Design and synthesis of chiral 1,10-phenanthroline ligand, and application in palladium catalyzed asymmetric 1,4-addition reactions

Article abstract of DOI:10.1016/j.tetlet.2017.08.041

Pd-catalyzed asymmetric 1,4-addition of phenylboronic acid to α,β-unsaturated carbonyl compounds was developed using chiral 1,10-phenanthroline derivative as ligand. Good yields (up to 97%), and high enantioselectivities (up to 97% ee) were achieved.

Full text of DOI:10.1016/j.tetlet.2017.08.041

Accepted Manuscript
Design and synthesis of chiral 1,10-phenanthroline ligand, and application in
palladium catalyzed asymmetric 1,4-addition reactions
Masafumi Tamura, Hayato Ogata, Yuu Ishida, Yasunori Takahashi
PII:
S0040-4039(17)31048-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.08.041
TETL 49231
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
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10 August 2017
17 August 2017
Please cite this article as: Tamura, M., Ogata, H., Ishida, Y., Takahashi, Y., Design and synthesis of chiral 1,10-
phenanthroline ligand, and application in palladium catalyzed asymmetric 1,4-addition reactions, Tetrahedron
Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.08.041
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Tetrahedron Letters
Design and synthesis of chiral 1,10-phenanthroline ligand, and application in
palladium catalyzed asymmetric 1,4-addition reactions
Masafumi Tamura,* Hayato Ogata, Yuu Ishida, Yasunori, Takahashi
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai Sakado, Saitama 350-0295, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Pd-catalyzed asymmetric 1,4-addition of phenylboronic acid to ,-unsaturated carbonyl
compounds was developed using chiral 1,10-phenanthroline derivative as ligand. Good yields
(up to 97%), and high enantioselectivities (up to 97% ee) were achieved.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
Chiral 1,10-phenanthroline ligand
Palladium catalyzed asymmetric 1,4-addition
reactions
Flavanone
8
and supramolecular chemistry. Because of their structural
rigidity, and hydrophobicity), 1,10-phenanthroline derivatives
and their metal complexes are currently used, in molecular
1
. Introduction
9
10
recognition and sensing, DNA/RNA binding/cleavage,
Transition metal-catalyzed asymmetric reactions are a very
1
1
molecular self-assembling, etc. Therefore, it is surprising that
despite the well-known coordination properties of 1,10-
phenanthroline, very few reports have been published on the
application of phenanthroline derivatives as chiral ligands for
important area of organic synthesis research and its focus has
been on the design and synthesis of highly efficient chiral ligands
as keys to obtaining highly reactivity and enantioselectivity.
Through careful fine-tuning of steric and electronic properties, a
chiral ligand’s coordination with a metal center can easily be
modulated, so as to create a chiral environment within the metal-
ligand complex that favors the formation of highly reactivity and
1
2
asymmetric catalysis.
In an attempt to design chiral phenanthroline ligands for
asymmetric catalysis, we focused on functionalizing the
peripheral region of the phenanthroline backbone, leaving the
aromaticity and, thus, the planarity of all three rings intact
1
enantioselectivity in a given reaction.
The use of nitrogen-based chiral ligands has become
extremely popular in asymmetric metal catalysis, which is based
on efficient and well-documented coordination to late-transition
metals. Prominent examples in this respect include chiral
(
Figure 1). A notable property of phenanthroline derivatives is
their -electron deficiency, which makes them excellent -
acceptors capable of stabilizing metal ions in lower oxidation
states. Moreover, the planar -system and the three rings rigidify
the conformation, which simplifies the prediction of
phenanthroline metal complex structure. The chiral system
resulting from adding bulky and rigid chiral substituents close to
the nitrogen atom of the phenanthroline backbone, could provide
a transition state in a well-defined chiral environment. Because
fewer reaction intermediates must be taken into account, the rigid
structure of the ligand has the advantage of facilitating analysis
of ligand-metal-substrate interactions in mechanistic studies.
In this way, our design of the chiral phenanthroline ligand is
based upon the modification of the phenanthroline backbone
upon annulation with chiral bicyclo[3.3.0]octane framework
2
3
4
semicorrins, , bisoxazolines, , pyridine-2,6-bisoxazolines, , 2,2’-
5
6
bipyridines, , and quinolone- and pyridine-oxazolines, in
7
addition to various hybrid type ligands, all of which have proven
to provide excellent levels of enantioselectivity in various
reactions.
1
,10-Phenanthroline is also a classic chelating bidentate ligand
for transition metal ions. It has played an important role in the
development of coordination chemistry and continues to be of
considerable interest as
inorganic,
a versatile material for organic,
1
3
(
Figure
1).

Corresponding author. Tel.: +81-492-717885; fax: +81-492-717885; E-mail: tamuraty@josai.ac.jp

2
Tetrahedron Letters
1
8
according to the previously published procedure. Oxidation
of
Figure 1. Design of a chiral 1,10-phenanthroline derived ligand.
The chiral bicyclo[3.3.0]octane framework at the stereogenic
center is in close proximity to the coordination site, and upon
chelation, a substituent on the bicyclo[3.3.0]octane framework
could become stereogenic and transmit stereogenic information
from the ligand to the metal center. Therefore, substituents on the
bicyclo[3.3.0]octane framework are expected to have a strong
optical yield direct effect on reactions taking place in the
coordination sphere. For this reason, the rigid and planar chiral
scaffold of 1,10-phenanthroline-derived chiral ligands have
gained considerable attention. We envisaged that this relatively
rigid bicyclo[3.3.0]octane moiety could increase the asymmetric
induction ability of 1,10-phenanthroline-derived chiral ligands.
The ketal can be readily converted back to the ketone
functional group by deprotection, and there is possibility the
carbonyl group can convert to another functional group.
Therefore, the 1,10-phenanthroline-derived chiral ligand is
readily modified by variation of the substituents at the
bicyclo[3.3.0]octane framework (Figure 1).
Scheme 1. Reagents and conditions: (a) c.HNO , c.H SO ,
3
2
4
1
00 °C, recrystallization from hexaneAcOEt, 72% (b)
DMFDMA, DMF, 140 °C, 80% (c) NaIO , THF/H O, r.t.,
4
2
90% (d) Fe, c.HCl, AcOH/EtOH/H O, r.t., 86% (e) KOH,
2
EtOH, 90 °C, recrystallization from hexanebenzene
the aminoalkene 5 is accomplished with sodium periodate to
provide the ortho-nitro aldehyde 6 in good yield. Reduction of
the analogous nitro group to amine is carried out with powdered
iron. The Friedländer condensation of
bicyclo[3.3.0]octanone derivative (+)-7 under basic conditions
KOH, EtOH, 90 °C) provides the corresponding 1,10-
phenanthroline derived chiral ligand 1 in 53% yield after
2
with chiral
(
1
9
recrystallization from hexanebenzene.
Catalytic asymmetric conjugate addition of C-nucleophiles to
In terms of all the results summarized in Table 1, ligand 1
demonstrated considerable potential for catalytic asymmetric 1,4-
addition of PhB(OH)2 to 2-cyclohexen-1-one (8) with high
activity and enantioselectivity.

,-unsaturated carbonyl compounds is a powerful method of
synthesizing asymmetric C-C bonds. The combination of
rhodium catalysts and organoboronic acids has emerged as a
1
4
powerful and ideal catalytic system for 1,4-addition. A method
of 1,4-addition of organoboronic acids to ,-unsaturated
carbonyl compounds has been developed, and various research
groups have reported the use of metals that are less expensive
a
Table 1. Optimization of the reaction conditions
1
5
than rhodium.
In, 1995, Uemura reported using
palladium/SbCl3 to catalyze 1,4-addition to ,-unsaturated
1
6
carbonyl compounds, giving racemic products.
Miyaura,
Entry
Pd source
Solvent
Temp
C )
Time
(h)
Yield
(%)
ee
(%)
developed the method of arylboronic acids addition to ,-
b
c
(
unsaturated carbonyl compounds using chiral cationic palladium-
1
7
phosphine complexes as catalysts. Recently, as an example of
using nitrogen-based ligand in palladium-catalyzed asymmetric
1
2
3
4
5
6
7
8
Pd(OTf)
Pd(OTf)
Pd(OTf)
Pd(OTf)
Pd(OTf)
Pd(OTf)
Pd(OTf)
2
2
2
2
2
2
2
ClCH
ClCH
ClCH
ClCH
2
2
2
2
CH
CH
CH
CH
2
2
2
2
Cl/H
2
O
60
60
23
40
60
60
60
60
17
16
144
17
48
24
24
18
16
48
97
96
94
91
-
Cl
1
,4-addition reactions, Stoltz and Houk reported a combined
d
experimental and computational investigation on the mechanism
Cl/H
2
2
O
O
n.d.
6
d-h
of enantioselectivity.
Cl/H
56
0
90
-
CH
DMF/H
toluene/H
ClCH CH
3
OH
Herein, we report on the development of a method of 1,10-
phenanthroline-derived chiral ligand synthesis and the
application of this new ligand to the catalytic asymmetric 1,4-
addition to ,-unsaturated carbonyl compounds.
2
O
59
58
0
81
76
-
2
O
PdCl
Pd(OAc)2
Pd(OTf)
2
2
2
Cl/H
2
O
2
. Results and Discussions
9
ClCH CH Cl/H O 60
41
90
90
91
2
2
2
e
1
0
2
ClCH
2
CH
2
Cl/H
2
O
60
The studies commenced with the synthesis of the new 1,10-
a
phenanthroline-derived chiral ligand 1, which was obtained by
performing a Friedländer condensation of 8-aminoquinoline-7-
carbaldehyde (2) with chiral bicyclo[3.3.0]octanone derivative
Reactions were carried out with phenylboronic acid (0.50
mmol), 8 (0.25 mmol), Pd source (5 mol%), ligand 1 (6 mol%)
in solvent (1.0 ml), and H O (0.1 ml) at the indicated
temperature.
2
1
9
(+)-7 as shown in Scheme 1.
Recently, we have accomplished a practical synthesis of
b
Isolated yield.
chiral bicyclo[3.3.0]octane derivative (+)-7 for use as a chiral
c
d
e
14
1
3
Determined by HPLC (Chiralcel OD-H) or optical rotation .
building block. Synthesis of 2 begins with 7-methylquinoline
3), and straightforward nitration produces 4 in excellent yield
(
n.d. = not determined.
after recrystallization from hexaneAcOEt. The 7-methyl group
can then be functionalized by the Leimgruber-Batcho method
with N, N-dimethylformamide dimethyl acetal (DMFDMA) to
provide the corresponding N, N-dimethylamino alkene 5
Reaction performed with 1 mol% of catalyst.

Initially, 2-cyclohexen-1-one (8) was added to PhB(OH) (2.0
Therefore, we consider that C symmetry phenanthroline ligands
2
2
eq.) in the presence of 5 mol% Pd(OTf) , ligand 1 in H O (0.1
are difficult to modify at the metal coordination center in this
2
2
ml), and ClCH CH Cl (1.0 ml) at 60 ºC for 17 h, and the desired
reaction, and C symmetry chiral ligands on the phenanthroline
2
2
1
adduct 9 was readily delivered with 97% yield and 94% ee
scaffold would be a suitable catalyst.
2
0
(
Table 1, entry 1). The reaction afforded the desired conjugate
An X-ray crystallographic study is also provided in support of
a proposed model for asymmetric induction. Unfortunately,
though, as an X-ray crystal structure of the [Pd(ligand 1)](OTf)2
complex was not available, so X-ray crystallographic analysis
was carried out on a single crystal of [Pd(ligand 1)](OAc)
complex (16) (Scheme 2). The [Pd(ligand 1)](OAc) complex
addition product without traces of either the 1,2-addition product
or the Heck coupling product. On the basis of the above analysis,
the effects of solvent and temperature were investigated with 1 as
the ligand in the presence of Pd(OTf) . The reaction requires the
2
2
1
2
presence of water to hydrolyze boroxine and to be an adequate
the source of protons for catalyst turnover. However, the reaction
occurred in 96% yield in the absence of water, in 97% yield
when water was added to the boronic acid (Table 1, entry 2). We
speculated that when performed on a small scale, the reaction
requires only a small amount of moisture (such as might be
present in the reagent and/or on glassware) to proceed to
2
(
16) was prepared by mixing ligand 1 and Pd(OAc) in acetone,
2
22
followed by a recrystallization from acetoneCH Cl hexane.
2
2
6
f,h
completion.
When the temperature was lowered to 0 ºC, the reaction did
not proceed and no product was detected. The reaction can
proceed at 40 ºC, but not at 23 ºC for 5 days (Table 1, entry 3, 4).
The reaction did not proceed in toluene, donating solvents such
as CH OH, DMF and proceeded best in ClCH CH Cl (Table 1,
3
2
2
entry 57). In addition, we examined other Pd sources such as
PdCl2 and Pd(OAc) . However, the combination of PdCl ,
2
2
Pd(OAc) , and ligand 1 did not give good results (Table 1, entry
2
8
, 9). The catalyst loading could be decreased, and on a 1 mmol
scale, 90% yield, 91% ee was obtained with 1 mol% of catalyst
in 48 h (Table 1, entry 10).
Scheme 2. Synthesis of [Pd(ligand 1)](OAc) complex (16).
2
As in Figure 3, an square planar, mononuclear [Pd(ligand
)](OAc)2 complex (16) was identified in which ligand 1
coordinate the palladium center in a cis topology, affording a C1-
symmetric palladium complex.
To close the investigation into ligand structure and
asymmetric induction of this reaction, the reaction of 2-
cyclohexen-1-one (8) with PhB(OH)2 was screened in the
presence of other bidentate nitrogen ligands under optimized
conditions (Table 2).
1
Figure 3. The ORTEP diagram of complex (16) (thermal ellipsoids
a
Table 2. Screening of bidentate nitrogen ligands
correspond to 50% probability). Noncoordinating molecules have been
omitted for clarity (CCDC-1557225).
This stereocontrol model can be applied to predict the absolute
configurations of 1,4-addition products with the ligand 1-Pd
intermediate and an X-ray crystallographic study of [Pd(ligand
1
)](OAc)2 complex (16). The stereochemical pathways with
ligand 1 are rationalized in Figure 4.
a
Reactions were carried out with phenylboronic acid (0.50
mmol), 8 (0.25 mmol), Pd(OTf) (5 mol%), and ligand (6 mol%)
2
in ClCH CH Cl (1.0 ml), H O (0.1 ml) at 60 °C for 16 h.
2
2
2
Unfortunately, the chiral bis-oxazoline ligand (13, 14) scaffold
failed to afford any conversion to the desired conjugate addition
product. The best conversion was observed with ligands having a
bite angle similar to that of 2,2’-bipyridine (10), 1,10-
phenanthroline (11) and pyridine-oxazoline ligand (15), which
also feature a five-membered chelate ring. Increasing the bite
angle of the ligand should force the metal closer to the ligand
center, and any substrates bound to the metal will then also be
brought closer to the substituents on the two oxazolines. Also,
when comparing 2,2’-bipyridine (10) and 2,2’-biquinoline (12),
which also features a five-membered chelate ring, both benzene
rings of 2,2’-biquinoline (12) will move closer to the metal ion.
Figure 4. Proposed stereochemical pathway for the 1,4-addition of
phenylboronic acid to 2-cyclohexen-1-one (8) using ligand 1.
The conformationally rigid framework of the ligand 1-Pd
intermediate with stereocenters close to the donor nitrogen atoms
imposes a well-ordered chiral environment at the catalytic site.
1
8

4
Tetrahedron Letters
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003, 68, 4727-4742. (d) Lötscher, D.; Rupprecht, S.; Collomb,
Since the 1,4-addition product of the R form was obtained, the
2
transmetalation proceeded so as to avoid steric repulsion between
the group on the bicyclo[3.3.0]octane moiety and the
phenanthroline skeleton of the ligand 1 -Pd catalyst. Thus, the
initial coordination of the Pd catalyst might result in a trans
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between
the
phenyl
group
and
the
bicyclo[3.3.0]octane moiety of the ligand 1. The ligand 1-Pd
intermediate should have an open space at the first quadrant of
the vacant coordination site, because the bicyclo[3.3.0]octane
moiety of the ligand 1 blocks the fourth quadrant. The olefinic
double bond of 2-cyclohexen-1-one (8) coordinates to palladium,
in the Re face rather than the Si face fashion, and the double bond
undergoes migratory insertion, leading to a product with R
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1
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7
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1
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PhB(OH)2
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2
3
9
6% yield with 97% ee.
8
9
.
.
Bencini, A.; Lippolis, V. Coord. Chem. Rev. 2010, 254, 2096-
2
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chromone (17) using ligand 1.
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3
. Conclusion
3
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In summary, we described the synthesis of chiral
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was an efficient catalyst for the palladium-catalyzed asymmetric
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1
,4-addition of phenyl boronic acid to enones with ee up to 97%.
Further studies on substrate and boronic acid scope, the
development of efficient ligands are in progress.
(
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This work was supported in part by a grant from Grant-Aid
for Scientific Research, Office of the President of Josai
University. We thank S. Yamaguchi and H. Mitsuhashi of the
Center for Instrumental Analysis at Josai University for NMR
and mass measurements.
3
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Chen, J.; Lu, X.; Lou, W.; Ye, Y.; Jiang, H.; Zeng, W. J. Org.
Chem. 2012, 77, 8541-8548. (n) Yang, G.; Zhang, W. Angew.
Chem. Int. Ed. 2013, 52, 7540-7544.
2
3
.
.
1
990, 31, 6005-6008. (b) Evans, D. A.; Woerpel, K. A.; Hinman,
M. M.; Faul, M. M. J. Am. Chem. Soc. 1991, 113, 726-728. (c)
Evans, D. A.; Miller, S. J.; Lectka, T. J. Am. Chem. Soc. 1993,
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15, 6460-6461. (d) Evans, D. A.; Barnes, D. M.; Johnson, J. S.;
Lectka, T.; von Matt, P.; Miller, S. J.; Murry, J. A.; Norcross, R.
D.; Shaughnessy, E. A.; Campos, K. R. J. Am. Chem. Soc. 1999,
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21, 7582-7594. (e) Gant, T. G.; Noe, M. C.; Corey, E. J.
Tetrahedron Lett. 1995, 36, 8745-8748. (f) Bedekar, A. V.;
Koroleva, E. B.; Andersson, P. G. J. Org. Chem. 1997, 62, 2518-
2
526. (g) Ghosh, A. K.; Mathivanan, P.; Cappiello, J.
Tetrahedron: Asymmetry 1998, 9, 1-45.
4
5
.
.
Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.;
Kondo, M.; Itoh, K. Organometallics 1989, 8, 846-848.
(a) Bolm, C.; Zehnder, M.; Bur, D. Angew. Chem. Int. Ed. 1990,
2
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9, 205-207. (b) Ito, K.; Tabuchi, S.; Katsuki, T. Synlett 1992,
75-576. (c) Malkov, A. V.; Pernazza, D.; Bell, M.; Bella, M.;

1
1
8. (a) Riesgo, E. C.; Jin, X.; Thummel, R. P. J. Org. Chem. 1996,
1, 3017-3022. (b) Siu, J.; Baxendale, I. R.; Ley, S. V. Org.
A Schlenk tube was charged with stir bar, Pd(OTf)
0.0125 mmol), ligand 1 (5.9 mg, 0.015 mmol), and the solids were
dissolved in ClCH CH Cl (1.0 ml), H O (0.1 ml) and the solution
was flushed with argon. After the yellow solution stirred for 5 min
at ambient temperature, phenyl boronic acid (61 mg, 0.5 mmol)
was added and followed by addition of 2-cyclohexen-1-one (8) (24
mg, 0.25 mmol). The resulting mixture was then stirred at 60 °C in
an oil bath for 16 h. Upon complete consumption of the starting
material (monitored by TLC, 5:1 hexane/EtOAc) the reaction
2
(4.2 mg,
6
Biomol. Chem. 2004, 2, 160-167. (c) Gladiali, S.; Chelucci, G.;
Mudadu, M. S.; Gastaut, M. A.; Thummel, R. P. J. Org. Chem.
2
2
2
2
001, 66, 400-405. (d) Chi-Ying, H.; Tie-Lin, W.; Zhiqiang, S.; P.
Thummel, R. Tetrahedron 1994, 50, 10685-10692.
9. Preparation of (3’a’S,6’a’S)-(hexahydro-2’’H-spiro[1’’,5’’-
dihydro-2’’,4’’-benzodioxepin-3’’,6’-pentalenyl])-[1,2-b]-1,10-
phenanthroline (1)
Into a 50 ml sealed tube, equipped with magnetic stirrer under an
atmosphere of argon was introduced a mixture of 8-
aminoquinoline-7-carbaldehyde (2) (500 mg, 2.9 mmol), (+)-7
mixture was eluted through short column of SiO
the eluent, and concentrated in vacuo. The crude residue was
purified by chromatography (SiO , 10:1 hexane/AcOEt) to provide
2
, using AcOEt as
2
(
750 mg, 2.9 mmol), and saturated ethanolic KOH (120 mg) in
absolute EtOH (4.0 ml), and the solution was 90 °C for 16 h. The
course of the reaction was followed by TLC on SiO eluting with
0:1 CH Cl /MeOH (R = 0.45). After cooling, the mixture
partitioned between CH Cl and water. The combined organic
phases were washed with brine, and dried over anhydrous Na
The solvent was removed under reduced pressure, and the residue
was purified by SiO column chromatography (SiO , 20:1
CH Cl /MeOH) to afford the title compound 1 (743 mg, 65%).
Recrystallization from hexane/benzene provided 1 as a white
solid; mp. 140-141 °C, TLC R = 0.45 (10:1 CH Cl /MeOH);
); IR (film) 2975, 2870, 1105 cm ; H
) 1.65-1.90 (m, 2H, C5’-H), 2.19-2.24
m, 2H, C6’-H), 3.01-3.07 (dd, J = 1.4, 16.9 Hz, 1H, C3’-H), 3.35-
the 3-phenylcyclohexanone (9) as colorless oil (39.8 mg, 0.23
mmol). The enantiomeric ratio was determined by HPLC using a
chiral column (Daisel Chiralcel OD-H), hexane/2-propanol 98:2,
0.5 ml/min, 254 nm, 29.7 min (minor), 30.7 min (major).
21. Tokunaga, Y.; Ueno, H.; Shimomura, Y. Heterocycles 2007, 74,
219-223.
2
1
2
2
f
2
2
2
4
SO .
2
22. CCDC-1557225 [for [Pd(ligand 1)](OAc) complex (16)] contain
2
2
the supplementary crystallographic data for this article. These data
can be obtained free of charge from The Cambridge
Crystallograohic Data Centre via
2
2
f
2
2
www.ccdc.cam.ac.uk/data_request/cif.
20
-1 1
[
]
D
-153 (c 1.07, CHCl
3
23. The typical experiment for the 1,4-addition of phenyl boronic acid
to chromone (17):
NMR (400 MHz, CDCl
(
3
4
3
A Schlenk tube was charged with stir bar, Pd(OTf)
0.0125 mmol), ligand 1 (5.9 mg, 0.015 mmol), and the solids were
dissolved in ClCH CH Cl (1.0 ml), H O (0.1 ml) and the solution
2
(4.2 mg,
.39 (m, 1H, C4’-H), 3.46-3.53 (dd, J = 9.8, 16.9 Hz, 1H, C3’-H),
.23 (d, J = 8.8 Hz, 1H, C7’-H), 5.06 (dd, J =2.3, 14.8 Hz, 2H,
2
2
2
OCH
Hz, 1H, OCH
2
Ar), 5.42 (d, J = 14.8 Hz, 1H, OCH
2
Ar), 5.63 (d, J = 15.3
was flushed with argon. After the yellow solution stirred for 5 min
at ambient temperature, phenyl boronic acid (61 mg, 0.5 mmol)
was added and followed by addition of chromone (17) (36.5 mg,
0.25 mmol). The resulting mixture was then stirred at 60 °C in an
oil bath for 17 h. Upon complete consumption of the starting
material (monitored by TLC, 5:1 hexane/EtOAc) the reaction
2
Ar), 7.10-7.19 (m, 4H, ArH), 7.57 (dd, J = 4.3, 8.1
Hz, 1H, phenanthrolineH), 7.73 (d, J = 8.8 Hz, 2H,
phenanthrolineH), 7.97 (s, 1H, phenanthrolineH), 8.20 (dd, J =
1
.8, 8.1 Hz, 1H, phenanthrolineH) , 9.16 (dd, J = 1.8, 4.3 Hz, 1H,
1
3
phenanthrolineH); C NMR (100 MHz, CDCl
2.2 (CH ), 37.9 (CH ), 39.7 (CH), 58.8 (CH), 66.3 (CH
CH ), 114.5 (C), 122.1 (CH), 125.5 (CH), 125.6 (CH), 125.8
CH), 126.4 (CH), 126.6 (CH), 126.7 (CH), 127.9 (C), 128.1 (C),
31.0 (CH), 135.8 (CH), 138.1 (C), 138.1 (C), 138.2 (C), 145.8
C), 146.3 (C), 150.8 (CH), 164.6 (C); EI-HRMS m/z calcd. for
3
) 30.2 (CH
2
),
), 68.4
mixture was eluted through short column of SiO
the eluent, and concentrated in vacuo. The crude residue was
purified by chromatography (SiO , 10:1 hexane/AcOEt) to provide
2
, using AcOEt as
3
2
2
2
(
(
2
2
the flavanone (18) as white solid (53.8 mg, 0.24 mmol). The
enantiomeric ratio was determined by HPLC using a chiral column
1
(
+
(Daisel Chiralcel OD-H), hexane/2-propanol 9:1, 1.0 ml/min, 254
26 22 2 2
C H N O (M ) 394.1681, found 394.1488.
nm, 8.4 min (minor), 10.1 min (major).
2
0. The typical experiment for the 1,4-addition of phenyl boronic acid
to 2-cyclohexen-1-one (8):

3
Research highlights



Design and synthesis of rigid 1,10-phenanthroline-derived chiral ligand.
New ligand demonstrated potential for catalytic 1,4-addition with high enantioselectivity.
This stereocontrol model can be applied to predict an X-ray crystallographic study.

Tetrahedron Letters
4
Graphical
Abstract
Design and synthesis of chiral 1,10-
Leave this area blank for abstract info.
phenanthroline ligand, and application in
palladium catalyzed asymmetric 1,4-addition
reactions
Masafumi Tamura,* Hayato Ogata, Yuu Ishida, Yasunori, Takahashi