Synthesis of enantiomerically pure P-stereogenic diphosphacrowns and their palladium complexes

Article abstract of DOI:10.1021/jo1024442

A practical synthetic route for enantiomerically pure P-stereogenic diphosphacrowns was developed by using a P-stereogenic bisphosphine as a chiral building block. Their molecular structures were confirmed by NMR spectroscopy and X-ray crystallography. Complexation of the diphosphacrowns with palladium was carried out, and the corresponding palladium complexes were obtained. The P-stereogenic diphosphacrowns were applicable to the chiral ligand for the asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated ketone catalyzed by palladium. This reaction proceeded smoothly to afford the corresponding 1,4-addition products in high yield with good enantioselectivities.

Full text of DOI:10.1021/jo1024442

ARTICLE
pubs.acs.org/joc
Synthesis of Enantiomerically Pure P-Stereogenic Diphosphacrowns
and Their Palladium Complexes
Yasuhiro Morisaki,*,† Hiroaki Imoto,† Koji Hirano,‡ Tamio Hayashi,‡ and Yoshiki Chujo*,†
†Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
‡Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
S Supporting Information
b
ABSTRACT: A practical synthetic route for enantiomerically
pure P-stereogenic diphosphacrowns was developed by using a
P-stereogenic bisphosphine as a chiral building block. Their
molecular structures were confirmed by NMR spectroscopy
and X-ray crystallography. Complexation of the diphospha-
crowns with palladium was carried out, and the corresponding
palladium complexes were obtained. The P-stereogenic dipho-
sphacrowns were applicable to the chiral ligand for the asymmetric 1,4-addition of arylboronic acids to R,β-unsaturated ketone
catalyzed by palladium. This reaction proceeded smoothly to afford the corresponding 1,4-addition products in high yield with good
enantioselectivities.
’ INTRODUCTION
Recently, we have successfully prepared P-stereogenic (S,S)-
and (R,R)-18-diphosphacrown-6 containing two chiral phos-
phorus atoms in the ring by using P-stereogenic (S,S)- and (R,R)-
bisphosphine-boranes as the building blocks, respectively.9 This
is the first example of the synthesis of P-stereogenic dipho-
sphacrowns possessing chiral heteroatoms (phosphorus atoms)
in the ring structure. This synthetic strategy makes it possible to
prepare various P-stereogenic diphosphacrowns. In this study,
we describe the synthesis and characterization of enantiomeri-
cally pure P-stereogenic diphosphacrowns with various ring sizes
in detail. One of our motivations is also to apply the P-stereo-
genic diphosphacrowns to a chiral ligand for realizing transition
metal-catalyzed asymmetric reactions. After many trials, we have
found an effective catalytic system for the asymmetric 1,4-
addition of arylboronic acids to enones. Thus, herein, we also
report the asymmetric 1,4-addition of arylboronic acids to cyclic
R,β-unsaturated ketones catalyzed using P-stereogenic dipho-
sphacrown-cationic palladium(II) complexes as well.
Crown ethers are macrocyclic compounds comprising a ring
with several ether groups. The most common crown ethers have
ethyleneoxy (-CH2CH2-O-) repeating units in their ring
skeletons, which can wrap and capture various metal cations as
well as cationic molecules owing to the presence of lone pair(s)
of oxygen atoms.1,2 A ground-breaking and simple method of
synthesizing crown ethers was discovered by Pederson in 1967.1
Subsequently, after his seminal work, crown ether chemistry was
developed further for diverse molecular systems.3-5 This re-
search made it possible to realize host-guest chemistry6 that can
be said to be the cornerstone of supramolecular chemistry.7
Since the first report on the synthesis of dibenzo-18-crown-6,1
numerous other crown ether derivatives have been reported.
Further, in many crown ether derivatives, the oxygen atoms have
been replaced by various heteroatoms. For example, azacrowns2c
and thiacrowns2d,2e comprise “-CH2CH2-NR-” and
“-CH2CH2-S-” repeating units, respectively, in addition to the
“-CH2CH2-O-” units; the guest selectivities and binding
strengths of these derivatives are different from those of crown
ethers. Phosphacrowns are an identical class of crown ether
derivatives containing phosphorus atoms instead of oxygen
atoms;2f-2h however, they have not attracted much attention
thus far. In fact, to our knowledge, there are no examples of the
synthesis of P-stereogenic phosphacrowns possessing chiral
phosphorus atoms, even though a phosphorus atom can be a
chiral center owing to its high inversion energy. On the other
hand, the optical resolution of racemic phosphorus-containing
macrocycles has been achieved previously by employing a
procedure that leads to the spontaneous crystallization of the
racemic macrocycle-Ni complex; the enantiomers are then
separated by Pasteur’s method.8
’ RESULTS AND DISCUSSION
To prepare the enantiomerically pure P-stereogenic dipho-
sphacrowns, the P-stereogenic precursor (S,S)-3-BH3 was synthe-
sized from (S,S)-1-BH3 as shown in Scheme 1. The synthetic
method of (S,S)-1-BH3 was established by Evans and co-workers,10a
and it was recently modified by us to yield (S,S)-1-BH3 with >
99% ee.10b The methyl group substituted at a borane-coordinated
phosphorus atom can be lithiated by alkyllithium reagents such as
sec-BuLi, and this enables us to prepare various P-stereogenic phos-
phines having different functional groups. Thus, the dilithiation of the
Received: December 10, 2010
Published: February 03, 2011
r
2011 American Chemical Society
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Scheme 1. Synthesis of (S,S)-3-BH3
The enantiomers (R,R)-diphosphacrowns (R,R)-5a-c-BH3
can be prepared from the corresponding P-stereogenic dialcohol
(R,R)-3-BH3; however, its straightforward synthesis is challen-
ging, because the precursor (R,R)-1-BH3 has to be prepared
with (þ)-sparteine11 (Scheme 3). Therefore, we attempted the
synthesis of (R,R)-18-diphosphacrown-6-BH3 “(R,R)-5b-
BH3” as a representative example, as shown in Scheme 4. One
methyl group of dimethylphenylphosphine-borane 6-BH3 was
enantioselectively lithiated with sec-BuLi/(-)-sparteine, which
was treated with dry CO2 gas and Hþ to yield the corresponding
carboxylic acid. BH3 THF reduced the carboxylic group and
3
provided (S)-7-BH3 in 71% isolated yield with 87% ee; the
estimations were performed by high performance liquid chro-
matography (HPLC), using a chiral column (Figure S1 in the
Supporting Information).12 Another methyl group in (S)-7-
BH3 was reacted with sec-BuLi/TMEDA. After the treatment
with CuCl2 and aqueous NH3, repeated recrystallizations with
toluene and hexane afforded (R,R)-3-BH3 in 36% yield.13 The
formation of the dialkoxide of (R,R)-3-BH3 with NaH followed
by the reaction with triethyleneglycol bis(p-toluenesulfonate) 4b
gave the desired enantiomer (R,R)-5b-BH3 in 22% yield.
The chemical structures of the P-stereogenic compounds were
1
confirmed by measuring H, 13C, and 31P{1H} NMR spectra
1
(Supporting Information). As an example, the H NMR spec-
trum of (S,S)-5b-BH3 exhibits a broad signal of two BH3 groups
at around 0.7 ppm that is split into a quartet by the boron atom
with JH-B of 119.4 Hz (Figure S9, Supporting Information). A
relatively sharp 31P{1H} signal of (S,S)-5b-BH3 appeared at δ
16.5 ppm, which was also split into a quartet (JP-B = 38.4 Hz) by
the coordination of BH3 (Figure S11, Supporting Information).
The 31P{1H} signals of (S,S)-5a-BH3 and (S,S)-5c-BH3
showed the expected peak at δ þ17.7 and þ16.3 ppm, respec-
tively, as shown in Figures S8 and S14 (Supporting Information).
Scheme 2. Synthesis of (S,S)-5a-c-BH3
The [R]D values of (S,S)-5a-c-BH3 were found to be [R]25
D
þ103.0 (c 0.5 in CHCl3), þ62.7 (c 1.0 in CHCl3), and þ50.2
(c 0.5 in CHCl3), respectively; these values were considerably
larger than that of (S,S)-3-BH3 ([R]22D þ9.1, c 1.0 in CHCl3).
This is because, in addition to the chirality of the two phosphorus
atoms, cyclization causes new chirality in the ring structure.
Single crystals of (S,S)-5a-BH3 and (S,S)-5b-BH3 could be
successfully obtained by recrystallization from CH2Cl2 and
hexane. Their molecular structures were confirmed by X-ray
crystallography. The ORTEP drawings are shown in Figures 1
and 2. The selected bond distances and bond angles of (S,S)-5a-
BH3 and (S,S)-5b-BH3 are listed in Tables 1 and 2, respectively.
The structure of each diphosphacrown can be rationalized as
being the expected absolute configuration comprising (S)-phos-
phorus atoms. As shown in Figure 1, (S,S)-5a-BH3 adopted one
conformation in the crystal, whereas (S,S)-5b-BH3 existed as
two conformations (Figure 2). Further, one conformer possessed
two phenyl groups on the side opposite to the diphosphacrown
ring (side view a in Figure 2), while the other possessed two
phenyl groups above the ring (side view b in Figure 2). On the
other hand, the 31P{1H} NMR spectrum of (S,S)-5b-BH3
exhibited a single signal with JP-B of 38.4 Hz (vide supra), as
shown in Figure S11 (Supporting Information), indicating that
the ring structure of (S,S)-5b-BH3 was flexible, and rapid
interconversion of the two conformers occurred in the solution.
The average phosphorus-carbon and oxygen-carbon bond
lengths of the ring structure in (S,S)-5a-BH3 were found to be
1.830 and 1.424 Å (Table 1), respectively. The average angles
between the segments joining a central phosphorus atom and
two methyl groups in (S,S)-1-BH3 was easily performed with sec-
BuLi/N,N,N0,N0-tetramethylenediamine (TMEDA), and the succes-
sive reaction with dry CO2 gas afforded the P-stereogenic dicarboxylic
acid (S,S)-2-BH3. Without purification, the carboxylic groups in
(S,S)-2-BH3 were reduced with BH3 THF to give the target pre-
3
cursor (S,S)-3-BH3 in 55% isolated yield.
The P-stereogenic diphosphacrowns were obtained according to
Scheme 2 by the Williamson ether synthesis. The reaction was
carried out under diluted condition (20 mM of each substrate in
THF). The treatment of (S,S)-3-BH3 with NaH and ethylenegly-
col bis(p-toluenesulfonate)s 4a-c afforded the corresponding
(S,S)-15-diphosphacrown-5-BH3 “(S,S)-5a-BH3”, (S,S)-18-
diphosphacrown-6-BH3 “(S,S)-5b-BH3”, and (S,S)-21-dipho-
sphacrown-7-BH3 “(S,S)-5c-BH3”, respectively. Further, the
diphosphacrowns could be readily purified by open SiO2 column
chromatography, and (S,S)-5a-c-BH3 were obtained as color-
less solids in 14%, 17%, and 20% isolated yields, respectively.
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Scheme 3. Synthetic Route for (S,S)-3-BH3 and (R,R)-3-BH3
Scheme 4. Synthesis of (R,R)-3-BH3 and (R,R)-5b-BH3
Figure 1. ORTEP drawing of (S,S)-5a-BH3. Thermal ellipsoids are
drawn at the 30% probability level. Hydrogen atoms are omitted for
clarity.
not be obtained, its ring size can be expected to be slightly larger
than that of 21-crown-7.
The complexations of P-stereogenic diphosphacrowns (S,S)-5a-
c-BH3 with palladium(II) were carried out with PdCl2(cod) (cod =
1,5-cyclooctadiene) as a precursor. The coordinated boranes of
(S,S)-5a-c-BH3 were readily removed by treating with a strong
organic base such as 1,4-diazabicyclo[2.2.2]octane (DABCO), as
shown in Scheme 5. The solvent was dried, and the crude product
was subjected to a SiO2 short column chromatography. The obtained
diphosphacrowns (S,S)-5a-c were used for the subsequent com-
plexation without further purification. The reactions of (S,S)-5b and
(S,S)-5c with PdCl2(cod) in CHCl3 proceeded smoothly to afford
the corresponding diphosphacrown-palladium complexes 8b and
8c in 69% and 74% isolated yields, respectively.14 However, almost
no reaction occurred with (S,S)-5a.
three vertex atoms in (S,S)-5a-BH3 were 109.4° and 109.3° for
P(1) and P(2), respectively, as listed in Table 1. This suggests
that each phosphorus atom is located at the center of a
tetrahedral molecular geometry with a small distortion. The
bond lengths and bond angles around the phosphorus atoms
in both conformers of (S,S)-5b-BH3 were almost identical with
those of (S,S)-5a-BH3 (Table 2). The ring sizes of (S,S)-5a-
BH3 and (S,S)-5b-BH3 are slightly larger than those of 15-
crown-5 and 18-crown-6, respectively. Although the single
crystal of (S,S)-5c-BH3 suitable for X-ray crystallography could
The structures of 8b and 8c were deduced on the basis of
1H, 13C, and 31P{1H} NMR analysis. 31P{1H} NMR signals
of phosphine-borane of (S,S)-5b-BH3 and (S,S)-5c-BH3
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Table 2. Selected Bond Distances (Å) and Angles (deg) in
(S,S)-5b-BH3
Bond Distances
conformer a
P(1)-C(17)
conformer b
1.820(3)
1.827(4)
1.821(4)
1.907(5)
1.829(4)
1.812(3)
1.827(4)
1.910(5)
1.431(5)
1.425(5)
1.401(5)
1.415(6)
1.422(6)
1.412(4)
1.410(5)
1.406(5)
P(2)-C(21)
1.817(4)
1.810(4)
1.812(5)
1.916(5)
1.810(4)
1.831(4)
1.816(4)
1.917(4)
1.426(6)
1.423(5)
1.421(4)
1.430(5)
1.422(5)
1.416(5)
1.427(5)
1.424(5)
P(1)-C(20)
P(1)-C(23)
P(1)-B(4)
P(2)-C(24)
P(2)-C(42)
P(2)-B(2)
P(4)-C(13)
P(4)-C(14)
P(4)-C(34)
P(4)-B(3)
P(3)-C(16)
P(3)-C(25)
P(3)-C(68)
P(3)-B(1)
O(7)-C(37)
O(7)-C(43)
O(9)-C(38)
O(9)-C(56)
O(11)-C(45)
O(11)-C(48)
O(13)-C(31)
O(13)-C(67)
O(5)-C(41)
O(5)-C(51)
O(6)-C(55)
O(6)-C(58)
O(8)-C(28)
O(8)-C(44)
O(12)-C(29)
O(12)-C(35)
Bond Angles
conformer a
conformer b
C(23)-P(1)-C(20)
C(17)-P(1)-C(20)
C(23)-P(1)-C(17)
B(4)-P(1)-C(17)
B(4)-P(1)-C(20)
B(4)-P(1)-C(23)
C(34)-P(4)-C(13)
C(14)-P(4)-C(13)
C(14)-P(4)-C(34)
B(3)-P(4)-C(13)
B(3)-P(4)-C(14)
B(3)-P(4)-C(34)
110.0(2)
103.8(2)
103.2(2)
112.5(2)
113.4(2)
113.1(2)
105.3(2)
107.7(2)
106.5(2)
113.4(2)
111.7(2)
114.5(2)
C(24)-P(2)-C(21)
C(24)-P(2)-C(42)
C(21)-P(2)-C(42)
B(2)-P(2)-C(21)
B(2)-P(2)-C(24)
B(2)-P(2)-C(42)
C(68)-P(3)-C(25)
C(25)-P(3)-C(16)
C(16)-P(3)-C(68)
B(1)-P(3)-C(16)
B(1)-P(3)-C(25)
B(1)-P(3)-C(68)
104.8(2)
107.5(2)
106.9(2)
111.9(2)
110.6(2)
114.5(2)
107.1(2)
109.7(2)
104.1(2)
113.6(2)
110.3(2)
111.8(2)
Figure 2. ORTEP drawings of (S,S)-5b-BH3 (conformers a and b).
Thermal ellipsoids are drawn at the 30% probability level. Hydrogen
atoms are omitted for clarity.
Table 1. Selected Bond Distances (Å) and Angles (deg) in
(S,S)-5a-BH3
Bond Distances
P(1)-C(1)
P(1)-C(10)
P(2)-C(2)
P(2)-C(3)
1.817(5)
1.845(5)
1.830(5)
1.828(5)
O(1)-C(4)
O(1)-C(5)
O(2)-C(6)
O(2)-C(7)
O(3)-C(8)
O(3)-C(9)
1.428(7)
1.431(6)
1.416(6)
1.427(6)
1.430(7)
1.412(7)
Scheme 5. Synthesis of Palladium Complexes 8a-c
Bond Angles
105.0(2)
C(1)-P(1)-C(10)
C(1)-P(1)-C(17)
C(10)-P(1)-C(17)
B(1)-P(1)-C(1)
B(1)-P(1)-C(10)
B(1)-P(1)-C(17)
C(2)-P(2)-C(3)
C(2)-P(2)-C(11)
C(3)-P(2)-C(11)
B(2)-P(2)-C(2)
B(2)-P(2)-C(3)
B(2)-P(2)-C(11)
107.8(2)
104.9(2)
104.5(2)
111.0(2)
115.2(3)
112.8(2)
106.7(2)
108.6(2)
113.0(3)
111.5(3)
111.6(3)
disappeared completely, while sharp singlet signals of the
phosphorus atoms of 8b and 8c could be observed at δ 72.1
and 71.0 ppm (Figures S20 and S23, Supporting Information),
respectively. Complexes 8b and 8c had negative [R]D values of
[R]22D -122.6 (c 1.0 in CHCl3) and [R]22D -110.0 (c 1.0 in
CHCl3), respectively.
hexane. The results are shown in Figures 3 and 4, and the selected
bond lengths and angles are listed in Tables 3 and 4, respectively.
Figure 3 shows the ORTEP drawings of 8b, and diphosphacrown
(S,S)-5b coordinated with palladium outside the ring as a
bidentate ligand. The P-Pd-P, P-Pd-Cl, and Cl-Pd-Cl
Air-stable crystals of 8b and 8c suitable for X-ray crystal-
lography were obtained by recrystallization from CH2Cl2 and
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Figure 4. ORTEP drawings of 8c. Thermal ellipsoids are drawn at the 30%
probability level. Hydrogen atoms and CHCl3 are omitted for clarity.
Figure 3. ORTEP drawings of 8b. Thermal ellipsoids are drawn at the
30% probability level. Hydrogen atoms are omitted for clarity.
Table 3. Selected Bond Distances (Å) and Angles (deg) in 8b
angles in 8b and 8c were around 90°, and the sum of the angles
was 360.3° and 360.2°, respectively; this indicates a square-planar
environment for palladium (top views in Figures 3 and 4). In
Figure 3, two phenyl groups of 8b were located at two diagonal
quadrants and occupy quasi-equatorial positions (front view).
This is similar to the case of a series of rhodium-(P-stereogenic
bisphosphine) complexes.15 The dihedral angles of the phenyl
groups were 44.8° and 50.9° (front view in Figure 3). On the
other hand, the coordination of (S,S)-5c to palladium created a
different asymmetric environment from (S,S)-5b. Figure 4 shows
the ORTEP drawings of 8c. The P-stereogenic 21-diphospha-
crown-7 skeleton could be confirmed, although single crystals of
(S,S)-5c-BH3 could not be produced. In Figure 4, palladium in
8c existed outside the ring, similarly to 8b, and the two phenyl
groups occupied quasi-axial positions in the crystal. The dihedral
angles of the phenyl groups were 76.6° and 76.1° (front view in
Figure 4). Lippard and co-workers have previously reported the
isolation of (rac)-5c from a mixture of anti-5c (racemic) and syn-
5c (meso), and the X-ray structure of racemic palladium complex
has also been revealed.8 This structure also suggested that two
phenyl groups were located at quasi-axial positions.
Bond Distances
Pd(1)-P(1)
Pd(1)-P(2)
2.2476(8)
2.2326(8)
Pd(1)-Cl(2)
Pd(1)-Cl(3)
2.3514(8)
2.3705(9)
Bond Angles
86.47(3)
P(1)-Pd(1)-P(2)
P(2)-Pd(1)-Cl(2)
Cl(2)-Pd(1)-Cl(3)
Cl(3)-Pd(1)-P(1)
C(30)-P(1)-Pd(1)
C(14)-P(1)-Pd(1)
C(25)-P(1)-C(14)
C(30)-P(1)-C(25)
C(10)-P(2)-Pd(1)
C(11)-P(2)-Pd(1)
C(9)-P(2)-C(10)
C(11)-P(2)-C(9)
104.6(1)
106.5(1)
118.2(1)
107.3(1)
101.9(1)
106.9(1)
88.83(3)
92.78(3)
92.22(3)
108.2(1)
110.4(1)
1,4-addition of arylboronic acids to 2-cyclopentenone was
examined in the presence of several palladium/P-stereogenic
bisphosphine/AgSbF6 catalytic systems; the results are summa-
rized in Table 5. An appropriate catalyst combined with P-stereo-
genic bisphosphine was critically important for the success of the
reaction. For example, no catalytic activity of PdCl2(cod)/(S,S)-
5a was observed (run 1 in Table 5). Considering that palladium
complex 8a did not form in the complexation study described
above, no active species for the 1,4-addition were generated in
situ in the PdCl2(cod)/(S,S)-5a/AgSbF6 catalytic system. The
use of 8b and 8c dramatically increased the catalytic activity to
afford the corresponding (R)-3-phenylcyclopentanone with an
expected absolute configuration in 90% (85% ee, run 2) and 81%
(30% ee, run 6) isolated yields, respectively. Quasi-equatorial
In a subsequent study, we focused on the application of the
P-stereogenic diphosphacrown to a chiral ligand for performing
transition metal-catalyzed asymmetric reactions. Among them,
we selected catalytic asymmetric 1,4-additions,16-19 because
palladium-catalyzed asymmetric 1,4-additions of arylboronic acids
to R,β-unsaturated ketones are relatively rare.17 Asymmetric
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Table 4. Selected Bond Distances (Å) and Angles (deg) in 8c
Scheme 6. Synthesis of Palladium Complexes 9 and 11
Bond Distances
Pd(1)-P(1)
Pd(1)-P(2)
2.230(1)
2.237(1)
Pd(1)-Cl(1)
Pd(1)-Cl(2)
2.367(1)
2.363(1)
Bond Angles
85.66(4)
P(1)-Pd(1)-P(2)
P(1)-Pd(1)-Cl(2)
Cl(2)-Pd(1)-Cl(1)
Cl(1)-Pd(1)-P(2)
C(1)-P(1)-Pd(1)
C(14)-P(1)-Pd(1)
C(14)-P(1)-C(15)
C(15)-P(1)-C(1)
C(2)-P(2)-Pd(1)
C(21)-P(2)-Pd(1)
C(21)-P(2)-C(3)
C(3)-P(2)-C(2)
105.6(2)
106.7(2)
108.8(1)
112.6(1)
103.4(2)
109.6(2)
89.98(4)
92.26(4)
92.30(4)
109.4(2)
114.1(2)
Table 5. Asmmetric 1,4-Addition of Boronic Acids to
2-Cyclopentenone
were obtained in high yields (91-95%) with good enantios-
electivities (72-82% ee).
temp/°C yielda/% % eeb
’ CONCLUSION
run
Ar
Pd catalyst
In summary, we have shown the practical synthesis of novel
enantiomerically pure crown ether derivatives, i.e., (S,S)-15-
diphosphacrown-5, (S,S)-18-diphosphacrown-6, (R,R)-18-di-
phosphacrown-6, and (S,S)-21-diphosphacrown-7, consisting
of the P-stereogenic phosphine and ethyleneoxy units in the
ring. These derivatives were prepared from P-stereogenic bi-
sphosphine-boranes as key precursors; therefore, the obtained
diphosphacrowns were also enantiomerically pure. The obtained
P-stereogenic diphosphacrowns have a chiral ring structure as
well as chiral heteroatoms (phosphorus atoms) that interact
directly with guest ions and molecules. Their palladium(II)
complexes were readily obtained and characterized by X-ray
crystallography. The bisphosphine unit was chelate-coordinated
to palladium(II) outside of the ring, and palladium(II) adopted
the typical square-planar structure. Two phenyl groups substi-
tuted at chiral phosphorus atoms in the palladium complexes
were located at two diagonal quadrants, which occupied quasi-
equatorial and quasi-axial positions, respectively. We applied the
P-stereogenic diphosphacrowns to the chiral ligand for the
palladium-catalyzed asymmetric 1,4-addition of arylboronic acids
to cyclopentenone. This reaction proceeded to afford the corre-
sponding 1,4-addition products in high yield with good enantios-
electivities. Further efforts are now being made to clarify the
reaction intermediates as well as to design the P-stereogenic
diphosphacrown ligand for enhancing the enantioselectivities;
the results will be reported in the near future. The complexation
of the P-stereogenic diphosphacrowns to various transition
metals and their application to transition metal-catalyzed asym-
metric reactions are also underway.
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
PdCl2(cod), (S,S)-5a
30
30
0
trace
90
8b
85 (R)
87 (R)
83 (R)
92 (R)
30 (R)
14 (R)
5 (S)
8b
89
8b/AgOTfc
8b/AgOTfc
30
0
quant
36
8c
9
30
30
30
30
30
30
30
81
54
11
80
4-MeO-Ph 8b
94
82 (R)
72 (R)
78 (R)
72 (R)
10 4-CF3-Ph
11 4-Br-Ph
12 2-Me-Ph
8b
8b
8b
91
95
94
a Isolated yield. b Enantiomeric excess was determined by HPLC with a
Daicel Chiralcel OB-H column (0.46 cm ꢀ 25 cm ꢀ 2), using
2-propanol/hexane (v/v = 2:98) as an eluent column. c AgOTf (6 mol %)
was used instead of AgSbF6.
phenyl groups of 8b blocked the open spaces of diagonal
quadrants more effectively than the quasi-axial phenyl groups
of 8c, as shown in Figures 3 and 4, leading to a higher percent ee.
AgOTf was also used as an additive, which provided (R)-3-
phenylcyclopentanone quantitatively (83% ee at 30 °C, run 4)
and in 36% yield (92% ee at 0 °C, run 5). Complexes 9 and 11
were prepared from (S,S)-1-BH3 and (S,S)-10-BH3, respec-
tively (Scheme 6), and their catalytic performance was also
examined. The 1,4-addition catalyzed by 9 proceeded to afford
(R)-3-phenylcyclopentanone in 54% (14% ee, run 7) yield,
while the reaction catalyzed by 11 yielded (S)-3-phenylcyclo-
pentanone in 80% (5% ee, run 8). This suggests that the
methoxyethyl (-CH2CH2OMe) arms substituted at the phos-
phorus atoms in 11 occupy the other open spaces and change
the face selectivities of 2-cyclopentenone. The present catalytic
system was also applied to the 1,4-addition of other arylboron
reagents (runs 9-12); the corresponding 1,4-addition products
’ EXPERIMENTAL SECTION
Materials. THF and Et2O were purchased and purified by passage
through purification column under Ar pressure.20 Dehydrated grade
solvents of toluene and CHCl3 were purchased and used without further
purification. N,N,N0,N0-Tetramethylethylenediamine (TMEDA) and
1800
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The Journal of Organic Chemistry
ARTICLE
(-)-sparteine were purchased and distilled from KOH under Ar atmo-
sphere. 1,4-Diazabicyclo[2.2.2]octane (DABCO), sec-BuLi (1.0 M in
Hz, 6H), 2.11 (m, 4H), 2.30 (m, 2H), 2.51 (m, 2H), 3.6-3.8 (m, 10H), 3.86
(m, 2H), 7.4-7.5 (m, 6H), 7.70 (m, 4H) ppm; 13C NMR (CDCl3, 100.3
MHz) δ 19.3 (d, JC-P = 33.0 Hz), 27.0 (d, JC-P = 34.8 Hz), 65.7, 70.3,
70.4, 127.8 (d, JC-P = 54.6 Hz), 128.8, 131.4, 131.7 ppm; 31P{1H} NMR
(CDCl3, 161.5 MHz) δ þ17.7 (br) ppm; HRMS (ESI) calcd for
C22H36O3B2P2 [M þ Na]þ 455.2223, found 455.2198. Anal. Calcd for
C22H36B2O4P2: C 61.15; H 8.40. Found: C 60.98; H 8.40.
cyclohexane and n-hexane solution), BH3 THF (1.0 M in THF), CuCl2,
3
aqueous NH3 (28%), NaH (60 wt % in mineral oil), diethylene glycol bis(p-
toluenesulfonate) 4a, triethylene glycol bis(p-toluenesulfonate) 4b, tetra-
ethylene glycol bis(p-toluenesulfonate) 4c, PdCl2(cod), AgSbF6, and
AgOTf were purchased and used without purification. 2-Cyclopentenone
and all arylboronic acids were also purchased and used without purification.
(S,S)-1,2-Bis(boranatophenylmethylphosphino)ethane (S,S)-1-BH3 was
prepared by the literature procedure10a with a minor modification.10b (S,S)-
1,2-Bis[boranatophenyl(2-hydroxyethyl)phosphino]ethane (S,S)-3-BH3
was prepared by the literature procedure9 with a minor modification; the
yield was improved by changing the molar ratio between sec-BuLi/TMEDA
and (S,S)-1-BH3. Dimethylphenylphosphine-borane 6-BH3 was pre-
pared according to the literature procedure.21 Although (S)-(2-hydro-
xyethyl)methylphenylphosphine-borane (S)-7-BH3 was prepared by
Ohashi, Imamoto, and co-workers,12 herein we describe our synthetic
procedure. Spectral data of all 1,4-addition products were matched with
the literature values.22 All reactions were performed under an Ar atmosphere,
using standard Schlenk techniques.
(S,S)-5b-BH3: 17% isolated yield; Rf 0.30 (hexane/EtOAc, v/v =
1:1); [R]25D þ62.7 (c 1.0 in CHCl3); 1H NMR (CDCl3, 399.2 MHz) δ
0.69 (br q, JH-B = 119.4 Hz, 6H), 2.14 (m, 4H), and 2.2-2.5 (m, 4H),
3.5-3.9 (m, 16H), 7.4-7.5 (m, 6H), 7.70 (m, 4H) ppm; 13C NMR
(CDCl3, 100.3 MHz) δ 19.2 (d, JC-P = 34.5 Hz), 26.5 (d, JC-P = 34.5
Hz), 65.6, 70.4, 70.6, 70.8, 127.5 (d, JC-P = 53.4 Hz), 128.9, 131.5, 131.9
ppm; 31P{1H} NMR (CDCl3, 161.5 MHz) δ þ16.5 (br) ppm; HRMS
(EI) calcd for C24H40B2O4P2 [M]þ 476.2588, found 476.2588. Anal.
Calcd for C24H40B2O4P2: C 60.54; H 8.47. Found: C 60.76; H 8.47.
(S,S)-5c-BH3: 20% isolated yield; Rf 0.1 (hexane/EtOAc: v/v =
1:2); [R]25D þ50.2 (c 0.5 in CHCl3); 1H NMR (CDCl3, 399.2 MHz) δ
0.69 (br q, JH-B = 96.1 Hz, 6H), 2.11 (m, 4H), and 2.30 (m, 4H), 3.5-3.8
(m, 20H), 7.4-7.5 (m, 6H), 7.70 (m, 4H) ppm; 13C NMR (CDCl3, 100.3
MHz) δ 19.3 (d, JC-P = 33.9 Hz), 26.3 (d, JC-P = 34.7 Hz), 65.5, 70.31,
70.34, 70.5, 70.8, 127.3 (d, JC-P = 52.8 Hz), 128.8, 131.5, 131.8 ppm;
31P{1H} NMR (CDCl3, 161.5 MHz) δ þ16.3 (br) ppm; HRMS (ESI)
calcd for C26H44O5B2P2 [M þ Na]þ 543.2748, found 543.2740. Anal.
Calcd for C26H44O5B2P2: C 60.03; H 8.53. Found: C 59.76; H 8.35.
Synthesis of (S)-7-BH3. A solution of (-)-sparteine (6.9 mL,
30 mmol) in Et2O (150 mL) was cooled to -78 °C under Ar atmos-
phere. To this stirred solution was added by syringe sec-BuLi (1.0 M in
cyclohexane and n-hexane solution, 30 mL, 30 mmol). After 15 min of
stirring, a solution of dimethylphenylphosphine-borane 6-BH3 (3.8 g,
25 mmol) in Et2O (40 mL) was added dropwise, and the mixture was
stirred at -78 °C over 3 h. Dry CO2 gas was bubbled through the
reaction mixture, then it was allowed to gradually warm to room
temperature. After an additional 2 h of stirring at room temperature,
the reaction mixture was acidified with 2 N HCl and extracted with
EtOAc (3 ꢀ 100 mL). The organic layer was washed with brine and
dried over MgSO4. After filtration of MgSO4, the solvent was dried in
Synthesis of (S,S)-3-BH3. A solution of TMEDA (1.6 mL, 11
mmol) in THF (100 mL) was cooled to -78 °C under Ar atmosphere.
To this stirred solution was added by syringe sec-BuLi (1.0 M in
cyclohexane and n-hexane solution, 11 mL, 11 mmol). After 15 min, a
solution of (S,S)-1-BH3 (1.51 g, 5.0 mmol) in THF (50 mL) was added
dropwise, and the mixture was stirred at -78 °C over 3 h. Dry CO2 gas was
bubbled through the reaction mixture, which was allowed to gradually warm
to room temperature. After an additional 2 h of stirring at roomtemperature,
the reaction mixture was acidified with 2 N HCl and extracted with EtOAc
(3 ꢀ 100 mL). The organic layer was washed with brine and dried over
MgSO4. After filtration of MgSO4, the solvent was dried in vacuo. To a
stirred solution of (S,S)-2-BH3 in THF (20 mL) was added BH3 THF
3
(1.0 M in THF, 30 mL, 30 mmol) at 0 °C under Ar atmosphere. The
reaction mixture was stirred for 2 h at room temperature and poured into
iced water. After extraction with EtOAc, the organic layer was washed with 2
N HCl and brine and dried over MgSO4. MgSO4 was removed by filtration,
and the solvent was dried in vacuo. The residue was subjected to column
chromatography on SiO2 with hexane/EtOAc (v/v = 1:1) as an eluent to
vacuo. To the residue was added BH3 THF (1.0 M in THF, 40 mL, 40
3
mmol) at 0 °C under Ar atmosphere. The reaction mixture was stirred
for 2 h at room temperature and poured into iced water. After extraction
with EtOAc, the organic layer was washed with 2 N HCl and brine and
dried over MgSO4. MgSO4 was removed by filtration, and the solvent
was dried in vacuo. The residue was subjected to column chromatog-
raphy on SiO2 with hexane/EtOAc (v/v = 3:1) as an eluent. Recrys-
tallization from toluene and hexane (good and poor solvent,
respectively) gave (S)-7-BH3 (3.21 g, 17.6 mmol, 71%, 87% ee) as a
colorless solid: Rf 0.40 (hexane/EtOAc: v/v = 1:1); 1H NMR (CDCl3,
399.2 MHz) δ 0.78 (br q, JH-B = 98.4 Hz, 3H), 2.07 (br, 1H), 2.18 (m,
2H), 3.86 (m, 2H), 7.50 (m, 3H), 7.75 (t, J = 8.1 Hz, 2H) ppm; 13C
give (S,S)-3-BH3 (1.00 g, 2.8 mmol, 55%) as a colorless solid: Rf 0.10
1
(hexane/EtOAc, v/v = 1:1); [R]22 þ9.1 (c 1.0 in CHCl3); H NMR
D
(CDCl3, 399.2 MHz) δ 0.73 (br q, JH-B = 118.4 Hz, 6H), 1.89 (m, 2H),
and 2.1-2.3 (m, 8H), 3.78 (m, 2H), 3.86 (m, 2H), 7.48 (t, J = 7.6 Hz, 4H),
7.52 (t, J= 7.6 Hz, 2H), 7.61 (m, 4H) ppm; 13CNMR(CDCl3, 100.3MHz)
δ 19.5 (d, JC-P = 34.5 Hz), 29.1 (d, JC-P = 35.3 Hz), 57.4, 126.8 (d, JC-P
=
52.8 Hz), 129.1 (m), 131.9, 132.0 ppm; 31P{1H} NMR (CDCl3, 161.5
MHz) δ þ14.7 (q, JP-B = 54.8 Hz) ppm; HRMS (EI) calcd for
C18H30B2O2P2 [M - H]þ 361.1829, found 361.1832. Anal. Calcd for
C18H30B2O2P2: C 59.72; H 8.35. Found: C 59.34; H 8.21.
Synthesis of (S,S)-5a-c-BH3. A typical procedure is as follows. A
solution of (S,S)-3-BH3 (362 mg, 1.0 mmol) in THF (40 mL) was
added to a suspension of NaH (120 mg, 3 mmol, 60 wt % in mineral oil;
after washing with dry hexane at room temperature) at room temperature
under Ar atmosphere. After being stirred for 30 min, the mixture was
refluxed for 2 h and cooled to room temperature. A solution of diethylene
glycol bis(p-toluenesulfonate) 4a (415 mg, 1.0mmol) inTHF(10mL) was
added by a syringe, and the reaction mixture was stirred for 48 h at room
temperature. H2O (10 mL) was added to the reaction mixture, and
extraction with EtOAc (3 ꢀ 50 mL) was carried out. The organic layer
was dried over MgSO4. MgSO4 was removed by filtration, and the solvent
was dried in vacuo. The residue was subjected to column chromatography
on SiO2 with hexane/EtOAc (v/v = 1:1) as an eluent to give (S,S)-5a-BH3
(63 mg, 0.14 mmol, 14%) as a colorless solid.
NMR (CDCl3, 100.3 MHz) δ 11.7 (d, JC-P = 39.6 Hz), 30.8 (d, JC-P
=
35.5 Hz), 57.7, 129 (m), 131 (m) ppm; 31P{1H} NMR (CDCl3, 161.5
MHz) δ þ4.4 (q, JP-B = 63.0 Hz) ppm; HRMS (EI) calcd for
C9H16BOP [M-H]þ 181.0954, found 181.0948.
Synthesis of (R,R)-3-BH3. A solution of TMEDA (2.2 mL,
15 mmol) in THF (150 mL) was cooled to -78 °C under Ar atmos-
phere. To this stirred solution was slowly added by syringe sec-BuLi (1.0
M in cyclohexane and n-hexane solution, 15 mL, 15 mmol). After 15
min, a solution of (S)-7-BH3 (1.09 g, 6.0 mmol) in THF (20 mL) was
added dropwise, and the mixture was stirred at -78 °C over 3 h. CuCl2
(1.21 g, 9.0 mmol) was added in one portion, and the mixture was
allowed to slowly warm to room temperature. After 6 h, the reaction was
quenched by the addition of 28% aqueous NH3 (20 mL) and extracted
with EtOAc (3 ꢀ 80 mL). The combined extracts were washed with 5%
aqueous NH3, 2 M HCl, and brine, and then dried over MgSO4. After
(S,S)-5a-BH3: Rf 0.30 (hexane/EtOAc, v/v = 1:1); [R]25D þ103.0 (c
0.5 in CHCl3); 1H NMR (CDCl3, 399.2 MHz) δ 0.69 (br q, JH-B = 127.7
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The Journal of Organic Chemistry
ARTICLE
filtration of MgSO4, the solvent was evaporated and dried in vacuo. The
residue was subjected to column chromatography on SiO2 with hexane/
EtOAc (v/v = 1:1) as an eluent. The repeated recrystallization (three or
four times) from toluene and hexane (good and poor solvent, re-
spectively) gave optically pure (R,R)-3-BH3 (0.39 g, 1.08 mmol,
36%, >99% ee) as a colorless solid: [R]25D -8.9 (c 1.0 in CHCl3).
Synthesis of (R,R)-5b-BH3. (R,R)-5b-BH3 was obtained from
(R,R)-3-BH3 by the same procedure as (S,S)-5b-BH3 in 22% isolated
yield as a colorless solid: [R]18D -67.6 (c 1.0 in CHCl3).
HRMS (ESI) calcd for C16H20Cl2P2Pd [M þ Na]þ 472.9350, found
472.9344. The specific rotation value of 9 could not be obtained because
of its low solubility and the relatively small value.
11: 21% isolated yield as a colorless solid; [R]20 -83.7 (c 0.1 in
D
CHCl3); 1H NMR (CDCl3, 399.2 MHz) δ 2.2-2.6 (m, 6H), 2.73 (m,
2H), 2.96 (s, 6H), 3.62 (m, 2H), 4.08 (m, 2H), 7.50 (m 6H), 8.06 (m,
4H) ppm; 13C NMR (CDCl3, 100.3 MHz) δ 27.6 (d, JC-P = 45.4 Hz),
29.5 (d, JC-P = 32.2 Hz), 58.5, 68.7, 128, 129.1, 131.9, 133.0 ppm;
31P{1H} NMR (CDCl3, 161.5 MHz) δ 71.4 ppm; HRMS (ESI) calcd
for C20H28Cl2O2P2Pd [M þ Na]þ 560.9874, found 560.9869.
General Procedure for the Pd-Catalyzed Aymmetric 1,4-
Addition Reaction. A mixture of Pd catalyst (3 μmol), AgSbF6 (6
μmol), and THF (0.25 mL) was placed in a flask under an Ar
atmosphere. After the mixture was stirred at room temperature for 10
min, 2-cyclopentenone (8.4 μL, 0.10 mmol) and arylboronic acid (0.15
mmol) were added. Then degassed H2O (0.05 mL) and THF (0.25 mL)
were added. After being stirred for 24 h at 30 °C under Ar atmosphere,
the reaction mixture was dried over Na2SO4. The solution was subjected
to flash column chromatography on Al2O3 with CH2Cl2 as an eluent.
The solvent was removed in vacuo, and the residue was subjected to
preparative TLC on SiO2 with hexane/EtOAc (v/v = 3:1) as an eluent to
yield 3-arylcyclopentanone.
Synthesis of 8b and 8c. A typical procedure is as follows. A
suspension of (S,S)-5b-BH3 (95.2 mg, 0.20 mmol) and DABCO
(224.4 mg, 2.0 mmol) in degassed toluene (10 mL) was heated to
55 °C under Ar atmosphere. After 13 h of stirring, the solvent was dried
in vacuo. The residue was dissolved in degassed EtOAc (100 mL) and
plugged through SiO2 column under Ar atmosphere. The solvent was
dried in vacuo, and the residue was dissolved in degassed CHCl3. To this
solution was added PdCl2(cod) (68.5 mg, 0.24 mmol) in one portion.
After the solution was stirred for 15 h at 55 °C under Ar atmosphere, the
solvent was dried in vacuo. The residue was washed with toluene and
hexane to give 8b (85.9 mg, 0.14 mmol, 69%) as a colorless solid.
8b: [R]22D -122.6 (c 1.0 in CHCl3); 1H NMR (CDCl3, 399.2 MHz)
δ 2.70-2.9 (m, 6H), 3.0-3.7 (m, 18H), 7.48 (m, 6H), 8.22 (t, J = 8.0
Hz, 4H) ppm; 13C NMR (CDCl3, 100.3 MHz) δ 27.7-28.6 (m), 66.1,
70.0, 70.2, 70.9, 128.5-129.1 (m), 131.4, 133.4 (m) ppm; 31P{1H}
NMR (CDCl3, 161.5 MHz) δ þ72.1 ppm; HRMS (EI) calcd for
C24H34Cl2O4P2Pd [M - Cl]þ 589.0656, found 589.0656. Anal. Calcd
for C24H34Cl2O4P2Pd: C 46.06; H 5.48. Found: C 45.96; H 5.43.
8c: 74% isolated yield; [R]22D -110.0 (c 0.5 in CHCl3); 1H NMR
(CDCl3, 399.2 MHz) δ 2.25 (m, 2H), 2.71 (m, 2H), 2.9-3.1 (m, 3H),
3.1-3.8 (m, 21H), 7.51 (m, 6H), 8.27 (m, 4H) ppm; 13C NMR (CDCl3,
100.3 MHz) δ 27.3 (d, J = 42.1 Hz), 29.9 (d, J = 33.1 Hz), 66.0, 69.6,
70.1, 70.6, 71.4, 126.1 (d, J = 50.5 Hz), 129.0, 131.7, 134.0 ppm; 31P{1H}
NMR (CDCl3, 161.5 MHz) δ þ71.0 ppm; HRMS (ESI) calcd for
C26H38Cl2O5P2Pd [M - Cl]þ 633.0918, found 633.0922. Anal. Calcd
for C26H38Cl2O5P2Pd: C 46.62; H 5.72. Found: C 45.74; H 5.29.
Synthesis of (S,S)-10-BH3. A solution of (S,S)-3-BH3
(181 mg, 0.5 mmol) in THF (10 mL) was added to a suspension of
NaH (80 mg, 2.0 mmol, 60 wt % in mineral oil; after washing with dry
hexane at room temperature) at room temperature under Ar atmo-
sphere. After the solution was stirred for 1.5 h at room temperature, MeI
(150 μL, 2.5 mmol) was added by syringe, and the reaction mixture was
stirred for 12 h at room temperature. HCl (aq) (1 N, 10 mL) was added
to the reaction mixture, and extraction with EtOAc (3 ꢀ 50 mL) was
carried out. The organic layer was dried over MgSO4. MgSO4 was
removed by filtration, and the solvent was dried in vacuo. The residue
was subjected to flash column chromatography on SiO2 with hexane/
EtOAc (v/v = 1:1) as an eluent to give (S,S)-10-BH3 as a colorless solid
quantitatively: Rf 0.5 (hexane/EtOAc: v/v = 1:1); [R]25D þ31.5 (c 0.5 in
CHCl3); 1H NMR (CDCl3, 399.2 MHz) δ 0.67 (br q, JH-B = 115.8 Hz,
3H), 1.92 (m, 2H), 2.1-2.3 (m, 6H), 3.25 (s, 6H), 3.43 (m, 2H), 3.61
(m, 2H), 7.44 (t, J = 7.6 Hz, 4H), 7.51 (t, J = 7.6 Hz, 2H), 7.61 (m, 4H)
ppm; 13C NMR (CDCl3, 100.3 MHz) δ 19.4 (d, JC-P = 34.7 Hz), 26.5
(d, JC-P = 35.5 Hz), 58.5, 66.8, 127.4, 128.9, 131.7, 131.9 ppm; 31P{1H}
NMR (CDCl3, 161.5 MHz) δ þ16.1 (m) ppm; HRMS (ESI) calcd for
C20H34O2B2P2 [M - H]þ 389.2142, found 389.2144. Anal. Calcd for
C20H34O2B2P2: C 61.59; H 8.79. Found: C 61.42; H 8.54.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedure and
b
spectral data for all new compounds and X-ray crystallographic
data for (S,S)-5a-BH3, (S,S)-5b-BH3, 8b, and 8c and the
corresponding CIF files. This material is available free of charge
via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Y.M.: phone þ81-75-383-2610; fax þ81-75-383-2607; e-mail:
ymo@chujo.synchem.kyoto-u.ac.jp. Y.C.: phone þ81-75-383-
2604; fax þ81-75-383-2605; e-mail chujo@chujo.synchem.kyo-
to-u.ac.jp.
’ ACKNOWLEDGMENT
This research was supported by Grant-in-Aid for Challenging
Exploratory Research (No. 21655049) from the Japan Society for
the Promotion of Science (JSPS) and Grant-in-Aid for the Global
COE Program, “International Center for Integrated Research
and Advanced Education in Materials Science” from the Ministry
of Education, Culture, Sports, Science and Technology (MEXT)
of Japan. Financial support from The Kurata Memorial Hitachi
Science and Technology Foundation is also gratefully acknowl-
edged. The authors are grateful to Dr. Ryo Shintani and Mr.
Momotaro Takeda, Department of Chemistry, Graduate School
of Science, Kyoto University, for HPLC analyses and valuable
discussion.
’ REFERENCES
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Synthesis of 9 and 11. Complexes 9 and 11 were obtained
from (S,S)-1-BH3 and (S,S)-10-BH3 by the same procedure as 8b,
respectively.
(2) (a) Crown Ethers and Analogous Compounds, Studies in Organic
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1
9: 47% isolated yield as a colorless solid; H NMR (CDCl3, 399.2
MHz) δ 1.79 (m, 2H), 2.13 (d, JH-P = 12.4 Hz, 6H), 2.42 (m, 2H), 2.54
(m, 2H), 7.5 (m, 6H), 8.0 (m, 4H) ppm; 13C NMR (CDCl3, 100.3
MHz) δ 14.7 (d, JC-P = 34.7 Hz), 29.0 (d, JC-P = 47.9 Hz), 127, 129.4,
132.4, 132.8 ppm; 31P{1H} NMR (CDCl3, 161.5 MHz) δ 60.8 ppm;
1802
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(d) Crown Compounds: Toward Future Applications; Cooper, R. S., Ed.;
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(13) Its optical purity (>99% ee) was confirmed by HPLC with
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(14) The corresponding platinum complex was also obtained by the
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