Synthesis, optical resolution, and stereochemical properties of a rationally designed chiral C-N palladacycle

Article abstract of DOI:10.1021/om401044z

A novel racemic tertiary amine, 1-(2,5-diisopropylphenyl)-N,N- dimethylethanamine, was synthesized from 2,5-diisopropylbenzaldehyde via a multistep approach in high overall yield. The ortho palladation of this ligand was found to be sensitive to the reaction conditions and the palladating reagents employed. The metal complexation process could thus generate a cyclopalladated complex in high yield, lead to an unexpected N-demethylated amine palladium(II) complex, or both. Both products have been isolated and characterized crystallographically in the solid state and spectroscopically in solution. The racemic cyclopalladated complex could be efficiently resolved via the formation of (S)-prolinato derivatives. The absolute stereochemistries of the resolved diastereomeric complexes were determined by single-crystal X-ray crystallography in the solid state and by ¹H-¹H rotating frame Overhauser effect (ROESY) NMR spectroscopy in solution. An evaluation of the sterically hindered resolved cyclopalladated units as chiral auxiliaries was conducted in the endo-cycloaddition reaction between 3,4-dimethyl-1- phenylphosphole (DMPP) and ethyl vinyl ketone. The two expected phosphanorbornene adducts were generated with moderate stereoselectivity.

Full text of DOI:10.1021/om401044z

Article
pubs.acs.org/Organometallics
Synthesis, Optical Resolution, and Stereochemical Properties of a
Rationally Designed Chiral C−N Palladacycle
Jeanette See Leng Yap, Houguang Jeremy Chen, Yongxin Li, Sumod A. Pullarkat, and Pak-Hing Leung*
Division of Chemistry & Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: A novel racemic tertiary amine, 1-(2,5-diiso-
propylphenyl)-N,N-dimethylethanamine, was synthesized from
2,5-diisopropylbenzaldehyde via a multistep approach in high
overall yield. The ortho palladation of this ligand was found to
be sensitive to the reaction conditions and the palladating
reagents employed. The metal complexation process could
thus generate a cyclopalladated complex in high yield, lead to
an unexpected N-demethylated amine palladium(II) complex,
or both. Both products have been isolated and characterized
crystallographically in the solid state and spectroscopically in solution. The racemic cyclopalladated complex could be efficiently
resolved via the formation of (S)-prolinato derivatives. The absolute stereochemistries of the resolved diastereomeric complexes
1
were determined by single-crystal X-ray crystallography in the solid state and by H−1H rotating frame Overhauser effect
(ROESY) NMR spectroscopy in solution. An evaluation of the sterically hindered resolved cyclopalladated units as chiral
auxiliaries was conducted in the endo-cycloaddition reaction between 3,4-dimethyl-1-phenylphosphole (DMPP) and ethyl vinyl
ketone. The two expected phosphanorbornene adducts were generated with moderate stereoselectivity.
unique structural feature makes this class of palladacycles
applicable to many asymmetric reactions such as cycloaddition,5
hydrophosphination,6,7 and hydroarsination reactions.6
INTRODUCTION
■
Since the first reported cyclopalladated complex in 1965 by
Cope and co-workers,1 palladacycles have gained much
attention due to their wide range of applications.2 In particular,
optically active palladacycles have found numerous practical
uses as efficient resolving agents,2c,3 as chiral derivatizing
reagents,4 and in asymmetric reactions (both stoichiometric
and catalytic).5−8 As such, these optically active complexes have
been developed significantly over the past few decades.5b−f,9
Our group is interested in the study of the chemistry of chiral
palladacycles and their applications. The enantiomerically pure
forms of the palladacycle 1 (Figure 1), and their derivatives,
Although enantiomerically pure complex 1 and its derivatives
usually show high efficiencies as chiral auxiliaries in many
synthetic reactions, satisfactory stereoselectivity could not be
achieved by these complexes in certain cases.5h Therefore,
palladacycles with structural modifications on the aromatic
framework were designed and synthesized.5b−e Introduction of
spacer groups or additional aromatic rings into the framework,
for instance in the case of complex 2 (Figure 1),5b has indeed
shown improvement in the stereoselectivity of cycloaddition
reactions. In such a complex, one of the methyl substituents on
the aromatic ring interacts with the methyl group at the
stereogenic carbon center, thus locking the organometallic five-
membered ring into a fixed chiral conformation, both in solid
state and in solution. Moreover, the introduction of another
methyl group on the phenyl ring functions as a spacer which
protrudes sterically toward the lower right corner of the square-
planar complex. With these designed structural features,
complex 2 has been shown to be a better chiral template in
some Diels−Alder reactions, in comparison to the original
naphthylamine analogues.5b
Figure 1. Chiral palladacycles (S)-1, (S)-2, and (S)-3.
have been extensively used in our group. An inherent internal
steric repulsion exists between the naphthylamine proton H(8)
and the methyl substituent at the stereogenic center of 1, which
confines the methyl group in the axial position. The five-
membered cyclopalladated ring is thus locked in a particular
skew chiral conformation, resulting in a stereochemically rigid
palladacycle both in the solid state and in solution.10 This
It should be noted that the introduction of sterically
demanding groups on the aryl rings in complexes such as 1
and 2 may hinder the formation of the desired ortho-metalated
Received: October 28, 2013
Published: February 5, 2014
© 2014 American Chemical Society
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complex as well as lower their reactivity in synthetic
applications. Nonetheless, the success of the palladacycle 2
has prompted us to take up the challenge of exploring the
impact and limitations of introducing bulky groups into the
organometallic ligand system with the objective to improve on
selectivity while maintaining the desired reactivity. The
isopropyl spacer group was, therefore, selected and introduced
onto the aromatic ring to give complex 3. In this article, we
report the preparation, resolution, comprehensive character-
ization, and novel organometallic chemistry of this highly
sterically hindered palladacycle variant and its subsequent
evaluation as a chiral template in a [4 + 2]-cycloaddition
scenario.
treated with Pd(NCMe)4(ClO4)2 at ambient temperature with
the amine recovered qualitatively via column chromatography.
On the other hand, separate treatment of the ligand ( )-7 with
PdCl2 or with Pd(OAc)2, upon subsequent treatment with
LiCl, gave a mixture of the desired product ( )-3 and the
unexpected product ( )-8, which involved a novel C−N bond
cleavage during the coordination process. The ratios of
complexes ( )-3 and ( )-8 were found to be affected by the
reaction temperature and the solvent employed.
The molecular structure of product ( )-8 was confirmed by
single-crystal X-ray crystallography (Figure 2). The structural
analyses of the complex confirmed that a C−N bond cleavage
indeed occurred during the coordination process. Selected
bond lengths and angles are provided in Table 2. The palladium
center exhibits a typical square-planar coordination geometry
with the bond angles of N(1)−Pd(1)−N(1A) and Cl(1)−
Pd(1)−Cl(1A) both being 180.0°. The two nitrogen donor
atoms are trans to each other, with each of the nitrogen atoms
bearing only one methyl substituent as a consequence of the
C−N cleavage. The relative stereochemistry of asymmetric
nitrogen and carbon atoms of complex ( )-8 in the solid state
RESULTS AND DISCUSSION
Ligand and Complex Syntheses. As illustrated in Scheme
1, the racemic amine ligand could be synthesized efficiently in
■
Scheme 1. Synthesis of 1-(2,5-Diisopropylphenyl)-N,N-
dimethylethanamine (( )-7)
1
was (RCSN,RCSN)*. The H NMR of complex ( )-8 shows
only one resonance for every chemically nonequivalent proton.
The presence of the bulky isopropyl groups on the aromatic
ring prevented the asymmetric nitrogen and carbon atoms from
isomerizing to other isomers as in the case of the unsubstituted
aromatic ring.11a It is noteworthy that such a type of C−N
bond cleavage is not usually observed in analogous naphthyl-
and benzylamine ligands. Pfeffer et al. and Aresta et al. reported
the Li2PdCl4-mediated dealkylation of N,N-dialkylanilines and
9-(diethylamino)naphthalene, respectively.11b The methanoly-
sis or hydrolysis, by traces of water, of iminium ions produced
in situ is the conceivable mechanism for this N-dealkylation.
Interestingly, in our case, the use of Li2PdCl4 as palladium
source afforded the dimeric complex ( )-3 instead of the N-
dealkylated complex ( )-8. It is notable that the chemo-
selectivity of cyclometalation will also be decreased when such
C−N cleavage occurs. Such precedents of C−N bond cleavage
during cycloplatination11c and C−C bond cleavage during
cyclopalladation of bulky benzylamines are known in the
literature.11d
three steps using 2,5-diisopropylbenzaldehyde (4) as the
starting material. Treatment of the aldehyde with methyl-
magnesium bromide gave racemic alcohol ( )-5 in 98% yield.
Bromination of the alcohol with PBr3 then provided the bromo
product ( )-6 in 99% yield. Finally, the reaction between
( )-6 and aqueous dimethylamine afforded the desired racemic
ligand ( )-7 in 96% yield.
As mentioned earlier, the bulky isopropyl groups in ligand
( )-7 indeed rendered some complications in the ortho-
palladation process (Scheme 2). Unlike the preparation of the
Scheme 2. Ortho Palladation of Tertiary Amine Ligand
( )-7
The desired ortho-metalated complex ( )-3 obtained from
the optimized reaction conditions (Table 1, entry 3) could be
1
recrystallized efficiently as bright yellow needles. In the H
NMR spectrum, complex ( )-3 showed broad and poorly
resolved resonance signals. The phenomenon can be attributed
to the well-documented dynamic syn−anti interconversion of
such dimeric complexes in solution (Figure 3).12
In the solid state, structural investigations confirmed that no
C−N bond cleavage occurred during the cyclopalladation
reaction, with each nitrogen atom bearing two methyl groups
(Figure 4). Selected bond lengths and bond angles of complex
are given in Table 3. In addition, the dimer exists in the crystal
in its transoid configuration with the two chiral organometallic
units adopting the same relative configurations. The palladium
atoms, Pd(1) and Pd(1A), were found to adopt a distorted-
square-planar coordination geometry; the dihedral angles
between the planes {Cl(1)−Pd(1)−Cl(1A)} and {N(1)−
Pd(1)−C(1)} and between the planes {Cl(1)−Pd(1A)−
Cl(1A)} and {N(1A)−Pd(1A)−C(1A)} were both equal to
13.6°. As predicted, the isopropyl substituents (C(8) and
C(8A)) interact with the methyl groups (C(14) and C(14A))
at the stereogenic center, thus forcing the methyl group to take
analogous complexes 1 and 2, the metal complexation process
of ligand ( )-7 was found to be highly sensitive to the reaction
conditions employed. The optimal yield (78%) of complex
( )-3 could be achieved by the treatment of the tertiary amine
( )-7 in methanol with Li2[PdCl4] at room temperature in the
presence of NaOAc (Table 1). Interestingly, the yield dropped
dramatically to 20% when the reaction was conducted under
similar conditions but at a higher temperature (55 °C).
Replacement of the palladating agent by PdCl2(NCMe)2
resulted in very low yields for the desired complex. Notably,
the complexation was not observed when the ligand ( )-7 was
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Table 1. Optimization of Conditions for Palladation of Tertiary Amine ( )-7
a
b
conditions
yield (%)
entry
palladating agent
PdCl2
Pd(OAc)2
solvent
base
T (°C)
55
( )-3
( )-8
1
2
3
4
5
6
7
8
9
MeOH
MeOH
MeOH
MeOH
MeOH
MeCN
MeOH
benzene
DMF
23
16
78
20
19
d
29
2
c
55
Li2(PdCl4)
Li2(PdCl4)
PdCl2(NCMe)2
Pd(NCMe)4(ClO4)2
PdCl2
NaOAc
NaOAc
room temp
0
55
55
r.t.
80
55
55
0
0
d
10
43
39
23
11
PdCl2
PdCl2
0
a
b
c
Unless otherwise specified, reaction employed 1 equiv of palladating agent for 16 h. Isolated yields following column chromatography. Use of
d
Pd(OAc)2 as palladating agent yielded μ-acetato dimer instead of μ-chloro dimer. No reaction.
Figure 3. Dynamic syn−-anti interconversion of the dimeric complex
( )-3.
Figure 2. Molecular structure of complex ( )-8.
up the axial position instead of the relatively more favorable
equatorial position.
The four-membered ring bridged by the chlorine atoms to
the palladium centers, Cl(1)−Pd(1)−Cl(1A)−Pd(1A), was
found to be noncoplanar, with a bent angle of 27.8° about the
Cl(1)−Cl(1A) axis. In addition, torsion angles for Cl(1)−
Pd(1)−C(1)−C(2) and Cl(1A)−Pd(1A)−C(1A)−C(2A)
were both calculated to be −45.0°. Such twisting of the rings
was partially a consequence of the internal steric repulsions
between the isopropyl substituent and the bridged chlorine
atoms.
Synthesis of Monomeric Complex ( )-9. In order to
study the impact of the bulky isopropyl groups on the
coordination chemistry of the adjacent palladium coordination
sites, the dimeric complex ( )-3 was converted to the
corresponding monomeric neutral complex ( )-9 by addition
of triphenylphosphine (Scheme 3).
Figure 4. Molecular structure of dimeric complex ( )-3.
slightly in bond lengths and bond angles. For clarity, only one
of these molecules is depicted in Figure 5. The coordination
geometry at palladium is distorted square planar, and the chiral
five-membered ring adopts an envelope-like conformation in
the solid state. More importantly, complex ( )-9 adopts the
highly unfavorable trans N−Pd−P geometry in which the bulky
isopropyl spacer and the PPh3 ligand are located at the adjacent
positions of the square-planar complex. The trans effect
(transphobia) for the C−Pd−P geometry is larger than that
of the N−Pd−P geometry, resulting in a greater degree of
destabilization for the C−Pd−P geometry. Clearly, the strong
electronic directing effects must be the dominating influence,
The monomeric complex ( )-9 could be isolated as yellow
prisms from dichloromethane−hexane. The coordination
chemistry of the complex was confirmed by an X-ray structural
analysis. Interestingly, four crystallographically unique mole-
cules were found in the unit cell, with each differing only
Table 2. Selected Bond Lengths (Å) and Angles (deg) for Complex ( )-8
Pd(1)−N(1)
Pd(1)−Cl(1)
N(1)−C(13)
N(1)−C(15)
2.057(4)
2.302(1)
1.486(7)
1.479(7)
Pd(1)−N(1A)
Pd(1)−Cl(1A)
N(1A)−C(13A)
N(1A)−C(15A)
2.057(4)
2.302(1)
1.486(7)
1.479(7)
N(1)−Pd(1)−Cl(1)
Cl(1A)−Pd(1)−N(1A)
N(1)−Pd(1)−N(1A)
C(13)−N(1)−Pd(1)
C(15)−N(1)−Pd(1)
C(15)−N(1)−C(13)
93.0(1)
N(1)−Pd(1)−Cl(1A)
N(1A)−Pd(1)−Cl(1)
Cl(1)−Pd(1)−Cl(1A)
C(13A)−N(1A)−Pd(1)
C(15A)−N(1A)−Pd(1)
C(15A)−N(1A)−C(13A)
87.0(1)
93.0(1)
180.0(2)
115.9(3)
112.6(3)
112.1(4)
87.0(1)
180.0(4)
115.9(3)
112.6(3)
112.1(4)
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Table 3. Selected Bond Lengths (Å) and Angles (deg) for Complex ( )-3
Pd(1)−C(1)
Pd(1)−N(1)
Pd(1)−Cl(1)
Pd(1)−Cl(1A)
C(1)−Pd(1)−N(1)
C(1)−Pd(1)−Cl(1)
N(1)−Pd(1)−Cl(1A)
Cl(1)−Pd(1)−Cl(1A)
C(1)−Pd(1)−Cl(1A)
N(1)−Pd(1)−Cl(1)
1.993(2)
2.071(2)
2.347(4)
2.463(4)
80.2(7)
98.8(5)
97.9(4)
83.8(2)
176.3(5)
167.2(5)
Pd(1A)−C(1A)
Pd(1A)−N(1A)
Pd(1A)−Cl(1A)
Pd(1A)−Cl(1)
C(1A)−Pd(1A)−N(1A)
C(1A)−Pd(1A)−Cl(1A)
N(1A)−Pd(1A)−Cl(1)
Cl(1A)−Pd(1A)−Cl(1)
C(1A)−Pd(1A)−Cl(1)
N(1A)−Pd(1A)−Cl(1A)
1.993(2)
2.071(2)
2.347(4)
2.463(4)
80.2(7)
98.8(5)
97.9(4)
83.8(2)
176.3(5)
167.2(5)
Scheme 3. Conversion to Monomeric Complex ( )-9
Scheme 4. Resolution of Dimeric Complex ( )-3
Figure 5. Molecular structure of monomeric complex ( )-9.
even in such sterically demanding complexation scenarios.9a,13
As a consequence of these strong steric repulsions, the
palladium center exhibits a large dihedral angle of 21.8°
between the planes {P(1)−Pd(1)−Cl(1)} and {N(1)−Pd(1)−
C(1)}.
Resolution of Complex ( )-3. The resolution of the
racemic dimeric complex ( )-3 was performed using sodium
(S)-prolinate as the resolving agent (Scheme 4) to give a 1:1
mixture of diastereomers (RC,SCSN)-10 and (SC,SCSN)-10. The
diastereomeric adducts were then separated via column
chromatography. The diastereomeric ratio of both fractions
was verified by 1H NMR spectroscopy. The less polar
diastereomer (RC,SCSN)-10 was eluted out first with acetone/
dichloromethane (1/1 v/v) and subsequently recrystallized to
give pale yellow platelike crystals. The more polar diastereomer
(SC,SCSN)-10 was obtained as colorless needles. The absolute
configurations and the solid-state structure of both diastereo-
meric adducts, (RC,SCSN)-10 and (SC,SCSN)-10, were confirmed
by single-crystal X-ray diffraction investigations.
Figure 6. Molecular structure of diastereomer (RC,SCSN)-10.
position, and the absolute conformation of the five-membered
ring is δ (Figure 7).14 The secondary stereogenic nitrogen atom
from the prolinato group is in the S absolute configuration.
The palladium center adopts a slightly distorted square
planar coordination geometry with tetrahedral distortion of
2.8°. The organometallic five-membered ring is in an envelope
conformation wherein N(1) is 0.803 Å below the mean plane
The molecular structure of the complex (RC,SCSN)-10 is
shown in Figure 6. The absolute configuration of the
stereogenic carbon center within the organometallic ring is R.
The C(1)−Pd(1)−N(1)−C(13) torsion angle is +40.9°. The
methyl group at the chiral center occupies the expected axial
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Figure 8. Molecular structure of diastereomer (SC,SCSN)-10.
C(1)−Pd(1)−N(1)−C(13) torsion angle is −43.5°, with the
skewed five-membered ring locked in a λ conformation (Figure
9).14 The coordination geometry at palladium is distorted
Figure 7. Chiral δ(RC) (a, c, e) and λ(RC) (b, d, f) conformations of
the (RC,SCSN)-10 five-membered ring: (a, b) in projections to the
plane orthogonal to the {C(1)−Pd(1)−N(1)} plane; (c, d) in
Newman projections relative to the N(1)−C(13) bond; (e, f) in
Newman projections relative to the N(1)−Pd(1) bond.
formed by C(1)−C(12)−C(13)−Pd(1). The two coordinated
nitrogen groups are in an unusual cis-(N,N) geometry.5b,e This
phenomenon can be attributed to the steric interaction between
the protruding isopropyl spacer adjacent to the Pd−C bond
and the nitrogen of the prolinato group, which forces the
complex to adopt the sterically more favorable cis-(N,N)
geometry, and the requirement of the crystal lattice. The angle
between the mean plane of the organometallic five-membered
ring C(1)−C(12)−C(13)−N(1)−Pd(1) and the mean plane
formed from O(1)−C(17)−C(18)−N(2)−Pd(1) of the
prolinato ligand is 13.1°. The Pd(1)−N(2) bond length is
2.140 Å (Table 4) and is comparable to reported values of the
cis-(N,N) geometry.5b,e On the other hand, the distance is
much longer than the reported value of 2.037−2.083 Å for the
trans-(N,N) geometry.5c,14a The bond lengthening is an
expected result of the trans influence caused by the aryl carbon
and the repulsion between the C(15) on the NMe and the
C(21) of the prolinate moiety.
Similarly, X-ray crystallographic studies on the diastereomer
(SC,SCSN)-10 were performed, and five crystallographically
unique molecules were observed in the asymmetric unit cell.
These molecules adopt the same stereochemistry, only differing
slightly in bond lengths and bond angles. For clarity, only one
of these molecules is shown in Figure 8. The crystallographic
study showed that the absolute stereochemistry at the
stereogenic carbon within the organometallic ring is S.
Similarly, the secondary stereogenic nitrogen atom in the
prolinato moiety also adopted the S absolute configuration. The
Figure 9. Chiral δ(SC) (a, c, e) and λ(SC) (b, d, f) conformations of
the (SC,SCSN)-10 five-membered ring: (a, b) in projections to the
plane orthogonal to the {C(1)−Pd(1)−N(1)} plane; (c, d) in
Newman projections relative to the N(1)−C(13) bond; (e, f) in
Newman projections relative to the N(1)−Pd(1) bond.
square planar. The dihedral angle between the planes {N(1)−
Pd(1)−C(1)} and {O(1)−Pd(1)−N(2)} is 5.5°. The two
coordinated nitrogen groups adopt the trans-(N,N) arrange-
ment.
The above structural analyses revealed that (RC,SCSN)-10 and
(SC,SCSN)-10 adopted the cis- and trans-(N,N) coordination
Table 4. Selected Bond Lengths (Å) and Angles (deg) for Complex (RC,SCSN)-10
Pd(1)−C(1)
Pd(1)−N(1)
C(17)−O(1)
C(1)−Pd(1)−O(1)
O(1)−Pd(1)−N(1)
O(1)−Pd(1)−N(2)
2.014(2)
2.053(2)
1.283(3)
99.6 (9)
177.4(8)
80.5(8)
Pd(1)−O(1)
Pd(1)−N(2)
C(17)−O(2)
C(1)−Pd(1)−N(1)
C(1)−Pd(1)−N(2)
N(1)−Pd(1)−N(2)
2.046(2)
2.140(2)
1.235(3)
80.5(9)
178.5(10)
99.3(9)
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geometries, respectively, in the solid state. However, due to the
aforementioned dynamic ligand redistribution processes in
solution, the cis- and trans-(N,N) arrangements may
interconvert. Hence, the properties of the complexes in
distance between the Me8 carbon C(14) and the NMe(eq)
carbon C(15) is 2.876 Å, and this is smaller than the
summation of the van der Waals radii of 3.40 Å15 and is
indicative of the steric repulsion between them. These signals
are consistent with the assignment shown in the solid state
investigations, wherein the organometallic ring exclusively
adopts the δ conformation. The interligand and intraligand
interactions of the CH (isopropyl) group with the NH of the
prolinato group and H7 are represented by NOE signals C and
D, respectively.
1
1
solution were examined through H NMR and 2D H−1H
ROESY NMR experiments. The numbering schemes of
diastereomers (RC,SCSN)-10 and (SC,SCSN)-10 used in the
NMR experiments are shown in Figures 10 and 11 respectively.
Similarly, Figure 13 shows the expanded 2D 1H−1H ROESY
NMR spectrum of the diastereomeric complex (SC,SCSN)-10.
Figure 10. Numbering scheme of complex (RC,SCSN)-10.
Figure 11. Numbering scheme of complex (SC,SCSN)-10.
1
Figure 12 shows the expanded 2D H−1H ROESY NMR
spectrum of complex (RC,SCSN)-10. The interaction between
Figure 13. Expanded 2D 1H−1H ROESY NMR spectrum of the
complex (SC,SCSN)-10 in CDCl3.
The presence of interaction of Me8 with NMe(eq) represented
by NOE signal A and the interactions of H7 with Hb,
NMe(eq), NMe(ax), and Me8 (corresponding to NOE signals
D−G) indicate that the five-membered organometallic ring is
locked in the λ conformation and that Me8 takes up the axial
position in solution (Figure 9).14 The distances between the
Me8 carbon C(14) and the NMe(eq) carbon C(15) and the
distance between the H7 proton H(13) and the Hb proton
H(9) are 2.925 and 2.072 Å, respectively. Both are smaller than
the summation of the corresponding van der Waals radii of 3.40
and 2.40 Å.15 The NOE signals in solution match the
interactions of the complex in solid-state investigations. The
presence of an interligand interaction between Ha and NH is
denoted as C, which indicates that the two nitrogen groups are
trans to each other. This is further supported by solid-state
investigations, where the distance between the Ha proton H(3)
and the NH proton N(2) is 1.962 Å.15
The enantiopure dimeric complex (S)-3 was prepared by
treating the diastereomer (SC,SCSN)-10 with 1 M aqueous
hydrochloric acid and was obtained in 90% yield as a yellow
solid (Scheme 4). Similarly, the enantiomer (R)-3 could also be
liberated from (RC,SCSN)-10 by acid treatment. Unfortunately,
the enantiomerically pure dimeric complex (S)-3 could not be
induced to crystallize, despite numerous solvent systems being
Figure 12. Expanded 2D 1H−1H ROESY NMR spectrum of the
complex (RC,SCSN)-10 in CDCl3.
H10/H11 of the prolinato group and NMe(eq), represented by
signal A, depicts that the two nitrogen groups are cis to each
other in solution, as observed in the solid-state investigations.
The presence of NOE signals between Me8 and the
equatorially disposed NMe group (B) and the interactions of
H7 with NMe(ax), NMe(eq), and Me8 (E−G, respectively)
shows that the methyl group (Me8) at the stereogenic center is
axially positioned and the five-membered organometallic ring is
locked in the δ conformation in solution (Figure 7).14 The
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employed. The optically pure dimers were used directly for
subsequent reactions.
Application of Complex (S)-3 as Chiral Auxiliary for
the [4 + 2] Endo-Cycloaddition Reaction between DMPP
and Ethyl Vinyl Ketone. A detailed structural analysis of
ortho-metalated complexes unambiguously revealed that the
isopropyl moiety had a significant steric impact on the
neighboring coordination sites. Although the formation of the
triphenylphosphine complex ( )-9 confirmed that the
dominating electronic directing forces originating from the
organometallic ring allowed the coordination of the bulky
monodentate phosphine ligand onto this sterically congested
position, we were uncertain if the ortho-metalated unit would
perform as a suitable template in sterically demanding
asymmetric reaction scenarios. In order to assess its efficiency
in such scenarios, (S)-3 was used as a chiral auxiliary for the
asymmetric [4 + 2] endo-cycloaddition reaction between 3,4-
dimethyl-1-phenylphosphole (DMPP) and ethyl vinyl ketone.5h
It has been well established that DMPP can be activated as a
cyclic diene via metal complexation.5h The DMPP-coordinated
complex (S)-11 (Scheme 5) was prepared by cleavage of the
Figure 15. Numbering scheme of DMPP-coordinated complex (S)-11.
Scheme 5. Synthesis of DMPP-Coordinated Complex (S)-11
Figure 16. Expanded 2D 1H−1H ROESY NMR spectrum of the
complex (S)-11 in CD3CN.
optically pure dimeric complex (S)-3 with 2 molar equiv of
DMPP. In the solid state, an X-ray structural analysis of (S)-11
confirmed that, like complex 9, the ligand was coordinated in
the position trans to the amine moiety (Figure 14). The C(1)−
within the values (5.4−6.5 Hz) for equatorially positioned
protons on the stereogenic carbon.14b The presence of strong
interactions between Me8 and NMe(eq) is noted as signal A in
the spectrum, and the distance between these two carbons is
2.878 Å, which is smaller than the summation of the van der
Waals radii of 3.40 Å. ROESY correlations C−F correspond to
the interactions of H7 with Hb, NMe(eq), NMe(ax), and Me8,
respectively. These signals are consistent with the solid-state
structural assignment, in which Me8 occupies an axial position
and the five-membered organometallic ring is locked into the λ
conformation in solution.14 The NOE signal B represents the
interaction of both NMe groups on the amine moiety. The
absence of any interactions between the phosphole and the
NMe groups indicates that they are not located next to each
other. The ROESY NMR study thus revealed that complex (S)-
11 does not undergo cis−trans isomerization in solution.
The cycloaddition reaction between complex (S)-11 and
ethyl vinyl ketone was conducted in chloroform at 50 °C
(Scheme 6). The reaction was monitored by 31P{1H} NMR
Figure 14. Molecular structure of complex (S)-11.
Pd(1)−N(1)−C(13) torsion angle is −39.3°, showing that the
organometallic five-membered ring is locked in a λ con-
formation and the methyl group on the sterogenic carbon is
axially positioned.14
Scheme 6. [4 + 2] Endo-Cycloaddition Reactions between
DMPP Complex (S)-11 and Ethyl Vinyl Ketone
The 31P{1H} NMR spectrum of (S)-11 in d3-acetonitrile
exhibited only one sharp singlet at δ 28.9, indicating that only
one structural isomer was present in solution. A 1H−1H
ROESY NMR experiment was subsequently conducted to
confirm that only the trans N−Pd−P species exists in solution.
The numbering scheme of the DMPP complex (S)-11 and the
1
corresponding H−1H ROESY NMR spectrum are given in
4
Figures 15 and 16, respectively. The JH,P value of 6.4 Hz falls
936
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3
1.26 (d, 3JH,H = 6.8 Hz, 1H, CH(CH3)2), 1.49 (d, JH,H = 6.4 Hz, 3H,
spectroscopy and was found to be complete in 5 days. The
spectrum of the crude reaction mixture displayed two new
sharp singlets at δ 118.2 and 119.4 with an intensity ratio of
1:4.4. The high-field 31P{1H} NMR signals are consistent with
the formation of the two stereoisomeric endo cycloadducts.5
No other signals could be detected in the 161 MHz spectrum.
We have previously conducted the same endo cycloaddition
reaction between DMPP and ethyl vinyl ketone under similar
conditions using complexes (S)-15a and (S)-25b as chiral
auxiliaries. When (S)-1 was used as the chiral template at 70
°C, the reaction was complete within 16 h to give a 1:1 mixture
of the two endo adducts.5a On the other hand, when (S)-2 was
used at 50 °C, the reaction was complete in 27 h, generating a
1:3.5 diastereomeric mixture.5b A comparison between the
three chiral inducers for the same cycloaddition reaction clearly
revealed that a suitable spacer attached to the meta position of
the ortho-palladated ligand indeed projects its stereochemical
influence more efficiently toward the neighboring coordination
and reaction site. However, these spacer groups also impose
steric hindrances that would slow down the desired reaction.
To balance off the aforementioned reactivity−stereoselectivity
effects, it appeared that the isopropyl substituent or its sterically
equivalent counterparts may be the largest substituents that
could be employed as spacers in this family of cyclopalladated
reagents.
3
CHCH3), 1.86 (brs, 1H, OH), 2.89 (sep, JH,H = 6.9 Hz, 1H,
CH(CH3)2), 3.19 (sep, 3JH,H = 6.8 Hz, 1H, CH(CH3)2), 5.25 (q, 3JH,H
3
4
= 6.4 Hz, 1H, CHCH3), 7.12 (dd, JH,H = 8.0 Hz, JH,H = 2.0 Hz, 1H,
Ar-C4H), 7.20 (d, 3JH,H = 8.0 Hz, 1H, Ar-C3H), 7.38 (d, 4JH,H = 2.0 Hz,
1H, Ar-C6H); 13C NMR (100 MHz, CDCl3) δ 23.96, 24.01, 24.41,
25.02, 27.82, 33.82, 66.30, 122.81, 125.53, 142.12, 142.52, 142.47;
HRMS (ESI) m/z [(M + Na)]+ calcd for C14H22O 229.1568, found
229.1559. Note: the isolated compound is highly hydroscopic and is
not suitable for elemental analysis.
2-(1-Bromoethyl)-1,4-diisopropylbenzene (( )-6). A solution
of PBr3 (1.3 mL, 13.9 mmol) dissolved in dichloromethane (10 mL)
was added dropwise to a solution of racemic alcohol ( )-5 (2.39 g,
11.6 mmol) in dry dichloromethane (10 mL) at 0 °C. The mixture was
stirred at room temperature for 3 h. The excess PBr3 was quenched by
dropwise addition of H2O (10 mL). The mixture was then extracted
with dichloromethane (3 × 10 mL), dried with MgSO4, filtered, and
evaporated to dryness, affording a colorless solution: yield 3.08 g
(99%); 1H NMR (400 MHz, CDCl3) δ 1.24−1.32 (m, 12H,
3
CH(CH3)2), 2.09 (d, JH−H = 6.8 Hz, 3H, CH(CH3)Br), 2.91 (sep,
3JH−H = 6.9 MHz, 1H, CH(CH3)2), 3.30 (sep, JH−H = 6.8 MHz, 1H,
3
3
CH(CH3)2), 5.59 (q, JH−H = 6.9 MHz, 1H, CH(CH3)Br), 7.15 (dd,
3JH,H = 8.0 Hz, JH,H = 1.6 Hz, 1H, Ar-C5H), 7.20 (d, JH,H = 8.0 Hz,
4
3
1H, Ar-C6H), 7.42 (d, JH,H = 1.2 Hz, 1H, Ar-C3H); 13C NMR (100
4
MHz, CDCl3) δ 23.27, 23.90, 23.94, 26.72, 28.13, 33.73, 45.77, 124.62,
125.50, 126.57, 139.34, 142.91, 146.53; HRMS (ESI) m/z [(M + H)]+
calcd for C16H28N 234.2222, found 234.2220. Note: the isolated
compound must be converted to the amine immediately, as it
decomposes, and is not suitable for elemental analysis.
1-(2,5-Diisopropylphenyl)-N,N-dimethylethanamine (( )-7).
A solution of aqueous dimethylamine (40 wt %, 19.3 mL, 17.1 mmol)
was added to a solution of the bromo compound ( )-6 (3.08 g, 11.4
mmol) in dichloromethane (20 mL). The mixture was then stirred at
room temperature for 16 h. The organic layer was separated, and the
aqueous layer was extracted further with dichloromethane (2 × 25
mL). The clear organic solution was then washed with brine (50 mL),
dried with MgSO4, filtered, and evaporated to dryness. The crude
product was purified via column chromatography using dichloro-
methane/ethyl acetate (2/1 v/v) as eluent, affording a colorless oil:
yield 2.62 g (98%); 1H NMR (400 MHz, CDCl3) δ 1.22 (d, 3JH,H = 6.8
We are currently exploring other applications of complex 3.
Furthermore, the mechanistic details of the unexpected C−N
bond cleavage observed during the metal complexation process
is also currently being investigated in depth.
EXPERIMENTAL SECTION
■
General Considerations. Reactions involving air-sensitive com-
pounds were performed under a positive pressure of purified nitrogen
by using standard Schlenk techniques. 2,5-Disopropylbenzaldehyde
(4) was prepared according to procedures as reported in the
literature.16 Proton nuclear magnetic resonance (1H NMR), carbon
nuclear magnetic resonance (13C NMR), and phosphorus nuclear
magnetic resonance (31P{1H} NMR) spectroscopy was performed on
a Bruker Avance III 400 spectrometer (1H at 400 MHz, 13C at 100
MHz, 31P{1H} at 161 MHz). Multiplicities are given as follows: s
(singlet); brs (broad singlet); d (doublet); t (triplet); q (quartet); qn
(quintet); sep (septet); dd (doublet of doublets); m (multiplet). The
number of protons (n) for a given resonance is indicated by nH.
Coupling constants are reported as J values in Hz. Chemical shifts are
quoted as δ in units of parts per million (ppm) and referenced to the
chemical shift of the residual solvent of d-chloroform (1H at δ 7.26 and
13C at δ 77.00), unless otherwise stated. All NMR experiments were
conducted at 300 K. Mass spectra were recorded on a Thermo
Finnigan Trace GC Ultra instrument with EI mode. Melting points
were determined on an SRS-Optimelt MPA-100 apparatus and were
uncorrected. Optical rotations were measured using a 0.1 dm cell at
589 nm with an Atago automatic polarimeter (AP-300). Elemental
analyses were obtained using a Perkin-Elmer 2400 Series II CHNS
instrument.
3
Hz, 6H, CH(CH3)2), 1.24 (d, JH,H = 6.8 Hz, 6H, CH(CH3)2), 1.32
(d, 3JH,H = 6.4 Hz, 3H, CHCH3), 2.22 (s, 6H, NCH3), 2.88 (sep, 3JH,H
= 6.9 Hz, 1H, CH(CH3)2), 3.34 (sep, 3JH,H = 6.9 Hz, 1H, CH(CH3)2),
3.47 (q, 3JH,H = 6.5 Hz, 1H, CHCH3), 7.07 (dd, 3JH,H = 8.0 Hz, 4JH,H
=
3
2.0 Hz, 1H, Ar-C4H), 7.18 (d, JH,H = 8.0 Hz, 1H, Ar-C3H), 7.31 (d,
4JH,H = 2.0 Hz, 1H, Ar-C6H); 13C NMR (100 MHz, CDCl3) δ 21.85,
24.24, 24.26, 24.27, 24.29, 27.86, 33.94, 44.32, 61.44, 124.51, 125.13,
125.16, 142.04, 143.33, 146.36; HRMS (ESI) m/z [(M + H)]+ calcd
for C16H28N 234.2222, found 234.2220. Note: the isolated compound
is highly hydroscopic and is not suitable for elemental analysis.
General Procedure for Palladation of Tertiary Amine Ligand
( )-7. A solution of ( )-7 (0.10 g, 0.43 mmol) in the preferred
solvent (3 mL) was added to a stirred mixture of palladating agent
(0.43 mmol, 1.0 equiv) in the presence of base (0.43 mmol, 1.0 equiv),
if required, in the same solvent (3 mL). The reaction mixture was then
stirred at the desired temperature for 16 h. The mixture was filtered
through a plug of Celite and concentrated. The crude product was
then washed with H2O, dried with MgSO4, filtered, and evaporated to
dryness. The crude product was purified via column chromatography.
Complex ( )-8 and palladacycle ( )-3 were eluted out using hexane/
dichloromethane (1/1 v/v) and dichloromethane as the mobile
phases, respectively.
1-(2,5-Diisopropylphenyl)ethanol (( )-5). A colorless solution
of methylmagnesium bromide (3 M, 7.9 mL, 23.70 mmol) in dry THF
(10 mL) was added dropwise to a stirred solution of 4 (2.25 g, 11.82
mmol) dissolved in the same solvent (10 mL) at 0 °C. The reaction
mixture was stirred at room temperature for 16 h. The pale yellow
mixture was poured into a mixture of ice water (20 mL) and
concentrated HCl (1 mL) and stirred for 5 min. The resulting mixture
was then extracted with dichloromethane (3 × 50 mL), dried with
MgSO4, filtered, and evaporated to dryness. The crude product was
purified via column chromatography using hexane/dichloromethane
(
)-trans-Dichlorobis[1-(2,5-diisopropylphenyl)-N-
methylethanamine]palladium(II) (( )-8). The complex ( )-8 was
obtained from PdCl2 as palladating agent in methanol at 55 °C and
recrystallized from a dichloromethane/diethyl ether solution to give
bright yellow prisms: yield 38.3 mg (29%); mp 193−196 °C; 1H NMR
(400 MHz, CDCl3) δ 1.17−1.27 (m, 12H, CH(CH3)2), 2.09 (d, 3JH,H
1
3
(1/1 v/v) as eluent, affording a colorless oil: yield 2.39 g (98%); H
= 6.7 Hz, 3H, CHCH3), 2.34 (d, JH,H = 6.0 Hz, 3H, NHCH3), 2.89
NMR (400 MHz, CDCl3) δ 1.24 (d, 3JH,H = 7.2 Hz, 6H, CH(CH3)2),
(sep, 3JH−H = 6.6 MHz, 1H, CH(CH3)2), 3.17 (sep, 3JH−H = 6.8 MHz,
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1H, CH(CH3)2), 3.45 (brs, 1H, NHCH3), 4.51 (q, 1H, CHCH3), 6.90
0.05CH2Cl2: C, 55.30; H, 7.52; N, 6.13. Found: C, 55.20; H, 7.48;
N, 5.94.
3
4
(s, 1H, Ar-C6H), 7.14 (dd, JH,H = 8.2 Hz, JH,H = 1.6 Hz, 1H, Ar-
3
C4H), 7.22 (d, JH,H = 8.2 Hz, 1H, Ar-C3H); 13C NMR (100 MHz,
(SC,SCSN)-{2-[1′-(Dimethylamino)ethyl]-3,6-diisopropylphen-
yl-C,N}(prolinato-N,O)palladium(II)) ((SC,SC,SN)-10). The other
diastereomer (SC,SCSN)-10 was obtained by using methanol as the
mobile phase. The complex was recrystallized from a solution of
dichloromethane and hexane to give colorless needlelike single
CDCl3) δ 23.36, 23.89, 24.06, 24.62, 25.02, 28.03, 33.75, 38.17, 56.04,
121.85, 125.81, 125.96, 136.91, 144.40, 147.33; HRMS (ESI) m/z [(M
− Cl)]+ calcd for C30H50N2ClPd 581.2701, found 581.2690. Anal.
Calcd for C30H50Cl2N2Pd: C, 58.49; H, 8.18; N, 4.55. Found: C,
58.30; H, 8.39; N, 4.64.
1
crystals: yield 0.43 g (80%); [α]23.4 = +196.9° (c 0.02, CH2Cl2); H
NMR (400 MHz, CDCl3) δ 1.13−1.33 (m, 12H, CH(CH3)2), 1.60−
(
)-Bis(μ-chloro)bis{2-[1′-(dimethylamino)ethyl]-3,6-diiso-
3
2.05 (m, 2H, CH2CH2CH2), 2.07 (d, JH,H = 6.4 Hz, 3H, CHCH3),
propylphenyl-C,N}dipalladium(II)) (( )-3). The complex ( )-3
was obtained from the reaction of Li2[PdCl4] with tertiary amine
( )-7 dissolved in methanol in the presence of NaOAc at room
temperature and recrystallized from a dichloromethane/diethyl ether
solution to give needlelike bright yellow crystals: yield 125.0 mg
2.17−2.39 (m, 2H, COCHCH2), 2.55 (s, 3H, NCH3(ax)), 2.67 (s, 3H,
3
NCH3(eq)), 2.72 (sep, JH,H = 6.8 Hz, 1H, CH(CH3)2), 2.81 (sep,
3JH,H = 6.8 Hz, 1H, CH(CH3)2), 3.10−3.25 (m, 2H, NHCH2), 2.51−
2.53 (m, 1H, NH), 3.63 (q, 3JH,H = 6.2 Hz, 1H, CHCH3), 4.06 (m, 1H,
COCHCH2), 6.84 (d, 3JH,H = 8.0 Hz, 1H, Ar-C4H), 6.91 (d, 3JH,H = 8.4
Hz, 1H, Ar-C5H); 13C NMR (100 MHz, CDCl3) δ 22.75, 23.07, 23.93,
24.89, 25.09, 26.34, 29.77, 30.45, 34.28, 48.30, 52.92, 53.43, 65.41,
73.22, 121.34, 122.79, 140.05, 145.60, 149.40, 149.89, 179.84. Anal.
Calcd for C21H34ClN2O2Pd·0.10CH2Cl2: C, 54.92; H, 7.47; N, 6.07.
Found: C, 55.05; H, 7.49; N, 5.95.
1
(78%); mp 189−190 °C dec; H NMR (400 MHz, CDCl3) δ 1.12−
1.25 (m, 12H, CH(CH3)2), 2.28−2.29 (m, 3H, CHCH3), 2.59−2.62
3
(m, 6H, NCH3), 2.78 (sep, JH,H = 6.8 Hz, 1H, CH(CH3)2), 3.61 (m,
1H, CH(CH3)2), 3.86 (m, 1H, CHCH3), 6.76−6.87 (m, 2H,
aromatic); 13C NMR (100 MHz, CD2Cl2) δ 23.39, 24.34, 25.04,
26.84, 31.22, 33.92, 50.71, 75.28, 122.24, 140.56, 149.56, 149.12,
151.03; HRMS (ESI) m/z [(M − Cl)]+ calcd for C32H52N2ClPd2
713.1893, found 713.1901. Anal. Calcd for C32H52Cl2N2Pd2: C, 51.35;
H, 7.00; N, 3.74. Found: C, 51.53; H, 6.71; N, 3.80.
(S,S)-Bis(μ-chloro)bis{2-[1′-(dimethylamino)ethyl]-3,6-diiso-
propylphenyl-C,N}dipalladium(II)) ((S,S)-3). The complex
(SC,SCSN)-10 (0.41 g, 0.93 mmol) dissolved in dichloromethane (10
mL) was treated with 1 M HCl (5 mL) and stirred at room
temperature for 30 min. The organic layer was then separated, washed
with water (2 × 10 mL), dried with MgSO4, filtered, and evaporated to
dryness to afford the dimeric complex (S)-3: yield 0.31 g (90%);
(
)-Chloro{2-[1′-(dimethylamino)ethyl]-3,6-diisopropyl-
phenyl-C,N}(triphenylphosphine-P)palladium(II) (( )-9). Tri-
phenylphosphine (0.35 g, 1.33 mmol) was added to a solution of
racemic dimer ( )-3 (0.50 g, 0.67 mmol) dissolved in dichloro-
methane (10 mL). The mixture was stirred for 1 h at room
temperature. The reaction mixture was then evaporated to dryness to
afford complex ( )-9, which was recrystallized from a dichloro-
methane/hexane solution to give bright yellow crystals: yield 0.20 g
1
[α]23.8 = +180.7° (c 0.02, CH2Cl2); H NMR (400 MHz, CDCl3) δ
3
1.14−1.25 (m, 12H, CH(CH3)2), 2.28 (d, JH,H = 6.0 Hz, 3H,
3
CHCH3), 2.59−2.62 (m, 6H, NCH3), 2.78 (sep, JH,H = 6.8 Hz, 1H,
CH(CH3)2), 3.61 (m, 1H, CH(CH3)2), 3.60−3.85 (m, 2H, CHCH3
and CH(CH3)2), 6.76−6.87 (m, 2H, aromatic); 13C NMR (100 MHz,
CDCl3) δ 22.96, 23.88, 24.81, 26.64, 30.67, 50.18, 74.61, 121.64,
123.62, 123.76, 139.90, 150.36; HRMS (ESI) m/z [(M − Cl)]+ calcd
for C32H52N2ClPd2 713.1893, found 713.1901. Anal. Calcd for
C32H52Cl2N2Pd2: C, 51.35; H, 7.00; N, 3.74. Found: C, 51.52; H,
7.11; N, 3.77.
1
(95%); mp 178−181 °C; H NMR (400 MHz, CDCl3) δ 0.22 (d,
3JH,H = 6.8 Hz, 3H, CH(CH3)2), 1.16 (d, JH,H = 6.8 Hz, 3H,
3
CH(CH3)2), 1.25−1.28 (m, 6H, CH(CH3)2), 2.08 (d, 3JH,H = 6.4 Hz,
3H, CHCH3), 2.43 (d, 4JP,H = 2.0 Hz, 3H, NCH3(ax)), 2.48−2.53 (m,
4
1H, CH(CH3)2), 2.81 (d, JH,P = 3.6 Hz, 3H, NCH3(eq)), 2.84−2.90
3
4
(m, 1H, CH(CH3)2), 3.73 (qn, JH,H = JP,H = 6.4 Hz, 1H, CHCH3),
6.39−7.64 (m, 17H, aromatic); 13C NMR (100 MHz, CD2Cl2) δ
19.72, 22.50, 23.38, 24.61, 29.25, 30.44, 33.84 (d, JC,P = 11.8 Hz),
49.09, 50.47, 74.31 (d, JC,P = 3.1 Hz), 121.08−158.70 (13C, aromatic);
31P{1H} NMR (161 MHz, CDCl3): δ 30.7 (s); HRMS (ESI) m/z [(M
(S)-{2-[1′-(Dimethylamino)ethyl]-3,6-diisopropylphenyl-
C,N}(3,4-dimethyl-1-phenylphosphole-P)palladium(II)) ((S)-11).
A solution of the dimeric complex (S)-3 (1.0 g, 1.3 mmol) dissolved in
degassed dichloromethane (5 mL) was added to a mixture of 3,4-
dimethyl-1-phenylphosphole (DMPP; 0.49 g, 2.6 mmol) in the same
solvent (5 mL). The mixture was subsequently stirred for 30 min at
room temperature. The reaction mixture was then evaporated to
dryness and purified via column chromatography using dichloro-
methane as eluent, affording yellow solids. The complex was
recrystallized from a solution of dichloromethane and hexane to give
yellow needlelike single crystals: yield 1.35 g (90%); mp 158−161 °C
dec; [α]23.4 = +431.5° (c 0.01, CH2Cl2); 1H NMR (400 MHz, CDCl3)
− Cl)]+ calcd for C34H41N2PPd 600.2011, found 600.1981. Anal.
Calcd for C34H41ClNPPd: C, 64.15; H, 6.49; N, 2.20. Found: C, 64.52;
H, 6.34; N, 2.22.
(RC,SCSN)-{2-[1′-(Dimethylamino)ethyl]-3,6-diisopropylphen-
yl-C,N}(prolinato-N,O)palladium(II)) ((RC,SC,SN)-10). A solution of
sodium (S)-prolinate (0.65 g, 4.74 mmol) in methanol (20 mL) was
added to a solution of racemic dimer, ( )-3 (1.79 g, 2.39 mmol)
dissolved in the same solvent (20 mL). The mixture was stirred for 1
h. The solvent was subsequently removed under reduced pressure
before being dissolved in dichloromethane. The solution was then
washed with water (3 × 100 mL), dried with MgSO4, filtered, and
evaporated to dryness. The (RC,SCSN)-10 adduct was separated via
column chromatography using dichloromethane/acetone (1/1 v/v).
The complex was recrystallized from a solution of dichloromethane
and diethyl ether to give yellow platelike single crystals: yield 0.44 g
3
δ 0.96−1.24 (m, 12H, CH(CH3)2), 1.87 (d, JH−H = 6.4 Hz, 3H,
CH(CH3), 1.98 (s, 3H, CCCH3), 2.01 (s, 3H, CCCH3), 2.43 (d,
3
4JP,H = 2.0 Hz, 3H, NCH3(ax)), 2.71 (sep, JH,H = 6.4 Hz, 1H,
CH(CH3)2), 2.67 (d, 4JP,H = 3.6 Hz, 3H, NCH3(eq)), 2.83 (sep, 3JH,H
3
4
= 6.8 Hz, 1H, CH(CH3)2), 3.67 (qn, JH,H = JH,P = 6.4 Hz, 1H,
2
2
CH(CH3), 6.06 (d, JP,H = 32.4 Hz, 1H, CCCH), 6.76 (d, JP,H
=
3
31.6 Hz, 1H, CCCH), 6.81 (d, JH,H = 8.0 Hz, 1H, Ar-C4H), 6.87
(d, JH,H = 8.0 Hz, 1H, Ar-C5H), 7.29−7.84 (m, 5H, PPh); 13C NMR
3
1
(82%) (based on /2 equiv of dimer used); mp 200−201 °C dec;
(100 MHz, CDCl3) δ 17.26 (d, JC,P = 20.2 Hz), 17.76 (d, JC,P = 19.7
Hz), 20.75, 22.53, 22.83, 23.08, 28.55, 30.42, 37.79 (d, JC,P = 20.1 Hz),
48.62, 50.54 (d, JC,P = 4.6 Hz), 73.44 (d, JC,P = 5.3 Hz), 121.16−152.91
(22C, aromatic); 31P{1H} NMR (161 MHz, CDCl3) δ 28.4 (s);
HRMS (ESI) m/z [(M − Cl)]+ calcd for C28H39NPPd 526.1855,
found 526.1874. Anal. Calcd for C28H39NPPd·0.1CH2Cl2: C, 59.11; H,
6.92; N, 2.45. Found: C, 59.35; H, 6.58; N, 2.59.
Asymmetric [4 + 2] Endo-Cycloaddition Reactions between
Complex (S)-11 and Ethyl Vinyl Ketone. A mixture of the DMPP-
coordinated complex (S)-11 (83.8 mg, 0.15 mmol) and ethyl vinyl
ketone (0.1 mL, 1.00 mmol) in chloroform (3 mL) was stirred at 50
°C and was monitored by 31P{1H} NMR spectroscopy. After 5 days,
two new peaks with a diastereomeric ratio of 4.4:1 were observed. The
1
[α]23.4 = +43.4° (c 0.02, CH2Cl2); H NMR (400 MHz, CDCl3) δ
1.13−1.29 (m, 12H, CH(CH3)2), 1.67−1.96 (m, 3H, CH2CH2CH2
3
and COCHCH2), 2.03 (d, JH,H = 6.4 Hz, 3H, CHCH3), 2.52−2.58
(m, 1H, COCHCH2), 2.59 (s, 3H, NCH3(eq)), 2.63 (s, 3H,
3
NCH3(ax)), 2.79 (sep, JH,H = 6.7 Hz, 2H, CH(CH3)2), 3.20−3.36
(m, 3H, NHCH2 and NH), 3.63 (q, 3JH,H = 6.4 Hz, 1H, CHCH3), 4.20
3
(m, 1H, COCHCH2), 6.85 (d, JH,H = 8.0 Hz, 1H, Ar-C4H), 6.92 (d,
3JH,H = 8.0 Hz, 1H, Ar-C5H); 13C NMR (100 MHz, CDCl3) δ 22.78,
23.17, 23.65, 23.78, 24.84, 26.24, 28.84, 30.40, 33.73, 48.51, 50.92,
53.33, 66.98, 73.14, 121.73, 122.48, 140.40, 144.06, 149.44, 150.09,
177.89; HRMS (ESI) m/z [(M + H)]+ calcd for C21H35N2O2Pd
453.1733, found 453.1742. Anal. Calcd for C21H34ClN2O2Pd·
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Organometallics
Article
reaction mixture was then filtered through a plug of Celite and
evaporated to dryness. The major product was eluted via column
chromatography using dichloromethane as the eluent, affording a
yellow oil: yield 6.8 mg (7.4%); 1H NMR (400 MHz, CDCl3) δ 0.69−
0.76 (m, 3H, COCH2CH3), 1.16−1.42 (m, 12H, CH(CH3)2), 1.55 (s,
3H, CCCH3), 1.60 (s, 3H, CCCH3), 1.91−2.06 (m, 3H,
J. Organomet. Chem. 2008, 693, 3289. (h) Leung, P.-H. Acc. Chem. Res.
2004, 37, 169.
(6) For selected examples in stoichiometric hydrophosphination or
hydroarsination: (a) Ding, Y.; Zhang, Y.; Li, Y.; Pullarkat, S. A.;
Andrews, P.; Leung, P.-H. Eur. J. Inorg. Chem. 2010, 4427. (b) Yeo, W.
C.; Tee, S. T.; Tan, G. K.; Koh, L. L.; Leung, P.-H. Inorg. Chem. 2004,
43, 8102. (c) Pullarkat, S. A.; Ding, Y.; Li, Y.; Tan, G. K.; Leung, P.-H.
Inorg. Chem. 2006, 45, 7455. (d) Yuan, M.; Pullarkat, S. A.; Ma, M.;
Zhang, Y.; Huang, Y.; Li, Y.; Goel, A.; Leung, P.-H. Organometallics
2009, 28, 780. (e) Zhang, Y.; Pullarkat, S. A.; Li, Y.; Leung, P.-H. Inorg.
Chem. 2009, 48, 5535. (f) Yuan, M.; Pullarkat, S. A.; Li, Y.; Leung, P.-
H. Organometallics 2010, 29, 3582. (g) Bungabong, M. L.; Tan, K. W.;
Li, Y.; Selvaratnam, S.; Dongol, K. G.; Leung, P.-H. Inorg. Chem. 2007,
46, 4733.
3
COCH2CH3 and CH2CHCO), 2.08 (d, JH,H = 6.4 Hz, 3H,
3
CHCH3), 2.41 (s, 3H), 2.71 (sep, JH,H = 6.4 Hz, 1H, CH(CH3)2),
2.41 (d, 4JP,H = 1.6 Hz, 3H, NCH3(ax)), 2.64 (sep, 3JH,H = 6.4 Hz, 1H,
4
CH(CH3)2), 2.76 (d, JP,H = 3.2 Hz, 3H, NCH3(eq)), 2.82−2.90 (m,
3
1H, CH(CH3)2), 3.73 (qn, JH,H = 6.4 Hz, 1H, CH(CH3), 6.87−7.92
(m, 5H, PPh); 31P{1H} NMR (161 MHz, CDCl3) δ 119.4 (s) (other
unknown byproducts peaks at δ 21.2 (s) and 67.4 (d)) were also
observed).
(7) For selected examples of catalytic hydrophosphination:
(a) Huang, Y.; Pullarkat, S. A.; Li, Y.; Leung, P.-H. Chem. Commun.
2010, 46, 6950. (b) Huang, Y.; Chew, R. J.; Pullarkat, S. A.; Li, Y.;
Leung, P.-H. Org. Lett. 2011, 13, 5862. (c) Xu, C.; Gan, J. H. K.;
Hennersdorf, F.; Li, Y.; Pullarkat, S. A.; Leung, P.-H. Organometallics
2012, 31, 3022. (d) Huang, Y.; Pullarkat, S. A.; Teong, S.; Chew, R. J.;
Li, Y.; Leung, P.-H. Organometallics 2012, 31, 4871. (e) Huang, Y.;
Pullarkat, S. A.; Li, Y.; Leung, P.-H. Inorg. Chem. 2012, 51, 2533.
(f) Huang, Y.; Chew, R. J.; Pullarkat, S. A.; Li, Y.; Leung, P.-H. J. Org.
Chem. 2012, 77, 6849.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures, tables, and CIF files giving H, 13C, 31P{1H}, and 2D
1
1H−1H ROESY spectra and single-crystal X-ray crystallographic
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for P.-H.L.: pakhing@ntu.edu.sg.
Notes
■
(8) For selected examples in other catalytic transformation:
(a) Leung, P.-H.; Ng, K.-H.; Li, Y.; White, A. J. P.; Williams, D. J.
Chem. Commun. 1999, 2435. (b) Chew, R. J.; Huang, Y.; Li, Y.;
Pullarkat, S. A.; Leung, P.-H. Adv. Synth. Catal. 2013, 355, 1403.
(c) Xu, Q.; Shen, R.; Ono, X.; Nagahata, R.; Shimada, S.; Goto, M.;
Han, L.-B. Chem. Commun. 2011, 47, 2333. (d) Cannon, J. S.;
Frederich, J. H.; Overman, L. E. J. Org. Chem. 2012, 77, 1939.
(e) Hyodo, K.; Nakamura, S.; Tsuji, K.; Ogawa, T.; Funahashi, Y.;
Shibata, N. Adv. Synth. Catal. 2011, 353, 3385. (f) Cantillo, D.;
Baghbanzadeh, M.; Kappe, C. O. Angew. Chem. 2012, 124, 10337.
(g) Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L. J. Am. Chem. Soc.
2010, 132, 5562. (h) Yang, M.-J.; Liu, Y.-J.; Gong, J.-F.; Song, M.-P.
Organometallics 2011, 30, 3793. (i) Weiss, M.; Frey, W.; Peters, R.
Organometallics 2012, 31, 6365. (j) Weber, M.; Jautze, S.; Frey, W.;
Peters, R. Chem. Eur. J. 2012, 18, 14792. (k) Arai, T.; Oka, I.;
Morihata, T.; Awata, A.; Masu, H. Chem. Eur. J. 2013, 19, 1554.
(l) Hyodo, K.; Kondo, M.; Funahashi, Y.; Nakamura, S. Chem. Eur. J.
2013, 19, 4128. (m) Gorunova, O. N.; Livantsov, M. V.; Grishin, Y. K.;
Ilyin, M. M., Jr.; Kochetkov, K. A.; Churakov, A. V.; Kuzmina, L. G.;
Khrustalev, V. N.; Dunina, V. V. J. Organomet. Chem. 2013, 737, 59.
(n) Churruca, F.; Hernandez, S.; Perea, M.; SanMartin, R.;
Dominguez, E. Chem. Commun. 2013, 49, 1413. (o) Leng, F.; Wang,
Y.; Li, H.; Li, J.; Zou, D.; Wu, Y.; Wu, Y. Chem. Commun. 2013, 49,
10697. (p) Hajipour, A. R.; Rafiee, F. Tetrahedron Lett. 2012, 53, 4661.
(q) Serrano, J. L.; Perez, J.; Garcia, L.; Sanchez, G.; Garcia, J.; Tyagi,
K.; Kapdi, A. RSC Adv. 2012, 2, 12237.
(9) For selected examples of cyclopalladated complexes: (a) Dunina,
V. V.; Gorunova, O. N. Russ. Chem. Rev. 2005, 74, 871. (b) Alonso, D.
A.; Najera, C. Chem. Soc. Rev. 2010, 39, 2891. (c) Reznichenko, A. L.;
Hultzsch, K. C. Organometallics 2010, 29, 24. (d) Jautze, S.; Diethelm,
S.; Frey, W.; Peters, R. Organometallics 2009, 28, 2001. (e) Dunina, V.
V.; Zykov, P. A.; Livantsov, M. V.; Glukhov, I. V.; Kochetkov, K. A.;
Gloriozov, I. P.; Grishin, Y. K. Organometallics 2009, 28, 425.
(f) Keuseman, K. J.; Smoliakova, I. P.; Dunina, V. V. Organometallics
2005, 24, 4159. (g) Ng, J. K.-P.; Chen, S.; Tan, G.-K.; Leung, P.-H.
Eur. J. Inorg. Chem. 2007, 3124. (h) Dunina, V. V.; Turubanova, E. I.;
Gorunova, O. N.; Livantsov, M. V.; Lyssenko, K. A.; Antonov, D. Yu.;
Grishin, Y. K. Polyhedron 2012, 31, 413. (i) Dunina, V. V.; Gorunova,
O. N.; Livantsov, M. V.; Grishin, Y. K.; Kochetkov, K. A.; Churakov, A.
V.; Kuz’mina, L. G. Polyhedron 2011, 30, 27. (j) Dunina, V. V.;
Turubanova, E. I.; Livantsov, M. V.; Lyssenko, K. A.; Vorontsova, N.
V.; Antonov, D. Yu.; Grishin, Y. K. Tetrahedron: Asymmetry 2009, 20,
1661. (k) Dunina, V. V.; Turubanova, E. I.; Livantsov, M. V.;
Lyssenko, K. A.; Grishin, Y. K. Tetrahedron: Asymmetry 2008, 19, 1519.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to Nanyang Technological University for
supporting this research and for research scholarships to J.S.L.Y.
■
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