Origin of enantioselectivity in palladium-catalyzed asymmetric allylic alkylation reactions using chiral N,N-ligands with different rigidity and flexibility

Article abstract of DOI:10.1039/b618347f

The chiral bidentate-N,N ligands, (S_a)-1, (S_a)-2, (S,S)-3 and (S,S)-4, were synthesized. They were shown to contain rigid 2-pyridinyl or 8-quinolinyl building blocks and the C₂-symmetric chiral frameworks trans-2,5-dimethylpyrrolidinyl or (S)-(+)-2,2′-(2- azapropane-1,3-diyl)-1,1′-binaphthalene. In the (S_a)-2, and (S,S)-4 ligands pair, the 8-quinolinyl skeleton is directly bonded to the C ₂-symmetric chiral frameworks (S)-(+)-2,2′-(2-azapropane-1,3- diyl)-1,1′-binaphthalene or trans-2,5-dimethylpyrrolidinyl. This feature induces rigidity in this pair of ligands upon the N,N-framework. However, this does not occur for the (S_a)-1 and (S,S)-3 ligands, in which the presence of the -CH₂- spacer between the frameworks bearing the nitrogen atom donors gives greater flexibility to the ligand. A further difference between the pairs of ligands is significant from the electronic properties of the chiral framework N-donor atom. The coordinating properties and the specific steric structural features of the (S_a)-1, (S _a)-2, (S,S)-3, and (S,S)-4 ligands are explained by their reactions with the [Pd(PhCN)₂Cl₂] and [Pd(η³- PhCHCHCHPh)(-Cl)]₂ substrates, in which the reported ligands form chelate complexes, with the exception of (S_a)-2, which failed to react with [Pd(η³-PhCHCHCHPh)(-Cl)]₂. The ligands were used in the palladium-allyl catalyzed substitution reaction of 1,3-diphenylallyl acetate with dimethylmalonate, with the best result being obtained using the (S_a)-1 ligand, giving the substitution product 2-(1,3-diphenylallyl)dimethylmalonate with an enantiomeric excess of 82% in the S form and a yield of 96%. The work demonstrates that in the presence of a steric ligand control, the electronic properties of the ligand donor atoms play a role though not significant in determining the enantioselectivity of palladium(ii) catalyzed allylic substitution reactions. The results of the catalytic reaction do not provide a convincing explanation considering the coordinated chiral ligand features, as rigidity or flexibility and electronic properties of the N-donor atoms. A rationalization of the results is proposed on the basis of NMR studies and DFT calculation on the cationic complexes [Pd(η³-PhCHCHCHPh)(N-N*)]CF₃SO₃, (N-N* = (S_a)-1, 9; (S,S)-3, 10; (S,S)-4, 11). The Royal Society of Chemistry 2007.

Full text of DOI:10.1039/b618347f

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/dalton | Dalton Transactions
Origin of enantioselectivity in palladium-catalyzed asymmetric allylic
alkylation reactions using chiral N,N-ligands with different rigidity
and flexibility†
Dario Drommi,*a Maria Saporita,a Giuseppe Bruno,a Felice Faraone,*a Patrizia Scafatob and Carlo Rosinib
Received 18th December 2006, Accepted 22nd February 2007
First published as an Advance Article on the web 9th March 2007
DOI: 10.1039/b618347f
The chiral bidentate-N,N ligands, (Sa)-1, (Sa)-2, (S,S)-3 and (S,S)-4, were synthesized. They were shown
to contain rigid 2-pyridinyl or 8-quinolinyl building blocks and the C2-symmetric chiral frameworks
trans-2,5-dimethylpyrrolidinyl or (S)-(+)-2,2ꢀ-(2-azapropane-1,3-diyl)-1,1ꢀ-binaphthalene. In the (Sa)-2,
and (S,S)-4 ligands pair, the 8-quinolinyl skeleton is directly bonded to the C2-symmetric chiral
frameworks (S)-(+)-2,2ꢀ-(2-azapropane-1,3-diyl)-1,1ꢀ-binaphthalene or trans-2,5-dimethylpyrrolidinyl.
This feature induces rigidity in this pair of ligands upon the N,N-framework. However, this does not
occur for the (Sa)-1 and (S,S)-3 ligands, in which the presence of the –CH2– spacer between the
frameworks bearing the nitrogen atom donors gives greater flexibility to the ligand. A further difference
between the pairs of ligands is significant from the electronic properties of the chiral framework
N-donor atom. The coordinating properties and the specific steric structural features of the (Sa)-1,
(Sa)-2, (S,S)-3, and (S,S)-4 ligands are explained by their reactions with the [Pd(PhCN)2Cl2] and
3
[Pd(g -PhCHCHCHPh)(l-Cl)]2 substrates, in which the reported ligands form chelate complexes, with
3
the exception of (Sa)-2, which failed to react with [Pd(g -PhCHCHCHPh)(l-Cl)]2. The ligands were
used in the palladium–allyl catalyzed substitution reaction of 1,3-diphenylallyl acetate with
dimethylmalonate, with the best result being obtained using the (Sa)-1 ligand, giving the substitution
product 2-(1,3-diphenylallyl)dimethylmalonate with an enantiomeric excess of 82% in the S form and a
yield of 96%. The work demonstrates that in the presence of a steric ligand control, the electronic
properties of the ligand donor atoms play a role though not significant in determining the
enantioselectivity of palladium(II) catalyzed allylic substitution reactions. The results of the catalytic
reaction do not provide a convincing explanation considering the coordinated chiral ligand features, as
rigidity or flexibility and electronic properties of the N-donor atoms. A rationalization of the results is
proposed on the basis of NMR studies and DFT calculation on the cationic complexes
3
[Pd(g -PhCHCHCHPh)(N-N*)]CF3SO3, (N-N* = (Sa)-1, 9; (S,S)-3, 10; (S,S)-4, 11).
been found to induce efficiency in the catalytic system include
Introduction
P-N and N-N donors,2,3 planar-chiral ferrocenyl derivatives4 and
dissymmetric diphosphines.5 The rigidity and the flexibility of the
Enantioselective palladium(II)-catalyzed allylic substitution reac-
tions are among the most studied reactions aimed at determining
carbon–carbon bond formation between allylic substrates and
carbon nucleophiles.1 Steric and electronic chiral chelating ligand
features were exploited to recognize factors, which enhance
differentiation between enantiotopic allyl carbon atoms, in the
cationic palladium(II)–allyl catalytic species, and direct nucle-
ophilic attack to afford the substitution product in high yield and
enantiomeric excess. These studies also allowed the establishment
of the reaction steps in which the enantioselectivity of the process
can be determined. Chiral chelating ligand classes which have
3
chiral chelating ligand involved in the catalytic species, [Pd(g -
PhCHCHCHPh)(N-N*)]+ (N-N* = chiral chelating ligand), have
been considered important features in the design of the catalyst,
even if these properties may often give ambiguous indications.
This study reports the use of two pairs of chiral N-N-chelating
ligands in conventional palladium-catalyzed asymmetric allylic
alkylation reactions; they contain rigid 2-pyridinyl or 8-quinolinyl
building blocks and the C2-symmetric chiral frameworks (S)-
(+)-2,2ꢀ-(2-azapropane-1,3-diyl)-1,1ꢀ-binaphthalene) or trans-2,5-
dimethylpyrrolidinyl (Fig. 1). The pairs of ligands differ from each
other in the sp2 or sp3 carbon atom spacer of the N-donor arms
(in each ligand the two N-donor arms are different) and in the
basic electronic properties of the N-donor atom of the chiral
framework. The aim of the study was to gain insight into the
effects of ligand properties, such as the rigidity or flexibility of
the chiral chelating ligand and the influence of the donor-atoms,
in determining asymmetric induction in the catalytic process and
namely, to establish the relation between regioselectivity induced
aDipartimento di Chimica Inorganica, Chimica Analitica, Chimica Fisica
dell’Universita` di Messina, Salita Sperone 31, Vill. S. Agata, 98166,
Messina, Italy. E-mail: faraone@chem.unime.it.
bDipartimento di Chimica dell’Universita` della Basilicata, 85100, Potenza,
Italy
† Electronic supplementary information (ESI) available: Experimental
data, spectral characterization, and DFT calculation table. See DOI:
10.1039/b618347f
This journal is
The Royal Society of Chemistry 2007
Dalton Trans., 2007, 1509–1519 | 1509
©

View Article Online
under reflux conditions. (Sa)-1 and (Sa)-2 ligands were purified
by chromatography and obtained as white and yellow solids,
respectively. They are found to be stable in the air, at room
temperature, for a long time. (S,S)-3 and (S,S)-4 ligands were
obtained by the reaction of (2R,5R)-2,5-hexanediol cyclic sulfate
with 2-aminomethylpyridine or 8-aminoquinoline, respectively, in
a molar ratio of 1 : 1.86 in THF solution under reflux. n-BuLi was
added to the resulting precipitate, indicating the presence of the
corresponding Zwitterionic amine-sulfate species, and the mixture
was refluxed for 72 h. (S,S)-3 was obtained as a yellow oil while
(S,S)-4 was in the form of a yellow crystalline solid. The (Sa)-1,
(Sa)-2, (S,S)-3 and (S,S)-4 ligands were characterized by elemental
analysis and 1H NMR spectroscopy (see Experimental section).
Reactions of (Sa)-1, (Sa)-2, (S,S)-3 and (S,S)-4 ligands with
[Pd(PhCN)2Cl2] and [Pd(g3-PhCHCHCHPh)(l-Cl)]2
Fig. 1 Used chiral ligands.
To gather information about the coordinating properties and the
specific structural features of the (Sa)-1, (Sa)-2, (S,S)-3 and (S,S)-
4 ligands, we explored their reactions with [Pd(PhCN)2Cl2] and
by the chelated chiral ligands in the catalytic process involving each
conformational isomer present in solution and the enantiomeric
excess of the obtained product. The here reported chiral bidentate-
N,N ligands, (Sa)-1, (Sa)-2, (S,S)-3, and (S,S)-4 (Fig. 1), include
both of the nitrogen donor atoms in a heterocyclic ring.
3
palladium(II)–allyl substrate [Pd(g -PhCHCHCHPh)(l-Cl)]2.
The reactions with [Pd(PhCN)2Cl2] were carried out at room
temperature in CH2Cl2 solution in a 1 : 1.2 complex : ligand
ratio. The products, [Pd(N-N*)Cl2], 5–8, (N-N*= (Sa)-1, 5;
(Sa)-2, 6; (S,S)-3, 7; and (S,S)-4, 8), were obtained in almost
quantitative yields as yellow solids by precipitation from CH2Cl2–
The (Sa)-1 ligand had been previously prepared by one of
us.6(S,S)-3 was briefly described7 but its application in metal-
catalyzed asymmetric synthesis has not been explored in detail.
In the (Sa)-2, and (S,S)-4 ligands, the 8-quinolinyl skeleton was
found to directly bind to the C2-symmetric chiral frameworks (S)-
(+)–2,2ꢀ-(2-azapropane-1,3-diyl)-1,1ꢀ-binaphthalene or trans-2,5-
dimethylpyrrolidinyl; these features induce rigidity in the N,N-
framework of this pair of ligands. However, no such properties
were observed for the (Sa)-1 and (S,S)-3 ligands, in which the
presence of the –CH2– spacer between the frameworks bearing
the nitrogen atom donors gives more flexibility to the ligands. A
further observed difference between the pairs of ligands concerns
the electronic properties of the chiral framework N-donor atom.
In the (Sa)-1 and (S,S)-3 pair, the basicity of the chiral framework
N-donor atom was evaluated as being considerably higher than
that of (Sa)-2 and (S,S)-4 pair.8 We also examined the coordi-
nating properties of the synthesized ligands toward palladium(II)
substrates obtaining information by a detailed multinuclear
1
hexane; which later underwent elemental analysis and H NMR
spectroscopy.10
3
The
cationic
complexes,
[Pd(g -PhCHCHCHPh)(N-
N*)]CF3SO3, (9–11) (N-N*= (Sa)-1, 9; (S,S)-3, 10; and
(S,S)-4, 11), which are the catalytic species in the allylic
3
substitution reaction, were synthesized by the reaction of [Pd(g -
PhCHCHCHPh)(l-Cl)]2 with a stoichiometric amount of the N-
N*-chiral ligand, in CH2Cl2 solution, and, subsequently, after 1 h,
with solid AgCF3SO3. Filtration through Celite and evaporation
of the solvent yields a solid product, which was recrystallized using
CH2Cl2–hexane. The (Sa)-2 ligand failed to give the corresponding
3
cationic complex [Pd(g -PhCHCHCHPh)((Sa)-2)]CF3SO3, but
3
it reacted easily with [Pd(g -H2CCHCH2)Cl]2, in the absence of
phenyl-substituents on terminal allylic carbon atoms, to give
3
[Pd(g -H2CCHCH2)((Sa)-2)]CF3SO3, 12.
The compounds 9–11 were characterized by elemental analysis,
conductivity measurements and spectroscopic multinuclear NMR
studies; these will be widely discussed in later sections. The
experimental data allowed us to establish that (Sa)-1, (Sa)-2, (S,S)-
3 and (S,S)-4 ligands act, in the compounds 5–11, as chelating
ligands leading to a square planar geometry.10 Unfortunately,
crystals of compounds 9–11 suitable for X-ray analysis could not
be obtained.
3
NMR study about the major conformational isomers [Pd(g -
PhCHCHCHPh)(N-N*)]+present in solution, their concentration
ratio and the existence of exchange processes. Theoretical DFT
calculations on the relative stability and the simulated structure of
3
the cationic catalytic species [Pd(g -PhCHCHCHPh)(N-N*)]+of
conformational isomers is also reported. Previously,9 we yielded
several reports focusing on the effect of the coordinated ligand
features in determining the enantiomeric excess in the allylic
alkylation palladium-catalyzed process.
NMR Studies
In the 1H NMR spectra of 5–8, the shift of the N-N* ligand signals
indicates their coordination to the palladium centre. For example,
in the 1H NMR spectra of [Pd((Sa)-1)Cl2], 5, and [Pd((S,S)-3)Cl2],
7, the pyridine ortho-hydrogen was observed to shift downfield.
The same shift of the ortho-hydrogen signal of the quinoline
Results
Synthesis of the chiral ligands
(Sa)-1 and (Sa)-2 ligands were obtained by reacting (S)-(+)-2,2ꢀ-
bis-bromomethyl-1,1ꢀ-binaphthalene with 2-aminomethylpyridine
or 8-aminoquinoline respectively, in a 1 : 6 molar ratio in THF
1
framework was observed in the H NMR spectra of [Pd((Sa)-
2)Cl2], 6, and [Pd((S,S)-4)Cl2], 8. However, a different effect was
1510 | Dalton Trans., 2007, 1509–1519
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
3
noted for the cationic complexes [Pd(g -PhCHCHCHPh)((Sa)-
3
1)]CF3SO3, 9, [Pd(g -PhCHCHCHPh)((S,S)-3)]CF3SO3, 10, and
3
[Pd(g -PhCHCHCHPh)((S,S)-4)]CF3SO3, 11, in which the ortho-
hydrogen lies at an upfield chemical shift due to the ring current
effect of the cis phenylic substituent in the allylic moiety (see
below). As expected, the signals of diastereotopic CH2-hydrogens
further split due to ligand chelation.
In order to gain information about the conformational isomers
of compounds 9–11 present in solution and their concentration
ratio, we undertook a multinuclear NMR study. Fig. 2 shows
the possible conformational isomers for a cationic species such
3
as [Pd(g -PhCHCHCHPh)(N-N*)]+, indicating the nomenclature
and the symbols used for the allyl-carbon atoms and the adopted
atoms numeration.11
Furthermore, it was delineated that in solution, the different
conformations can be in equilibrium and may give rise to exchange
processes.12 Thus, preliminarily to a catalytic test, it was very
useful to have knowledge about the allylic conformational isomers
present under the catalytic conditions and to retrieve information
about the possible steric or electronic effects, which determine the
site of nucleophilic attack.13,14 As far as the asymmetric C2-chiral
bidentate ligands (Sa)-1, (Sa)-2, (S,S)-3 and (S,S)-4, are concerned,
they exhibit a chiral framework on the more basic and more steri-
cally demanding nitrogen atom; it is clear that their coordination to
the palladium(II) centre modifies differently the electronic features
of terminal allylic carbon atoms and induces a desymmetrization
of the allyl moiety. As pointed out above, in the (Sa)-1 and (S,S)-3
ligands, the basicity of the chiral framework N-donor atom is of
ca. five pKa units higher than that of (Sa)-2 and (S,S)-4.8
Fig. 2 Possible allyl–palladium conformational isomers and adopted
atoms numeration.
3
In a typical experiment, a weighed amount of any species Pd(g -
PhCHCHCHPh)(N-N*)CF3SO3, 9–11, is dissolved in CDCl3, in
the NMR tube. When equilibrium is reached, the conformational
isomers present in solution are detected by 1H, and13C NMR
spectroscopy. A combination of 1H COSY, 13C, 1H heteronuclear
correlation (HMQC), and 2D NOESY experiments is used to
ascertain the allylic arrangement in the conformational isomers
and the related structures in solution. Relevant 1H and 13C NMR
data are summarized in Table 1.
of two prevalent isomers, the endo-syn-syn, 9a, and the exo-anti-
syn, 9b, in an ca. 70 : 30 ratio (Fig. 3). The NMR spectra failed
to clearly show the presence of the exo-syn-syn conformational
isomer in solution, that is normally considered on the basis of
the DFT calculation, the conformer, at lowest energy, together
with endo-syn-syn.3g The 2-D exchange spectra indicate that the
9a and 9b isomers exchange at room temperature with a g :g :g
mechanism, on the NMR time-scale.12 Selective NOEs between
the allyl protons and the proximate ligand protons allow the
3
1
3
3
The 1,3-diphenylallyl cationic complex [Pd(g -PhCHCH-
CHPh)((Sa)-1)]CF3SO3, 9, exists in CDCl3 solution as a mixture
Table 1 Selected 1H and 13C NMR data for complexes 9–11a,b
H1
H2
H3
C1
C3
endo-syn-syn-9 (9a)
4.33 6.48 4.95 78.3 77.5 7.48 (d, 1H, Hopy) 4.72 (d, 1H, 2J 15 Hz, CH2, 4a), 4.08 (d, 1H, 2J 12 Hz, CH2, 5a),
3.70 (d, 1H, 2J 15 Hz, CH2, 4b), 3.35 (d, 1H, 2J 14 Hz, CH2, 6a), 2.89 (d, 1H, 2J 12 Hz,
CH2, 5b), 2.35 (d, 1H, 2J 14 Hz, CH2, 6b)
exo-anti-syn-9 (9b)
5.38 6.35 4.84 85.1 73.2 7.53 (d, 1H, Hopy), 5.47 (br, 1H, CH2, 4a), 4.27 (br, 1H, CH2, 5a), 3.69 (br, 1H, CH2,
4b), 3.44 (br, 1H, CH2, 6a), 2.95 (br, 1H, CH2, 5b), 2.64 (br, 1H, CH2, 6b)
exo-syn-syn-10 (10ad)
4.84 6.52 4.88 77.9 76.3 7.56 (d, 1H, Hopy), 4.48 (d, 1H, 2J 15 Hz, CH2, 4a), 3.73 (d, 1H, 2J 15 Hz, CH2, 4b),
2.73 (m, 1H, CH, 5), 2.28 (m, 1H, CH, 6), 1.44 (d, 3H, 3J 7 Hz, CH3), 1.01 (d, 3H, 3J
7 Hz, CH3)
endo-syn-syn-10 (10bd) 4.65 6.58 4.79 78.2 77.7 7.16 (d, 1 H, Hopy), 3.94 (d, 1H, 2J 15 Hz, CH2, 4a), 3.78 (d, 1H, 2J 15 Hz, CH2, 4b),
3.09 (m, 1H, CH, 6), 2.43 (m, 1H, CH, 5), 1.57 (d, 3H, 3J 7 Hz, CH3), 0.70 (d, 3H, 3J
7 Hz, CH3)
endo-syn-syn-11 (11a)
exo-syn-syn-11 (11b)
5.10 6.57 5.14 79.0 83.4 7.79 (d, 1H, Hopy), 3.69 (m, 1H, CH, 5), 2.17 (m, 1H, CH, 6), 1.67 (d, 3H, 3J 7 Hz,
CH3), 0.70 (d, 3H, 3J 7 Hz, CH3)
5.08 6.64 5.19 78.8 75.9 7.48 (d, 1H, Hopy), 4.67 (m, 1H, CH, 6), 3.55 (m, 1H, CH, 5), 1.15 (d, 3H, 3J 7 Hz,
CH3), 0.98 (d, 3H, 3J 7 Hz, CH3)
a Chemical shifts, d, are reported in ppm. b In CDCl3 solution. c Coupling constants are in Hz. d At 223 K.
This journal is
The Royal Society of Chemistry 2007
Dalton Trans., 2007, 1509–1519 | 1511
©

View Article Online
Fig. 3 Interpretation of NOESY data in determining the 9a and 9b
isomers.
Fig. 4 Proposed transition state models for the asymmetric allylic
substitutions in 9.
distinction between the endo-syn-syn and exo-anti-syn isomers 9a
and 9b, respectively. The major isomer exhibits an endo-syn-syn
arrangement of the allyl unit, as shown by the coupling constants
of 12 Hz between the terminal allylic protons H3 and H1 with the
central H2 proton. The strong NOE cross peak observed between
the two terminal allylic protons H3 and H1 in 9a, also supports
the syn-syn configuration. The unambiguous assignment of the
major isomer 9a as endo-syn-syn is based on several critical NOE
contacts (Fig. 3). For the exo-anti-syn isomer 9b, all the signals
are broad, also at lower temperatures, due to the exchange process
with the isomer 9a; the exchange obviously involves the isomer
9b in minor population with a faster rate constant, i.e. a wider
line-width. Its conformation was assigned considering the NOE
contact shown in Fig. 3, and particularly the contact between H2
and H1 and especially the selective one between H2 and a proton
on the CH2 group bonded to the N1 nitrogen atom in the azepine
fragment, since such NOE contact is not observed for the major
isomer 9a.
Further positive cross peaks show that a mechanism exchange
involves other minor isomers whose characterization was not pos-
sible due to their very low concentration and signal broadening.
We do not exclude the fact that one of these minor isomers could
be the exo-syn-syn conformer; as yet we are not able to explain
its low concentration with the DFT calculations indicating a
low energy difference between the endo-syn-syn and exo-syn-syn
conformational isomers.
A different situation was found for the species 10 containing
the (S,S)-3 ligand. The 2D NOESY experiment, run at low
temperature, made it possible to assign the configuration of the
major isomers present in solution as endo-syn-syn (about 54%)
and exo-syn-syn (about 42%) (see Fig. 5).
In both isomers, the chemical shift of the ortho-hydrogen of the
pyridine moves to high field because it is affected by the resonance
cone of the phenyl bonded to the allylic fragment.
A correlation between the 13C NMR chemical shifts of the
terminal allylic carbons and their electrophilicity, provided by
the different trans influence of the chelating heteroatom donors
and/or repulsive steric interaction of the substituents on the
chelating donor atoms with the allylic carbon substituents, has
been reported and used as a tool for predicting their reactivity.13
In both isomers, 9a and 9b, the 13C chemical shift values indicate
that the terminal allyl carbons trans to the pyridinyl nitrogen atom
are more deshielded (C1 78.3 ppm for 9a and 85.1 ppm for 9b) than
those trans to the chiral framework nitrogen atom (C3 77.5 ppm
for 9a and 73.2 ppm for 9b); this means that C1 of both 9a and 9b
would be more sensitive than C3 towards nucleophilic attack. The
weakening of the Pd–C1 bond is enhanced due steric hindrance
between the phenyl on the C1 allyl carbon and the CH2 group
bonded to the nitrogen atom in the azepine fragment as shown
by cross peaks in the 2D NOESY experiment (see also theoretical
calculations section).
In addition, the increased downfield shift observed for C1 of
9a versus C1 of 9b, and the larger difference in the chemical
shift between C3 and C1 in 9b (ca. 12 ppm), compared to that
observed for the same carbon atoms in 9a (almost negligible, ca. 1
ppm), allow us to reason that 9b is more reactive than 9a towards
nucleophilic attack at allylic carbon. All these data support the
general model of the complex 9 proposed in Fig. 4, which shows
nucleophilic addition occurring at an allyl carbon atom trans
to the pyridinyl group consistent with the observed S absolute
configuration of the allylic alkylation products.
Fig. 5 Interpretation of NOESY data in determining 10a and 10b
isomers.
Both the endo-syn-syn 10a and exo-syn-syn 10b species are
involved in an exchange process, not between themselves, but with
other minor isomers, as shown by a broadening of the proton
signals at room temperature. In fact, all signals are broad at
room temperature and we observed coalescence. By lowering the
temperature to 223 K, all the signals sharpened except for the
methyl and hydrogen protons close to the pyrrolidinyl nitrogen
atom on account of undergoing a quick exchange and therefore
they appeared broad. In this case, a steric hindrance between the
phenyl on the allylic carbon atom and the CH2 of the pyrrolidinyl
group was observed; this is not able to occur with the methyl
group that is free to move at low temperatures too. Under
catalytic conditions, however, the nucleophile did not distinguish
between the two terminal allyl-carbon atoms because at room
temperature, the complex undergoes a fast exchange, determining
the coalescence state.
3
The 2D NOESY experiment allowed the detection of [Pd(g -
PhCHCHCHPh)((S,S)-4)]CF3SO3, 11, with the configuration in
solution of only two isomers in a greater amount as endo-syn-
syn (67%), 11a, and exo-syn-syn (29%), 11b. For the other two
1512 | Dalton Trans., 2007, 1509–1519
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
Table 2 Calculated (DFT) distances, angles and relative energies of 9–11
DE/kJ mol−1
Pd–C1/A
Pd–C3/A
Pd–N1/A
Pd–N2/A
N1–Pd–C1/◦
N2–Pd–C3/◦
˚
˚
˚
˚
endo-syn-syn 9
exo-syn-syn 9
0
2.248
2.272
2.241
2.252
2.271
2.299
2.231
2.273
2.290
2.292
2.251
2.300
2.220
2.203
2.239
2.218
2.228
2.207
2.266
2.289
2.223
2.213
2.260
2.191
2.224
2.226
2.216
2.222
2.257
2.262
2.241
2.283
2.255
2.259
2.250
2.250
2.136
2.138
2.132
2.148
2.130
2.129
2.122
2.142
2.108
2.106
2.100
2.110
108.08
108.06
106.51
107.26
110.12
109.88
106.68
110.89
108.78
108.30
106.40
109.34
105.60
105.40
105.24
106.17
103.59
103.40
104.44
103.22
104.50
104.19
104.65
103.35
5.56
21.46
26.90
0
3.15
15.96
50.28
0
exo-anti-syn 9
endo-syn-anti 9
endo-syn-syn 10
exo-syn-syn 10
exo-anti-syn 10
endo-syn-anti 10
endo-syn-syn 11
exo-syn-syn 11
exo-anti-syn 11
endo-syn-anti 11
1.91
19.03
21.53
The N1–Pd–N2 and C1–Pd–C3 averaged bite angle values of the coordinated ligands and of the diphenylallyl-moiety coordination are 79.7◦ (78.0–80.8◦)
and 66.8◦ (65.4–68.6◦), respectively.
isomers evidenced, it was not possible to establish an accurate
configuration because they were found in low concentration and
gave rather broad signals.
a static molecule, the difference between real binaphthyl species
and the biphenyl-optimized model did not produce different
results. We further verified that other phenylic groups present in
the binaphthyl do not interact with phenyl-substituents on the
palladium coordinated allyl moiety; in fact, the aforesaid groups
are directed towards the less congested region of the cationic
species. The observed geometrical parameters reported in Table 2,
because of basis-set used (SDD) in the DFT calculation, gave bond
distances around the transition metal atom, which were slightly
longer than the experimental ones.15
The two species 11a and 11b do not exchange in solution
at 298 K temperature. The syn-syn configuration for the major
isomers was assigned through the NOE peaks between the two
allylic protons H1 (5.14 ppm) and H3 (5.10 ppm) for 11a and
H1 (5.19 ppm) and H3 (5.08 ppm) for 11b and by the coupling
constants of 12 Hz between the two terminal hydrogens and
the central proton H2. In both isomers, the chemical shift of
the ortho-hydrogen of the quinoline shifted to high field because
they are affected by the resonance cone of the allylic phenyl.
The pyrrolidinyl ring hydrogens were in exchange due to the
intramolecular axial–equatorial interconversion.
The terminal allylic carbon atoms C1 signals of 11a and 11b
are shifted to a lower frequency than the C3 atoms because they
were cis to the sterically bulky pyrrolidinyl group. The different
electronic characteristics of the two isomers led to different
chemical shifts for the two terminal allylic carbons (11a: 83.4 ppm,
C3; 79.3 ppm, C1; 11b: 79.2 ppm, C3; 75.9 ppm, C1); therefore
the allylic carbon atoms exhibit a different behaviour and the
two isomers give the product in a different conformation. The
endo-syn-syn isomer was characterized by a higher chemical shift
difference (4.1 ppm) between the two terminal allylic carbons than
the exo-syn-syn isomer (3.3 ppm) present at minor concentration,
and this, not being the isomers involved in an exchange process
and not occurring under Curtin–Hammett conditions, may be the
reason why the ee of the obtained products is not notable.
The adopted atom numeration is reported in Fig. 2. Selected
computed bond distances, angles and relative energies for the
isomers at lower energy are reported in Table 2. In all optimized
models of 9–11, theoretical calculations indicate that the endo-
syn-syn and exo-syn-syn conformational isomers are those at
lower energy and of those, concerning the Pd–C bond distances,
the Pd–C1 (C1 being the allyl-carbon atom trans to the 2-
pyridinyl or the 8-quinolinyl nitrogen atom), are longer than
the Pd–C3 (C3 being the allyl-carbon atom in trans position to
nitrogen of the chiral frameworks (S)-(+)–2,2ꢀ-(2-azapropane-1,3-
diyl)-1,1ꢀ-binaphthalene) or trans-2,5-dimethylpyrrolidinyl. For
3
[Pd(g -PhCHCHCHPh)((Sa)-1)]+, 9, the models indicate that the
energy difference between the endo-syn-syn and the exo-syn-
syn conformational isomers is low (5.56 kJ), while the energy
difference between the endo-syn-syn and the exo-anti-syn isomers
is 21.46 kJ mol−1; the difference between the Pd–C1 and Pd–C3
˚
is lower for the endo-syn-syn conformational isomer (0.028 A)
˚
than for the exo-anti-syn isomer (0.069 A). In the conformational
Theoretical calculations
Theoretical calculations have been performed on some conforma-
3
tional isomers of the cationic palladium(II)–allyl species [Pd(g -
PhCHCHCHPh)(N-N*)]+ (N-N*= (Sa)-1, 9; (S,S)-3, 10; (S,S)-
4, 11), to obtain information about their stability and structural
features. The models used reproduce the features of the complete
structures in a reliable way, namely the coordination environment
of the palladium(II) centre and the chelate ring formed by the (Sa)-
1, (S,S)-3 and (S,S)-4, ligands. We performed DFT calculations on
a molecule analogous to 9, containing a biphenyl moiety instead
of a binaphthyl one. Since the DFT calculations were applied to
Fig. 6 Minimized structures of the Pd–allyl complex 9 in which is seen
the repulsions between the allylic-phenyl group and the CH2 group of the
azepine fragment.
This journal is
The Royal Society of Chemistry 2007
Dalton Trans., 2007, 1509–1519 | 1513
©

View Article Online
Table 3 Allylic alkylation of 1,3-diphenylprop-2-enyl acetate with
isomers of 9, the models used clearly show the existence of repul-
sive interactions between the phenyl-substituent on the terminal
allylic carbon atoms and the heterocyclic ring of coordinated
(Sa)-1. Both the endo-syn-syn or exo-anti-syn isomers show the
pyridinyl ortho-hydrogen directed toward the centre of the phenyl-
substituent on the allyl carbon in a cis position (Fig. 6); the
distance between the ortho-hydrogen and the Cpivot of the phenyl
dimethyl malonatea
Entry Ligand
Solvent
Time/h
Yieldb (%)
eec (%)
1
2
3
4
5
(Sa)-1
(Sa)-1
(Sa)-2
(S,S)-3
(S,S)-4
CH2Cl2
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
2.5
2.5
No reaction
3
96
100
82 (S)
82 (S)
100
58
6 (R)
32 (R)
˚
ring of about 2.65 A indicates a short contact between the
36
pyridinyl-ring and the phenyl-substituent. Also, in the exo-syn-
syn isomer, we observed the same short contact with a mean value
of 2.64 A.
Likewise, the minimized models indicate repulsive interactions
between one –CH2– of the chiral frameworks (S)-(+)–2,2ꢀ-(2-
azapropane-1,3-diyl)-1,1ꢀ-binaphthalene) moiety and the Cpivot of
the phenyl-substituent on the allyl carbon atom in a cis position to
azepine nitrogen atom. The distance between the –CH2– and the
3
a [(g -C3H5)PdCl]2 (0.0064 mmol), ligand (0.0128 mmol), H2C(COOMe)2
(2.56 mmol), BSA (2.56 mmol), KOAc (0.06 mmol), CH2Cl2 . b Yield of
5
˚
analytically pure product after column chromatography. c Determined by
1H NMR spectroscopy (CDCl3: 0.25 equiv. [Eu(hfc)3]).5
˚
Cpivot of the phenyl ring was shown to be about 2.68 A. This short
contact interaction contributed to make the palladium–carbon
bond (Pd–C1) in a trans position to pyridinyl longer than the one
in a trans position to the azepine moiety.
Scheme 1
3
Geometry optimization of models for [Pd(g -PhCHCHCHPh)-
3
((S,S)-3)]+, 10, and [Pd(g -PhCHCHCHPh)((S,S)-4)]+, 11, indi-
2)]CF3SO3 synthesis, the ligand (Sa)-2 did not result in a catalytic
process.
cate the endo-syn-syn and exo-syn-syn conformational isomers
as being more stable and the exo-anti-syn as the isomer having
stability closer to that of the above-mentioned isomers. For 10 and
11, the endo-syn-syn was observed to be a more stable isomer and
the energy difference with respect to the exo-syn-syn was estimated
as 3.15 and 1.91 kJ mol−1 respectively.
It is noteworthy that a trans-2,5-dimethylpyrrolidinyl chiral
framework was almost perpendicular to the metal coordination
plane. In the complexes 10 and 11, containing the trans-2,5-
dimethylpyrrolidinyl chiral framework, the (S,S)-3 and (S,S)-
4 coordinated chiral ligands established important repulsive
interactions between the allylic phenyl-substituent and the CH2
and CH of the pyrrolidinyl ring. The distances between the Cpivot
The product 2-(1,3-diphenylallyl)dimethylmalonate was ob-
tained in a yield and an enantiomeric excess strongly depending
on the features of the chiral ligand used in the catalytic process.
The best result was obtained using the ligand (Sa)-1, in which case,
the substitution product of 1,3-diphenyl-2-propenyl acetate with
dimethylmalonate was obtained with an enantiomeric excess of
82% (S) and a yield of 96% (Table 3, entry 1). Changing the
solvent exerted no significant effect either on the yield or the
enantiomeric excess (Table 3, entry 2). The (S,S)-3 and (S,S)-4
ligands afforded the 2-(1,3-diphenylallyl)dimethylmalonate substi-
tution product with a lower enantiomeric excess than (Sa)-1 ligand;
respectively in 6% (R), 100%, 32% (R), and 58% yield (Table 3,
entries 4 and 5). Using the ligand in the (S,S)-configuration,
the 2-(1,3-diphenylallyl)dimethyl-malonate was obtained in the
R configuration.
˚
of the phenyl ring and the CH2 and CH were about 2.69 A. In
this case, no significant interactions between the allylic phenyl-
substituent and the methyl groups were found. In all optimized
models, we found a pronounced unsymmetrization in the terminal
allyl carbon–palladium distances.
Discussion
In the compounds 9–11, the computed angle values of N1–Pd–
N2, N1–Pd–C1, N2–Pd–C3 and C1–Pd–C3 changed in a restricted
range, particularly in their more stable conformational isomers
exo-syn-syn and endo-syn-syn (Table 2). There was a significant
difference between the N1–Pd–C1 and N2–Pd–C3 angle values;
the larger value of the N1–Pd–C1 average angle 108.9◦ (108.1–
110.1◦) than the N2–Pd–C2 one 104.4◦ (103.4–105.6◦) was the
result of the important short contact interactions between the
phenyl substituent on the C1 allyl-carbon atom and the (S)-
(+)–2,2ꢀ-(2-azapropane-1,3-diyl)-1,1ꢀ-binaphthalene or trans-2,5-
dimethylpyrrolidinyl chiral frameworks.
The different performances of the reported ligands in the catalytic
process could be classified in relation to the different sp3 or
sp2 carbon atom spacer of the ligand arms. In the (Sa)-1, and
(S,S)-3 ligands, the sp3 carbon atom spacer induces higher
flexibility than the sp2 spacer carbon atom present in (Sa)-2
and (S,S)-4. The N1–C(sp2)–C(sp2)–N2 atom arrangement induces
rigidity on (Sa)-2 and (S,S)-4; consequently, their coordination as
3
chelating N-N-ligands to the g -diphenylallyl–palladium moiety
is not much favourite. The fact that (Sa)-2 failed to react with
3
3
[Pd(g -PhHCCHCHPh)Cl]2 to give the cationic complex [Pd(g -
3
PhHCCHCHPh)((Sa)-2)]CF3SO3, but it reacts easily with [Pd(g -
H2CCHCH2)Cl]2, in which phenyl-substituents are not present on
terminal allylic carbon atoms, to give [Pd(g -H2CCHCH2)((Sa)-
Palladium-catalyzed asymmetric allylic alkylation reactions
3
We tested the versatility of the chelating C2-chiral ligands (Sa)-
1, (S,S)-3 and (S,S)-4, in the palladium–allyl catalyzed substitu-
tion reaction of 1,3-diphenylallyl acetate with dimethylmalonate
(Scheme 1). In accord with the previous results indicating the
2)]CF3SO3, 12, strongly supports the viewpoint that the electronic
properties of the chiral framework N-donor atom are not respon-
sible for this behaviour. Moreover, the reaction which utilizes 11
as a catalyst requires an induction time to occur. Differently, the
flexibility of the N1–C(sp3)–C(sp2)–N2 atom arrangement allows
3
failure of the cationic complex [Pd(g -PhCHCHCHPh)((Sa)-
1514 | Dalton Trans., 2007, 1509–1519
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
both nitrogen atoms of the (Sa)-1 and (S,S)-3 ligands to easily
approach the palladium atom and also to form conformational
isomers, which are not of high stability, as for the 9b isomer of the
(Sa)-1 ligand.
Hammett conditions, the exo-anti-syn conformational isomer
determines the enantioselectivity of the process and the absolute
configuration of the substitution product. However, nucleophilic
attack at C1 allylic carbon atoms in the endo-syn-syn and in the exo-
anti-syn isomers, gives 2-(1,3-diphenylallyl)dimethylmalonate in
the S absolute configuration for both cases; this allows the retrieval
of the allylic alkylation reaction product in high enantiomeric
excess and in the S absolute configuration.
The behaviour of 10, as a catalyst, is very significant. As
expected, the major isomers in solution are exo-syn-syn, 10a, and
endo-syn-syn, 10b, which have been suggested to be involved in a
fast exchange process, with coalescence at catalytic experimental
conditions. It can be assumed that under these conditions, the
nucleophile does not distinguish between the two terminal allylic
carbons and as a result the catalytic reaction gives the product
in low yield with very low enantiomeric excess, even if a more
accurate analysis should take into account a comparison between
the typical rate of allylic alkylation reaction and that of the
dynamic process observed for this system.
Compound 11 contains the more rigid chiral ligand (S,S)-
4 and allows us to obtain the allylic substitution product only
with a very low enantiomeric excess. This contrasts with the fact
that (S,S)-4 induces the greatest difference observed (comparing
conformational isomer which differs only for the coordinated
chiral ligand16) between th e13C chemical shift values of the
terminal allylic carbon atoms, respectively of 4.1 and 3.3 ppm,
in the endo-syn-syn, 11a, and exo-syn-syn, 11b, conformational
isomers. The comparison of these 13C NMR data with those
of the conformational isomers, which are different only for the
chelated chiral ligands, indicates that the ligand rigidity enhances
the regioselectivity of the nucleophilic attack, more than the ligand
flexibility. It is noteworthy that the endo-syn-syn, 11a, and exo-syn-
syn, 11b conformational isomers are not involved in an exchange
process with each other.
The situation observed for every isomer would reasonably
suppose that the (S,S)-4 ligand, owing to its rigidity, induces high
regioselectivity in allylic carbon nucleophilic attack; consequently,
the 2-(1,3-diphenyl-allyl)dimethylmalonate product would have
to be obtained with high enantiomeric excess. As a matter of
fact, every isomer catalyzes the related process and gives the
product with the prevalence of one enantiomer (ee). The observed
enantiomeric excess of 2-(1,3-diphenylallyl)dimethylmalonate is
the result of a balance between the amounts of 2-(1,3-
diphenylallyl)dimethylmalonate, in the R and S absolute confor-
mation, produced from each catalyst isomer present in solution.
The models indicate that the dimethylmalonate nucleophilic attack
at C1 allylic carbon atoms of isomers 11a and 11b, should obtain
the 2-(1,3-diphenylallyl)dimethylmalonate in the R and S absolute
configuration, respectively. It can reasonably be supposed that, in
this case, the low enantiomeric excess can be due to the presence,
in solution, of more isomers that give the product in the different
absolute configuration.
It is a widely proven fact that the enantioselectivity of the allylic
substitution reaction process is determined by the regioselectivity
of the nucleophilic attack at the terminal allylic carbon atoms.14 As
shown by NMR studies and confirmed by theoretical calculations,
in the palladium–diphenyl–allyl catalysts 9–11, the regioselectivity
is mainly induced by the different intra-complex steric hindrances
between the trans-2,5-dimethylpyrrolidinyl or the (S)-(+)–2,2ꢀ-(2-
azapropane-1,3-diyl)-1,1ꢀ-binaphthalene) moieties, contained in
the (Sa)-1, (S,S)-3, and (S,S)-4 ligands, and the phenyl-substituent
on the allyl carbon atom in a cis position.12–14 As discussed in the
“NMR studies” section and results from Pd–C bond distances
deduced by DFT calculations, the trans-influence of the N-donor
atoms bound to the palladium centre, is not the main factor
determining the regioselectivity of the catalytic process. Very
indicative of the negligible role of the ligand N-donor atom’s power
are the computed bond distances Pd–N1, Pd–N2, Pd–C1 and Pd–
˚
C3 average value (A) for the most stable conformational isomers
exo-syn-syn and endo-syn-syn (the result is practically unchanged
considering all the conformational isomers reported in Table 2):
9: Pd–N1 2.250, Pd–N2 2.137, Pd–C1 2.260, Pd–C3 2.211; 10:
Pd–N1 2.259, Pd–N2 2.129, Pd–C1 2.285, Pd–C3 2.217; 11: Pd–
N1 2.257, Pd–N2 2.107, Pd–C1 2.291, Pd–C3 2.218. The distance
of the Pd–C3 bond, in a trans position to the chiral framework
N1, having higher donor power is always shorter than the Pd–C1
bond distance; the reported data clearly indicate that repulsive
interactions between the chiral framework coordinated through
N1-donor atom and the phenyl-substituent at C1-allylic carbon
atom minimizes the electronic effect of the N1-donor atom. While
the Pd–N2 bond distance discriminates between the pyridinyl- and
quinolidinyl ligands, the Pd–N1 bond distance, the same as Pd–C1
and Pd–C3 ones, is nearly unchanged in compounds 9–11.
The understanding of the origin of the enantioselectivity of
the catalytic allylic substitution process requires, in principle, a
knowledge of the regioselectivity of the nucleophilic attack at the
terminal allylic carbon atoms for each conformational isomers
of the catalytic species. Fortunately, the regioselectivity of the
nucleophilic attack at terminal allylic carbons is supplied by the 13C
NMR spectra, from the chemical shift values of the allylic carbon
atoms and, in a more specific way, from the difference between
their relative values. The results discussed here clearly prove that
structural features of the coordinated chiral ligand, like flexibility
or rigidity, are not able to fully explain the experimental data.
In fact, in the catalytic intermediate 9, the downfield chemical
shift of 13C allylic carbon C1 in the exo-anti-syn conformer
indicated that it is more suited to nucleophilic attack with respect
to the same carbon atom in the other prevalent conformer. 13C
NMR spectra indicate that in the exo-anti-syn isomer, nucleophilic
attack at carbon C1 is also favoured by the smaller steric hindrance
of the closer S-binaphthyl fragment (see Fig. 4). The endo-syn-
syn and the exo-anti-syn isomers are involved in an exchange
process, and the exo-anti-syn conformational isomer is the most
reactive towards nucleophilic attack (in the exo-anti-syn isomer the
difference in the 13C NMR chemical shift of terminal allylic carbon
atoms is about 12.0 ppm). The related reaction is faster than the
endo-syn-syn conformer (Fig. 4) and, occurring under Curtin–
The results also indicate that rigidity of the 2-pyridinyl and
8-quinolinyl heterocyclic rings containing the nitrogen donor
atom also induces repulsive interactions with the substituent on
the terminal allylic carbon atom in a cis-position, even if to a
more minor extent than the chiral N-donor chiral framework.
Therefore, this is also a factor determining the regioselectivity of
the nucleophilic attack.
This journal is
The Royal Society of Chemistry 2007
Dalton Trans., 2007, 1509–1519 | 1515
©

View Article Online
It is noteworthy to mention that the metallacycle ring effect is
not a factor which influences the process, since all the ligands
reported here form a five-membered ring by chelation to the
palladium centre.
Preparations
(Sa)-(−)-2,2ꢀ-[(7-Quinolinyl)-2-azapropane-1,3-diyl]-1,1ꢀ-binaph-
thalene (Sa)-2. To a solution of (S)-(−)-2,2ꢀ-dibromomethyl-
1,1ꢀ-binaphthalene (400 mg, 0.91 mmol) in anhydrous THF
(40 mL) under an inert atmosphere was added 8-aminoquinoline
(792 mg, 5.5 mmol). The solution was stirred under reflux for
18 h then cooled to rt. The solution was filtered and the solid
residue was washed with THF. The resulting collected solution
was concentrated in vacuo. The recovered residue was dissolved
in CHCl3, washed sequentially with H2O and brine, and the
organic layer was dried over anhydrous Na2SO4. The solid residue
recovered after evaporation of the solvent was then purified
by column chromatography (neutral Al2O3; CH2Cl2–Et2O, 85 :
Conclusions
The rigidity or flexibility features of the coordinated chiral
chelating ligands (Sa)-1, (Sa)-2, (S,S)-3 and (S,S)-4 do not explain
the results obtained in the palladium–allyl catalyzed substitution
reaction of 1,3-diphenylallyl acetate with dimethylmalonate. In
order toovercome theseemingcontradictions thatemerge from the
results, the characterization of the conformational isomers of the
palladium–diphenylallyl catalytic species (at least, occurring under
Curtin–Hammett conditions, those in major concentrations) and
the identification of exchange processes are indispensable. An
indicative knowledge of the amount and of the absolute con-
figuration of the 2-(1,3-diphenylallyl)dimethylmalonate reaction
product, for every catalytically active palladium–diphenylallyl
conformational isomer present in solution, is of fundamental
importance for a reasonable and rigorous explanation about the
origin of the observed enantioselectivity of the catalytic product.
Therefore, deeper NMR studies and theoretical calculations are
indispensable supports to the interpretation of the experimental
results and to the reached conclusions in the palladium(II)
catalyzed allylic substitution reactions.
15) affording (Sa)-2 as a yellow powder. Yield: 82% (315 mg,
0.74 mmol). [a]26 = −318.2 (c 1, CHCl3). H NMR (CDCl3): d
1
D
3
4
3
4
8.91 (dd, 1H, J 4 Hz, J 2 Hz, Ar-H), 8.15 (dd, 1H, J 8 Hz, J
2 Hz, Ar-H), 7.91 (dd, 2H, 3J 8 Hz, Ar-H), 7.88 (d, 2H, 3J 8 Hz,
Ar-H), 7.57 (d, 2H, 3J 8 Hz, Ar-H), 7.53–7.18 (m, 9H, Ar-H), 6.97
3
4
3
(dd, 1H, J 7 Hz, J 2 Hz, Ar-H), 4.73 (d, 2H, J 12 Hz, CH2),
3
4.17 (d, 2H, J 12 Hz, CH2). Anal. Calcd for C31H22N2 (422.52):
C, 88,12; H, 5,25; N, 6,63. Found: C, 88,03; H, 5,37; N, 6,60%.
(S,S)-(+)-2-(2,5-Dimethylpyrrodin-1-ylmethyl)pyridine (S,S)-3.
2-Aminomethylpyridine (447 mg, 4.13 mmol) and (2R,5R)-2,5-
hexandiol cyclic sulfate (400 mg, 2.22 mmol) were refluxed in dry
THF (10 mL) for 16 h. The resulting precipitate indicated the
presence of the Zwitterionic amine–sulfate species. The Schlenk
flask was cooled to −78 ◦C and n-butyllithium (1.6 M, 1.53 mL,
2.42 mmol) was added. The mixture was warmed to room
temperature and then refluxed for 72 h. Diethyl ether was added
to the solution which was then washed with 10% ammonium
chloride, water, and brine and extracted into diethyl ether. The
extract was dried (MgSO4) and concentrated to yield the crude
material. Purification using column chromatography, alumina,
hexane–diethyl ether 2 : 1, gave (S,S)-3 as a yellow oil. Yield:
75% (320 mg, 1.68 mmol). [a]26D = −101.1 (c 1, CHCl3). 1H NMR
(CDCl3): d 8.51 (d, 1H, 3J 4 Hz, Ar-H), 7.61 (td, 1H, 3J 8 Hz, 4J
Experimental
General methods
All manipulation were carried out under an argon atmosphere
using standard Schlenk techniques. Freshly distilled solvents
were used throughout and dried by standard procedures. Pub-
lished methods were used to prepare the compound (2R,5R)-
2,5-hexandiol cyclic sulfate,17 (Sa)-(+)–2,2ꢀ-[2-(methyl-2-pyridyl)-
3
2-azapropane-1,3-diyl]-1,1ꢀ-binaphthalene, 17, and [Pd(g -PhCH-
3
2 Hz, Ar-H), 7.47 (d, 1H, J 8 Hz, Ar-H), 7.10 (m, 1H, Ar-H),
CHCHPh)(l-Cl)]2.18 All other reagents were purchased from
3.89 (d, 1H, 2J 14 Hz, CH2), 3.76 (d, 1H, 2J 14 Hz, CH2), 3.08 (m,
2H, CH), 2.01 (m, 2H, CH2), 1.38 (m, 2H, CH2), 0.97 (d, 6H, 3J
7Hz, CH3). Anal. Calcd for C12H18N2 (190.28): C, 75.74; H, 9.53;
N, 14.72. Found: C, 75.78; H, 9.51; N, 14.68%.
Sigma-Aldrich and Strem and were used as supplied. For column
chromatography, silica gel 60 (220
440 mesh) and neutral
aluminium oxide activity grade 1 (70–290 mesh) purchased from
Fluka was used. Optical rotations were obtained with a JASCO
P-1010 Automatic Polarimeter in a 1 dm cell; c in g per 100 mL. 1D
and 2D NMR experiments were carried out using a Bruker AMX
R300 spectrometer. 1H NMR spectra were referenced to internal
tetramethylsilane. For the 9–11 compounds, the resonances of
the terminal allylic carbon C1 and C3 are reported in Table 1.
Standard pulse sequences were employed for phase-sensitive (TPPI
(S,S)-(+)-8-(2,5-Dimethylpyrrodin-1-yl)quinoline (S,S)-4. 8-
Aminoquinoline (595 mg, 4.13 mmol) and (2R,5R)-2,5-hexandiol
cyclic sulfate (400 mg, 2,22 mmol) were refluxed in dry THF
(10 mL) for 16 h. The resulting precipitate indicated the presence
of the Zwitterionic amine–sulfate species. The Schlenk flask was
cooled to −78 ◦C and n-butyllithium (1.6 M, 1.53 mL, 2.42 mmol)
was added. The mixture was warmed to room temperature and
then refluxed for 72 h. Diethyl ether was added to the solution
which was then washed with 10% ammonium chloride, water,
and brine and extracted into diethyl ether. The extract was dried
(MgSO4) and concentrated to yield the crude material which was
purified using column chromatography, alumina, hexane–diethyl
ether 2 : 1, to give (S,S)-4 as a yellow oil which crystallize on
1
method) H-2D-NOESY, 13C–1H-correlation (HMQC) studies.19
Elemental analyses were performed by Redox s.n.c., Cologno
Monzese, Milano.
All calculations were carried out using the Gaussian G03W
program package.15 The structures and bonding parameters were
computed at the density functional (DFT) B3LYP level of theory,
using Becke’s exchange functional, which includes the Slater
exchange along with corrections involving the gradient of the
density20 and Perdew and Wang’s gradient-corrected correlation
functional.21, 22
cooling. Yield: 77% (390 mg, 1.72 mmol). [a]26 = −220.2 (c 1,
D
1
3
4
CHCl3). H NMR (CDCl3): d 8.85 (dd, 1H, J 4 Hz, J 2 Hz,
Ar-H), 8.06 (dd, 1H, 3J 8 Hz, 4J 2 Hz, Ar-H), 7.41 (t, 1H, 3J 8 Hz,
1516 | Dalton Trans., 2007, 1509–1519
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
3
4
3
Ar-H), 7.33 (dd, 1H, J 8 Hz, J 4 Hz, Ar-H), 7.29 (dd, 1H, J
8 Hz, 4J 2 Hz, Ar-H), 7.00 (dd, 1H, 3J 8 Hz, Ar-H), 4.62 (b, 2H,
CH), 2.30 (m, 2H, CH2), 1.67 (m, 2H, CH2), 0.95 (b, 6H, CH3).
Anal. Calcd for C15H18N2 (226.32): C, 79.61; H, 8.02; N, 12.38.
Found: C, 79.55; H, 8.12; N, 12.36%.
PhCHCHCHPh)(l-Cl)]2 (0.020 g, 0.030 mmol) with the ligand
(N-N*) (0.06 mmol) in CH2Cl2 (25 ml) at room temperature. After
1 h AgCF3SO3 (0.015 g, 0.06 mmol) was added and the mixture
was stirred for 10 min. The suspension was filtered through a pad
of Celite, the solvent evaporated in vacuo except for a few millilitres,
and the product precipitated with hexane. Recrystallized from
CH2Cl2–hexane in a 3 : 1 ratio, a yellow powder was obtained.
[Pd(N-N*)Cl2] (5–8). The [Pd(N-N*)Cl2] complexes with N-
N* = (Sa)-1 (5), (Sa)-2 (6), (S,S)-3 (7), (S,S)-4 (8), were synthesized
in the same way with the following procedure.
3
[Pd(g -PhCHCHCHPh)((Sa)-1)]CF3SO3 (9). Yield: 75%
(38 mg, 0.045 mmol). 1H NMR (CDCl3) at 298 K: endo-syn-syn d
8.23 (d, 1H, 3J 8 Hz, Ar-H), 8.10 (d, 1H, 3J 8 Hz, Ar-H), 8.06–7.88
(m, 4H, Ar-H), 7.86 (t, 1H, 3J 8 Hz, Ar-H), 7.62 (t, 1H, 3J 8 Hz,
Ar-H), 7.48 (d, 1H, Hopy), 7.47–7.23 (m, 10H, Ar-H), 7.24 (m, 6H,
To a solution of [Pd(benzonitrile)2Cl2] (20 mg, 52.1 mmol) in
CH2Cl2 the ligand (62.6 mmol) was added. After the addition the
colour of the solution switches from orange to light yellow. After
3 h solvent was removed in vacuo and the residue was washed with
hexane. Recrystallization from a 3 : 1 ratio of CH2Cl2–hexane gave
the complex as a yellow solid product.
3
3
Ar-H), 7.05 (t, 1H, J 8 Hz, Ar-H), 6.80 (t, 1H, J 8 Hz, Ar-H),
2
2
6.48 (dd, 1H, J 12 Hz, CH2, 2), 4.95 (d, 1H, J 12 Hz, CH2, 3),
2
2
4.72 (d, 1H, J 15 Hz, CH2, 4a), 4.33 (d, 1H, J 12 Hz, CH2, 1),
4.08 (d, 1H, 2J 12 Hz, CH2, 5a), 3.70 (d, 1H, 2J 15 Hz, CH2, 4b),
3.35 (d, 1H, 2J 14 Hz, CH2, 6a), 2.89 (d, 1H, 2J 12 Hz, CH2, 5b),
2.35 (d, 1H, 2J 14 Hz, CH2, 6b); exo-anti-syn: d 8.26 (br, 1H, Ar-
H), 8.07 (br, 1H, Ar-H), 8.04–7.86 (m, 4H, Ar-H), 7.85 (br, 1H,
Ar-H), 7.59 (br, 1H, Ar-H), 7.53 (d, 1H, Hopy), 7.48–7.21 (m, 10H,
[Pd((Sa)-1)Cl2] (5). Yield: 85% (25 mg, 0.044 mol). 1H NMR
3
4
(CDCl3): d 8.97 (dd, 1H, J 6 Hz, J 2 Hz, Ar-H), 8.28 (d, 1H,
3J 8 Hz, Ar-H), 8.07 (d, 1H, J 8 Hz, Ar-H), 8.00–7.88 (td, 3H,
3
3J 8 Hz, J 2 Hz, Ar-H), 7.83 (td, 1H, J 8 Hz, J 2 Hz, Ar-H),
4
3
4
3
7.72 (d, 1H, J 8 Hz, Ar-H), 7.48 (m, 3H, Ar-H), 7.28 (m, 5H,
Ar-H), 5.75 (d, 1H, 2J 15 Hz, CH2), 4.83 (d, 1H, 2J 14 Hz, CH2),
3
Ar-H), 7.20 (m, 6H, Ar-H), 7.02 (br, 1H, Ar-H), 6.80 (t, 1H, J
2
2
4.45 (d, 1H, J 14 Hz, CH2), 4.43 (d, 1H, J 12 Hz, CH2), 3.64
(d, 1H, 2J 15 Hz, CH2), 3.02 (d, 1H, 2J 12 Hz, CH2). Anal. Calcd
for C28H22Cl2N2Pd (563.81): C, 59.65; H, 3.93; N, 4.97. Found: C,
59.61; H, 3.92; N, 4.91%.
[Pd((Sa)-2)Cl2] (6). Yield: 81% (25.3 mg, 0.042 mol). 1H
NMR (CDCl3): d 9.65 (dd, 1H, J 5 Hz, J 2 Hz, Ar-H), 8.43
8 Hz, Ar-H), 6.35 (br, 1H, CH2, 2), 5.47 (br, 1H, CH2, 4a), 5.38
(br, 1H, CH2, 1), 4.84 (br, 1H, CH2, 3), 4.27 (br, 1H, CH2, 5a), 3.69
(br, 1H, CH2, 4b), 3.44 (br, 1H, CH2, 6a), 2.95 (br, 1H, CH2, 5b),
2.64 (br, 1H, CH2, 6b). Conductivity value of 89 lS in methanol
solution, using a 5 × 10−4–1 × 10−4 molar concentration. Anal.
Calcd for C44H35F3N2O3PdS (835.24): C, 63.27; H, 4.22; N, 3.35.
Found: C, 64.51; H, 3.98; N, 3.41%.
3
4
3
4
3
(dd, 1H, J 8 Hz, J 2 Hz, Ar-H), 8.28 (d, 1H, J 8 Hz, Ar-H),
8.08 (dd, 2H, 3J 8 Hz, 4J 4 Hz, Ar-H), 8.00 (dd, 2H, 3J 19 Hz, 4J
8 Hz, Ar-H), 7.87 (dd, 1H, 3J 8 Hz, 4J 2 Hz, Ar-H), 7.63 (dd, 1H,
3
[Pd(g -PhCHCHCHPh)((S,S-3)]CF3SO3 (10). Yield: 76%
1
(29.2 mg, 0.046 mmol). H NMR (CDCl3) at 223 K: exo-syn-
3J 5 Hz, Ar-H), 7.56 (t, 1H, J 7 Hz, Ar-H), 7.49–7.40 (m, 5H,
3
syn d 7.80–7.61 (m, 8H, Ar-H), 7.56 (d, 1H, Hopy), 7.51–7.37 (m,
6H, Ar-H), 6.52 (dd, 1H, 2J 12 Hz, CH2, 2), 4.88 (d, 1H, 2J 12 Hz,
CH2, 3), 4.84 (d, 1H, 2J 12 Hz, CH2, 1), 4.48 (d, 1H, 2J 15 Hz, CH2,
4a), 3.73 (d, 1H, 2J 15 Hz, CH2, 4b), 2.73 (m, 1H, CH, 5), 2.28 (m,
1H, CH, 6), 2.00 (m, 1H, CH2, 7a), 1.65 (m, 1H, CH2, 8a), 1.44
(d, 3H, 3J 7 Hz, CH3), 1.28 (m, 1H, CH2, 8b), 1.17 (m, 1H, CH2,
7b), 1.01 (d, 3H, 3J 7 Hz, CH3); endo-syn-syn: d 7.80–7.61 (m, 8H,
Ar-H), 7.16 (d, 1H, Hopy), 7.51–7.37 (m, 6H, Ar-H), 6.58 (dd, 1H,
2J 12 Hz, CH2, 2), 4.79 (d, 1H, 2J 12 Hz, CH2, 3), 4.65 (d, 1H, 2J
Ar-H), 7.31 (t, 1H, 3J 7 Hz, Ar-H), 7.21 (d, 2H, 3J 4 Hz, Ar-H),
2
2
6.06 (d, 1H, J 14 Hz, CH2), 4. 94 (d, 1H, J 12 Hz, CH2), 4.48
(d, 1H, 2J 14 Hz, CH2), 4.14 (d, 1H, 2J 12 Hz, CH2). Anal. Calcd
for C31H22Cl2N2Pd (599.85): C, 62.07; H, 3.70; N, 4.67. Found: C,
62.12; H, 3.64; N, 4.61%.
1
[Pd((S,S)-3)Cl2] (7). Yield: 75% (14.5 mg, 0.039 mol). H
NMR (CDCl3): d 9.05 (d, 1H, 3J 6 Hz, Ar-H), 7.94 (t, 1H, 3J 8 Hz,
Ar-H), 7.65 (d, 1H, 3J 8 Hz, Ar-H), 7.40 (t, 1H, 3J 7 Hz, Ar-H),
2
2
4.54 (d, 1H, J 15 Hz, CH2), 4.12 (m, 1H, CH), 3.62 (d, 1H, J
15 Hz, CH2), 3.03 (m, 1H, CH), 2.30 (m, 1H, CH2), 2.11 (m, 1H,
CH2), 1.93 (d, 3H, 3J 7 Hz, CH3), 1.89 (m, 1H, CH2), 1.63 (m, 1H,
CH2), 1.61 (d, 3H, 3J 7 Hz, CH3). Anal. Calcd for C12H18Cl2N2Pd
(367.61): C, 39.21; H, 4.94; N, 7.62. Found: C, 39.30; H, 4.92; N,
7.57%.
2
2
12 Hz, CH2, 1), 3.94 (d, 1H, J 15 Hz, CH2, 4a), 3.78 (d, 1H, J
15 Hz, CH2, 4b), 3.09 (m, 1H, CH, 6), 2.43 (m, 1H, CH, 5), 2.14
(m, 1H, CH2, 7a), 1.57 (d, 3H, 3J 7 Hz, CH3), 1.40 (m, 1H, CH2,
7b), 1.28 (m, 1H, CH2, 8a), 1.24 (m, 1H, CH2, 8b), 0.70 (d, 3H,
3J 7 Hz, CH3). Conductivity value of 83 lS in methanol solution,
using a 5 × 10−4–1 × 10−4 molar concentration. Anal. Calcd for
C28H31F3N2O3PdS (639.04): C, 52.63; H, 4.89; N, 4.38. Found: C,
53.68; H, 4.86; N, 4.42%.
1
[Pd((S,S)-4)Cl2] (8). Yield: 78% (16.4 mg, 0.041 mol). H
3
4
NMR (CDCl3): d 9.62 (dd, 1H, J 5 Hz, J 1 Hz, Ar-H), 8.43
(dd, 1H, 3J 8 Hz, 4J 2 Hz, Ar-H), 7.91 (dd, 1H, 3J 7 Hz, 4J 2 Hz,
Ar-H), 7.78–7.70 (m, 2H, Ar-H), 7.58 (dd, 1H, 3J 8 Hz, 4J 5 Hz,
Ar-H), 5.70 (m, 1H, CH), 3.76 (m, 1H, CH), 2.73 (m, 1H, CH2),
2.27 (m, 1H, CH2), 2.12 (m, 1H, CH2), 2.19 (d, 3H, 3J 7 Hz, CH3),
1.97 (m, 1H, CH2), 1.06 (d, 3H, J 7 Hz, CH3). Anal. Calcd for
C15H18Cl2N2Pd (403.64): C, 44.63; H, 4.49; N, 6.94. Found: C,
44.60; H, 4.53; N, 6.91%.
3
[Pd(g -PhCHCHCHPh)((S,S)-4)]CF3SO3 (11). Yield: 82%
(33.2 mg, 0.049 mmol). 1H NMR (CDCl3) at 298 K: endo-syn-syn d
8.35 (d, 1H, 3J 4 Hz, Ar-H), 8.33 (t, 1H, 3J 6 Hz, Ar-H), 7.92–7.45
(m, 9H, Ar-H), 7.79 (d, 1H, Hopy), 7.22–7.13 (m, 4H, Ar-H), 6.57
(dd, 1H, 2J 12 Hz, CH2, 2), 5.14 (d, 1H, 2J 12 Hz, CH2, 3), 5.10 (d,
1H, 2J 12 Hz, CH2, 1), 3.69 (m, 1H, CH, 5), 2.17 (m, 1H, CH, 6),
3
3
1.91 (m, 1H, CH2, 7a), 1.67 (d, 3H, J 7 Hz, CH3), 1.61 (m, 1H,
[Pd(g3-PhCHCHCHPh)(N-N*)]CF3SO3 (9–11). The follow-
ing procedure for the preparation of 11 is representative and the
CH2, 8a), 1.38 (m, 1H, CH2, 8b), 0.70 (d, 3H, 3J 7 Hz, CH3), 0.49
(m, 1H, CH2, 7b); exo-syn-syn: d 8.92 (d, 1H, 3J 4 Hz, Ar-H), 8.35
(t, 1H, 3J 6 Hz, Ar-H), 7.92–7.45 (m, 9H, Ar-H), 7.48 (d, 1H, Hopy),
7.22–7.13 (m, 4H, Ar-H), 6.64 (dd, 1H, 2J 12 Hz, CH2, 2), 5.19 (d,
3
[Pd-(g -PhCHCHCHPh)(N-N*)]CF3SO3 complexes (N-N*) =
(Sa)-1 (9), (S,S)-3 (10), (S,S)-4 (11), were synthesized in a similar
3
2
2
manner. This complex was synthesized by reaction of [Pd(g -
1H, J 12 Hz, CH2, 3), 5.08 (d, 1H, J 12 Hz, CH2, 1), 4.67 (m,
This journal is
The Royal Society of Chemistry 2007
Dalton Trans., 2007, 1509–1519 | 1517
©

View Article Online
1H, CH, 6), 3.55 (m, 1H, CH, 5), 2.10 (m, 1H, CH2, 7a), 1.52 (m,
1H, CH2, 7b), 1.36 (m, 1H, CH2, 8a), 1.15 (d, 3H, 3J 7 Hz, CH3),
1.05 (m, 1 H, CH2, 8b), 0.98 (d, 3 H, 3J 7 Hz, CH3). Conductivity
value of 80 lS in methanol solution, using a 5 × 10−4–1 × 10−4
molar concentration. Anal. Calcd for C31H31F3N2O3PdS (675.07):
C, 55.15; H, 4.63; N, 4.15. Found: C, 55.20; H, 4.64; N, 4.18%.
Publishers, New York, 1993; (e) R. Noyori, Asymmetric Catalysis in
Organic Synthesis, John Wiley & Sons, New York, 1994; (f) B. M. D.
Trost and T. R. Verhoeven, J. Am. Chem. Soc., 1976, 98, 630; (g) B. M. D.
Trost and T. R. Verhoeven, J. Am. Chem. Soc., 1978, 100, 3435; (h) G. A.
Molander, J. P. Burke and P. J. Carroll, J. Org. Chem., 2004, 69, 8062;
(i) O. G. Manchen˜o, J. Priego, S. Cabrera, R. G. Arraya´s, T. Llamas
and J. C. Carretero, J. Org. Chem., 2003, 68, 3680.
2 (a) A. Pfaltz, Acc. Chem. Res., 1993, 26, 339; (b) U. Leutenegger, G.
Umbricht, C. Fahrni, P. von Matt and A. Pfaltz, Tetrahedron, 1992, 48,
2143; (c) P. G. Andersson, A. Harden, D. Tanner and P. O. Norrby,
Chem.–Eur. J., 1995, 1, 12; (d) B. M. Trost and I. Hachiya, J. Am.
Chem. Soc., 1998, 120, 1104; (e) H. Kubota, M. Nakajima and K.
Koga, Tetrahedron Lett., 1993, 34, 8135; (f) K. Nordstro¨m, E. Macedo
and C. Moberg, J. Org. Chem., 1997, 62, 1604; (g) P. Gamez, B. Dunjic,
F. Fache and M. Lemaire, J. Chem. Soc., Chem. Commun., 1994, 1417;
(h) J. M. Canal, M. Go´mez, F. Jime´nez, M. Rocamora, G. Muller,
E. Dun˜ach, D. Franco, A. Jime´nez and F. H. Cano, Organometallics,
2000, 19, 966; (i) M. Go´mez, S. Jansat, G. Muller, M. A. Maestro and
J. M. Saavedra, Organometallics, 2002, 21, 1077; (j) M. Svensson, U.
Bremberg, K. Hallman, I. Cso¨regh and C. Moberg, Organometallics,
1999, 18, 4900; (k) M. Go´mez, S. Jansat, G. Muller, M. A. Maestro,
J. M. Saavedra, M. Font-Bard´ıa and X. Solans, J. Chem. Soc., Dalton
Trans., 2001, 1432.
3 (a) G. Helmchen and A. Pfaltz, Acc. Chem. Res., 2000, 33, 336; (b) J. M.
Brown, D. I. Hulmes and P. J. Guiry, Tetrahedron, 1994, 50, 4493;
(c) P. E. Blo¨chl and A. Togni, Organometallics, 1996, 15, 4125; (d) G.
Helmchen, S. Kudis, P. Sennhenn and H. Steinhagen, Pure Appl. Chem.,
1997, 69, 513; (e) P. S. Pregosin and G. Trabesinger, J. Chem. Soc.,
Dalton Trans., 1998, 727; (f) G. Helmchen, J. Organomet. Chem., 1999,
576, 203; (g) M. Widhalm, U. Nettekoven, H. Kalchhauser, K. Mereiter,
M. J. Calhorda and V. Felix, Organometallics, 2002, 21, 315; (h) O. G.
Bondarev, S. E. Lyubinov, A. A. Shiryaev, N. E. Kadilnikov, V. A.
Davankov and K. N. Gavrilov, Tetrahedron: Asymmetry, 2002, 13,
1587; (i) R. Hilgraf and A. Pfaltz, Synlett, 1999, 11, 1814; (j) K.
Selvakumar, M. Valentini, M. Wo¨rle, P. S. Pregosin and A. Albinati,
Organometallics, 1999, 18, 1207; (k) A. J. Blacker, M. L. Clarke, M. S.
Loft, M. F. Mahon, M. E. Humphries and J. M. J. Williams, Chem.–
Eur. J., 2000, 6, 353; (l) R. Pre´toˆt and A. Pfaltz, Angew. Chem., Int. Ed.,
1998, 37, 323; (m) C. J. Martin, D. J. Rawson and J. M. J. Williams,
Tetrahedron: Asymmetry, 1998, 9, 3723.
4 (a) See for example: T. Hayashi, A. Yamamoto, Y. Ito, E. Nishioka,
H. Miura and K. Yanagi, J. Am. Chem. Soc., 1989, 111, 6301;
(b) W. Zhang, T. Hirao and I. Ikeda, Tetrahedron Lett., 1996, 37,
4545.
5 (a) See for example: B. M. Trost and D. L. Van Vranken, Angew. Chem.,
Int. Ed. Engl., 1992, 31, 228; (b) B. M. Trost, B. Breit, S. Peukert, J.
Zambrano and J. W. Ziller, Angew. Chem., Int. Ed. Engl., 1995, 34,
2386; (c) M. Widhalm, P. Wimmer and G. Klintschar, J. Organomet.
Chem., 1996, 523, 167; (d) A. Saitoh, M. Misawa and T. Morimoto,
Tetrahedron: Asymmetry, 1999, 10, 1025; (e) D. Zhao and K. Ding,
Org. Lett., 2003, 5, 1349.
6 T. Mecca, S. Superchi, E. Giorgio and C. Rosini, Tetrahedron:
Asymmetry, 2001, 12, 1225.
7 (a) H. Kubota and K. Koga, Heterocycles, 1996, 42, 543; (b) K. Warn-
mark, R. Stranne, M. Cernerud, I. Terrien, F. Rahm, K. Nordstrom
and C. Moberg, Acta Chem. Scand., 1998, 7, 961; (c) J. A. Sweet, J. M.
Cavallari, W. A. Price, J. W. Ziller and D. V. McGrath, Tetrahedron:
Asymmetry, 1997, 8, 207.
[Pd(g3-CH2CHCH2)((Sa)-2)]CF3SO3 (12). This complex was
3
synthesized by reaction of [Pd(g -C3H5)(l-Cl)]2 (0.010 g,
0.027 mmol) with the ligand (Sa)-2 (0.023 g, 0.065 mmol) in
CH2Cl2 (5 ml) at room temperature. After 1 h AgCF3SO3 (0.014 g,
0.055 mmol) was added and was stirred for 10 min. The suspension
was filtered through a pad of Celite, the solvent evaporated in
vacuo except for a few millilitres, and the product precipitated
with hexane. Recrystallized from CH2Cl2–hexane in a 3 : 1 ratio, a
light pink powder was obtained. Yield: 70% (13.7 mg, 0.019 mol).
3
1H NMR (CDCl3): d 9.28 (d, 1 H, J 5 Hz, Ar-H), 8.51 (d, 1H,
3J 8 Hz, Ar-H), 8.17 (t, 2H, 3J 9 Hz, Ar-H), 8.07 (d, 2H, 3J 8 Hz,
Ar-H), 8.01 (d, 1H, 3J 8 Hz, Ar-H), 7.95 (d, 1H, 3J 8 Hz, Ar-H),
3
7.82 (dd, 1H, J 8 Hz, Ar-H), 7.59 (m, 5H, Ar-H), 7.37 (m, 4H,
Ar-H), 5.83 (b, 1H, CH2), 5.05 (d, 1H, CH), 5.00 (b, 2H, CH2),
4.86 (b, 2H, CH2), 4.46 (b, 1H, CH2), 4.30 (d, 1H, CH2), 3.37
(d, 1H, CH2). Conductivity value of 82 lS in methanol solution,
using a 5 × 10−4–1 × 10−4 molar concentration. Anal. Calcd for
C35H27F3N2O3PdS (719.08): C, 58.46; H, 3.78; N, 3.90. Found: C,
58.50; H, 3.75; N, 3.91%.
Palladium-catalyzed allylic alkylation
General procedure. In a 30 ml Schlenk tube equipped with
3
magnetic stirring bar, under argon, [Pd(g -C3H5)(l-Cl)]2 (2.34 mg,
0.0064 mmol) was treated with the N-N* ligand (0.0128 mmol)
in CH2Cl2 (0.7 ml). The solution was degassed (three freeze–thaw
cycles) and stirred for 0.5 h. After this period, to the solution was
sequentially added the 1,3-diphenyl-1-acetoxypropene (323 mg,
1.28 mmol), dimethylmalonate (338.2 mg, 2.56 mmol), N,O-
bis(trimethylsilyl)acetamide (520.8 mg, 2.56 mmol), and KOAc
(6 mg, 0.06 mmol) and then degassed (three freeze–thaw cycles).
The reaction was monitored by TLC (eluent: hexane–AcOEt
3 : 1) and, at the end, the mixture was diluted with Et2O and
extracted with two portions of ice-cold saturated aqueous NH4Cl
solution. The solution was dried (MgSO4) and evaporated in vacuo;
the residue was purified by column chromatography (silica gel,
4 × 30 cm, hexane–AcOEt 3 : 1) to afford the product as a
colourless oil. The optical purity was determinated by NMR using
paramagnetic shift reagent [Eu(hfc)3]. Assignment of the absolute
configuration was made by the sign of the optical rotation.
8 The basicity of the N-donor atom chiral framework in the (Sa)-1 and
(Sa)-2 ligands can be correlated with that of dialkylsubstituted azepine
type compounds, while in the (S,S)-3 and (S,S)-4 ligands with that
of dialkylsubstituted pyrrolidine type compounds. The pKa values for
dialkylsubstituted azepine and dialkylsubstituted pyrrolidine are ca. 9
and 10, respectively. The pKa value for pyridine and quinoline are very
close (ca. 5).
9 (a) G. Calabro`, D. Drommi, G. Bruno and F. Faraone, Dalton Trans.,
2004, 81; (b) C. G. Arena, D. Drommi and F. Faraone, Tetrahedron:
Asymmetry, 2000, 11, 2765; (c) C. G. Arena, D. Drommi and F. Faraone,
Tetrahedron: Asymmetry, 2000, 11, 4753.
10 The structure of 8 was also confirmed by X-ray diffraction: G. Bottari,
G. Brancatelli, M. Saporita, D. Drommi, F. Nicolo` and F. Faraone,
work in progress. The compound [Pd(CH3)Cl((Sa)-2)], similar to 6,
was also characterized by X-ray diffraction analysis:; B. Milani, F.
Amoroso, M. R. Axet, E. Zangrando, D. Drommi, M. Saporita and F.
Faraone, private communication.
Acknowledgements
This work was supported by Ministero dell’Istruzione,
dell’Universita`
2005035123).
e della Ricerca (MIUR-Rome; PRIN Nos
Notes and references
1 (a) C. G. Frost, J. Howarth and J. M. J. Williams, Tetrahedron:
Asymmetry, 1992, 3, 1089; (b) B. M. D. Trost and L. Van Vranken,
Chem. Rev., 1996, 96, 395; (c) B. M. D. Trost and C. Lee, in Catalytic
Asymmetric Synthesis, ed. I. Ojima, Wiley-VCH, New York, 2nd edn,
2000, p. 593; (d) I. Ojima, Catalytic Asymmetric Synthesis, VCH
1518 | Dalton Trans., 2007, 1509–1519
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
11 Nomenclature note: the structures endo- or exo- are defined if the
(e) H. Hoarau, J.-C. Daran Ait-Haddou, D. Cramaliere and G. G. A.
Balavoine, Organometallics, 1999, 18, 4718.
central allyl proton is down or up with respect to the coordination
2
3
plane having an sp or sp N1 nitrogen atom (quinolinyl or pyridinyl
moiety) on the left side (see Fig. 2). According to ref. 18(b), the sequence
numbering of the allyl part starts with C1 cis to N1, C2 for the central
carbon, and C3 cis to N2. Consequently the first geometric descriptor,
syn or anti, refers to the configuration of phenyl allylic substituents at
C1 and C3 with respect to C2.
15 M. J. Frisch, G. W. Trucks, H. B. Schlegel, P. M. W. Gill, B. G. Johnson,
M. A. Robb, J. R. Cheeseman, T. Keith, G. A. Petersson, J. A. Mont-
gomery, K. Raghavachari, M. A. AlLaham, V. G. Zakrzewski, J. V.
Ortiz, J. B. Foresman, J. Cioslowski, B. B. Stefanov, A. Nanayakkara,
M. Challacombe, C. Y. Peng, P. Y. Ayala, W. Chen, M. W. Wong, J. L.
Andres, E. S. Replogle, R. Gomperts, R. L. Martin, D. J. Fox, J. S.
Binkley, D. J. Defrees, J. Baker, J. P. Stewart, M. Head-Gordon, C.
Gonzalez and J. A. Pople, GAUSSIAN 03, Gaussian Inc., Pittsburgh,
PA, 2003.
12 (a) P. S. Pregosin and R. Salzmann, Coord. Chem. Rev., 1996, 155, 35;
(b) S. K. Mandal, G. A. N. Gowda, S. S. Krishnamurthy, C. Zheng, S. Li
and N. S. Hosmane, Eur. J. Inorg. Chem., 2002, 2047; (c) S. K. Mandal,
G. A. N. Gowda, S. S. Krishnamurthy and M. Nethaji, Dalton Trans.,
2003, 1016.; (d) S. K. Mandal, G. A. N. Gowda, S. S. Krishnamurthy,
C. Zheng, S. Li and N. S. Hosmane, J. Organomet. Chem., 2003, 22,
676; (e) U. Burckhardt, D. Drommi and A. Togni, Inorg. Chim. Acta,
1999, 296, 183.
13 (a) J. Sprinz, M. Kiefer, G. Helmchen, M. Reggelin, G. Huttner and
O. L. Walter Zsolnai, Tetrahedron Lett., 1994, 35, 1523; (b) C. Breutel,
P. S. Pregosin, R. Salzmann and A. Togni, J. Am. Chem. Soc., 1994,
116, 4067; (c) B. M. Trost, G. M. Schroeder and J. Kristensen, Angew.
Chem., Int. Ed., 2002, 18, 41; (d) J. V. Allen, S. J. Coote, G. J. Dawson,
G. C. Frost, C. J. Martin and J. M. Williams, J. Chem. Soc., Perkin
Trans. 1, 1994, 2065; (e) A. Chesney, M. R. Bryce, R. W. J. Chubb,
A. S. Batsanov and J. A. K. Howard, Tetrahedron: Asymmetry, 1997,
8, 2337; (f) H. Steinhagen, M. Reggelin and G. Helmchen, Angew.
Chem., Int. Ed. Engl., 1997, 36, 2108; (g) G. C. Lloyd-Jones and S. C.
Stephen, Chem.–Eur. J., 1998, 4, 2539; (h) B. M. Trost and F. D. Toste,
J. Am. Chem. Soc., 1999, 121, 4545; (i) H. Eichelmann and H. J. Gais,
Tetrahedron: Asymmetry, 1995, 3, 643.
16 The differences between the 13C chemical shift values of the terminal
allylic carbon atoms can be significantly compared, and utilized as a
measure of the coordinated ligand capability to induce regioselectivity
in the nucleophilic attack at allylic carbon atoms, only when the
conformational isomers are the same except for the coordinated chiral
ligand. Therefore, the value of 12.0 ppm, found in the exo-anti-syn
isomer of 9b, is not indicative of a more regioselectivity induction in
the nucleophilic attack than 11a and 11b due to the fact that these latter
compounds contain a rigid framework vs. the flexible ligands present
in the former 9 species.
17 M. J. Burk, J. E. Feaster, W. A. Nugent and R. L. Harlow, J. Am. Chem.
Soc., 1993, 115, 10125.
18 (a) P. Von Matt, G. C. Lloyd-Jones, A. B. E. Midinis, A. Pfaltz, L.
Macko, M. Neuburger, M. Zehnder and P. S. Pregosin, Helv. Chim.
Acta, 1995, 78, 265; (b) A. Togni, U. Burckhardt, V. Gramlich and P. S.
Pregosin, J. Am. Chem. Soc., 1996, 118, 1031.
´
19 V. SklenaAr, H. Miyashiro, G. Zon, H. T. Miles and A. Bax, FEBS
Lett., 1986, 208, 94.
14 (a) K. Selvakumar, M. Valentini, P. S. Pregosin and A. Albinati,
Organometallics, 1999, 18, 4591; (b) P. S. Pregosin, R. Salzmann and
A. Togni, Organometallics, 1995, 14, 842; (c) P. Dierkes, S. Ramdeehul,
L. Barloy, A. De Cian, J. Fischer, P. C. J. Kamer, P. W. N. M. van
Leeuwen and J. A. Osborne, Angew. Chem., Int. Ed., 1998, 37, 3116;
(d) P. Dierkes, S. Ramdeehul, R. Aguado, P. C. J. Kamer, P. W. N. M.
van Leeuwen and J. A. Osborne, Angew. Chem., Int. Ed., 1998, 37, 3118;
20 A. D. Becke, Phys. Rev. A, 1988, 38, 3098.
21 K. Burke, J. P. Perdew, Y. Wang, in Electronic Density Functional
Theory: Recent Progress and New Directions, ed. J. F. Dobson,
G. Vignale and M. P. Das, Plenum, New York, 1998 and references
therein.
22 J. P. Perdew, K. Burke and Y. Wang, Phys. Rev. B: Condens. Matter,
1996, 54, 16533.
This journal is
The Royal Society of Chemistry 2007
Dalton Trans., 2007, 1509–1519 | 1519
©