Enantioselective synthesis of a novel chiral 2,9-disubstituted 1,10-phenanthroline and first applications in asymmetric catalysis

Article abstract of DOI:10.1002/ejoc.200901038

The asymmetric synthesis of a novel, C₂-symmetric, tetradentate 1,10-phenanthroline is described; it is based on the stereoselective preparation of two functionalized pyridine subunits, which were subsequently joined through two consecutive car

Full text of DOI:10.1002/ejoc.200901038

FULL PAPER
DOI: 10.1002/ejoc.200901038
Enantioselective Synthesis of a Novel Chiral 2,9-Disubstituted
1,10-Phenanthroline and First Applications in Asymmetric Catalysis
Mecheril Valsan Nandakumar,[a] Subrata Ghosh,[a] and Christoph Schneider*[a]
Keywords: Amination / Asymmetric catalysis / Desymmetrization / Phenanthrolines / Scandium
The asymmetric synthesis of a novel, C2-symmetric, tetra-
dentate 1,10-phenanthroline is described; it is based on the
stereoselective preparation of two functionalized pyridine
subunits, which were subsequently joined through two con-
secutive carbon–carbon bond-forming reactions to assemble
the heteroaromatic system. Some initial applications of this
new chiral ligand in metal-catalyzed, enantioselective ring-
opening reactions of meso-epoxides and aminations of β-keto
esters are presented.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
phenanthroline core by appendage or upon annulations
with one or two chiral units.[4b,11] The heteroaromatic sys-
tems of the phenanthroline cores, however, have remained
intact throughout these modifications. Some of the impor-
tant applications of chiral phenanthroline derivatives in
asymmetric catalysis, which have mainly come from the
Chelucci group, include Pd-catalyzed allylic alkylation of
allylic acetates,[12] Cu-catalyzed cyclopropanation of sty-
renes,[13] Rh-catalyzed asymmetric hydrosilylation[14] and
transfer hydrogenation of ketones,[15] and Cu-catalyzed al-
lylic oxidation of alkenes.[16] In addition, Helquist and co-
workers recently reported the synthesis of a functionalized
chiral phenanthroline in 17–42% yield through SmI2-medi-
ated coupling of the parent 1,10-phenanthroline with (R)-
1,2-epoxybutane.[11j] However, no application of this ligand
in asymmetric catalysis has yet been reported in the litera-
ture.
In recent years we have developed scandium- and in-
dium-bipyridine-catalyzed ring-opening reactions of meso-
epoxides with alcohols, amines, thiols, and selenols, to fur-
nish 1,2-diol monoethers, 1,2-amino alcohols, 1,2-hydroxy
sulfides, and 1,2-hydroxy selenides, respectively, in part with
excellent enantioselectivities (Scheme 1).[17] As chiral ligand
we employed the 2,2Ј-bipyridine 1 with appended hy-
droxyalkyl groups, first synthesized and introduced into the
field of asymmetric catalysis by Bolm and co-workers.[18]
Here we report the straightforward synthesis of a confor-
mationally rigid C2-symmetric phenanthroline ligand with
appended hydroxyalkyl groups, resembling the Bolm bipyr-
idine ligand 1. In contrast with previous approaches to such
structures we first assembled two completely functionalized
pyridine subunits and subsequently joined them to form the
phenanthroline core through two consecutive C–C-coupling
reactions. Some initial applications of this new chiral ligand
in metal-catalyzed epoxide-opening reactions and in amina-
tions of β-keto esters are also presented.
Introduction
The design and synthesis of novel chiral ligands and their
application in enantioselective, metal-catalyzed reactions
continues to be an important area of research in the field
of organic synthesis.[1] Through careful fine-tuning of the
electronic and steric properties of a ligand its coordination
to a metal can easily be modulated, with the aim of creating
a chiral environment within the metal–ligand complex that
leads to a high enantioselectivity in a given reaction. Nitro-
gen-based chiral ligands have become extremely popular in
asymmetric metal catalysis on the basis of their efficient
and well-documented coordination to late-transition metals
and their facile preparation, typically starting from natural
amino acids. Prominent examples in this respect include
chiral bisoxazolines,[2] pyridine-2,6-bisoxazolines,[3] and
2,2Ј-bipyridines,[4] in addition to various mixed P,N- and
N,S-type ligands, all of which have proven to provide excel-
lent levels of enantioselectivity in various reactions.
1,10-Phenanthrolines occupy a prominent position in or-
ganometallic chemistry as very rigid ligands that are known
to coordinate tightly to several metal ions in a chelate fash-
ion.[5] Accordingly, they have been used for a broad range
of metal-catalyzed reactions such as the Mizoroki–Heck re-
action,[6] aryl and alkenyl aminations and amidations,[7] oxi-
dation of alcohols,[8] conjugate addition reactions,[9] and cy-
clopropanations.[10] Only a few reports, however, have dealt
with the use of chiral 1,10-phenanthroline ligands in asym-
metric catalysis, which is mainly due to difficulties in syn-
thesizing these compounds in enantiomerically pure form.
The majority of reported synthetic routes to chiral phenan-
throlines are based either upon the modification of the
[a] Institut für Organische Chemie, Universität Leipzig,
Johannisallee 29, 04103 Leipzig, Germany
Fax: +49-341-9736599
E-mail: schneider@chemie.uni-leipzig.de
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. V. Nandakumar, S. Ghosh, C. Schneider
FULL PAPER
Scheme 1. Enantioselective ring-opening reactions of meso-epox-
ides catalyzed by scandium or indium together with bipyridine 1.[17]
Results and Discussion
Scheme 2. Synthesis of the chiral phenanthroline 7: i) LDA, THF,
–78 °C, 2 h, then DMF, –78 °C, 4 h; ii) pTsNHNH2, CH2Cl2, 2 d;
iii) a) (C6H5CH2)Et3N+Cl–, NaOH (aq., 14% ), toluene, 65 °C, 2 h;
b) Rh2OAc)4, –20 to 0 °C, 16 h; iv) TBAF·3H2O, THF, 6 h (pure
Z); v) PdCl2(PhCN)2 (20 mol-%), TDAE, DMF, 75 °C, 48 h.
TDAE = tetrakis(dimethylamino)ethylene.
Generally, one method for the synthesis of 2,9-disubsti-
tuted 1,10-phenanthrolines is through the attachment of the
2- and 9-substituents to a commercially available or easily
prepared 1,10-phenanthroline derivative. One of the prob-
lems with this approach is the inherent reactivity of the
phenanthroline ring towards undesired nucleophilic imine and E isomers were best separated by chromatography after
addition to furnish 1,2-addition products, especially with removal of the silyl ethers with TBAF in THF, which af-
organometallic reagents, which eventually foiled this ap- forded the pure Z-stilbene 6 in 67% yield.
proach.[4] The alternative option, which we ultimately pur-
The final Ullmann-type coupling reaction in this steri-
sued, called for the stereoselective synthesis of two fully cally quite congested situation proved to be challenging. Al-
functionalized pyridine units, later to be coupled with each though the conditions developed by Bolm for the synthesis
other to yield the desired phenanthroline skeleton. A sim- of 2,2Ј-bipyridines were not suitable in this particular situa-
ilar approach was recently reported for simpler systems by tion the protocol used by Kobayashi for similar pyridine
Chelucci and co-workers, who employed a Wittig ole- coupling reactions worked much better.[20] Thus, in the
fination to construct the 5,6-double bond within the phen- presence of PdCl2(PhCN)2 (20 mol-%) and stoichiometric
anthroline backbone.[19]
amounts of tetrakis(dimethylamino)ethylene used simulta-
We started the synthesis from the known TBS-protected neously as ligand and reductant, the intramolecular
2-bromo pyridyl alcohol 2 (Scheme 2),[17b] readily prepared Ullmann coupling of the Z-stilbene 6 afforded the chiral
through enantioselective Noyori hydrogenation of the cor- phenanthroline 7 in 60–70% isolated yield by direct
responding ketone in good yield and with excellent enantio- crystallization. Any attempt to purify this highly polar
selectivity,[20] and subsequent silylation. The introduction of product by chromatography resulted in significant loss of
the aldehyde moiety was achieved by the highly regioselec- material. Subsequently we were able to obtain a crystal
tive metalation of the pyridine ring in 2 with LDA in THF structure of this new ligand, which established its structure
at –78 °C and subsequent treatment with DMF to afford unequivocally (Figure 1).[23]
the 3-pyridyl carbaldehyde 3 in 50% yield, along mainly
with unreacted starting material.[21] Despite many attempts
to optimize the conversion of this reaction (e.g., by the ad-
dition of more base and electrophile) the yield could not be
increased beyond this mark. Along with some dehaloge-
nated starting material we isolated as the main byproduct
in this reaction the starting material in significant amounts
which we could submit again in this reaction. It is impor-
tant to note here that the metalation had not affected the
chiral center in the pyridyl silyl ether, because the enantio-
meric excesses both of the recovered material and of the
product were determined to be 99% ee.
Figure 1. X-ray crystal structure of the phenanthroline 7.
Aldehyde 3 was then converted into the corresponding
sulfonyl hydrazone 4 by treatment with p-toluenesulfonyl
As a first test of this novel chiral ligand in asymmetric
hydrazide. The sulfonyl hydrazone 4 was in turn converted catalysis we chose scandium- and indium-catalyzed enantio-
under phase-transfer conditions into the corresponding di- selective ring-openings of meso-epoxides with aniline and
azoalkane, which was subsequently dimerized through the thiophenol, respectively (Scheme 3).[17] Treatment of cis-stil-
action of catalytic amounts of Rh2(OAc)4 to afford a 4:1 bene oxide with aniline in the presence of Sc(OTf)3 (10 mol-
mixture of the Z- and E-alkenes 5 in 94% yield.[22] The Z %) and 7 (10 mol-%) in CH2Cl2 at room temperature thus
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Eur. J. Org. Chem. 2009, 6393–6398

Chiral Tetradentate 1,10-Phenanthroline for Asymmetric Catalysis
afforded the 1,2-amino alcohol 8 in 73% yield and 92% ee.
Likewise, the thiolysis reaction in the presence of a catalyst
system composed of InBr3 and 7 (each 10 mol-%) furnished
the 1,2-hydroxy sulfide 9 in 65% yield and 97% ee. The re-
sults obtained with the new phenanthroline ligand thus did
not differ much from those obtained previously with the
bipyridine 1.
Conclusions
We have synthesized the novel chiral tetradentate 2,9-di-
substituted 1,10-phenanthroline 7 through two consecutive
carbon–carbon coupling reactions starting from two fully
elaborated pyridine subunits. Additionally, we have revealed
some initial applications of this chiral ligand in asymmetric
ring-openings of meso-epoxides, as well as in asymmetric
aminations of β-keto esters. Because of its rigid structure
and the additional coordination sites in the form of the hy-
droxy groups this novel ligand might offer some advantages
over existing chiral ligands and may be applicable in reac-
tions that are intractable with other known ligands. Further
work to explore the potential of this novel chiral ligand in
asymmetric catalysis fully is in progress in our laboratory.
Experimental Section
General Methods: All reactions were performed under nitrogen in
oven-dried glassware. 1H and 13C NMR spectra were recorded with
a Varian Gemini 2000 (200, 300, or 400 MHz) NMR spectrometer.
NMR spectra were obtained in CDCl3 as solvent. Chemical shifts
are given in the δ scale with tetramethylsilane or the CHCl3 proton
as the internal standard. IR spectra were obtained with a FTIR
spectrometer (Genesis ATI Mattson/Unicam). UV spectra were re-
corded with a UV spectrometer (DU-650 Beckmann). Optical rota-
tions were measured with a Polarotronic polarimeter (Schmidt &
Haensch). HPLC analyses were performed with a JASCO MD-
2010 plus instrument with a chiral stationary phase column (Chi-
ralcel OD column). Solvents were purified by distillation from ap-
propriate drying agents. All ESI mass spectra were recorded with
a Bruker APEX II FT-ICR instrument. All EI mass spectra were
recorded with a Finnigan MAT 8230 instrument. Melting points
were determined with a Boetius heating table and are uncorrected.
Scheme 3. Enantioselective amine and thiol additions to cis-stilb-
ene oxide catalyzed by scandium or indium and the phenanthroline
7.
As a novel application of this chiral phenanthroline li-
gand in asymmetric metal catalysis we found it to be highly
suitable for the copper-catalyzed amination of β-keto es-
ters.[24] Thus, when the β-keto ester 10a was treated with
diethyl azodicarboxylate (DEAD) and with 10 mol-% Cu-
(OTf)2 and phenanthroline 7 each in CH2Cl2 at room temp.,
the α-hydrazino-β-keto ester 11a was obtained in 85% yield
and with 93% ee (Table 1, Entry 1). It is especially note-
worthy that even the more commonly used methyl ester and
the commercially available reagent DEAD were already giv-
ing rise to a highly enantioselective reaction. Other chiral
catalysts that have been developed for this reaction fre-
quently require the use of bulkier and less convenient β-
keto esters and/or bulky azo compounds such as the corre-
sponding diisopropyl or di-tert-butyl derivatives to achieve
high enantioselectivities. This protocol was subsequently
applied to the asymmetric α-amination of the other β-keto
esters 10b–e, which proceeded with uniformly high levels of
enantioselectivity (Table 1).
2-Bromo-6-[(R)-1-(tert-butyldimethylsiloxy)-2,2-dimethylpropyl]pyr-
idine-3-carbaldehyde (3): LDA (2.63 g, 24.6 mmol), was added
dropwise under argon at –78 °C to a solution of 2-bromo-6-[(R)-
1-(tert-butyldimethylsiloxy)-2,2-dimethylpropyl]pyridine (2, 2.93 g,
8.19 mmol) in dry THF (50 mL) and the solution was stirred for
2 h at –78 °C. Dry DMF (2.39 g, 32.8 mmol) was then added drop-
wise over a period of 10 min and the reaction mixture was stirred
at –78 °C for another 4 h, after which it was hydrolyzed with a
degassed aqueous solution of KH2PO4 (10%, 20 mL). It was then
allowed to warm to room temperature and was extracted with ethyl
acetate (3ϫ50 mL). The combined organic layers were washed
with brine, dried with anhydrous MgSO4, concentrated, and puri-
fied by flash chromatography on a silica gel column. Elution with
ethyl acetate/hexane (2%) afforded aldehyde 3 as a viscous, light
yellow liquid (1.59 g, 50%) along with unreacted starting material
that could be used again for this reaction. [α]2D2 = +33 (c = 1,
CHCl3). HPLC (Daicel Chiracel OD-phase, 95:5 n-hexane/propan-
2-ol, flow rate 0.5 mLmin–1): tR (major) 19.56 min (99% ee) and tR
(minor) 21.78 min. 1H NMR (400 MHz, CDCl3): δ = –0.30 (s, 3 H,
CH3), 0.06 (s, 3 H, CH3), 0.90 [s, 9 H, C(CH3)3], 0.91 [s, 9 H,
C(CH3)3], 4.50 (s, 1 H, CH), 7.54 (d, J = 8.4 Hz, 1 H, ArH), 8.11
(d, J = 8.4 Hz, 1 H, ArH), 10.31 (s, 1 H, CHO) ppm. 13C NMR
(75 MHz, CDCl3): δ = –4.91, –4.27, 18.40, 26.18, 26.28, 36.75,
Table 1. Enantioselective α-aminations of the β-keto esters 10, cata-
lyzed by copper(II) and the phenanthroline 7.
Entry
X
R
Product Yield [%][a] ee [%][b]
1
2
3
4
5
H
H
5-OMe
6-OMe
6-Me
Me
Et
Me
Me
Me
11a
11b
11c
11d
11e
85
84
88
86
82
93
93
98
95
95
82.97, 121.5, 126.3, 138.0, 165.2, 191.2 ppm. IR (film): ν = 2955,
˜
2930, 2858, 1698, 1582, 1544, 1471, 1445, 1392, 1353, 1252, 1235,
1184, 1122, 1091, 1055, 1030, 1006 cm–1. UV (CHCl3): λmax (lgε)
= 248 (3.926), 290 (3.811) nm. MS (EI, 70 eV): m/z (%) = 410.1 [M
[a] Yield of isolated product after flash column chromatography.
[b] Determined by chiral HPLC analysis.
Eur. J. Org. Chem. 2009, 6393–6398
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6395

M. V. Nandakumar, S. Ghosh, C. Schneider
FULL PAPER
+ Na + 1]+. HRMS-ESI: m/z [M + H]+ calcd. for C17H28BrNO2Si:
386.11454; found 386.11432.
(R,R)-2,9-Bis(1-hydroxy-2,2-dimethylpropyl)-1,10-phenanthroline-
(7): The Z-stilbene 6 (222 mg, 0.44 mmol) and tetrakis(dimethyl-
amino)ethylene (TDAE, 176 mg, 0.88 mmol) were added at room
temperature to a solution of PdCl2(PhCN)2 (34 mg, 20 mol-%) in
degassed DMF (2 mL). The reaction mixture was heated at 75 °C
for 24 h and was then allowed to cool to room temperature. The
reaction mixture was then filtered through a short celite column
with CH2Cl2 and the solvents were evaporated under high vacuum.
Crystallization of the product from the crude reaction mixture in
CH2Cl2 afforded 7 (93–102 mg, 60–70%) as colorless crystals; m.p.
228–230 °C. [α]2D2 = –254 (c = 1, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 1.03 [s, 18 H, C(CH3)2], 4.72 (d, J = 6.8 Hz, 2 H, CH),
5.92 (d, J = 6.8 Hz, 2 H, OH), 7.42 (d, J = 8.4 Hz, 2 H, ArH), 7.62
(s, 2 H, CH=CH), 7.93 (d, J = 8 Hz, 2 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 26.50, 36.82, 82.18, 122.9, 125.9, 127.8,
Toluenesulfonylhydrazone 4: p-Toluenesulfonylhydrazide (176 mg,
0.95 mmol) was added to a solution of aldehyde 3 (365 mg,
0.95 mmol) in CH2Cl2 and the reaction mixture was stirred for 48 h
at room temperature. After completion of the reaction (TLC), the
solvent was evaporated and the crude product was purified by flash
chromatography (ethyl acetate/hexane 30%) to give rise to hydra-
zone 4 (490 mg, 93%) as a colorless solid; m.p. 70–72 °C. [α]2D2
=
1
+50 (c = 1, CHCl3). H NMR (300 MHz, CDCl3): δ = –0.32 (s, 3
H, CH3), 0.04 (s, 3 H, CH3), 0.86 [s, 9 H, C(CH3)2], 0.90 [s, 9 H,
C(CH3)2], 2.43 (s, 3 H, CH3), 4.41 (s, 1 H, –CH), 7.33–7.42 (m, 3
H, ArH, NH), 7.86–7.89 (m, 2 H, ArH, CH=N), 8.03–8.09 (m, 3
H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = –4.91, –4.23,
18.38, 21.99, 26.15, 26.26, 36.93, 82.76, 122.1, 128.3, 130.1, 135.4,
135.3, 144.0, 161.5 ppm. IR (KBr): ν = 3354, 3279, 3042, 2949,
˜
135.5, 140.6, 144.5, 166.7 ppm. IR (KBr): ν = 3196, 2955, 2929,
˜
2885, 1619, 1608, 1589, 1552, 1497, 1477, 1464, 1444, 1419, 1390,
1363, 1327, 1304, 1240, 1175, 1146, 1139, 1096, 1072, 1059,
1016 cm–1. UV (CHCl3): λmax (lgε) = 205 (4.095), 236 (4.031), 272
(4.097) nm. MS (EI, 70 eV): m/z (%) = [M + Na]+ 375.1. HRMS-
ESI: m/z [M + H]+ calcd. for C22H28N2O2: 353.22235; found
353.22202.
2856, 1585, 1539, 1471, 1435, 1393, 1362, 1321, 1251, 1216, 1185,
1168, 1126, 1086, 1048, 1030, 1006 cm–1. UV (MeOH): λmax (lgε)
= 222 (4.221), 279 (4.160), 303 (4.188) nm. MS (EI, 70 eV): m/z (%)
= 578 [M + Na]+, 554 [M]+. HRMS-ESI: m/z [M + H]+ calcd. for
C24H36BrN3O3SSi: 554.15028; found 554.14970.
Z/E-Stilbene 5: Benzyltriethylammonium chloride (154 mg,
0.68 mmol) and aqueous NaOH (14%, 30 mL) were added to a
solution of hydrazone 4 (2.88 g, 5.20 mmol) in toluene (30 mL).
After the reaction mixture had been heated for 2 h at 65 °C, the
red colored organic layer was separated and dried with anhydrous
MgSO4. The reaction mixture was then cooled to –20 °C,
Rh2(OAc)4 (10 mg) was added, and the reaction mixture was al-
lowed to warm slowly to 0 °C and then to room temp. The organic
layer was separated and dried with anhydrous MgSO4, and the sol-
vent was removed under vacuum. The product 5 was isolated as a
colorless solid (1.82 g, 94%, 4:1 Z/E) by flash chromatography on
a silica column (ethyl acetate/hexane 3%). Data for the Z-stilbene:
m.p. 119–120 °C. [α]2D3 = +23 (c = 1, CHCl3). 1H NMR (300 MHz,
CDCl3): δ = –0.32 (s, 3 H, CH3), 0.32 (s, 3 H, CH3), 0.83 [s, 18 H,
C(CH3)3], 0.87 [s, 18 H, C(CH3)3], 4.41 (s, 2 H, CH), 6.78 (s, 2 H,
CH=CH), 7.11 (m, 2 H, ArH), 7.18 (m, 2 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = –4.99, –4.10, 18.37, 26.17, 26.24, 36.77,
Typical Procedure for the α-Amination of β-Keto Esters 10: A solu-
tion of Cu(OTf)2 (1.8 mg, 10 mol-%) and the chiral phenanthroline
7 (1.94 mg, 11 mol-%) in CH2Cl2 (2 mL) was stirred for 45 min at
room temperature. Subsequently one of the β-keto esters 10
(0.05 mmol) and DEAD (9.57 mg, 55 µmol) were added and the
solution was stirred for 12 h at room temperature. The crude prod-
uct was purified by flash chromatography over silica gel (ethyl ace-
tate/hexane 30%) to afford the α-aminated products 11 as viscous
liquids.
Data for 11a: [α]2D3 = +140 (c = 0.5, CHCl3). HPLC (Daicel Chira-
cel OD-phase, n-hexane/propan-2-ol 95:5, flow rate 1 mLmin–1): tR
(major) 19.53 min (93% ee) and tR (minor) 23.60 min. 1H NMR
(400 MHz, CDCl3): δ = 1.24 (m, 6 H, CH3), 3.73 (s, 3 H, CH3),
4.16 (mc, 6 H, OCH2, CH2), 6.97 (br. s, 1 H, NH), 7.34 (m, 1 H,
ArH), 7.46 (d, J = 7.5 Hz, 1 H, ArH), 7.60 (t, J = 7.5 Hz, 1 H,
ArH), 7.74 (d, J = 7.5 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.39, 36.01, 53.67, 62.13, 62.34, 63.37, 76.54, 81.49,
125.3, 126.6, 127.8, 133.2, 136.5, 154.2, 156.0, 167.5, 195.0 ppm.
82.66, 121.2, 130.4, 131.9, 138.1, 141.1, 164.1 ppm. IR (KBr): ν =
˜
2956, 2930, 2884, 2857, 1584, 1575, 1539, 1471, 1462, 1393, 1355,
1253, 1207, 1182, 1127, 1101, 1088, 1056, 1031, 1007 cm–1. UV
(CHCl3): λmax (lgε) = 216 (4.027), 225 (3.808), 279 (4.272) nm. MS
(EI, 70 eV): m/z (%) = 739.3 [M]+. HRMS-ESI: m/z [M + H]+
calcd. for C34H56Br2N2O2Si2: 739.23198; found 739.23326.
IR (KBr): ν = 3316, 2983, 1731, 1608, 1590, 1466, 1379, 1337, 1305,
˜
1237, 1172, 1154, 1082, 1060, 1042 cm–1. HRMS-ESI: m/z [M +
Na]+ calcd. for C17H20N2O7: 387.11627; found 387.11651.
Data for 11b: [α]2D3 = +144 (c = 0.5, CHCl3). HPLC (Daicel Chira-
cel OD-phase, 95:5 n-hexane/propan-2-ol, flow rate 1 mLmin–1): tR
(major) 14.39 min (93% ee) and tR (minor) 18.24 min. 1H NMR
(300 MHz, CDCl3): δ = 1.20 (t, J = 7.2 Hz, 9 H, CH3), 3.75–4.22
(m, 8 H, CH2, OCH2), 7.00 (br. s, 1 H, NH), 7.35 (t, J = 7.5 Hz,1
H, ArH), 7.47 (d, J = 7.5 Hz, 1 H, ArH), 7.62 (t, J = 7.5 Hz, 1 H,
ArH), 7.73–7.75 (m, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 13.72, 14.09, 36.67, 62.02, 62.56, 62.95, 76.34, 77.92,
124.9, 126.2, 127.5, 133.0, 135.5, 136.1, 154.1, 155.9, 167.0,
Z-Stilbene 6: TBAF·3H2O (4.63 g, 14.6 mmol) was added to a
solution of the Z/E mixture of 5 (1.81 g, 2.44 mmol) in THF. The
reaction mixture was stirred at room temp. for 6 h and the solvent
was removed under vacuum. The crude product was dissolved in
CH2Cl2 and washed with water. The organic layer was collected
and dried with anhydrous MgSO4, and the solvents were evapo-
rated. Purification of the crude product by flash chromatography
(ethyl acetate/hexane 30%) on a basic alumina column afforded the
Z-stilbene 6 as a light yellow solid (843 mg, 67%); m.p. 85–87 °C.
194.8 ppm. IR (KBr): ν = 3312, 2983, 2937, 1726, 1608, 1590, 1466,
˜
[α]2D2 = –50 (c = 1, CHCl3). H NMR (400 MHz, CDCl3): δ = 0.85
1
1445, 1402, 1377, 1337, 1304, 1237, 1201, 1173, 1154, 1095, 1081,
1041, 904, 860, 787, 760, 617 cm–1. HRMS-ESI: m/z [M + H]+
calcd. for C18H23N2O7: 379.14998; found 379.14993.
[s, 18 H, C(CH3)3], 3.59 (d, J = 7.2 Hz, 2 H, –CH), 4.24 (d, J =
7.2 Hz, 2 H, OH), 6.77 (s, 2 H, CH=CH), 6.91 (d, J = 7.6 Hz, 2
H, ArH), 7.11 (d, J = 7.6 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 26.11, 36.65, 80.52, 121.6, 130.5, 132.5, 138.5, 142.0,
Data for 11c: [α]2D3 = +176 (c = 0.5, CHCl3). HPLC (Daicel Chira-
cel OD-phase, n-hexane/propan-2-ol 95:5, flow rate 1 mLmin–1): tR
(major) 37.68 min (98% ee) and tR (minor) 45.44 min. 1H NMR
(400 MHz, CDCl3): δ = 1.17–1.29 (m, 6 H, CH3), 3.75 (s, 3 H,
OCH3), 3.78 (br. s, 1 H, CH2), 3.89 (s, 3 H, OCH3), 3.98–4.24 (m,
5 H, CH2, OCH2), 6.91 (s, 2 H, ArH), 6.97 (s, 1 H, NH), 7.69 (br.
161.2 ppm. IR (KBr): ν = 3356, 3042, 2951, 2866, 1697, 1581, 1541,
˜
1477, 1455, 1440, 1393, 1344, 1272, 1230, 1213, 1172, 1131, 1062,
1015 cm–1. UV (CHCl3): λmax (lgε) = 278 (4.071) nm. MS (EI,
70 eV): m/z (%) = 535 [M + Na]+. HRMS-ESI: m/z [M + H]+ calcd.
for C22H28Br2N2O2: 511.05903; found 511.05874.
6396
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 6393–6398

Chiral Tetradentate 1,10-Phenanthroline for Asymmetric Catalysis
s, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.40, 38.79,
53.66, 55.86, 62.05, 62.32, 63.28, 78.43, 109.3, 116.6, 125.4, 126.5,
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˜
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Crystallographic data for phenanthroline 7, C22H28N2O2: M
= 352.46, orthorhombic, a = 10.6346(4), b = 17.0974(7), c =
22.3379(10) Å, U = 4061.6(3) Å3, T = 213(2) K, space group
P212121, Z = 8, µ(Mo-Kα) = 0.074 mm–1, Dc = 1.153 gcm–3,
20431 reflections measured, 8500 unique (Rint = 0.0300), which
were used in all calculations. The final wR(F2) was 0.0585 (all
data). G. M. Sheldrick, SHELXS-97, SHELXL-97. Programs
for crystal structure determination, University of Göttingen,
Germany, 1997. CCDC-739471 contains the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
2982, 1717, 1600, 1491, 1466, 1445, 1404, 1337, 1259, 1173, 1152,
1082, 1062, 1041 876, 787, 762, 656, 621 cm–1. HRMS-ESI: m/z [M
+ H]+ calcd. for C18H23N2O8: 395.14489; found 395.14499.
Data for 11d: [α]2D3 = +156 (c = 0.5, CHCl3). HPLC (Daicel Chira-
cel OD-phase, n-hexane/propan-2-ol 95:5, flow rate 1 mLmin–1): tR
(minor) 40.51 min and tR (major) 48.49 min (95% ee). 1H NMR
(400 MHz, CDCl3): δ = 1.22–1.34 (m, 6 H, CH3), 3.69–3.71 (m, 1
H, CH2), 3.75 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3), 3.97–4.24 (m,
5 H, CH2, OCH2), 6.96 (br. s, 1 H, NH), 7.16–7.25 (m, 2 H, ArH),
7.37 (d, J = 8.4 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
δ = 14.35, 38.05, 53.64, 55.62, 62.03, 62.35, 63.28, 78.75, 106.2,
125.4, 126.1, 127.2, 134.2, 147.4, 156.1, 159.6, 167.5, 194.4 ppm.
IR (KBr): ν = 3316, 2983, 1722, 1618, 1494, 1466, 1433, 1404,
˜
1377, 1339, 1302, 1238, 1161, 1084, 1060, 1030, 861, 788, 762 cm–1.
HRMS-ESI: m/z [M + H]+ calcd. for C18H23N2O8: 395.14489;
found 395.14454.
[12]
[13]
Data for 11e: [α]2D3 = +148 (c = 0.5, CHCl3). HPLC (Daicel Chira-
cel OD-phase, n-hexane/propan-2-ol 95:5, flow rate 1 mLmin–1): tR
(minor) 24.16 min and tR (major) 27.06 min (95% ee). 1H NMR
(400 MHz, CDCl3): δ = 0.91–1.27 (m, 6 H, CH3), 2.38 (s, 3 H,
CH3), 3.74 (s, 3 H, OCH3), 3.78 (br. s, 1 H, CH2), 4.11–4.20 (m, 5
H, CH2, OCH2), 7.07 (br. s, 1 H, NH), 7.38 (d, J = 7.5 Hz, 1 H,
ArH), 7.46 (d, J = 7.5 Hz, 1 H, ArH), 7.56 (br. s, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3): δ = 14.33, 21.05, 38.40, 53.60, 62.07,
62.30, 63.24, 78.41, 125.1, 126.1, 127.3, 133.3, 137.1, 137.8, 151.5,
[14]
[15]
[16]
[17]
156.1, 167.4, 194.4 ppm. IR (KBr): ν = 3311, 2983, 2954, 1727,
˜
1619, 1584, 1494, 1405, 1377, 1338, 1238, 1174, 1150, 1085, 1042,
872, 762, 682, 605, 501 cm–1. HRMS-ESI: m/z [M + H]+ calcd. for
C18H23N2O7: 379.14998; found 379.15002.
Acknowledgments
We thank the Deutsche Forschungsgemeinschaft (DFG) for gener-
ous financial support of this work and the Alexander von Hum-
boldt foundation for a postdoctoral fellowship awarded to one of
the authors (S. G.). Prof. Harald Krautscheid (University of Le-
ipzig) is gratefully acknowledged for solving the crystal structure
of the phenanthroline ligand 7.
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www.eurjoc.org
6397

M. V. Nandakumar, S. Ghosh, C. Schneider
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Received: September 10, 2009
Published Online: November 9, 2009
6398
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 6393–6398