Diastereoinduction in the synthesis of pallada(II)pyrrolidinones: Palladacycles with two Pd-bonded stereogenic carbons

Article abstract of DOI:10.1021/om800630f

Stable palladapyrrolidinones (L-L)Pd-CH(p-MeC₆H ₄)NBnC(=O)CHPh representing endocyclic carbon-bonded palladium(II) amide enolates with two Pd-bonded sp³-hybridized stereogenic carbons and bidentate auxiliary ligands (tetra

Full text of DOI:10.1021/om800630f

810
Organometallics 2009, 28, 810–818
Diastereoinduction in the Synthesis of Pallada(II)pyrrolidinones:
Palladacycles with Two Pd-bonded Stereogenic Carbons
John C. Hershberger, Victor W. Day, and Helena C. Malinakova*
Department of Chemistry, UniVersity of Kansas, 1251 Wescoe Hall DriVe, Lawrence, Kansas 66045
ReceiVed July 4, 2008
Stable palladapyrrolidinones (L-L)Pd-CH(p-MeC6H4)NBnC(dO)CHPh representing endocyclic carbon-
bonded palladium(II) amide enolates with two Pd-bonded sp3-hybridized stereogenic carbons and bidentate
auxiliary ligands (tetramethylethylenediamine (TMEDA), bis(diphenylphosphino)ethane (dppe), and (S,S)-
CHIRAPHOS) were synthesized. The syntheses proceeded with a significant diastereoinduction from
the Pd-bonded stereocenter in racemic cationic palladium amide complexes [(L-L)Pd-CH(p-
-
MeC6H4)NBnC(dO)CH2Ph]+OTf favoring the formation of cis diastereomers (denoting the relative
stereochemistry of the two sp3-hybridized carbons in the adjacent positions of the square planar Pd(II)
complexes), whereas epimerization of the Pd-bonded stereocenters favoring the formation of the more
stable trans diastereomers was achieved under basic conditions. Studies of the stereochemical relationships
between Pd-bonded stereocenters in palladapyrrolidinones bearing chiral nonracemic auxiliary ligands
((S,S)-CHIRAPHOS) indicated a lack of double diastereodifferentiation induced by the auxiliary ligands.
Molecular structures of the cis diastereomers of pallada(II)pyrrolidinones bearing TMEDA and dppe
ligands were established by X-ray crystallography.
Introduction
In the past, systematic studies on the structure and reactivity
of stable organopalladium complexes have facilitated the
development of new Pd-catalyzed reactions important to organic
synthesis.1 The design of palladium-catalyzed protocols for the
formation of a bond between two sp3-hybridized and potentially
stereogenic carbons represents one of the frontiers of current
organopalladium chemistry.2 However, explorations of the
chemistry of stable isolated organopalladium complexes pos-
sessing two Pd-bonded sp3-hybridized stereogenic carbons3
remain rare. Aiming to extend our program investigating the
chemistry of pallada(II)cycles I with a Pd-bonded stereogenic
carbon,4 we became intrigued by related structures of complexes
II possessing two Csp3-Pd bonds in cis positions of a square
planar Pd(II) complex (Figure 1). We envisioned that the first
Csp3-Pd bond would be formed via an oxidative cyclization
of acyliminium salts and a Pd(0) source as reported by Arndtsen
Figure 1
and co-workers5 and a subsequent intramolecular nucleophilic
attack of an amide enolate at the cationic Pd(II) center would
afford the desired complex II (Figure 1).6 Complexes II could
serve as models for investigating the stereoinduction between
the Pd-bonded stereocenters and the chiral nonracemic ligands
(L-L).7
* To whom correspondence should be addressed. E-mail: hmalina@
ku.edu.
(1) (a) Heck, R. F. Synlett 2006, 2855. (b) Heck, R. F. J. Am. Chem.
Soc. 1968, 90, 5518.
(2) (a) Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 9602. (b)
Netherton, M. R.; Dai, C.; Neuschu¨tz, K.; Fu, G. C. J. Am. Chem. Soc.
2001, 123, 10099. (c) Ishiyama, T.; Abe, S.; Miyaura, N.; Suzuki, A. Chem.
Lett. 1992, 691.
Herein, we describe the preparation of the palladapyrrolidi-
none complexes II, representing rare examples of stable
(3) (a) Hashimi, A. S. K.; Grundl, M. A.; Bats, J. W.; Bolte, M. Eur. J.
Org. Chem. 2002, 1263. (b) Hashmi, A. S. K.; Naumann, F.; Nass Rivas,
A.; Degen, A.; Bolte, M.; Bats, J. W. Chem.sEur. J. 1999, 5, 2836. For
additional examples of complexes with two unsubstituted sp3-hybridized
methylene groups bonded to Pd, see. (c) Byers, P. K.; Canty, A. J.; Crespo,
M.; Puddephatt, R, J.; Scott, J. D. Organometallics 1988, 7, 1363. (d)
Diversi, P.; Ingrosso, G.; Lucherini, A.; Lumini, T.; Marchetti, F. J. Chem.
Soc., Dalton Trans. 1988, 133.
(4) (a) Lu, G.; Portscheller, J. L.; Malinakova, H. C. Organometallics
2005, 24, 945. (b) Lu, G.; Malinakova, H. C. J. Org. Chem. 2004, 69, 4701.
(c) Lu, G.; Malinakova, H. C. J. Org. Chem. 2004, 69, 8266. (d) Portscheller,
J. L.; Lilley, S. E.; Malinakova, H. C. Organometallics 2003, 22, 2961. (e)
Portscheller, J. L.; Malinakova, H. C. Org. Lett. 2002, 4, 3679.
(5) (a) Davis, J. L.; Dhawan, R.; Arndtsen, B. A. Angew. Chem., Int.
Ed. 2004, 43, 590. (b) Dghaym, R. D.; Dhawan, R.; Arndtsen, B. A. Angew.
Chem., Int. Ed. 2001, 40, 3228. (c) Dghaym, R. D.; Yaccato, K. J.; Arndtsen,
B. A. Organometallics 1998, 17, 4.
(6) Culkin, D. A.; Hartwig, J. F. Organometallics 2004, 23, 3398.
(7) In principle, any stereocenters present in chiral nonracemic auxiliary
ligands (L*-L*) in palladium-chelated amide complexes could either enhance
or diminish the diastereoselectivity observed for the formation of pallada-
cycles II from palladium-chelated amide complexes possessing a single
palladium-bonded sp3-hybridized stereogenic carbon and achiral (!) auxiliary
ligands (L-L).
10.1021/om800630f CCC: $40.75
2009 American Chemical Society
Publication on Web 01/15/2009

Diastereomers of Pallada(II)pyrrolidinones
Organometallics, Vol. 28, No. 3, 2009 811
Scheme 1
Scheme 2
endocyclic carbon-bonded palladium amide enolates8 with two
sp3-hybridized stereogenic carbons attached to the palladium(II)
center, and investigations of the effects of chiral nonracemic
auxiliary ligand on the stereoinduction during the formation of
the second Pd-bonded sp3-hybridized stereocenter. Notably,
whereas the diastereoinduction from the R-N-substituted Pd-
bonded carbon in the final step of the synthesis of complexes
II was found to be substantial providing racemic complexes II
highly enriched in a single diastereomer (diastereomeric ratio,
dr ) 94:6 or 87:13), the chiral nonracemic auxiliary ligands
(L-L) present in palladapyrrolidinones did not induce significant
double diastereodifferentiation.
a
b
Longer reaction times result in lower yields. Run for 5 h at rt.
c
d
From (()-3. From (()-2.
Next, racemic palladium amide complexes (()-1 and (()-2
featuring a single palladium-bonded stereocenter were treated
with a base to explore the possibility of creating a second
palladium-bonded sp3-hybridized stereogenic carbon. Mecha-
nistically, the transformation was anticipated to involve an initial
deprotonation of the methylene group R to the amide group,
generating O-bonded amide enolates,6 the concentration of
which would depend on the choice of base and reaction
conditions. Subsequent tautomerization of the O-bonded cationic
amide enolates into the endocyclic C-bonded palladium enolates6,8
would deliver the second palladium-bonded stereocenter in
palladacycles II (Scheme 2). Thus, the treatment of the racemic
complexes (()-1 and (()-2 with t-BuOK at elevated temper-
atures (45 °C, 0.5 h, THF) afforded good yields of the desired
racemic palladacycles (()-3 and (()-4, respectively (Scheme
Results and Discussion
Reasoning that oxidative cyclization of N-acyliminium ions
with a stoichiometric Pd(0) source would provide an effective
alternative to Csp3-H activation or Csp3-X activation9 for the
generation of a sterically encumbered Pd-bonded stereocenter,
cationic palladium-chelated amide complex (()-1 was synthe-
sized by a modification of the protocol reported by Arndtsen et
al.5b (Scheme 1).
Establishing a sufficient concentration of the acyliminium ion
resulting from the equilibrium between the imine and the acyl
chloride relative to the concentration of palladium(0) proved
to be critical to achieving a high conversion of the Pd2dba3
limiting reagent. The difficulties encountered in our initial
attempts to isolate the unstable cationic palladium-chelated
amide complexes bearing the nucleophilic chloride counterion
were circumvented by a final anion metathesis induced by the
addition of silver triflate (3.3 equiv) (Scheme 1). Racemic
complex (()-1 was conveniently isolated as a yellow solid in
67% yield by column chromatography over silica. When the
tetramethylethylenediamine ligand (TMEDA) was replaced with
bis(diphenylphosphino)ethane (dppe), the isolation of the cor-
responding palladium amide was complicated by a difficult
separation of the product from the complex of the residual dppe
ligand with Ag+ salt. Thus, a yellow solid of the racemic cationic
palladium amide (()-2 bearing the dppe ligand was obtained
via a high-yielding ligand exchange reaction of complex (()-1
and was fully characterized (Scheme 2).
1
2). H NMR spectral data for palladacycles (()-3 and (()-4
are consistent with the presence of two methine carbons bonded
to palladium and indicate that two diastereomers were formed
in unequal ratios. Additional evidence supporting the structures
of palladacycles (()-3 and (()-4 with two Pd-bonded sp3-
hybridized carbons, rather than O-bonded Pd-amide enolates,
includes IR CdO stretches associated with the amide bonds in
palladacycles (()-3 and (()-4 found at 1617 and 1606 cm-1
,
respectively, contrasting with the IR CdO stretch signals at 1578
and 1554 cm-1 found in the palladium-chelated amide com-
1
plexes (()-1 and (()-2, respectively. Furthermore, H NMR
spectra of palladacycles (()-3 and (()-4 are not consistent with
the presence of vinylic protons. The signals assigned to the
palladium-bonded carbons appear as two pairs of singlets at
4.12 and 3.99 ppm (the major diastereomer) and at 4.13 and
3.94 ppm (the minor diastreomer) in the spectra of complex
(()-3, and as two sets of triplets or doublet of doublets at 4.75
ppm (t, J ) 7.6 Hz) and 4.40 ppm (dd, J ) 8.8 Hz, 6.0 Hz)
(the major diastereomer) and 4.78 ppm (t, J ) 7.0 Hz) and 4.53
ppm (t, J ) 7.0 Hz) (the minor diastereomer) in the spectra of
complex (()-4. Notably, 31P NMR spectra recorded at room
temperature on complex (()-4 revealed the presence of two
pairs of broad singlet signals, instead of the anticipated two
(8) For examples of complexes featuring palladium ester and ketone
enolate groups, see (a) Campora, J.; Maya, C. M.; Palma, P.; Carmona, E.;
Guterrez, E.; Ruiz, C.; Graiff, C.; Tiripicchio, A. Chem.sEur. J. 2005, 11,
6889. (b) Albeniz, A. C.; Catalina, N. M.; Espinet, P.; Redon, R.
Organometallics 1999, 18, 5571.
(9) (a) Lu, Y.; Arndtsen, B. A. Org. Lett. 2007, 9, 4395. (b) Giri, R.;
Maugel, N.; Foxman, B. N.; Yu, J.-Q. Organometallics 2008, 27, 1667. (c)
Watanabe, T.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2008, 10, 1759.

812 Organometallics, Vol. 28, No. 3, 2009
Hershberger et al.
Figure 2. Thermal ellipsoid diagram of complex cis (()-3. The
ellipsoids are drawn at 50% probability level (for experimental
details, see the Supporting Information).
pairs of doublets resulting from the two unequivalent P-atoms.10
We have observed a similar phenomenon in 31P NMR spectra
of palladacycles featuring sterically encumbered fully substituted
tertiary sp3-hybridized Pd-bonded carbon, which we prepared
in our prior studies.11 Conceivably, the steric hindrance at the
Pd-bonded stereocenter could cause a facile reversible dissocia-
tion of one of the two P-atoms from the Pd-center.11 To establish
the ratios of the diastereomers in palladacycles (()-3 and (()-
4, the relative integration of the signals for one of the two
diastereotopic benzylic protons in the N-benzyl group for each
diastereomer was employed, revealing that the palladacycle
(()-3 was produced in dr 89:11 and palladacycle (()-4 in dr
72:28.12
Figure 3. Thermal ellipsoid diagram of complex cis (()-4. The
ellipsoids are drawn at 50% probability level (for experimental
details, see the Supporting Information).
Diffusion-controlled crystallization of palladacycle (()-3 (dr
75:25)13 from a benzene/pentane mixture afforded yellow single
crystals suitable for X-ray crystallographic analysis, which
established the molecular structure of the crystalline complex
as the cis diastereomer14 (Figure 2). The sample of the crystalline
cis palladacycle (()-3 was subjected to 1H NMR analysis
allowing us to assign the chemical shifts to the cis and trans
diastereomers of complex (()-3, revealing that the cis diaste-
reomer of palladacycle (()-3 was the major product (Scheme
2). Our prior studies4b,d indicate that no C-Pd bond breaking
Figure 4. Superimposed molecular structures of cis (()-3 and cis
(()-4 based on X-ray crystallographic data.
and therefore no change in the diastereomeric composition of
palladacycles is expected to occur during a ligand exchange
reaction. Accordingly, the treatment of palladacycle (()-3 (dr
89:11) with the dppe ligand afforded palladacycle (()-4
possessing the corresponding (dr 87:13) ratio of diastereomers,
identifying the major diastereomer of palladacycle (()-4 as cis
and the minor as trans. The diffusion-controlled crystallization
of palladacycle (()-4 (dr 86:14) afforded single crystals suitable
for X-ray crystallographic analysis, which provided the molec-
ular structure of the cis diastereomer of palladacycle (()-4
(Figure 3).
The only significant differences in the metrical parameters
for the metallacycles of cis (()-3 and cis (()-4 involve the
bonds to the metal. The Pd-C(1) bond lengths (2.040(4) Å in
cis (()-3 and 2.082(2) Å in cis (()-4) in both compounds are
slightly shorter than the Pd-C(4) bond lengths (2.048(3) Å in
cis (()-3 and 2.096(2) Å in cis (()-4). Additionally, both Pd-C
bonds in cis (()-3 are shorter than either Pd-C bond in cis
(()-4, presumably due to the greater trans influence of
phosphines over amines. Notably, the conformations of the five-
atom square planar coordination grouping and pyrrolidinone
ligands in cis (()-3 and cis (()-4 are remarkably similar,
causing the 21 nonhydrogen atoms of the two complexes to
superimpose with a root-mean-square (rms) deviation of 0.17
Å (Figure 4). The five-atom square-planar coordination group-
ings, as well as the five nonhydrogen atoms (Pd, O, C(1), C(2),
(10) Temperature dependent 31P NMR spectra of complex (()-4 (in d8-
toluene) were recorded ranging the temperatures from-70 to +80 °C.
However, a significant sharpening of the signals has not been achieved.
For experimental details, see the Supporting Information.
(11) For the discussion of the effects of steric hindrance on the stability
of palladacycles of type I, see ref 4a.
(12) The 1H NMR signals for the benzylic protons in the spectra of
palladacycles (()-3 and (()-4 allowed for the most precise integration. In
the 1H NMR spectrum of palladacycle (()-3, the signals of the benzylic
protons that were used for the assignment of dr were found at 4.89 ppm (d,
J ) 14.8 Hz) for the minor diastereomer and at 4.84 ppm (d, J ) 14.5 Hz)
for the major diastereomer. In the 1H NMR spectrum of palladacycle (()-
4, the signals of the benzylic protons that were used for the assignment of
dr were found at 5.12 ppm (dd, J ) 14.0 Hz, 1.6 Hz) for the minor
diastereomer and at 5.03 ppm (dd, J ) 14.4 Hz, 2.0 Hz) for the major
diastereomer.
(13) An inappropriate choice of the elution system for the chromato-
graphic purification of complex (()-3 causes decomposition of the major
diastereomer of the complex (()-3 during the separation. The sample of
(()-3 with dr 75:25 was obtained in our initial studies using a relatively
weak elution system (low gradient of ethyl acetate in hexane).
(14) Herein, the designation “cis” and “trans” diastereomer of pallada-
cycles (()-3, (()-4, and 6a-d refers to the relative stereochemistry at the
palladium-bonded sp3-hybridized stereogenic carbons. In the cis diastere-
omers, the two aryl substituents attached to the Pd-bonded sp3-hybridized
carbons are both located on the same face of the square planar palladium(II)
complex. In the trans diastereomers, the two aryl substituents are bonded
to the opposite faces of the square planar palladium(II) complex.

Diastereomers of Pallada(II)pyrrolidinones
Organometallics, Vol. 28, No. 3, 2009 813
N(3) and C(4)) in both cis (()-3 and cis (()-4 palladacycles,
are coplanar to within 0.05 Å.
with 0.1 equiv or 0.5 equiv of t-BuOK at room temperature for
1 h did not produce any change in the cis:trans ratios detectable
by H NMR. No epimerization in the sample of palladacycle
1
Interestingly, a distinct folding, defined by the dihedral angle
(R) between the normals to the mean planes of the five-atom
square planar coordination groupings (plane labeled a in Figure
4) and the six-atom L · · · L groupings containing the two
heteroatoms and their four methyl or phenyl carbons (plane
labeled b in Figure 4), was observed in the solid phase structures
of complexes cis (()-3 and cis (()-4. Thus, the pyrrolidinone
ligands “fold” by 6° or 9° along the C(1) · · · C(4) polyhedral
edge, and the TMEDA and dppe (L · · · L) ligands “fold” by 13°
or 25° along their respective N(1) · · · N(2) and P(1) · · · P(2)
polyhedral edges away from the pyrrolidinone ligands. As
expected, both the “fold” angles are larger for the complex cis
(()-4. Experiments reported in Scheme 2 showed that, in the
presence of both types of auxiliary ligands (TMEDA and dppe),
the formation of the cis diastereomer of palladacycles (()-3
and (()-4 from palladium-chelated amide complexes (()-1 and
(()-2 was favored (Scheme 2). Conceivably, this “folding” of
the pyrrolidinone and the L · · · L ligands is sterically induced
by nonbonded interactions between atoms in the secondary
coordination sphere, and if preserved in the solution-phase
structures it may play a significant role in inducing the initial
preponderance of the cis-isomers as the kinetically favored
products (vide infra).
(()-3 (dr 88:12, cis:trans) has been observed upon heating of
a solution of complex (()-3 in THF at 45 °C for 3 h in the
absence of a base (recovery yield 92%). Heating of a solution
of complex (()-4 (dr 91:9, cis:trans) in THF at 45 °C for 3 h
in the absence of a base led to minimal epimerization and
afforded the recovered (yield 90%) complex (()-4 in dr 83:17
(cis:trans). The results suggest that an alternative pathway to
epimerization involving a reversible interconversion of the cis
and trans C-bonded Pd-amide enolates via the O-bonded Pd-
enolates as intermediates does not operate to a significant
extent.16
Table 1
The treatment of palladium amide complex (()-1 with
t-BuOK for longer time periods afforded complex (()-3 in
reduced yields (67%) but increased levels of diastereoselectivity
(dr 94:6, cis:trans). However, variations in the choice of the
base (potassium hexamethyldisilazide, KHMDS, or lithium
diisopropyl amide, LDA) and conditions (time, temperature)
used for the ring-closure reactions of complexes (()-1 and (()-2
led only to minimal variation in the ratios of diastereomers found
in complexes (()-3 and (()-4.15
a A solution of the palladacycles in THF was treated with 1 equiv of
t-BuOK (1 M in THF). The yield of the palladacycle recovered after
flash chromatography is indicated in the last column.
Our earlier studies of the diastereocontrol in the synthesis of
palladacycles of type I bearing chiral nonracemic bidentate
ligands indicated that high levels of stereoinduction at the
palladium-bonded sp3-hybridized R-carbon in exocyclic ester
and amide enolates can be achieved.4b,d In this context, the
cationic chelated amide complexes described above provide us
with a unique opportunity to investigate how stereocenters
present in the auxiliary ligand sphere of the complex may
interact with the existing palladium-bonded sp3-hybridized
stereogenic carbon to either reinforce, diminish, or override the
preference for the formation of cis diastereomers of pallada-
cycles of type II (Figure 1, Scheme 2, and Table 1).
A C2 symmetric bidentate phosphine ligand (2S,3S)-2,3-
bis(diphenylphosphino)butane ((S,S)-CHIRAPHOS) was se-
lected for these studies. Formation of a tight five-membered
chelate ring including the P-Pd-P bonds was anticipated to
provide favorable conditions for maximum stereoinduction.4b
Thus, ligand exchange reaction of the racemic complex (()-1
with (S,S)-CHIRAPHOS (2.0 equiv) afforded the anticipated
equimolar mixture of two diastereomeric cationic complexes
(S,S,S)-5a and (R,S,S)-5b in a quantitative yield (Scheme 3).
Characteristic signals in 31P NMR that allow us to differentiate
the two diastereomers include doublets at 59.7 ppm (J ) 45.4
Hz) and at 47.5 ppm (J ) 45.4 Hz) for 5a and doublets at 57.6
ppm (J ) 50.2 Hz) and at 42.9 ppm (J ) 50.2 Hz) for 5b.
However, in the absence of X-ray crystallographic analyses17
The palladium bonded stereocenter corresponding to the
R-carbon in the palladium amide enolate possesses an acidic
hydrogen potentially rendering the stereocenter configurationally
unstable under basic conditions. The pathway to epimerization
could involve deprotonation yielding complex III (Table 1)
followed by reprotonation delivering the epimeric palladacycle.
Indeed, palladacycles (()-3 (dr 90:10, cis:trans) and (()-4 (dr
87:13, cis:trans) underwent epimerization when treated with 1.1
equiv of t-BuOK in THF at room temperature. Complex (()-3
proved to be sensitive to decomposition, and prolonged reaction
times led to low recovery yields. Regardless, within 30 minutes,
significant epimerization was observed favoring the formation
of the trans diastereomer of palladacycle (()-3 (dr 78:22, cis:
trans, Table 1). In a similar fashion, the more stable palladacycle
(()-4 (dr 87:13, cis:trans) underwent epimerization, reaching
an equilibrium ratio of dr 42:58 (cis:trans) in 1 h with a recovery
yield greater than 90% (Table 1). Experiments described in
Scheme 2 indicate that the existing stereocenter in cationic
complexes (()-1 and (()-2 significantly differentiates the
activation energies for the formation of cis and trans pallada-
cycles (()-3 and (()-4, allowing for a more rapid (kinetic
control) formation of the cis diastereomer of (()-3 and (()-4
(Scheme 2). Data in Table 1 demonstrate that the trans
diastereomers of complexes (()-3 and (()-4 are more thermo-
dynamically stable. Notably, the equilibration of the cis and
trans isomers apparently requires the presence of a sufficient
concentration of base to allow for the deprotonation. Thus,
treatment of the solutions of complex (()-3 (dr 90:10, cis:trans)
(16) The slow epimerization of complex (()-4 upon heating in the
absence of base (from dr 91:9 to 83:17, cis:trans) could be rationalized by
a reversible interconversion of the C-bonded and O-bonded palladium amide
enolate forms of palladacycle (()-4.
(17) Despite numerous attempts at the diffusion-controlled crystallization
of mixtures of diastereomeric complexes 5a and 5b, we were unable to
obtain a single crystal suitable for X-ray crystallographic analyses.
(15) For the details of the additional experiments, see the Supporting
Information.

814 Organometallics, Vol. 28, No. 3, 2009
Hershberger et al.
Scheme 3
Scheme 4
mixture of diastereomers trans 6c and 6d. Indeed, the 31P NMR
spectrum of the isolated palladacycle 6 revealed the presence
of two groups of four broadened signals11 with equal peak areas
with the groups, and the ratio of the combined peak areas of
the two groups of peaks 91:9, thus identifying the signals in
the dominant group as those arising from cis palladacycles 6a,b
and the signals comprising the minor group as those arising
from the trans palladacycles 6c,d. On the basis of these data,
we were able to assign the 31P NMR signals for the two cis
diastereomers 6a and 6b and for the trans diastereomers 6c and
6d. The signals (broad singlets) in 31P NMR (162 MHz) of
complex 6 assigned to the cis complexes 6a and 6b are found
at 45.1, 42.8, 38.8, and 36.0 ppm. The signals (broad singlets)
in 31P NMR (162 MHz) of complex 6 assigned to the trans
complexes 6c and 6d are found at 46.3, 42.8, 41.7, and 39.7
ppm. Despite our attempts at crystallization of palladacycle 6,
we were unable to secure X-ray quality crystals of pure
that would yield molecular structures of the individual com-
plexes, the assignment of absolute configurations of complexes
5a and 5b (see above) to specific spectral (31P NMR) signals
remains purely arbitrary. The mixture of diastereomers of
complex 5 (dr 1:1) was treated with t-BuOK under the
conditions identical to those in the ring-closure protocols
employed for the synthesis of palladacycles (()-3 and (()-4
(compare Schemes 2 and 3). As anticipated, the reaction
afforded the palladacycle 6 as a mixture of four diastereomers
in unequal ratios. In principle, the reaction can afford four
diastereomers 6a-d with structures shown in the inset of
Scheme 3, complexes 6a and 6b corresponding to palladacycles
with cis relative stereochemistry14 at the two palladium-bonded
stereocenters, and complexes 6c and 6d with trans relative
stereochemistry14 at the palladium-bonded stereogenic carbons.
Accordingly, 31P NMR of the isolated complex 6 indicated the
presence of seven broad signals (singlets, one representing an
overlap of signals for two different P atoms),18 apparently
divided into two groups of four signals according to relative
integration. In the first group corresponding to the major
product(s), the four 31P NMR singlet signals had approximately
equal intensity (peak areas in relative ratios of 1:1.3:1.3:1). The
four 31P NMR signals in the second group represented the minor
products and had peak areas in relative ratios of approximately
2:2:1:1 (for details, see Supporting Information). Overall, the
combined integrated 31P NMR signal areas for the four signals
comprising each of these two groups were found to be in the
ratio of 81:19.18 In order to assign the signals in the 31P NMR
spectra of complex 6 to either cis or trans diastereomers,
palladacycle (()-3 with known unequal ratio of cis:trans
diastereomers (dr 91:9, cis:trans) was subjected to a ligand
exchange reaction with an excess of the chiral nonracemic ligand
(S,S)-CHIRAPHOS (Scheme 4). On the basis of prior studies,4d
we were anticipating that the cis diastereomer of complex (()-3
will afford a 1:1 mixture of cis diastereomers 6a and 6b and
the trans diastereomer of complex (()-3 will afford a 1:1
1
diastereomers 6a-d, and therefore, the assignment of the H
and 31P NMR signals for the specific diastereomers 6a versus
6b and 6c versus 6d could not be realized. Data acquired in
this experiment were employed to analyze the 31P NMR signals
of complex 6 prepared via the ring-closure reaction reported in
Scheme 3, revealing that the cis diastereomers 6a + 6b were
generated in approximately equal ratio and represent the
dominant diastereomers in the mixture consisting of 81% cis
diastereomers 6a + 6b and 19% trans diastereomers 6c + 6d,
which were generated in approximately 2:1 ratio.
It is notable that the ring-closure reactions of racemic cationic
amide complex (()-2 (Scheme 2) as well as of the equimolar
mixture of diastereomers of cationic amide complex 5 (Scheme
3) proceed with almost identical cis:trans selectivity, regardless
of the presence of stereogenic centers in the chiral nonracemic
auxiliary phosphine ligand in complexes 5a,b.19 Apparently, the
chiral nonracemic auxiliary ligand does not exert a significant
amplifying (matched pair) or diminishing (mismatched pair)
effect on the stereocontrol realized by the palladium-bonded
stereogenic sp3-hybridized carbon present in the cationic amide
complexes 5 during the base-mediated conversion of the in situ
formed O-bonded palladium amide enolates into the C-bonded
palladium amide enolates (the palladacycles 6).
(19) Analogous experiments to those reported in Scheme 3 but involving
an enantiomer of the chiral nonracemic ligand, for example, (R,R)-
CHIRAPHOS, would afford a mixture of four diastereomers 6a′-d′, each
of which would represent an enantiomer of the complexes 6a-d shown in
the insert of Scheme 3. Thus, identical ratios of diastereomers would be
expected to arise from these experiments.
(18) The 31P NMR (162 MHz) signals found in the mixture of four
diastereomers 6a-d were as follows: 46.3 ppm (s br, 0.12 P), 45.1 ppm (s
br, 0.38 P), 42.8 ppm (s br, 0.55 P, signal for two distinct overlapping P’s),
41.7 ppm (s br, 0.063 P), 39.7 ppm (s br, 0.067 P), 38.8 ppm (s br, 0.44 P),
36.0 ppm (s br, 0.38 P).

Diastereomers of Pallada(II)pyrrolidinones
Organometallics, Vol. 28, No. 3, 2009 815
Scheme 5
Figure 5
To evaluate the effect of the chiral nonracemic auxiliary
ligands on the thermodynamic stability of the palladacycles, the
mixture of diastereomeric palladacycles 6 obtained in the ring
closure reaction of complex 5a,b described in Scheme 3 (6a:
6b:6c:6d ) 5.9:7.3:2.0:1.0; cis:trans 81:19) was treated with
t-BuOK (1.1 equiv) under the conditions identical (3 h, rt, THF)
to the conditions used in entry 4, Table 1 (Scheme 4). As
anticipated, the 31P NMR analysis of the recovered palladacycle
6 (75% recovery yield) indicated a significant increase in the
content of both the trans diastereomers 6c,d, reaching the ratio
of 6a:6b:6c:6d ) 1.1:1.6:1:1; cis:trans 57:43) (Scheme 4).
Conceivably, the preference for the initial formation of the cis
palladacycles (()-3, (()-4, and 6 could be rationalized based
on an interesting structural feature elucidated by the comparison
of the molecular structures of cis (()-3 and cis (()-4 established
by X-ray crystallography (see Figure 4, vide supra). Assuming
that similar features are found in the solution phase structures
of the relevant complexes, we can envision that nonbonded
interactions between the phenyl substituent attached to the
palladium-bonded carbon C(4) and the ligand sphere (L · · · L)
force the ligand L · · · L to fold away from the C(4) phenyl along
the N(1) · · · N(2) or P(1) · · · P(2) polyhedral edge as indicated
by the angle R between the normal plane a and the “fold” plane
b highlighted in the structure of the O-bonded Pd enolate
intermediate IV (Figure 5). The formation of the (E)-enolate,
which presumably arises via the deprotonation of the cationic
amide complexes (()-1, (()-2, and 5 (Figure 5), is anticipated
to be favored due to minimized steric interactions between the
phenyl substituent and the ligand sphere (L · · · L).
The methine carbon C(5) in the intermediate IV can replace
the oxygen in the Pd coordination sphere by rotating ∼180°
about the C(2)-N(3) bond. The amount of steric hindrance will
be different for the different directions of rotation and will be
determined by the order in which the hydrogen and phenyl
substituents are moved past the nearest methyl or phenyl groups
of the L · · · L ligands (TMEDA, dppe, or (S,S)-CHIRAPHOS).
If the predominant conformation for the L · · · L ligands in the
intermediate IV is similar to the one observed in the solid phase
structures for cis (()-3 and cis (()-4, the cis isomers would be
expected to be formed preferentially. Notably, this mechanism
for the transfer of the stereochemical information is independent
of the absolute configuration of the of the stereocenters present
in the auxiliary ligand (S,S)-CHIRAPHOS, since only the angle
of the “fold” is controlling the diastereoselectivity of the process,
and the presence of additional methyl groups in (S,S)-CHIRA-
PHOS would be expected to have little additional influence,
being distant from the important nonbonding interactions.
Equilibration of the cis palladacycles via reversible deprotona-
tion yielding the C-bonded Pd-enolate III (Table 1) allows the
phenyl ring to move along a less sterically encumbered plane
ultimately providing the more stable trans palladacycles.
Finally, we explored possible approaches to enantiomerically
pure or enriched complexes 5 and 6. In agreement with
observations of Arndtsen et al.,5a our attempts at modifying the
synthetic protocol for the preparation of cationic palladium-
chelated amide complexes to introduce auxiliary ligands prior
to the formation of the palladium-bonded stereocenter were
unsuccessful.20 Thus, we considered kinetic resolution of
racemic palladium-chelated amide complex (()-1 and an
essentially pure cis diastereomer of racemic palladacycle (()-3
via ligand exchange reactions with substoichiometric quantities
of chiral nonracemic ligand (S,S-CHIRAPHOS) (Scheme 5).
Palladacycle (()-3 with the ratio of cis:trans diastereomers
dr > 20:1 was obtained by precipitation of complex (()-3 in
the final stages of the concentration of the ethyl acetate eluent
from column chromatography following the preparation of
complex (()-3 according to the method described in Scheme 2
(vide supra). Thus, complex (()-1 was treated with either 10,
20, or 40 mol % of the (S,S)-CHIRAPHOS ligand at room
1
temperature. H NMR analyses of the crude reaction mixtures
indicated that complete conversion of the phosphine ligand to
the two diastereomers of the cationic palladium-amide com-
plexes 5a,b occurred.21 Only low levels of differentiation
between the rates of the ligand exchange reactions involving
the enantiomers of complex (()-1 were realized providing an
approximately 1.4:1 ratio of the two diastereomers of the
cationic complex 5 in all three experiments. The cis diastereomer
of palladacycle (()-3 (dr > 20:1, cis:trans) reacted with 40
mol % of the (S,S)-CHIRAPHOS ligand to afford the corre-
sponding two cis diastereomers 6a and 6b in an essentially equal
1
molar ratio as established by the analysis of the H NMR
spectrum of the crude reaction mixture.22 These experiments
indicate a lack of noticeable differentiation in the reaction rates
of the enantiomers of complexes (()-1 and cis (()-3 with chiral
nonracemic ligand (S,S)-CHIRAPHOS.
Conclusions
In conclusion, the results described herein yielded insights
into features controlling the stereochemical relationships in
unique organopalladium(II) complexes featuring two Pd-bonded
stereocenters as well as chiral nonracemic bidentate ligands.
Significant stereoinduction between the two sp3-hybridized Pd-
bonded stereocenters has been observed and utilized to obtain
racemic complexes (()-3 and (()-4 highly enriched (dr 94:6
or 87:13) in the kinetically favored cis diastereomer. The
molecular structures of the cis diastereomers in complexes
bearing TMEDA and dppe auxiliary ligands were established

816 Organometallics, Vol. 28, No. 3, 2009
Hershberger et al.
in dichloromethane, and the dichloromethane solution was filtered
through celite. Solvents were removed under reduced pressure to
afford a crude product which was purified by flash chromatography
over silica eluting with dichloromethane/acetonitrile (3:1) to afford
the amide complex (()-1 (0.544 g, 67%) as a yellow solid: mp )
by X-ray crystallography. Analysis of the molecular structures
of the complexes cis (()-3 and cis (()-4 provided insights that
allowed us to propose a plausible rationale for the mechanism
of transfer of the stereochemical information in the described
reaction system. Notably, the formation of C-bonded tautomer
of the palladium amide enolates II was strongly favored, and
epimerization of the Pd-bonded stereocenter corresponding to
the R-carbon of the amide functionality could only be induced
in the presence of an excess of base, favoring the thermody-
namically more stable trans isomers of complexes II. Further-
more, no effects consistent with the involvement of either
stereochemically matched or mismatched pairs have been
observed when a chiral nonracemic auxiliary bidentate phos-
phine ligand ((S,S)-CHIRAPHOS) was employed in the prepa-
ration of a palladacycle of type II (complex 6), indicating a
lack of stereochemical induction from the auxiliary ligand sphere
during the formation of the second Pd-bonded sp3-hybridized
stereogenic carbon. Thus, the preparation of enantiomerically
pure complexes of type II would require an efficient ligand
control of the absolute configuration of the Pd-bonded stereo-
center generated in the first step, a result consistent with our
prior findings on the mechanims of stereoinduction in the
formation of chiral nonracemic palladacycles of type I.23 To
date, attempts at the formation of enantiomerically enriched
palladacycles 6 via kinetic resolution based approaches have
not proven to be practical. At present, we are exploring the
reactivity of palladacycles (()-3 and (()-4 in carbon-carbon
bond-forming reactions aiming to uncover reaction pathways,
which could be utilized toward the development of catalytic
reactions.
1
54-74 °C; Rf ) 0.50 (9:1 CH2Cl2/MeOH); H NMR (500 MHz,
CDCl3) δ 7.37-7.27 (m, 6 H), 7.20 (d, J ) 6.9 Hz, 2 H), 7.08 (br
s, 4 H), 6.92 (d, J ) 6.6 Hz, 2 H), 4.46 (s, 1 H), 4.45 (d, J ) 16.1
Hz, 1 H), 3.91 (d, J ) 16.1 Hz, 1 H), 3.77 (s, 2 H), 3.16 (td, J )
13.0 Hz, 3.5 Hz, 1 H), 2.73 (td, J ) 13.9 Hz, 3.15 Hz, 1 H), 2.62
(s, 3 H), 2.61 (s, 3 H), 2.49-2.39 (m, 5 H), 2.25 (s, 3 H), 1.64 (s,
3 H); 13C NMR (125 MHz, CDCl3) δ 180.9, 138.0, 137.3, 133.5,
132.3, 129.9, 129.0 128.9, 128.5, 128.2, 127.7, 127.6, 127.0, 120.7
(q, J(13C - 19F) ) 320.8 Hz), 65.1, 64.0, 57.2, 52.3, 51.0, 49.9,
47.3, 46.7, 39.4, 21.1, several signals account for more than one
carbon; 19F NMR (376 MHz) δ -76.84 (s, 3 F); IR (thin film, cm-1
)
1578 (s), 1153 (s); HRMS (ES+) calcd for C29H38N3OPd
[(M-CF3SO3)+], 550.2050; found, 550.2038. Anal. Calcd for
C30H38F3N3O4PdS: C, 51.47; H, 5.47; N, 6.00. Found: C, 52.34;
H, 5.29; N, 5.66.
Amide Complex (()-2. Amide complex (()-1 (0.464 g, 0.663
mmol) and 1,2-bis(diphenylphosphino)ethane (0.528 g, 1.325 mmol)
were dissolved in dichloromethane (7 mL). The resulting yellow
solution was stirred for 5 h at rt under argon. Solvents were removed
under reduced pressure, and the crude product was purified by flash
chromatography over silica eluting with dichloromethane/acetoni-
trile (6:1) to afford complex (()-2 (0.479 g, 74%) as a yellow solid:
1
mp ) 75-90 °C; Rf ) 0.46 (9:1 CH2Cl2/MeOH); H NMR (500
MHz, CDCl3) δ 7.70-7.64 (m, 2 H), 7.50-7.16 (m, 22 H), 7.12
(td, J ) 7.8 Hz, 2.5 Hz, 2 H), 6.88 (d, J ) 12.3 Hz, 1 H), 6.87 (d,
J ) 11.3 Hz, 1 H), 6.82 (d, J ) 6.6 Hz, 2 H), 6.78 (d, J ) 7.9 Hz,
2 H), 6.30 (br s, 2 H), 4.74 (dd, J ) 15.5 Hz, 2.8 Hz, 1 H), 4.34
(dd, J ) 8.2 Hz, 3.5 Hz, 1 H), 4.02 (dd, J ) 15 Hz, 2 H), 3.95 (d,
J ) 15.8 Hz, 1 H), 2.74-2.44 (m, 3 H), 2.21 (s, 3 H), 2.00-1.84
(m, 1 H); 13C NMR (125 MHz, CDCl3) δ 182.0 (dd, J(13C - 31P)
) 8.3 Hz, 1.8 Hz), 138.7 (d, J(13C - 31P) ) 5.5 Hz), 136.0, 134.0,
133.4 (d, J(13C - 31P) ) 11.0 Hz), 132.8, 132.75 (d, J(13C - 31P)
) 11.9 Hz), 132.5 (d, J(13C - 31P) ) 13.8 Hz), 132.3 (d, J(13C -
31P) ) 11.9 Hz), 132.0 (dd, J(13C - 31P) ) 31.2, 2.8 Hz), 131.5
(dd, J(13C - 31P) ) 14.7, 2.8 Hz), 130.4, 130.1, 129.5, 129.4 (d, J
(13C - 31P) ) 15.0 Hz), 129.3, 129.2, 129.1, 129.0, 128.92 (d, J
(13C - 31P) ) 11.0 Hz), 128.2, 127.7, 127.3, 127.2, 126.8, 125.2,
124.0, 123.5, 120.9 (q, J(13C - 19F) ) 320.8 Hz), 76.8 (dd, J (13C
Experimental Section
Amide Complex (()-1. To a stirred solution of (E)-N-(4-
methylbenzylidene)-1-phenylmethanamine (0.733 g, 3.503 mmol)
in acetonitrile (5 mL) was added neat phenyl acetyl chloride (0.541
g, 3.503 mmol) to afford a pale yellow solution, which was stirred
for 15 min at rt under argon. Acetonitrile (25 mL) was added,
followed by Pd2dba3 (0.529 g, 0.578 mmol), and the reaction
mixture was allowed to stir for additional 10 min. Neat TMEDA
(0.814 g, 7.006 mmol) was added, and the reaction mixture was
stirred for 1 h. Silver trifluoromethanesulfonate (0.990 g, 3.854
mmol) was added, and the reaction mixture was allowed to stir for
an additional 1 h. The resulting suspension was filtered through a
plug of celite, and the celite was washed with additional acetonitrile
until the eluent was colorless. Solvents were removed under reduced
pressure, the crude product was triturated with ether and dissolved
-
31P) ) 99.4 Hz, 5.0 Hz), 52.2 (d, J (13C - 31P) ) 4.6 Hz), 40.0,
31.4 (dd, J (13C - 31P) ) 37.6 Hz, 20.2 Hz), 21.1 (dd, J (13C -
31P) ) 30.0 Hz, 7.3 Hz), 20.9, several signals account for more
than one carbon; 31P NMR (162 MHz, CDCl3) δ 51.5 (br s, 1 P),
38.5 (br s, 1 P); 19F NMR (376 MHz) δ -76.8 (s, 3 F); IR (thin
film, cm-1
)
1554 (s), 1150 (s); HRMS (ES+) calcd for
C49H46NOP2Pd [(M-CF3SO2)+], 832.2089; found, 832.2062. Anal.
Calcd for C50H46F3NO4P2PdS: C, 61.13; H, 4.72; N, 1.43. Found:
C, 61.09; H, 4.39; N, 1.36.
(20) An attempt to prepare complex 5 via the oxidative cyclization
protocol employing Pd2dba3 pretreated with dppe ligand (a modified
Arndtsen’s protocol) proved unsuccessful.
(21) For additional information, see the Supporting Information.
(22) For additional information, see the Supporting Information.
(23) Our prior studies on the mechanism of stereoinduction in the
formation of related palladacycles I (Figure 1) suggested that the control
of the ratio of atropisomers arising from a restricted rotation around the
aryl-Pd bonds in complexes V (see below) is essential for achieving high
levels of diastereoselectivity in the formation of palladacycles I (see ref
4b).
Amide Complex 5a,b. Amide complex (()-1 (0.203 g, 0.291
mmol) and (2S,3S)-bis(diphenylphosphino)butane (0.124 g, 0.291
mmol) were dissolved in dichloromethane (6 mL). The resulting
yellow solution was stirred for 3.5 h at rt under argon. Solvents
were removed under reduced pressure, and the resulting crude
product was purified by flash chromatography over silica, eluting
with dichloromethane/MeOH (19:1) to afford complex 5a,b (0.292
g, 99%) (dr 1:1) as a yellow solid: mp ) 77-100 °C; Rf ) 0.58
(6.5:1 CH2Cl2/MeOH); 1H NMR (500 MHz, CDCl3) δ 7.78-7.72
(m, 1 H), 7.70-7.45 (m, 13.5 H), 7.44-7.38 (m, 0.5 H), 7.33-7.07
(m, 12 H), 7.02-6.95 (m, 1 H), 6.79 (d, J ) 7.0 Hz, 1 H),
6.74-6.68 (m, 2 H), 6.66 (d, J ) 7.88 Hz, 1 H), 6.31 (d, J ) 6.9
Hz, 1 H), 6.14 (d, J ) 6.9 Hz, 1 H), 4.64 (dd, J ) 16.8 Hz, 3.2 Hz,
0.5 H), 4.62 (dd, J ) 15.8 Hz, 2.8 Hz, 0.5 H), 4.20 (dd, J ) 8.5
Hz, 2.8 Hz, 0.5 H), 4.01 (dd, J ) 7.6 Hz, 4.0 Hz, 0.5 H), 3.93-3.77

Diastereomers of Pallada(II)pyrrolidinones
Organometallics, Vol. 28, No. 3, 2009 817
(m, 3 H), 2.67-2.56 (m, 0.5 H), 2.32-2.20 (m, 2 H), 2.18-2.10
(m, 0.5 H), 2.09 (s, 1.5 H), 1.90-1.80 (m, 0.5 H), 1.10-0.94 (m,
6 H); 13C NMR (125 MHz, CDCl3) δ 181.93, 181.87, 139.0 (d,
J(13C - 31P) ) 6.4 Hz), 137.4 (d, J(13C - 31P) ) 4.6 Hz), 136.1 (t,
J(13C - 31P) ) 12.0 Hz), 135.8 (d, J(13C - 31P) ) 1.8 Hz), 135.4
(d, J(13C - 31P) ) 13.8 Hz), 135.0 (d, J(13C - 31P) ) 12.8 Hz),
133.9 (d, J(13C - 31P) ) 16.5 Hz), 133.1 (d, J(13C - 31P) ) 2.8
Hz), 132.7, 132.5, 132.3 (d, J(13C - 31P) ) 1.8 Hz), 132.16, 132.13,
132.11, 132.08, 131.8 (d, J(13C - 31P) ) 11.0 Hz), 131.6 (d, J(13C
1617 (s); HRMS (ES+) calcd for C29H38N3OPd (M + H+),
550.2050; found, 550.2025. Anal. Calcd for C29H37N3OPd: C, 63.32;
H, 6.78; N, 7.64. Found: C, 63.38; H, 6.52; N, 6.97.
A sample of complex (()-3 highly enriched in the cis diastere-
1
omer (dr > 20:1 by H NMR) was obtained by precipitation and
trituration (benzene) of solids obtained directly from the EtOAc
eluent after chromatography. Analytical data for complex cis-(()-3
1
(dr > 20:1): H NMR (500 MHz, CDCl3) δ 7.67 (d, J ) 8.3 Hz,
2 H), 7.37 (d, J ) 7.5 Hz, 2 H), 7.32-7.23 (m, 7 H), 7.14-7.09
(m, 3 H), 4.89 (d, J ) 14.5 Hz, 1 H), 4.16 (s, 1 H), 4.03 (s, 1 H),
3.43 (d, J ) 14.5 Hz, 1 H), 2.56-2.52 (m, 1 H), 2.45 (s, 3 H),
2.42 (s, 3 H), 2.34-2.29 (m, 5 H), 2.17-2.13 (m, 1 H), 1.60 (s, 3
H), 1.50 (s, 3 H); 13C NMR (125 MHz, CDCl3) δ 182.0, 147.5,
144.2, 139.0, 134.0, 130.8, 129.1, 129.0, 127.9, 126.3, 124.2, 60.2,
50.2, 49.2, 48.9, 48.6, 47.8, 47.0, 21.1, several signals account for
more than one carbon.
-
31P) ) 10.1 Hz), 131.3, 131.2 (d, J(13C - 31P) ) 2.8 Hz), 130.3,
129.5 (d, J(13C - 31P) ) 11.0 Hz), 129.47, 129.42, 129.34, 129.32,
129.26, 129.24, 129.21, 129.18, 129.14, 129.07, 128.9 (d, J(13C -
31P) ) 4.6 Hz), 128.8 (d, J(13C - 31P) ) 12.5 Hz), 128.5 (d, J(13C
-
31P) ) 11.0 Hz), 128.3, 128.05 (d, J(13C - 31P) ) 2.8 Hz), 128.0,
127.7, 127.5 (d, J(13C - 31P) ) 2.8 Hz), 127.3, 127.2, 127.1, 127.0,
126.9, 126.84, 126.79, 126.7, 126.63, 126.60, 126.5, 126.2, 125.2
(d, J(13C - 31P) ) 54.1 Hz), 124.1 (d, J(13C - 31P) ) 51.5 Hz),
123.9 (d, J(13C - 31P) ) 48.6 Hz), 121.3 (q, J(13C - 19F) ) 319.3
Hz), 120.1 (d, J(13C - 31P) ) 49.5 Hz), 76.9 (dd, J(13C - 31P) )
402.3 Hz, 6.0 Hz), 76.8 (d, J(13C - 31P) ) 208.0 Hz, 5.8 Hz),
53.4, 52.3 (dd, J(13C - 31P) ) 12.0 Hz, 4.3 Hz), 43.9 (dd, J(13C -
31P) ) 35.8 Hz, 23.8 Hz), 42.6 (dd, J(13C - 31P) ) 34.8 Hz, 22.9
Hz), 39.9, 31.8, 31.3 (dd, J(13C - 31P) ) 44.0 Hz, 10.1 Hz), 31.1
(dd, J(13C - 31P) ) 44.0 Hz, 11.0 Hz), 29.6, 21.0, 20.8, 14.1 (m),
14.08 (dd, J(13C - 31P) ) 54.6 Hz, 5.5 Hz), 14.01 (d, J(13C - 31P)
) 5.5 Hz), 14.0 (dd, J(13C - 31P) ) 5.5 Hz), several signals account
for more than one carbon; 31P NMR (162 MHz, CDCl3) δ 59.7 (br
s, 1 P), 57.6 (br s, 1 P), 47.5 (br s, 1 P), 42.9 (br s, 1 P); 19F NMR
(376 MHz) δ -76.7 (s, 3 F); IR (thin film, cm-1) 1562 (s), 1150
(s); HRMS (ES+) calcd for C51H50NOP2Pd [(M-CF3SO2)+],
860.2402; found, 860.2389. Anal. Calcd for C52H50F3NO4P2PdS:
C, 61.81; H, 4.99; N, 1.39. Found: C, 62.36; H, 4.65; N, 1.37.
Palladacycle (()-4. Amide complex (()-2 (0.089 g, 0.091
mmol) was treated with t-BuOK (0.100 mL, 0.100 mmol) at 45 °C
under argon according to the general procedure above. Elution with
EtOAc/Hex (1:1) followed by trituration with pentane afforded
palladacycle (()-4 (0.068 g, 90%) as a yellow powder in dr 72:28,
cis:trans.
Alternatively, palladacycle (()-4 was also synthesized via ligand
exchange reaction. Thus, complex (()-3 (dr 89:11, cis:trans) (0.396
g, 0.719 mmol) and 1,2-bis(diphenylphosphino)ethane (0.573 g, 1.44
mmol) were dissolved in dichloromethane (10 mL). The resulting
yellow solution was stirred for 3.5 h at rt under argon. Solvents
were removed under reduced pressure, and the crude product was
purified by flash chromatography over silica, eluting with EtOAc/
hexane (1:1) to afford palladacycle (()-4 (0.534 g, 89%) as a yellow
powder (dr 87:13).
Complex (()-4 was characterized as a mixture of diastereomers
in the ratio dr 91:9, cis:trans (obtained from an analogous but
separate experiment in 89% yield) providing the analytical data
below: mp ) 150-165 °C (dec.); Rf ) 0.50 (2:1 EtOAc/Hex); 1H
NMR (500 MHz, CDCl3) δ 7.63-7.56 (m, 2.2 H), 7.54-7.45 (m,
5.8 H), 7.42 (td, J ) 7.6 Hz, 1.6 Hz, 2 H), 7.39-7.16 (m, 7 H),
7.12 (td, J ) 7.6 Hz, 1.6 Hz, 1.9 H), 7.08 (td, J ) 7.6 Hz, 1.6 Hz,
1.9 H), 7.02-6.82 (m, 7.8 H), 6.79-6.61 (m, 5.0 H), 6.58-6.44
(m, 0.4 H), 5.12 (dd, J ) 14.0 Hz, 1.6 Hz, 0.09 H), 5.03 (dd, J )
14.4 Hz, 2.0 Hz, 0.91 H), 4.78 (t, J ) 7.0 Hz, 0.09 H), 4.75 (t, J
) 7.6 Hz, 0.91 H), 4.53 (t, J ) 7.0 Hz, 0.09 H), 4.40 (dd, J ) 8.8
Hz, 6.0 Hz, 0.91 H), 3.61 (d, J ) 14.2 Hz, 0.91 H), 3.55 (d, J )
14.2 Hz, 0.09 H), 2.19 (s, 3H), 2.17-1.85 (m, 3.7 H), 1.78-1.61
(m, 0.3 H); 13C NMR (125 MHz, CDCl3) δ 182.5 (t, J(13C - 31P)
) 6.4 Hz), (182.2 (t, J(13C - 31P) ) 6.4 Hz)), 148.2 (t, J(13C -
31P) ) 3.0 Hz), (146.1 (d, J(13C - 31P) ) 7.3 Hz)), 145.4 (d, J(13C
General Procedure for the Synthesis of Palladacycles via
Ring Closure. To a solution of cationic palladium complex (0.1
M) in THF at a given temperature was added a solution of base
(t-BuOK 1.0 M in THF, KHMDS 0.5 M in toluene, LDA 2.0 M in
heptane/THF/ethylbenzene), and the reaction mixture was stirred
for the designated time(s) under argon. The suspension was diluted
with dichloromethane, and the solvents were removed under reduced
pressure. The oily residue was dissolved in dichloromethane and
filtered through celite to remove any insoluble materials. Solvents
were removed under reduced pressure, and the crude product was
purified by flash chromatography over silica eluting with ethyl
acetate (EtOAc) and hexane mixtures or with EtOAc to afford the
corresponding palladacycles as yellow or orange solids.
Palladacycle (()-3. Amide complex (()-1 (0.540 g, 0.7710
mmol) was treated with t-BuOK (0.85 mL, 0.85 mmol) at 45 °C
according to the general procedure described above. Elution with
EtOAc/Hex (1:1) and EtOAc followed by trituration with pentane
afforded complex (()-3 (0.3471 g, 82%) (dr 88:12, cis:trans) as a
light orange powder: mp ) 162-170 (dec.); Rf ) 0.36 (100%
-
31P) ) 3.0 Hz), (144.6 (d, J(13C - 31P) ) 4.5 Hz)), 138.9, (138.7),
134.2 (dd, J(13C - 31P) ) 16.9 Hz, 14.0 Hz), 133.5 (d, J(13C -
31P) ) 13.8 Hz), 133.2 (d, J(13C - 31P) ) 13.8 Hz), 133.0 (d, J(13C
-
31P) ) 12.8 Hz), 132.8 (d, J(13C - 31P) ) 12.8 Hz), 132.46,
1
132.35 (d, J(13C - 31P) ) 1.8 Hz), 132.30 (dd, J(13C - 31P) )
EtOAc); H NMR (500 MHz, CDCl3) δ 7.62 (d, J ) 7.0 Hz, 1.8
31.2 Hz, 1.8 Hz), 132.31, 132.2, 132.19, (131.9), 131.59 (dd, J(13C
H), 7.38 (d, J ) 7.5 Hz, 0.3 H), 7.33 (d, J ) 7.9 Hz, 2 H),
7.30-7.23 (t, J ) 7.0 Hz, 1 H), 7.24-7.12 (m, 5.5 H), 7.12-6.97
(m, 3.4 H), 4.89 (d, J ) 14.8 Hz, 0.12 H), 4.84 (d, J ) 14.5 Hz,
0.88 H), 4.13 (s, 0.12 H), 4.12 (s, 0.88 H), 3.99 (s, 0.88 H), 3.94
(s, 0.12 H), 3.40 (d, J ) 14.5 Hz, 0.88 H), 3.34 (d, J ) 14.5 Hz,
0.12 H), 2.65-2.56 (m, 0.2 H), 2.50-2.46 (m, 1 H), 2.45-2.34
(m, 5.6 H), 2.33-2.20 (m, 5.2 H), 2.13-2.06 (m, 1 H), 1.55 (s,
2.7 H), 1.44 (s, 2.7 H), 1.40 (s, 0.3 H), 1.35 (s, 0.3 H); 13C NMR
(125 MHz, CDCl3) δ (182.5), 182.2, (148.4), 147.4, (144.5), 144.0,
(139.0), 138.8, 134.1, (132.5), 130.7, (130.1), (129.8), (129.7),
(129.2), 129.1, 128.8, 128.6, (128.5), 127.94, 127.91, 126.3, 124.2,
(123.7), (60.6), (60.5), (60.4), 60.23, 60.18, (53.4), (50.5), 50.3,
(50.0), (49.5), 49.2, 48.8, 48.6, 47.8, 47.5, 47.0, 46.1, 45.6, (29.7),
21.9, 21.1, 21.0, (minor diastereomer signals in parentheses), some
signals account for more than one carbon; IR (thin film, cm-1):
-
31P) ) 29.3 Hz, 1.8 Hz), (131.4), (131.15), (131.07), (130.71),
(130.61), 130.3 (dd, J(13C - 31P) ) 10.1 Hz, 1.8 Hz), 129.84,
129.63, (129.55), 129.5 (d, J(13C - 31P) ) 12.5 Hz), 129.3 (d, J(13C
-
31P) ) 15.0 Hz), 129.26, 128.80, 128.70, 128.67, 128.59,
(128.50), (128.46), (128.29), 128.24, 128.17, 127.79, 127.38, 127.3,
(126.3), 126.16, 126.0 (d, J(13C - 31P) ) 2.5 Hz), (125.46), 122.90,
(122.31), (64.3), 57.0 (t, J(13C - 31P) ) 3.7 Hz), 56.7 (dd, J(13C -
31P) ) 70.1 Hz, 2.8 Hz), 56.3 (dd, J(13C - 31P) ) 86.6 Hz, 3.7
Hz), 49.1 (d, J(13C - 31P) ) 3.7 Hz), 29.2 (td, J(13C - 31P) ) 24.7
Hz, 17.4 Hz), (27.6 (d, J(13C - 31P) ) 16.5 Hz)), (27.4 (d, J(13C
-
31P) ) 16.5 Hz)), (27.1 (d, J(13C - 31P) ) 16.5 Hz)), (26.9 (d,
J(13C - 31P) ) 16.5 Hz)), (20.9), 20.8, (signals for the minor
diastereomer are in parentheses), some signals account for more
than one carbon;31P NMR (162 MHz, CDCl3) δ (39.5 (br s, 0.05

818 Organometallics, Vol. 28, No. 3, 2009
Hershberger et al.
P)), (35.9 (br s, 0.05 P)), 34.8 (br s, 0.45 P), 32.7 (br s, 0.45 P),
(signals for the minor diastereomer in parentheses); IR (thin film,
cm-1): 1607 (s); HRMS (ES+) calcd for C49H46NOP2Pd (M + H+),
832.2089; found, 832.2108. Anal. Calcd for C49H45NOP2Pd: C,
70.71; H, 5.45; N, 1.68. Found: C, 70.86; H, 5.34; N, 1.64.
Palladacycle 6a-d. Amide complex 5a,b (dr 1:1) (0.155 g,
0.154 mmol) was treated with t-BuOK (0.170 mL, 0.170 mmol) at
45 °C according to the general procedures described above. Elution
with EtOAc/Hex (1:1) followed by trituration with pentane afforded
complex 6a-d (0.120 g, 91%) as a yellow powder, dr 6a:6b:6c:
6d ) 5.9:7.3:2:1, cis:trans, 81:19.
2.8 Hz)), 131.0, 130.93, 130.86, 130.80, 130.7 (dd, J(13C - 31P) )
4.6 Hz, 1.8 Hz), 130.6 (d, J(13C - 31P) ) 2.8 Hz), 130.5, 130.4 (d,
J(13C - 31P) ) 1.8 Hz), 130.3, 130.1 (d, J(13C - 31P) ) 4.6 Hz),
(130.0 (d, J(13C - 31P) ) 1.8 Hz)), 129.8 (d, J(13C - 31P) ) 4.6
Hz), 129.7 (d, J(13C - 31P) ) 2.8 Hz), 129.6, 129.5, 129.44, 129.36,
129.2, 129.1 (d, J(13C - 31P) ) 1.2 Hz), 129.0 (d, J(13C - 31P) )
3.7 Hz), (128.93), 128.89, 128.87, 128.8, 128.63, 128.58, 128.5,
128.4, (128.3), 128.25, 128.20, 128.18, 128.14, 128.11, (127.84),
(127.82), 127.76, 127.7 (d, J(13C - 31P) ) 3.7 Hz), 127.6 (d, J(13C
-
-
31P) ) 10.0 Hz), 127.4, (127.1), 126.7, (126.6), (126.5 (d, J(13C
31P) ) 2.8 Hz)), (126.4), 126.2 (d, J(13C - 31P) ) 3.0 Hz),
Alternatively, palladacycle 6 was also synthesized via a ligand
exchange reaction. Thus, complex (()-3 (dr 91:9, cis:trans) (0.082
g, 0.149 mmol) and (S,S)-CHIRAPHOS (0.095 g, 0.223 mmol) were
dissolved in dichloromethane (2 mL). The yellow solution was
stirred for 3.5 h at rt under argon. Solvents were removed under
reduced pressure, and the crude product was purified by flash
chromatography over silica, eluting with EtOAc/hexanes (1:1) to
afford palladacycle 6 (0.107 g, 83%) (dr 91:9, 6a:6b:6c:6d ) 4.5:
4.5:0.5:0.5, cis:trans) as a yellow powder after trituration with
pentane. Analytical data for this sample of complex 6a-d: mp )
126.05, 126.01 (d, J(13C - 31P) ) 3.5 Hz), 125.8, (125.7 (d, J(13C
-
31P) ) 2.8 Hz)), 125.6 (d, J(13C - 31P) ) 2.4 Hz), 125.5,
(125.33), 125.28, 64.3, 59.0 (dd, J(13C - 31P) ) 38.0 Hz, 2.8 Hz),
58.4 (dd, J(13C - 31P) ) 28.4 Hz, 1.8 Hz), 57.8 (dd, J(13C - 31P)
) 52.2 Hz, 2.8 Hz), (57.4 (dd, J(13C - 31P) ) 7.3 Hz, 2.8 Hz)),
57.1 (dd, J(13C - 31P) ) 40.0 Hz, 1.8 Hz), 56.9 (d, J(13C - 31P) )
2.8 Hz), (56.0 (d, J(13C - 31P) ) 2.8 Hz)), (49.4 (d, J(13C - 31P)
) 2.8 Hz)), 49.1 (d, J(13C - 31P) ) 3.7 Hz), 49.0 (d, J(13C - 31P)
) 2.8 Hz), (48.9 d, J(13C - 31P) ) 3.7 Hz)), 41.8 (d, J(13C - 31P)
) 2.8 Hz), 41.71 (dd, J(13C - 31P) ) 45.8 Hz, 14.7 Hz), 41.66 (d,
J(13C - 31P) ) 3.7 Hz), 37.0 (d, J(13C - 31P) ) 22.0 Hz, 17.4 Hz),
35.7 (dd, J(13C - 31P) ) 23.3 Hz, 18.8 Hz), 34.02, (33.98), 30.5,
22.3, 20.98, (20.94), 20.85 (20.80), 20.7, 19.0, 15.9 (dd, J(13C -
31P) ) 15.6, 5.5 Hz), 15.2 (dd, J(13C - 31P) ) 15.6, 5.5 Hz), 14.31,
14.26, 14.23, 14.18, 14.12, 14.06, 14.00, (13.39), (13.34), (13.27),
(13.20), (13.08), (13.04), (signals for the minor diastereomers are
in parentheses), several signals account for more than one carbon;
31P NMR (162 MHz, CDCl3) δ (46.3 (br s, 0.12 P)), 45.1 (br s,
0.38 P), 42.8 (br s, 0.55 P (major + minor), (41.7 (br s, 0.063 P)),
(39.7 (br s, 0.067 P)), 38.8 (br s, 0.44 P), 36.0 (br s, 0.38 P), (signals
for the minor diastereomers in parentheses); IR (thin film, cm-1):
1607 (br); HRMS (ES+) calcd for C51H50NOP2Pd (M + H+),
860.2402; found, 860.2382. Anal. Calcd for C51H49NOP2Pd: C,
71.20; H, 5.74; N, 1.63. Found: C, 71.01; H, 5.59; N, 1.58.
1
90-135 °C (dec.); Rf ) 0.52 (2:1 EA/Hex); H NMR (500 MHz,
CDCl3) δ 7.64 (td, J ) 8.2 Hz, 1.6 Hz, 1.9 H), 7.60-7.39 (m, 7.5
H), 7.38-7.09 (m, 11 H), 7.09-6.91 (m, 4.5 H), 6.86-6.55 (m, 8
H), 6.51 (d, J ) 7.3 Hz, 1 H), 6.19 (d, J ) 7.9 Hz, 0.1 H), 5.10
(dd, J ) 14.0 Hz, 2.2 Hz, 0.05 H), 4.97 (d, J ) 2.2 Hz, 0.22 H),
4.96 (d, J ) 1.9 Hz, 0.23 H), 4.93 (d, J ) 2.2 Hz, 0.22 H), 4.92 (d,
J ) 2.2 Hz, 0.23 H), 4.58 (t, J ) 6.3 Hz, 0.05 H), 4.54 (dd, J )
8.1 Hz, 6.7 Hz, 0.45 H), 4.42 (dd, J ) 8.8 Hz, 6.0 Hz, 0.05 H),
4.32 (dd, J ) 9.5 Hz, 4.0 Hz, 0.45 H), 4.28 (t, J ) 8.0 Hz, 0.45
H), 4.17 (dd, J ) 9.8 Hz, 4.0 Hz, 0.03 H), 4.08 (t, J ) 6.9 Hz,
0.22 H), 3.86 (t, J ) 7.6 Hz, 0.45 H), 3.57 (d, J ) 14.2 Hz, 0.45
H), 3.53 (s, 0.05 H), 3.49 (d, J ) 14.5 H, 0.45 H), 3.44 (d, J )
14.2 Hz, 0.05 H), 2.28 (s, 0.1 H), 2.25-2.18 (m, 1 H), 2.17-2.09
(m, 1.3 H), 2.08-2.02 (m, 0.5 H), 1.68-1.46 (m, 1.0 H), 1.45-1.25
(m, 1.0 H), 1.03-0.93 (m, 3 H), 0.92-0.86 (m, 1 H), 0.84-0.75
(m, 0.4 H), 0.72 (dd, J ) 10.0 Hz, 7.0 Hz, 1.3 H), 0.69-0.64 (m,
0.3 H); 13C NMR (125 MHz, CDCl3) δ 182.9 (t, J(13C - 31P) )
7.0 Hz), (182.6 (t, J(13C - 31P) ) 6.4 Hz)), 182.1 (t, J(13C - 31P)
) 7.0 Hz), (182.0 (t, J(13C - 31P) ) 6.4 Hz)), 148.6 (t, J(13C -
31P) ) 2.8 Hz), (148.3), 147.0 (t, J(13C - 31P) ) 1.8 Hz), (146.0
(d, J(13C - 31P) ) 5.5 Hz)), 145.7 (d, J(13C - 31P) ) 2.8 Hz),
145.2 (d, J(13C - 31P) ) 4.6 Hz), (143.9 (d, J(13C - 31P) ) 7.3
Hz)), (143.3 (d, J(13C - 31P) ) 6.4 Hz)), (138.9), 138.8, (138.4),
(136.96 (d, J(13C - 31P) ) 15.6 Hz)), 136.92 (d, J(13C - 31P) )
14.7 Hz), 136.7 (d, J(13C - 31P) ) 14.7 Hz), (135.7 (d, J(13C -
31P) ) 13.8 Hz)), (135.4 (d, J(13C - 31P) ) 13.2 Hz)), 134.9 (t,
J(13C - 31P) ) 12.5 Hz), (133.9 (d, J(13C - 31P) ) 8.0 Hz)), (133.7
(d, J(13C - 31P) ) 8.4 Hz), 133.2 (d, J(13C - 31P) ) 12.3 Hz),
132.2 (d, J(13C - 31P) ) 16.8 Hz), 132.16, (132.1), 132.04, (132.01),
131.94 (d, J(13C - 31P) ) 3.6 Hz), 131.86 (d, J(13C - 31P) ) 2.9
Hz), (131.4 (d, J(13C - 31P) ) 2.8 Hz)), (131.3 (d, J(13C - 31P) )
Acknowledgment. Support for this work from the Na-
tional Science Foundation via CAREER Award (Grant No.
CHE-0239123) to H.C.M. is gratefully acknowledged.
Supporting Information Available: Description of the experi-
ments reported in Scheme 4, Scheme 5, and Table 1, description
of the assignment of 31P NMR signals for complexes 6a-d,
including printouts of 31P NMR spectra for 6a-d, temperature
dependent 31P NMR spectra of complex 6, 1H and 13C NMR spectra
of all new compounds prepared in this study as well as CIF files
providing X-ray crystallographic data for complexes cis (()-3 and
cis (()-4. This material is available free of charge via the Internet
at http://pubs.acs.org.
OM800630F