New chiral 2,2'-bipyridine diols as catalysts for enantioselective addition of diethylzinc to benzaldehyde

Article abstract of DOI:10.1016/S0957-4166(99)00399-7

New C₂-symmetric chiral 2,2'-bipyridine diols were prepared from readily available homochiral materials such as menthone and camphor. Their catalytic activities in the reaction of diethylzinc with benzaldehyde to give 1-phenyl-1-propanol were studied. In all cases, the yields were good and enantioselectivities up to 95% were observed.

Full text of DOI:10.1016/S0957-4166(99)00399-7

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3791–3801
New chiral 2,20-bipyridine diols as catalysts for enantioselective
addition of diethylzinc to benzaldehyde
Hoi-Lun Kwong ∗ and Wing-Sze Lee
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong,
People’s Republic of China
Received 29 July 1999; accepted 27 August 1999
Abstract
New C2-symmetric chiral 2,20-bipyridine diols were prepared from readily available homochiral materials such
as menthone and camphor. Their catalytic activities in the reaction of diethylzinc with benzaldehyde to give
1-phenyl-1-propanol were studied. In all cases, the yields were good and enantioselectivities up to 95% were
observed. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
The presence of a C2 symmetry axis within a chiral auxiliary can serve the very important function
of dramatically reducing the number of possible competing diastereomeric transition states.1 Many C2-
symmetric chiral N,N bidentate ligands such as semicorrines and bisoxazolines are found to be highly
effective chiral controllers in asymmetric reactions.2–4 Although bipyridines are structurally similar
to these ligands and are well known to form complexes with various metal ions,5 relatively few C2-
symmetric bipyridine ligands were reported and used in asymmetric catalysis.6,7 One reason associated
with this problem is the lack of an efficient synthetic route to them.
Bolm et al. reported the synthesis of the C2-symmetric chiral bipyridine ligands 1 through asymmetric
reduction of prochiral ketones and studied their use in various asymmetric reactions.8,9 Katsuki et al.
∗
Corresponding author. Fax: (852)-2788-7406; e-mail: bhhoik@cityu.edu.hk
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00399-7

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reported the synthesis of chiral bipyridine 2 from 2,3-cyclohexenopyridine and its use in asymmetric
cyclopropanation.10 We recently reported the use of Bolm’s ligand 1 (R=Me) in asymmetric cyclo-
propanation and allylation reactions.11,12 In order to increase the scope of chiral bipyridine ligands in
asymmetric reactions, we report here the synthesis of new C2-symmetric chiral bipyridine ligands based
on homocoupling of readily available chiral pyridylalcohols and a study of their catalytic activities in the
asymmetric diethylzinc addition to aldehydes.
2. Results and discussion
Bromopyridylalcohols 3 could be obtained from the commercially available 2,6-dibromopyridine. C2-
Symmetric 2,20-bipyridines 4 could then be obtained by metal-mediated homocouplings of 3 (Scheme 1).
Scheme 1.
The synthesis of bromopyridylalcohols 3a–d started from monolithiation of 2,6-dibromopyridine in
ether followed by trapping with optically active naturally occurring ketones (Scheme 2). Compounds
3a–d were obtained as single diastereomers as shown by GLC and NMR analysis of the product mixtures.
The configurations are reported in Scheme 2. Similar observations had been observed previously with
condensation of 2-pyridyllithium with the same chiral ketones.13,14 The yields were 43–58% based on
2,6-dibromopyridine, depending only slightly on the nature of ketone.
Scheme 2. (a) n-BuLi, Et2O, −78→−40°C; (b) menthone, −78°C→rt; (c) camphor, −78°C→rt; (d) fenchone, −78°C→rt; (e)
nopinone, −78°C→rt
The optically active C2-symmetric 2,20-bipyridines of type 4 were then synthesized by nickel(0)-
mediated homocoupling of 3a–d (Scheme 3).15,16 As with the previously reported homocoupling, no

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3793
protection of the hydroxy groups was required.8 The yields of bipyridines for all the reactions were
45–47% after column chromatography.
Scheme 3.
Having prepared these 2,20-bipyridine diol ligands, we tested their properties as catalysts for the
addition of diethylzinc to benzaldehyde (Table 1).17 In all cases, the yields of the isolated 1-phenyl-
1-propanol were good and the enantioselectivities obtained were also high. Catalyst 4a induces the
formation of the (S)-enantiomer in 82% ee (entry 1) while 4b–d induce the formation of (R)-enantiomer
in 92, 77 and 79% ee, respectively (entries 3, 11 and 12). Temperature and solvent have great effects on
both the rate and enantioselectivity. Lowering the temperature from 22 to 0°C leads to slightly slower
reactions but to an increase of asymmetric induction from 81 to 85% ee for 4a (entry 2) and from 92
to 95% ee for 4b (entry 4). Toluene (entry 3), hexane (entry 7) and THF (entry 8) gave similar results
while CH2Cl2 (entry 9) and CH3CN (entry 10) decreased the enantioselectivity and the rate as well.
Changing the amount of catalyst from 2 to 8 mol% had only a small effect on the enantioselectivity
(entries 3, 5 and 6). More remarkable is that all the reactions were completed within an hour at
room temperature with 5 mol% catalysts. These observed reaction rates are very fast when compared
with pyridylalcohol type ligands reported previously.7a,9a,13,14 Use of pyridylalcohol prepared from 2-
bromopyridine and chiral ketones for ethylation of benzaldehyde were reported previously by Chelucci
and Dimitrov independently.13,14 Our results here are much better in terms of rate and enantioselectivity.
With bipyridine 4b being the best ligand, other aldehydes were also tested (Table 2). Several obser-
vations were noticed: in all cases, chemical yields of the alcohols were good; the enantioselectivities
were all lower than benzaldehyde; all the reactions required more time for completion; not all substrates
favor the (R)-configuration isomer. The observation of (S)-configuration products with cyclohexanecar-
boxaldehyde and 1-naphthaldehyde is not easy to understand, but it may be due to the bulkiness of the
substrate, which changes the structure of the active catalyst upon coordination.
Although these C2-symmetric bipyridine ligands can function as N,N bidentate ligands, studies by

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Table 1
Enantioselective addition of diethylzinc to benzaldehydes catalyzed by bipyridines 4a–da
Table 2
Enantioselective addition of diethylzinc to aldehydes catalyzed by 4ba

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Bolm et al. on a related ligand have shown that it is not essential to have C2 symmetry for achieving high
enantioselectivity in the alkylation of aldehyde.9a Optically active pyridylalcohols with aromatic substi-
tuents in the 6-position of the heterocycle were equally efficient. In order to reveal more details of the
nature of the active catalytic species, we prepared the phenyl substituted pyridylalcohols 5a and 5b and
pyridyl substituted pyridylalcohols 6a and 6b to compare them with 4a and 4b, respectively. Ligands 5a
and 5b were prepared by palladium(0)-catalyzed cross couplings of bromopyridines 3a and 3b with phe-
nylboronic acid (Scheme 4),9a,19 whereas bipyridines 6a and 6b were prepared by cross coupling of 3a
and 3b with 2-pyridylzinc chloride using catalytic amounts of tetrakis(triphenylphosphine)palladium(0)
(Scheme 5).9a
Scheme 4.
Scheme 5.
Ligands 5a, 5b, 6a and 6b were all active in catalyzing ethylation of benzaldehyde. With 5a and 5b, the
enantiomeric excesses were 76% (S) and 78% (R), respectively, and complete conversion of benzaldehyde
was achieved within 1.5 h for both ligands. Since the configurations of the products are the same as their
bipyridine counterparts and the enantioselectivities, though a bit lower, are comparable to those with
bipyridines, the results seem to suggest that ligands 4a–d function as pyridylalcohol (N,O) ligands. In
view of the high concentration of diethylzinc in the reaction mixture, we believe that the remaining N,O-
part of the ligand coordinates to other zinc atoms during reaction and the two N,O units probably function
independently. Further comparison of results with 6a and 6b provides more information. Ethylation of
benzaldehyde with 6a and 6b gave 21% (R) and 65% (R) and complete conversions of benzaldehyde were
achieved in 1 and 3 h, respectively. Although 6a and 6b are closer in structure to 4a and 4b than 5a and
5b, respectively, ligand 6a gave the (R)-alcohol as the major product, in contrast to 4a and 5a, whereas

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6b gave a lower ee than 5b. Similar results have also been observed previously with other pyridylalcohols
and bipyridylalcohols.7a The result here hints at a different mechanism for reactions with ligands 6a and
6b.
In summary, we have successfully synthesized four new C2-symmetric 2,20-bipyridine diol ligands
in good yields using organometallic addition of chiral ketones and homocoupling of bromopyridine
intermediates. These ligands are good catalysts for addition of diethylzinc to aldehydes. Enantiomeric
excesses of up to 95% were observed. Comparison of reactivity and enantioselectivity of ligands 4a, 5a,
6a and 4b, 5b, 6b indicated that bipyridines 4 function as N,O ligands in diethylzinc addition reactions.
We are continuing our efforts to study the use of these ligands in other catalytic asymmetric reactions.
3. Experimental
3.1. General methods
Toluene was distilled under N2 from sodium. Dichloromethane and acetonitrile were distilled over
calcium hydride. Diethyl ether and THF were distilled under N2 over sodium/benzophenone. Chemicals
were of reagent-grade quality obtained commercially. Infrared spectra in the range of 500–4000 cm−1 as
Nujol matrices or KBr plates were recorded on a Perkin–Elmer model FTIR-1600 spectrometer. Proton
and 13C NMR spectra were recorded on a Varian 300 MHz Mercury instrument. Positive ion FAB mass
spectra as 3-nitrobenzylalcohol matrices were recorded on a Finnagin MAT 95 spectrometer. Electron
ionization mass spectra were recorded on a Hewlett–Packard 5890II GC instrument coupled with a
5970 mass selective detector. Elemental analyses were performed on a Vario EL elemental analyser.
Optical rotation was measured by JASCO DIP-370 digital polarimeter. Melting point was measured by
Electrothermal digital melting point apparatus.
3.2. General procedures for the synthesis of N,O ligands 3a–d
To an ether solution (100 ml) of 2,6-dibromopyridine (20 mmol, 4.74 g) was added a 1.6 M solution of
n-butylithium (14 ml) in hexane (22 mmol) at −78°C, over 30 min. This was allowed to warm to −45°C
slowly and stirred for 15 min; a clear yellow solution was obtained. The mixture was cooled back to
−78°C and chiral ketone (20 mmol) in dry ether (10 ml) was added dropwise over 10 min. The solution
was allowed to warm to room temperature over 1 h and stirred for another 2.5 h. Water (50 ml) was then
added. The layers were separated and the aqueous layer was extracted with ether (three times by 50 ml).
The combined organic layers were washed with brine (50 ml) and dried with Na2SO4. The solvent was
removed under reduced pressure and the crude product was purified by column chromatography (19:1
1
petroleum ether:ethyl acetate). All ligands were characterized by spectral (IR, H NMR, 13C NMR and
MS) and elemental analyses.
3.2.1. N,O ligand 3a
The above procedure was followed using (−)-menthone. After workup, it gave 3.62 g (58%) of 3a: mp
43–45°C; [α]D25=−5.2 (c=0.52, CHCl3); IR (NaCl): 3447.3 m, 1581.9 m, 1553.1 s; 1H NMR (CDCl3): δ
0.62 (d, 3H, J=6.9 Hz), 0.76 (d, 3H, J=6.9 Hz), 0.80 (d, 3H, J=6.3 Hz), 1.10–1.30 (m, 2H), 1.40–1.60 (m,
4H), 1.70–2.0 (m, 3H), 4.15 (s, 1H), 7.28 (m, 2H), 7.48 (t, 1H, J=7.7 Hz); 13C NMR (CDCl3): δ 18.53,
21.80, 22.22, 23.59, 27.53, 28.33, 34.97, 49.48, 50.52, 77.54, 117.96, 125.54, 138.82, 139.93, 167.57;

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MS (EI) m/z (rel. intensity): 311 and 313 (M+, 11 and 11), 293 and 295 (14 and 14), 226 and 228 (48 and
47), 200 and 202 (base and 68), 184 and 186 (39 and 35).
3.2.2. N,O ligand 3b
The above procedure was followed using (R)-camphor. After workup, it gave 2.68 g (43%) of 3b: mp
103–105°C; [α]D25=−27.7 (c=0.51, CHCl3); IR (KBr): 3455.7 s, 1577.8 s, 1550.1 vs; 1H NMR (CDCl3):
δ 0.74 (s, 3H), 0.79 (s, 3H), 1.14 (s, 3H), 1.10–1.30 (m, 2H), 1.50–1.20 (m, 5H), 4.20 (s, 1H), 7.21 (d,
1H, J=7.7 Hz), 7.27 (d, 1H, J=7.7 Hz), 7.39 (t, 1H, J=7.7 Hz); 13C NMR (CDCl3): δ 9.79, 21.13, 21.18,
26.76, 30.67, 43.71, 45.16, 50.45, 53.54, 82.75, 119.14, 125.77, 137.74, 139.98, 165.35; MS (EI) m/z
(rel. intensity): 309 and 311 (M+, 8 and 9), 199 and 201 (base and 95).
3.2.3. N,O ligand 3c
The above procedure was followed using (1R)-(−)-fenchone. After workup, it gave 2.97 g (48%) of
1
3c: mp 93–95°C; [α]D25=−33.3 (c=0.52, CHCl3); IR (KBr): 3400.0 s, 1577.8 vs, 1544.4 vs; H NMR
(CDCl3): δ 0.46 (s, 3H), 0.99 (s, 3H), 1.00 (s, 3H), 1.15 (m, 1H), 1.35 (d, 1H, J=10.4 Hz), 1.49 (m, 1H),
1.80 (m, 2H), 2.30 (m, 2H), 5.00 (s, 1H), 7.3–7.50 (m, 3H); 13C NMR (CDCl3): δ 17.05, 22.00, 24.33,
29.13, 32.37, 41.78, 46.09, 48.77, 52.05, 83.80, 121.43, 125.37, 137.29, 139.09, 164.34; MS (EI) m/z
(rel. intensity): 309 and 311 (M+, 3 and 2), 294 and 296 (6 and 6), 281 and 283 (9 and 8), 228 and 230
(base and 64).
3.2.4. N,O ligand 3d
The above procedure was followed using (1R)-(+)-nopinone. After workup, it gave 3.38 g (57%) of 3d
as a liquid: [α]D25=+4.3 (c=0.56, CHCl3); IR (KBr): 3444.4 s, 1572.2 s, 1550.0 vs; 1H NMR (CDCl3): δ
1.13 (d, 1H, J=10.2 Hz), 1.24 (s, 3H), 1.26 (s, 3H), 1.80–2.40 (m, 6H), 2.56 (m, 1H), 3.78 (s, 1H), 7.34
(d, 1H, J=7.7 Hz), 7.39 (d, 1H, J=7.7 Hz), 7.52 (t, 1H, J=7.7 Hz); 13C NMR (CDCl3): δ 23.39, 24.79,
27.60, 27.68, 29.32, 38.71, 39.93, 52.87, 78.88, 118.29, 125.88, 138.44, 140.50, 168.15; MS (EI) m/z
(rel. intensity): 295 and 297 (M+, 4 and 4), 278 and 280 (20 and 18), 213 and 215 (base and 88).
3.3. General procedures for synthesis of bipyridines 4a–d
To a solution of NiCl2·6H2O (6 mmol, 1.43 g) in degassed DMF (30 ml) at 70°C under N2,
triphenylphosphine (24 mmol, 6.30 g) was added to give a blue solution. Zinc powder (13 mmol, 0.87 g)
was then added and the resulting mixture was stirred for 1 h which resulted in the formation of a dark-
brown mixture. N,O ligand 3 (5 mmol) in degassed DMF (5 ml) was added slowly and the mixture was
stirred for another 3 h. The mixture was then allowed to cool to room temperature and 5% aqueous NH3
(50 ml) was added. The layers were separated, and the aqueous layer was extracted with CH2Cl2 (three
times by 70 ml). The combined organic layers were washed with water (three times by 50 ml) and once
with brine (50 ml). Drying with Na2SO4 and removal of the solvent under reduced pressure yielded a pale
yellow solid. This was purified by column chromatography (25:1 petroleum ether:ethyl acetate) to give a
white solid which was characterized by IR, 1H NMR, 13C NMR, CHN, MS and elemental analyses.
3.3.1. Bipyridine 4a
The above general procedure was followed using N,O ligand 3a. The usual workup gave 0.53 g (46%)
of 4a: mp 159–161°C; [α]D25=−40.5 (c=0.50, CCl4); IR (KBr): 3380.6 s, 1577.8 s; 1H NMR (CDCl3): δ
0.63 (d, 6H, J=6.69 Hz), 0.77 (d, 6H, J=6.9 Hz), 0.84 (d, 6H, J=6.6 Hz), 1.00 (m, 2H), 1.20 (m, 2H), 1.32
(m, 2H), 1.48–1.73 (m, 8H), 1.78–2.02 (m, 4H), 5.35 (s, 2H), 7.30 (d, 2H, J=7.7 Hz), 7.79 (t, 2H, J=7.7

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Hz), 8.24 (d, 2H, J=7.7 Hz); 13C NMR (CDCl3): 18.67, 20.08, 22.50, 23.77, 27.64, 28.69, 35.38, 50.01,
50.85, 77.36, 118.79, 119.49, 137.89, 152.65, 164.72; positive ion FAB mass spectra m/z: 465 (M++H).
Anal. calcd for C30H44N2O2: C, 77.54; H, 9.54; N, 6.03. Found: C, 77.58; H, 9.41; N, 6.01.
3.3.2. Bipyridine 4b
The above general procedure was followed using N,O ligand 3b. The usual workup gave 0.52 g (45%)
of 4b: mp 232–234°C; [α]D25=−59.8 (c=0.51, CCl4); IR (KBr): 3466.7 s, 3433.4 vs, 1566.7 vs; 1H NMR
(CDCl3): δ 0.82 (s, 6H), 0.85 (s, 6H), 1.22 (s, 6H), 1.16–1.34 (m, 4H), 1.68–1.82 (m, 4H), 1.87 (t, 2H,
J=4.4 Hz), 2.16 (d, 2H, J=14.0 Hz), 2.22–2.34 (s, 2H), 5.20 (s, 2H), 7.41 (d, 2H, J=7.7 Hz), 7.74 (t,
2H, J=7.7 Hz), 8.19 (d, 2H, J=7.7 Hz); 13C NMR (CDCl3): δ 10.11, 21.30, 21.42, 27.11, 30.90, 44.12,
45.46, 50.58, 53.55, 82.89, 118.75, 120.70, 136.74, 153.25, 162.90; positive ion FAB mass spectra m/z:
461 (M++H). Anal calcd for C30H40N2O2: C, 78.22, H, 8.75; N, 6.08. Found: C, 76.48; H, 8.46; N, 5.46.
3.3.3. Bipyridine 4c
The above general procedure was followed using N,O ligand 3c. The usual workup gave 0.54 g (47%)
of 4c: mp 176–178°C; [α]D25=+27.2 (c=0.51, CCl4); IR (KBr): 3366.7 s, 3300.1 s, 1572.3 vs; 1H NMR
(CDCl3): δ 0.52 (s, 6H), 1.02 (s, 6H), 1.05 (s, 6H), 1.20 (m, 2H), 1.40 (m, 2H), 1.50 (m, 2H), 1.85
(m, 4H), 2.35 (m, 4H), 6.10 (s, 2H), 7.57 (d, 2H, J=7.7 Hz), 7.80 (t, 2H, J=7.7 Hz), 8.22 (d, 2H,
J=7.7 Hz); 13C NMR (CDCl3): δ 17.30, 22.41, 24.51, 29.48, 32.60, 42.08, 46.10, 48.88, 52.08, 83.84,
118.45, 123.16, 136.16, 152.41, 161.63; positive ion FAB mass spectra m/z: 461 (M++H). Anal. calcd
for C30H40N2O2: C, 78.22; H, 8.75; N, 6.08. Found: C, 78.79, H, 8.65; N, 5.41.
3.3.4. Bipyridine 4d
The above general procedure was followed using N,O ligand 3d. The usual workup gave 0.50 g (46%)
of 4d: mp 142–144°C; [α]D25=−19.1 (c=0.51, CCl4); IR (KBr): 3444.2 s, 1570.8 s; 1H NMR (CDCl3):
δ 0.87 (m, 2H), 1.28 (s, 6H), 1.30 (s, 6H), 1.90–2.30 (m, 12H), 2.62 (m, 2H), 4.70 (s, 2H), 7.50 (d, 2H,
J=7.7 Hz), 7.82 (d, 2H, J=7.7 Hz), 8.29 (t, 2H, J=7.7 Hz); 13C NMR (CDCl3): δ 23.50, 25.05, 27.77,
29.90, 38.91, 40.10, 53.55, 78.86, 118.86, 119.79, 137.22, 153.55, 165.67; positive ion FAB mass spectra
m/z: 433 (M++H). Anal. calcd for C28H36N2O2: C, 77.74; H, 8.39; N, 6.48. Found: C, 77.76, H, 8.86; N,
6.67.
3.4. General procedures for the synthesis of N,O ligands 5a,b
A solution of N,O ligand 3 (5.76 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.17 mmol, 0.2
g) in toluene (12 ml) was treated with a solution of Na2CO3 (11.53 mmol, 1.22 g) in H2O (6 ml) followed
by a solution of phenylboronic acid (6.92 mmol, 0.84 g) in MeOH (3 ml). The mixture was stirred at 85°C
for 4 h under N2. After cooling to room temperature, a solution of concentrated aqueous NH3 (2.9 ml) in
saturated aqueous Na2CO3 (29 ml) was added and the mixture was extracted with CH2Cl2 (three times by
50 ml). The combined organic layers were washed with brine (50 ml) and dried with Na2SO4. Removal
of the solvent under reduced pressure gave a crude product which was purified by chromatography (25:1,
petroleum ether:ethyl acetate). This product was characterized by IR, 1H NMR, 13C NMR, MS and CHN.
3.4.1. N,O ligand 5a
Following the above procedure using N,O ligand 3a and the usual workup gave 0.84 g (47%) of 5a:
mp 102–103°C; [α]D25=−35.5 (c=0.51, CCl4); IR (KBr): 3377.8 s, 1572.2 s; 1H NMR (CDCl3): δ 0.69
(d, 3H, J=7.1 Hz), 0.84 (d, 3H, J=7.1 Hz), 0.91 (d, 3H, J=7.1 Hz), 1.07 (m, 1H), 1.26 (m, 1H), 1.38 (m,

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1H), 1.56–1.80 (m, 4H), 1.84–2.10 (m, 2H), 5.66 (s, 1H), 7.27 (d, 1H, J=7.7 Hz), 7.45 (m, 3H), 7.64 (d,
1H, J=7.7 Hz), 7.78 (t, 1H, J=7.7 Hz), 8.03 (d, 2H, J=6.9 Hz); 13C NMR (CDCl3): δ 18.57, 22.05, 22.39,
23.63, 27.51, 28.53, 35.30, 50.01, 50.73, 77.08, 117.54, 117.97, 126.64, 128.52, 128.93, 137.56, 138.45,
154.18, 164.83; MS (EI) m/z (rel. intensity): 309 (M+, 23), 266 (17), 224 (85), 198 (64), 169 (31), 154
(base). Anal. calcd for C21H27NO: C, 81.51; H, 8.79; N, 4.53. Found: C, 81.71; H, 8.43; N, 4.32.
3.4.2. N,O ligand 5b
Following the above procedure using N,O ligand 3b and the usual workup gave 0.94 g (53%) of 5b:
mp 88–89°C; [α]D25=−61.4 (c=0.51, CCl4); IR (KBr): 3377.8 s, 1572.2 s; 1H NMR (CDCl3): δ 0.88 (s,
3H), 0.92 (s, 3H), 1.30 (s, 3H), 1.24–1.40 (m, 3H), 1.76–1.96 (m, 2H), 2.14–2.40 (m, 2H), 5.45 (s, 1H),
7.36–7.52 (m, 4H), 7.64 (d, 1H, J=7.7 Hz), 7.74 (t, 1H, J=7.7 Hz), 8.01 (d, 2H, J=6.9 Hz); 13C NMR
(CDCl3): δ 10.17, 21.30, 21.44, 27.15, 30.89, 44.22, 45.45, 50.58, 53.55, 82.85, 118.15, 118.94, 126.67,
128.60, 128.96, 136.45, 138.72, 154.64, 163.13; MS (EI) m/z (rel. intensity): 307 (M+, 27), 264 (12), 198
(base), 169 (31), 154 (52). Anal. calcd for C21H25NO: C, 82.04; H, 8.20; N, 4.56. Found: C, 82.17; H,
8.02; N, 4.01.
3.5. General procedures for the synthesis of bipyridine ligands 6a,b
A solution of 2-bromopyridine (1.1 g, 7 mmol) in THF (30 ml) at −78°C was treated slowly with a 2.5
M solution of n-butyllithium in n-hexane (2.8 ml, 7 mmol). The resulting red-brown solution was stirred
at this temperature for 30 min and transferred through a cannula into a cold (−78°C) solution of dry
ZnCl2 (0.96 g) in THF (20 ml) (ZnCl2 was used after fusion by flame-drying under reduced pressure).
The color of the solution remained the same at this temperature. After warming to room temperature, the
mixture was stirred until the color changed to yellow-brown. This mixture was transferred into a stirred
solution of N,O ligand 3 (3.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.4 mmol, 0.4 g) in
THF (20 ml). After stirring for 16 h at room temperature, 100 ml of saturated aqueous NaHCO3 was
added, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (three times by 50
ml) and the combined organic layers were washed with brine (50 ml) and dried with Na2SO4. The solvent
was removed under reduced pressure to give a crude product which was purified by chromatography on
1
a silica gel column (10:1, petroleum ether:triethyl amine). Product was characterized by IR, H NMR,
13C NMR, MS and CHN.
3.5.1. Bipyridine ligand 6a
The above procedure was followed using ligand 3a. The usual workup gave 0.85 g (78%) of 6a: mp
1
77–78°C; [α]D25=−28.7 (c=0.52, CCl4); IR (KBr): 3366.7 s, 1577.8 s, 1562.6 s; H NMR (CDCl3): δ
0.69 (d, 3H, J=6.9 Hz), 0.84 (d, 3H, J=6.9 Hz), 0.91 (d, 3H, J=6.6 Hz), 1.08 (m, 1H), 1.27 (m, 1H), 1.40
(m, 1H), 1.56–1.80 (m, 4H), 1.84–2.08 (m, 2H), 5.46 (s, 1H), 7.28–7.40 (m, 2H), 7.78–7.90 (m, 2H),
8.32 (d, 1H, J=7.7 Hz), 8.41 (d, 1H, J=8.0 Hz), 8.69 (d, 1H, J=4.4 Hz); 13C NMR (CDCl3): δ 18.55,
22.03, 22.38, 23.61, 27.48, 28.55, 35.28, 50.00, 50.68, 77.16, 118.75, 119.24, 120.80, 123.61, 136.69,
137.76, 148.94, 153.13, 155.36, 164.49; MS (EI) m/z (rel. intensity): 310 (M+, 36), 267 (34), 225 (base),
199 (83), 170 (32), 155 (86). Anal. calcd for C20H26N2O: C, 77.38; H, 8.44; N, 9.02. Found: C, 77.12;
H, 8.47; N, 8.74.
3.5.2. Bipyridine ligand 6b
The above procedure was followed using ligand 3b. The usual workup gave 0.95 g (88%) of 6b: mp
1
97–99°C; [α]D25=−49.6 (c=0.52, CCl4); IR (KBr): 3388.9 s, 1577.8 s, 1560.7 s; H NMR (CDCl3): δ

3800
H.-L. Kwong, W.-S. Lee / Tetrahedron: Asymmetry 10 (1999) 3791–3801
0.89 (s, 3H), 0.93 (s, 3H), 1.30 (s, 3H), 1.20–1.45 (m, 2H), 1.70–2.00 (m, 3H), 2.20–2.40 (m, 2H), 5.21
(s, 1H), 7.32 (m, 1H), 7.48 (d, 1H, J=7.7 Hz), 7.78–7.85 (m, 2H), 8.30–8.40 (m, 2H), 8.67 (m, 1H); 13
C
NMR (CDCl3): δ 9.94, 21.16, 21.29, 26.96, 30.75, 43.97, 45.35, 50.44, 53.42, 82.77, 118.81, 120.46,
120.67, 123.57, 136.59, 136.69, 148.88, 153.52, 155.48, 162.67; MS (EI) m/z (rel. intensity): 308 (M+,
20), 265 (12), 199 (base), 170 (21), 155 (34). Anal. calcd for C20H24N2O: C, 77.89; H, 7.84; N, 9.08.
Found: C, 77.88; H, 7.92; N, 8.56.
3.6. General procedures for the addition of diethylzinc to aldehydes
Chiral ligand (0.05 mmol, 5 mol%) in dry toluene (1.0 ml) was cooled to 0°C and 1 M diethylzinc in
hexane (1.5 mmol, 1.5 ml) was added slowly. The mixture was allowed to stir at room temperature for
30 min. Freshly distilled aldehyde (1 mmol) was added and the reaction was monitored by GC. After
the reaction was completed, it was quenched by addition of 2 N HCl (5 ml). The layers were separated
and the aqueous layer was extracted with ether (three times by 20 ml). The combined organic layers
were dried by Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography.
Enantiomeric excesses for the products were determined by chiral GC with a Chrompack Chirasil-DEX
CB column.
Acknowledgements
Financial support for this research from the Hong Kong Research Grants Council and City University
of Hong Kong is gratefully acknowledged.
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