 1999, 576, 147. (b) Kotha, S.;
Lahiri, K.; Kishanath, D. Tetrahedron 2002, 58, 9633. (c) Dupont, J.; Pfeffer,
M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917. Dounay, A. B.; Overman,
L. E. Chem. ReV. 2003, 103, 2945. (d) Barder, T. E.; Walker, S. E.;
Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685. (e)
Kantchev, E. A. B.; Brien, C. J. O.; Organ, M. G. Angew. Chem., Int. Ed.
2007, 46, 2768.
13C NMR spectra showed that the chemical shift for the
coordinated imine carbon (HCdN) had shifted downfield to δ
176.0 while the uncoordinated imine remained upfield at δ
161.8. Similarly, two CdN stretches were observed by FT-IR
spectroscopy. One CdN stretch appeared at 1633 cm-1
,
corresponding to the uncoordinated imine, while the other CdN
stretch was observed at 1618 cm-1, consistent with coordination
of an imine nitrogen atom to an electrophilic metal center.The
solid-state structure of 5 has been determined by X-ray
diffraction and is depicted in Figure 7. The structure revealed
that 5 is a dinuclear chloride-bridged complex with a slightly
distorted square planar coordination geometry about each
palladium atom. The environment around each palladium
consists of two bridging chlorides, one terminal chloride, and a
monodentate γ-diimine ligand with one of the ligand imine
functionalities remaining uncoordinated. The ligand again
preferentially adopts the same rotational conformer as that of
the solid-state structure of the free ligand, thereby effectively
inhibiting a bidentate coordination mode at the metal center.
(16) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. ReV. 2004,
248, 2283.
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1998, 39, 9793. (b) Miyazaki, F.; Yamaguchi, K.; Shibasaki, M. Tetrahedron
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P.; Hartwig, J. F. J. Am. Chem. Soc. 1999, 121, 2123.
(18) (a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 9550. (b) Yin, J.; Rainka, M. P.; Zhang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162. (c) Walker, S. D.;
Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew. Chem., Int. Ed.
2004, 43, 1871. (d) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald,
S. L. J. Am. Chem. Soc. 2005, 127, 4685. (e) Billingsley, K. L.; Barder,
T. E.; Buchwald, S. L. Angew. Chem., Int. Ed. 2007, 46, 5359.
(19) (a) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989. (b)
Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176. (c)
Firmansjah, L.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 11340.
(20) Cope, A. C.; Siekman, R. W. J. Am. Chem. Soc. 1965, 87, 3272.
(11) Polamo, M.; Hamalainen, M. Z. Kristallogr. NCS 2002, 217, 561.
(12) Jouaiti, A.; Geoffroy, M.; Bernardinelli, G. Chem. Commun. 1996,
437.

From Pyrroles to Isoindolines
Organometallics, Vol. 27, No. 10, 2008 2341
1
Figure 5. H NMR (CDCl3) spectra showing the cyclization of γ-diimine 2 to iminoisoindoline 4 at 60 °C: (a) γ-diimine 2 at t ) 0.25 h;
(b) 1:1 mixture of 2 and 4 observed at t ) 12 h; (c) complete cyclization to 4 observed at t ) 24 h.
Scheme 6
Figure 6. ORTEP plot of 4-DCl · CDCl3 at the 50% probability
level. The hydrogen/deuterium atoms, chloride counterion, and
solvent molecule have been omitted for clarity. Selected bond
lengths (Å) and angles (deg): N(1)-C(1) ) 1.345(3), N(1)-C(9)
) 1.442(3), N(1)-C(8) ) 1.469(4), N(2)-C(1) ) 1.304(4);
C(1)-N(1)-C(9) ) 126.1(2), C(9)-N(1)-C(8) ) 121.0(2),
C(1)-N(2)-C(21) ) 120.6(2), N(2)-C(1)-N(1) ) 123.3(2).
reaction were not reported until 1995.21 Palladacyclic com-
pounds currently rank among the best precatalysts for a variety
of C-C coupling reactions.21,22
γ-diimine ligand. No activity was observed with aryl chlorides.
Palladacycle 6, on the other hand, was a comparatively
exceptional precatalyst, even in the absence of stabilizing agents
such as tetrabutylammonium iodide. Reactions were carried out
in DMA at 145 °C in the presence of either CsOAc or Cs2CO3.
The precatalyst was active for both activated and deactivated
aryl bromides (Table 2). Palladacycle 6 also demonstrated
activity for aryl chlorides; however, longer reaction times (24
h) were required. Palladacycle 6 was active for the coupling of
butyl acrylate with 4-chloroacetophenone (18%) and 4-chlo-
robenzaldehyde (99%).
The catalytic activities of complexes 5 and 6 were investigated
in the standard Heck coupling reaction of aryl halides with butyl
acrylate (Table 2). Complex 5 showed catalytic activity similar
to that of ligand-free PdCl2, suggesting the ligand plays little,
if any, role in the catalytic cycle. This is not unexpected, given
the monodentate nature and poor σ-donating ability of the
(21) (a) Herrmann, W. A.; Brossmer, C.; Ofele, K.; Reisinger, C.-P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed. Engl. 1995,
34, 1844. (b) Beller, M.; Fischer, H.; Herrmann, W. A.; Olefe, K.; Brossmer,
C. Angew. Chem., Int. Ed. 1995, 34, 1848.
(22) (a) Farina, V. AdV. Synth. Catal. 2004, 346, 1553. (b) Dupont, J.;
Consorti, C. S.; Spencer, J. Chem. ReV. 2005, 105, 2527. (c) Beletskaya,
I. P.; Cheprakov, A. V. J. Organomet. Chem. 2004, 689, 4055. (d)
Herrmann, W. A.; Ofele, K.; von Preysing, S. K.; Schneider, D. J.
Organomet. Chem. 2003, 687, 229.
The catalytic activity of 6 was compared to that of Pd(OAc)2,
which is a known precatalyst. Under the conditions employed,
Pd(OAc)2 showed no activity for the coupling of aryl chlorides.

2342 Organometallics, Vol. 27, No. 10, 2008
Chitanda et al.
Figure 7. ORTEP plot of 5 at the 50% probability level. The
hydrogen atoms have been omitted for clarity. Selected bond lengths
(Å) and angles (deg): Cl(1)-Pd(1) ) 2.2796(9), Cl(2)-Pd(1) )
2.3141(9), Cl(2)-Pd(1)′ ) 2.3338(9), N(1)-C(7) ) 1.276(4),
N(1)-Pd(1) ) 2.028(3), N(2)-C(20) ) 1.259(5); C(7)-N(1)-Pd(1)
) 122.6(2), N(1)-Pd(1)-Cl(1) ) 90.79(8), Cl(1)-Pd(1)-Cl(2)
) 91.15(3), N(1)-Pd(1)-Cl(2)′ ) 93.50(8), Cl(2)-Pd(1)-Cl(2)′
) 84.63(3).
Figure 9. ORTEP plot of 6 at the 50% probability level, illustrating
the S-shape derived from the Pd3(OAc)4 core. The 2,6-iPr2-C6H3
groups and hydrogen atoms have been omitted for clarity.
Conclusion
We have prepared and structurally characterized a bulky
γ-diimine ligand and its corresponding Pd(II) complexes.
Analogous γ-diimines are likely intermediates in the reaction
of phthalaldehyde with primary amines to form the correspond-
ing iminoisoindolines and isoindolinones due to rapid intramo-
lecular cyclization reactions.9 γ-Diimine 2 can, however, be
isolated, due to the presence of bulky diisopropylphenyl groups
which likely inhibit or retard cyclization reactions. Depending
on the reaction conditions, cyclization of the γ-diimine can be
induced to form either the corresponding iminoisoindoline or
the isoindolinone. Unlike analogous R- and ꢀ-diimine com-
plexes, the γ-diimine ligand does not coordinate in a chelating
mode but instead adopts a monodentate coordination mode upon
reaction with PdCl2. On the other hand, reaction of γ-diimine
2 with Pd(OAc)2 results in C-H activation of the ligand and
formation of an air-stable palladacyclic species containing a rare
Pd3(OAc)4 core. The resulting palladacyclic complex is an active
precatalyst for the Suzuki and Heck coupling reactions when
para-functionalized aryl chlorides and aryl bromides are em-
ployed. The non-palladacyclic analogue [(γ-diimine)PdCl(µ-
Cl)]2 is a relatively inferior precatalyst, exhibiting no activity
for aryl chlorides. Due to intermolecular cyclization reactions,
it is unlikely that γ-diimines will emerge as a new class of ligand
comparable to R- and ꢀ-diimine analogues.
Figure 8. ORTEP plot of 6 at the 50% probability level. The
hydrogen atoms have been omitted for clarity. Selected bond lengths
(Å) and angles (deg): Pd(1)–C(3) ) 1.949(6), Pd(1)–N(1) )
2.018(4), Pd(1)–O(3) ) 2.057(4), Pd(1)–O(1) ) 2.127(4), Pd(1)–
Pd(2) ) 2.9721(6); C(3)–Pd(1)–N(1) ) 81.1(2), C(3)–Pd(1)–O(3)
) 92.57(19), N(1)–Pd(1)–O(1) ) 93.67(17), O(3)–Pd(1)–O(1) )
92.83(17).
Under different conditions, Pd(OAc)2 has been reported to be
active for the coupling of aryl bromides and aryl chlorides.23
The catalytic activity of complexes 5 and 6 were also tested
in the Suzuki coupling reaction of aryl halides with phenylbo-
ronic acid, using Cs2CO3 or CsOAc as base and DMA as solvent
at 80 °C (Table 3). As with the Heck reactions, while complex
5 was active for the catalytic coupling of aryl bromides, little
or no activity was observed with aryl chlorides. Palladacycle 6
again demonstrated good activity for activated aryl chlorides,
producing the target biphenyls in 73–86% conversions; however,
lower conversions were achieved for deactivated aryl chlorides
(entries 7 and 11 in Table 3).
Experimental Section
General Information. Unless otherwise stated, all reactions were
performed under N2 or vacuum using standard Schlenk techniques
or in an N2-filled drybox. All reaction temperatures for catalytic
reactions refer to the temperature of pre-equilibrated oil or sand
baths. All melting points were recorded on a Gallenkamp melting
point apparatus and are uncorrected. 1H and 13C{1H} NMR spectra
were recorded on a Bruker 500 MHz Avance spectrometer.
Chemical shifts for 1H and 13C NMR are reported in ppm,
referenced to the residual 1H and 13C resonances of CDCl3 (1H, δ
7.24; 13C, δ 77.24). Coupling constants are given in Hz. Elemental
analyses were performed on a Perkin-Elmer 2400 CHN elemental
(23) (a) Kohler, K.; Kleist, W.; Prockl, S. S. Inorg. Chem. 2007, 46,
1876. (b) Yao, Q.; Kinney, E. P.; Yang, Z. J. Org. Chem. 2003, 68, 7528.

From Pyrroles to Isoindolines
Organometallics, Vol. 27, No. 10, 2008 2343
Table 2. Heck Cross-Coupling of Aryl Halides with Butyl Acrylatea
entry
R
X
base
time (h)
cat. (amt (mol %))
conversn (%)b
TONc
1
2
3
4
5
6
7
8
H
H
COMe
CN
I
Cs2CO3
Cs2CO3
CsOAc
CsOAc
Cs2CO3
CsOAc
CsOAc
Cs2CO3
CsOAc
Cs2CO3
Cs2CO3
CsOAc
CsOAc
Cs2CO3
CsOAc
CsOAc
Cs2CO3
3
3
14
14
3
42
14
3
3
3
3
3
24
24
6
3
24
5 (0.1)
5 (1)
5 (1)
5 (3)
5 (1)
>99
50
97
86
66
0
>99
48
>99
>99
88
65
95
1000
50
97
29
66
0
100
48
10000
1000
88
65
95
100
18
0
Br
Br
Br
Br
Cl
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Me
COMe
COMe
H
COMe
COH
CN
OMe
Me
COH
COMe
COMe
COH
5 (3)
PdCl2 (1)
PdCl2 (1)
6 (0.01)
6 (0.1)
6 (1)
6 (1)
6 (1)
6 (1)
6 (1)
Pd(OAc)2 (1)
Pd(OAc)2 (1)
9
10
11
12
13
14
15
16
17
>99
18
0
0
0
a Reaction conditions: aryl halide (1.0 mmol), acrylate (2.0 mmol), base (2.0 mmol), Pd catalyst, solvent (DMA, 3 mL), 145 °C. b Determined by 1H
NMR on the basis of residual aryl halide.26 c TON ) turnover number ((mol of product)/(mol of catalyst)).
Table 3. Suzuki Cross-Coupling of Aryl Halides with Phenylboronic
Acida
7.04 (m, 3H), 6.99 (d, J ) 6.7 Hz, 2H), 6.66 (d, J ) 7.1 Hz, 1H),
4.94 (s, 2H). 13C NMR (CDCl3, ppm): δ 153.52, 150.87, 141.81,
140.59, 130.48, 129.34, 129.12, 127.53, 126.70, 123.33, 122.92,
122.44, 121.44, 120.18, 53.18. Anal. Calcd for C20H15N2: C, 84.48;
H, 5.67; N, 9.85. Found: C, 84.57; H, 5.62; N, 9.60. MS (TOF;
m/z): calcd for C20H15N2284.1313, found 285.1392 (M + 1). FT-
IR (KBr): 1646 (CdN), 1590, 1498.
Synthesis of 2,5-Dimethyl-1-(2,6-diisopropylphenyl)pyrrole
(1). A Schlenk flask was charged with 2,5-hexanedione (1.425 g,
0.0125 mol), 2,6-disopropylaniline (6.65 g, 0.0375 mol), methanol
(10 mL), and 1 drop of formic acid and the mixture stirred at
ambient temperature for 12 h. The flask was then placed in a -30
°C freezer, where colorless needlelike crystals formed. The solvent
was decanted and the resulting product washed with cold methanol
and then dried under vacuum to yield a white powder of the title
cat.
entry
R
X
base
time (h) (amt (mol %)) conversn (%)b
1
2
3
4
5
6
7
8
H
H
I
Cs2CO3
3
3
3
3
3
5 (1)
5 (1)
5 (1)
5 (1)
5 (3)
5 (3)
6 (1)
6 (1)
6 (1)
6 (1)
6 (1)
>99
94
92
98
3
Br Cs2CO3
Br Cs2CO3
Me
COMe Br Cs2CO3
COMe Cl Cs2CO3
H
Cl Cs2CO3
Cl Cs2CO3
Cl Cs2CO3
3
0
1
compound (2.03 g, 90%). H NMR (CDCl3): δ 7.39 (t, J ) 7.7,
OMe
COH
24
24
24
3
8
1H, C6H3), 7.61 (d, J ) 7.7, 2H, C6H3), 5.92 (s, 2H, C4H2N), 2.35
(sept, J ) 6.9, 2H, CH(CH3)2), 1.89 (s, 6H, C4H2N(CH3)2), 1.1 (d,
J ) 6.9, 12H, CH(CH3)2). 13C NMR (CDCl3): δ 147.8, 134.3, 129.3,
129.0, 124.0, 105.5, 28.0 (CH(CH3)2), 24.3 (CH(CH3)2), 12.9 (CH3).
Anal. Calcd for C18H25N: C, 84.65; H, 9.87; N, 5.48. Found: C,
84.41; H, 9.60; N, 5.45. EI-MS (m/z): calcd for C18H29N 255.1987,
found 255.1985.
73
86
78
17
9
10
11
COMe Cl CsOAc
CN
Me
Cl Cs2CO3
Cl Cs2CO3
24
a Reaction conditions: aryl halide (1.0 mmol), phenylboronic acid (1.5
mmol), base (2 mmol), Pd catalyst, DMA (3 mL), 80 °C,
3 h.
b Determined by 1H NMR on the basis of residual aryl halide.26
Synthesis of the γ-Diimine 1,2-(2,6-iPr2-C6H3NC)2-C6H4 (2)
and N-(2,6-Diisopropylphenyl)isoindolinone (3). A flask was
charged with phthaldehyde (1.502 g, 11.2 mmol), 2,6-diisopropy-
laniline (14.1 g, 79.5 mmol), and methanol (15 mL) under a nitrogen
atmosphere. Formic acid (0.4 mL) was added and the mixture stirred
at 0 °C. A yellow precipitate appeared within 10 min of stirring.
After 4 h of stirring, the precipitate was filtered, washed with
methanol (3 × 10 mL), and dried under vacuum to yield 2 as a
yellow powder (3.371 g, 66%). Yellow crystals were obtained from
slow evaporation of ether at ambient temperature. The colorless
filtrate was transferred back to the flask, where continued stirring
was allowed for 12 h. Methanol and excess 2,6-diisopropylaniline
were removed at 100 °C by vacuum distillation. Ether (10 mL)
was added, and the flask was placed in a -30 °C freezer, whereupon
colorless crystals of 3 were obtained (0.985 g, 30%).
analyzer. IR data were collected by diffuse reflectance spectroscopy.
Reagents such as PdCl2, Pd(OAc)2, 2,6-diisopropylaniline, phthala-
ldehyde, and cyclooctene (COE) were purchased from Sigma-
Aldrich Chemical Co. and used as received, except for 2,6-
diisopropylaniline, which was distilled prior to use.
(CH3CN)2PdCl224 and [(COE)PdCl2]225 were synthesized according
to literature procedures.
Synthesis of 1-(Phenylimino)-2-phenylisoindoline. A Schlenk
flask was charged with phthalaldehyde (500 mg, 3.73 mmol), aniline
(695 mg, 7.46 mmol), methanol (10 mL), and 2 drops of formic
acid and stirred at ambient temperature for 12 h. The resulting
precipitate was filtered, washed with methanol (3 × 20 mL), and
then dried under vacuum to obtain a white solid (795 mg, 75%,
1
mp 127.8–129.5 °C). H NMR (CDCl3, ppm): δ 8.01 (d, J ) 6.0
Hz, 2H), 7.44 (d, J ) 7.5 Hz, 1H), 7.38 (m, 3H), 7.31 (m, 2H),
1,2-(2,6-iPr2-C6H3NC)2-C6H4 (2). 1H NMR (CDCl3): δ 8.82 (s,
2H, CdNH), 8.11 (dd, J ) 5.7, 3.4, 2H, C6H4), 7.63 (dd, J ) 5.7,
3.4, 2H, C6H4), 7.07 (m, 6H, 2,6-iPr2-C6H3), 2.94 (sept, J ) 6.6,
4H, CH(CH3)2), 1.08 (d, 24H, J ) 6.9, CH(CH3)2). 13C NMR
(CDCl3): δ 161.8, 149.8, 137.5, 135.9, 131.5, 130.3, 124.7, 123.4,
(24) Mathews, C. J.; Smith, P. J.; Welton, T. J. Mol. Catal. A: Chem.
2004, 214, 27.
(25) Dneprovskii, A. S.; Ermoshkin, A. A.; Kasatochkin, A. N.;
Boyarskii, V. P. Russ. J. Org. Chem. 2003, 39, 933.

2344 Organometallics, Vol. 27, No. 10, 2008
Chitanda et al.
28.4 (CH), 24.9 (CH3). Anal. Calcd for C32H40N2: C, 84.90; H,
8.90; N, 6.18. Found: C, 84.30; H, 8.61; N, 6.02. Mp: 180.0-182.5
°C. FT-IR (KBr, cm-1): 1633 (CdN). EI-MS (m/z): calcd for
C32H40N2 452.3191, found 452.3185.
0.88–0.80 (m, 39H, CH(CH3)2). 13C NMR (CDCl3): δ 176.0, 161.8,
148.8, 145.9, 142.8, 137.6, 135.8, 133.8, 132.9, 132.8, 131.9, 130.4,
128.7, 125.1, 124.6, 123.3, 28.9, 28.4, 23.9, 23.8. FT-IR (KBr,
cm-1): 1633 (free imine, CdN), 1618 (coordinated imine, CdN-Pd).
Synthesis of {1,2-(2,6-iPr2-C6H3NC)2-C6H3]Pd(µ-OAc)2}2Pd
(6). A Schlenk flask was charged with 2 (657 mg, 1.45 mmol),
Pd(OAc)2 (362 mg, 1.45 mmol), and ether (20 mL) under nitrogen.
After 16 h of stirring at ambient temperature, the resulting orange
precipitate was filtered in air, washed with cold ether (3 × 10 mL),
and dried under vacuum. Orange crystals of 6 were obtained from
dichloromethane/hexanes (1:1) by slow evaporation at ambient
Alternative Synthesis of N-(2,6-Diisopropylphenyl)isoindoli-
none (3). A flask was charged with phthalaldehyde (0.526 g, 3.92
mmol), 2,6-diisopropylaniline (0.696 g, 3.92 mmol), formic acid
(0.032 g, 0.695 mmol), and methanol (10 mL). After 19 h of stirring
at ambient temperature, the flask was placed in a -30 °C freezer,
whereupon colorless needlelike crystals formed. The solvent was
decanted and the crystals dried under vacuum to yield a white
powder of the title compound (0.861 g, 75%). Mp ) 155.0–157.0
°C. 1H NMR (CDCl3): δ 7.98 (d, J ) 7.5, 1H, C6H4), 7.61 (m, 1H,
C6H4), 7.53 (d, J ) 7.5, 1H, C6H4), 7.50 (d, J ) 7.5, 1H, C6H4),
7.39 (t, J ) 7.7, 1H, C6H3), 7.25 (d, J ) 7.7, 2H, C6H3), 4.56 (s,
2H, CH2), 2.76 (sept, J ) 6.9, 2H, CH(CH3)2), 1.19 (d, J ) 6.9,
12H, CH(CH3)2). 13C NMR (CDCl3): δ 168.8 (CdO), 147.8, 141.6,
133.0, 132.6, 131.8, 129.4, 128.5, 124.8, 124.3, 123.1, 54.0, 29.0
(CH), 24.7 (CH3), 24.5 (CH3). Anal. Calcd for C20H23NO: C, 81.87;
H, 7.90; N, 4.77. Found: C, 81.70; H, 7.80; N, 4.76. FT-IR (KBr,
cm-1): 1694.8 (CdO). EI-MS (m/z): calcd for C20H23NO 293.1779,
found 293.1774.
1
temperature (504 mg, 24%). Mp: 206.5–208.5 °C dec. H NMR
(CDCl3): 9.50 (s, 2H, HCdN), 8.09 (s, 2H, HCdN), 7.44 (dd, J )
6.3, 2.5 Hz, 2H), 7.30 (m, 4H), 7.19 (m, 4H), 7.05 (m, 8H), 4.17
(sep, J ) 7.0 Hz, 2H, CH(CH3)2), 3.51 (sept, J ) 7.0 Hz, 2H),
2.84 (sept, 4H, CH(CH3)2), 1.98 (s, 6H, OAc), 1.44 (d, J ) 7 Hz,
6H, CH(CH3)2), 1.15 (d, J ) 7 Hz, 6H, CH(CH3)2), 1.14 (s, 6H,
OAc), 1.05 (d, J ) 7 Hz, 12H, CH(CH3)2) 1.04 (d, J ) 7 Hz, 18H,
CH(CH3)2), 1.01 (d, J ) 7 Hz, 6H, CH(CH3)2). 13C NMR (CDCl3):
δ 184.1, 183.0, 177.7, 162.6, 161.0, 148.9, 144.6, 143.6, 143.0,
141.8, 137.5, 135.5, 134.7, 130.7, 130.0, 127.6, 124.6, 123.3, 123.3,
123.2, 66.1, 28.5, 28.2, 27.8, 26.2, 24.8, 23.8, 23.6, 23.5, 23.5, 23.0,
22.9, 22.8, 15.5. Anal. Calcd for C72H90N4O8Pd3: C, 59.28; H, 6.22;
N, 3.84. Found: C, 58.89; H, 6.44; N, 3.71. FT-IR (KBr, cm-1):
1631 (free imine, CdN), 1580 (coordinated imine, CdN-Pd).
General Procedure for Heck Coupling Reactions. In a typical
run, an oven-dried 25 mL two-necked flask equipped with a stir
bar was charged with a known mole percent of catalyst and base
(2.0 mmol). Under nitrogen, DMA (3 mL), aryl halides (1.0 mmol)
and n-butyl acrylate (2.0 mmol) were added via syringe. The flask
was then placed in a preheated sand bath at 145 °C. After the
specified time the flask was removed from the sand bath and water
(20 mL) added, followed by extraction with dichloromethane (4 ×
10 mL). The combined organic layers were washed with water (3
× 10 mL), dried over anhydrous MgSO4, and filtered. Solvent was
removed under vacuum. The residue was dissolved in CDCl3 and
analyzed by 1H NMR. Percent conversions were determined against
the remaining aryl halide.26
General Procedure for Suzuki Coupling Reactions. In a typical
run, an oven-dried 25 mL two-necked flask equipped with a stir
bar was charged with a known mole percent of catalyst, base (2.0
mmol), and phenylboronic acid (1.5 mmol). Under nitrogen, DMA
(3 mL) and aryl halides (1.0 mmol) were added via syringe. The
flask was placed in a preheated sand bath at 80 °C. After the
specified time the flask was removed from the sand bath and water
(20 mL) added, followed by extraction with dichloromethane (4 ×
10 mL). The combined organic layers were washed with water (3
× 10 mL), dried over anhydrous MgSO4, and filtered. Solvent was
removed under vacuum. The residue was dissolved in CDCl3 and
analyzed by 1H NMR. Percent conversions were determined against
the remaining aryl halide.26
Synthesis of N,N′-Bis(2,6-diisopropylphenyl)iminoisoindoline
(4). A flask was charged with γ-diimine 2 (100 mg, 0.220 mmol)
and chloroform-d (10 mL). After 48 h of stirring at 60 °C under an
ambient atmosphere, the solution had changed from yellow to
colorless. The solvent was removed under vacuum to yield a white
powder (91 mg, 91%). The cyclization was observed to proceed
considerably more slowly when the reaction was performed under
1
nitrogen in place of air. H NMR (CDCl3): δ 7.37 (m, 3H), 7.26
(d, J ) 2, 2H), 7.05 (m, 4H), 6.38 (d, J ) 8.0, 1H), 4.69 (s, 2H,
CH2), 3.19 (sept, J ) 6.8, 2H, CH(CH3)2), 3.10 (sept, J ) 6.8, 2H,
CH(CH3)2), 1.32 (d, J ) 6.8, 6H, CH(CH3)2), 1.23 (d, J ) 6.8,
6H, CH(CH3)2), 1.07 (d, J ) 6.9, 6H, CH(CH3)2), 0.87 (d, J )
6.9, 6H, CH(CH3)2). 13C NMR (CDCl3): δ 155.0, 147.88, 146.26,
140.97, 139.21, 134.47, 131.42, 129.75, 128.56, 127.15, 126.44,
124.09, 122.64, 122.27, 55.22, 28.44, 27.44, 25.81, 24.17, 23.62,
23.52. FT-IR (KBr, cm-1): 1644 (CdN). EI-MS (m/z): calcd for
C32H40N2 452.3191, found 452.3185.
NMR-Tube Reaction for the Cyclization of γ-Diimine 2 to
Iminoisoindoline 4. An NMR tube was charged with 2 (3 mg, 6.6
µmol) and CDCl3 (0.6 mL) in air. The reaction was monitored over
24 h at 60 °C. During the course of the reaction, the solution
changed from yellow to colorless. 1H NMR spectra showed
complete conversion of 2 to 4 after 24 h. Prolonged exposure of 4
to CDCl3 over the course of 2 weeks resulted in precipitation of
colorless crystals of the DCl salt of 4 (4-DCl).
Cyclization of γ-Diimine 2 To Form N-(2,6-Diisopropylphe-
nyl)isoindolinone (3). A flask was charged with 2 (28.00 mg,
0.0619 mmol), methanol (15 mL), and 2 drops of formic acid. After
the mixture was stirred for 24 h, the solution changed from yellow
1
X-ray Structure Determinations. Data were collected at -100
°C on a Nonius Kappa CCD diffractometer, using the COLLECT
program.27 Cell refinement and data reductions used the programs
DENZO and SCALEPACK.28 SIR9729 was used to solve the
to colorless. Solvent was removed under vacuum, and H NMR
analysis showed the quantitative conversion of 2 to 4, along with
formation of 1 equiv of 2,6-diisopropylaniline.
Synthesis of [(γ-diimine)PdCl(µ-Cl)]2 (5). A Schlenk flask was
charged with 2 (0.168 g, 0.371 mmol), (CH3CN)2PdCl2 (0.053 g,
0.204 mmol), and benzene (20 mL) under nitrogen. Within 0.5 h
of stirring at ambient temperature, the yellow-green mixture became
a red-brown homogeneous solution. After 16 h, the resulting yellow-
brown precipitate was filtered and washed with cold benzene (3 ×
10 mL) under air. The product was then crystallized by slow
evaporation from CHCl3 to give orange crystals of 5 (0.121 g, 47%).
Mp: 181.5–182.0 °C dec. 1H NMR (CDCl3): 9.69 (d, J ) 7.4 Hz,
2H), 8.25 (s, 2H, HCdN), 8.17 (s, 2H, HCdN), 8.04 (t, J ) 7.5
Hz, 2H), 7.86 (m, 2H), 7.64 (d, J ) 7.4 Hz, 2H), 7.17 (t, J ) 7.5
Hz, 2H), 7.04 (d, J ) 7.6 Hz, 4H, C6H3), 7.00 (br, 6H), 3.26 (m,
4H, CH(CH3)2), 2.57 (m, 4H, CH(CH3)2), 1.64 (br, 9H, CH(CH3)2).
(26) (a) Peris, E.; Mata, J.; Loch, J. A.; Crabtree, R. H. Chem. Commun.
2001, 201. (b) Chen, C. L.; Liu, Y. H.; Peng, S. H.; Liu, S. T.
Organometallics 2005, 24, 1075. (c) Albisson, D. A.; Bedford, R. B.; Noelle,
S. P.; Lawrence, S. E. Chem. Commun. 1998, 19, 2095. (d) Evans, P.; Hogg,
P.; Grigg, R.; Nurnabi, M.; Hinsley, J.; Sridharan, V.; Suganthan, S.; Korn,
S.; Collard, S.; Muir, J. E. Tetrahedron 2005, 61, 9696.
(27) Nonius., COLLECT; Nonius BV, Delft, The Netherlands, 1998.
(28) Otwinowski, Z.; Minor, W. Methods in Enzymology, Macromo-
lecular Crystallography, Part A; Carter, C. W., Sweet, R. M., Eds.;
Academic Press: London, 1997; Vol. 276, pp 307–326..
(29) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G; Giacovazzo,
C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl.
Crystallogr. 1999, 32, 115.

From Pyrroles to Isoindolines
Organometallics, Vol. 27, No. 10, 2008 2345
structures, and SHELXL9730 was used to refine the structures.
ORTEP-3 for Windows31 was used for molecular graphics, and
PLATON32 was used to prepare material for publication. H atoms
were placed in calculated positions with Uiso constrained to be 1.5
times the Ueq value of the carrier atom for methyl protons and 1.2
times the Ueq value of the carrier atom for all other hydrogen atoms.
Acknowledgment. We gratefully thank the NSERC for
financial support and the Canadian Government through the
Commonwealth Scholarship fund for a doctoral fellowship
(J.M.C.).
Supporting Information Available: CIF files giving gull
crystallographic data for compounds 2, 3, 4-DCl · CDCl3,
5 · 2CHCl3, and 6 · 2CH2Cl2. This material is available free of charge
via the Internet at http://pubs.acs.org.
(30) Sheldrick, G. M. SHELXL-97; University of Göttingen, Go¨ttingen,
Germany, 1997.
(31) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
(32) Spek, A. L. PLATON; University of Utrecht, Utrecht, The
Netherlands, 2001.
OM800080E