Catalytic asymmetric synthesis and asymmetric autocatalysis of chiral 5,5'-(3,3'-bipyridyl)-dialkanediol

Article abstract of DOI:10.3987/com-00-8979

(S,S)-(-)-5,5'-(3,3'-Bipyridyl)dialkanediols (5a, b) with up to 98.6% e.e. was synthesized by the enantioselective addition of dialkylzincs to 3,3'-bipyridine-5,5'-dicarbaldehyde (4) using N,N-dipropylnorephedrine as a chiral catalyst. Chiral diol (5a) was found to work as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to aldehyde (4).

Full text of DOI:10.3987/com-00-8979

HETEROCYCLES, Vol. 53, No.10, 2000, pp. 2183 - 2189, Received, 19th June, 2000
CATALYTIC ASYMMETRIC SYNTHESIS AND ASYMMETRIC
AUTOCATALYSIS
DIALKANEDIOL
OF
CHIRAL
5,5'-(3,3'-BIPYRIDYL)-
Shigehisa Tanji, Tomohiko Nakao, Itaru Sato, and Kenso Soai*
Department of Applied Chemistry, Faculty of Science, Science University of
Tokyo, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601 Japan
Abstract – (S,S)-(-)-5,5´-(3,3´-Bipyridyl)dialkanediols (5a, b) with up to 98.6%
e.e. was synthesized by the enantioselective addition of dialkylzincs to 3,3´-
bipyridine-5,5´-dicarbaldehyde (4) using N,N-dipropylnorephedrine as a chiral
catalyst. Chiral diol (5a) was found to work as an asymmetric autocatalyst in the
enantioselective addition of diisopropylzinc to aldehyde (4).
Chiral diols with C2-symmetry axis are known to be useful ligands in asymmetric synthesis.1,2 However, the
synthesis of chiral diols by the enantioselective alkylation of dialdehyde has not been extensively examined.3
On the other hand, asymmetric autocatalysis,4 in which a chiral product catalyzes its own production, has
attracted much attention. An asymmetric autocatalysis of a chiral diol is important because a bifunctional
molecule automultiplies by constructing two stereogenic centers.5 We previously reported asymmetric
autocatalysis of chiral pyridyl alkanols6 in the enantioselective alkylation of pyridine-3-carbaldehyde and its
derivatives with dialkylzinc.
In this paper, we report an enantioselective dialkylation of 3,3´-bipyridine-5,5´-dicarbaldehyde (4) with
dialkylzincs which affords highly enantiomerically enriched (S,S)-5,5´-(3,3´-bipyridyl)dialkanediols (5a,
b). We also report an asymmetric autocatalytic reaction of (S,S)-(-)-5,5´-bis(1-hydroxy-2-methylpropyl)-
3,3´-bipyridine (5a), in which a chiral diol (5a) automultiplies without the need for any other chiral auxiliary,
in the enantioselective dialkylation of dicarbaldehyde (4) with diisopropylzinc (i-Pr2Zn).
Synthetic rout of 3,3´-bipyridine-5,5´-dicarbaldehyde (4) is shown in Scheme 1. 5-Bromonicotinic acid (1)
was converted into acid chloride using thionyl chloride. Subsequent treatment with N,O-
dimethylhydroxylamine hydrochloride and triethylamine gave Weinreb’s amide (2)7 in a total yield of 96%
from acid (1). Nickel(0)-mediated homocoupling8 of 2 afforded 3,3´-bipyridine (3) in 82%. Subsequent
reduction of 3 using DIBAL in THF at –100 ˚C gave dialdehyde (4) in 51%.
The results of the catalytic enantioselective dialkylation of dialdehyde (4) are summarized in Table 1. When
dialdehyde (4) was treated with i-Pr2Zn in the presence of (1S,2R)-N,N-dipropylnorephedrine (DPNE),9
enantiomerically enriched diol ((S,S)-(-)-5a)10 with 83.6% e.e. (dl/meso = 68/32) was obtained (Entry 1).
When the amount of (1S,2R)-DPNE was increased, the reaction afforded almost enantiomerically pure

Scheme 1.
O
O
Br
COOH
SOCl2
reflux
Br
MeONHMe•HCl
Et3N, CH2Cl2
Br
OMe
Cl
N
Me
N
N
N
1
2 96%
MeO
Me
O
N
O
OMe
OHC
CHO
N
N
NiCl2, Zn, PPh3
DMF, 50 ˚C
DIBAL
Me
THF, -100 ˚C
N
N
N
3 82%
4 51%
Table 1. Enantioselective synthesis of chiral (S,S)-(-)-5,5´-(3,3´-bipyridyl)dialkanediols (5a, b) using
(1S,2R)-DPNE
Ph
Me
R
R
OHC
CHO
HO
OH
HO
N(n-Pr)2
(1S,2R)-DPNE
toluene, 0 ˚C
+ R2Zn
N
N
N
N
4
5a; R=i-Pr
5b; R=Et
Chiral diol (2)
E.e.(%)a
83.6
Entry
R
Yield (%)
dl / mesoa
68 / 32
1b
2c
3c
i-Pr
i-Pr
Et
5a
5a
5b
34
52
47
98.6
85 / 15
92.3
72 / 28
a Determined by HPLC analyses using a chiral column (Chiralpak AD). b Molar ratio. (1S,2R)-DPNE :
4 : i-Pr2Zn = 0.4 : 1.0 : 10. c Molar ratio. (1S,2R)-DPNE : 4 : i-Pr2Zn = 0.8 : 1.0 : 10.
(S,S)-5a (98.6% e.e.) in a yield of 52% (dl/meso = 85/15) (Entry 2). In a similar manner, enantioselective
diethylation of (4) using diethylzinc in the presence of (1S,2R)-DPNE afforded (S,S)-(-)-5b10 with a high
enantiomeric purity (92.3% e.e., dl/meso = 72/28) (Entry 3).
Next, the enantioselective addition of i-Pr2Zn to dialdehyde (4) was examined by using chiral (S,S)-5a as an
asymmetric autocatalyst. The results are shown in Table 2. The product ((S,S)-5a), possessing the same
structure and the same configuration as those of the initial autocatalyst ((S,S)-5a) (>99.5% e.e., 10

mol%),11 was newly formed with 18.8% e.e. (Entry 1). When the asymmetric autocatalyst with 98.6% e.e.
was used (40 mol%), improved enantioselectivity of 28.9% e.e. was observed (Entry 3). We suppose that
chiral bis(alkylzinc alkoxide) ((S,S)-6a) formed in situ by the treatment of diisopropylzinc with (S,S)-5a
acts as an asymmetric autocatalyst for its own production.
Table 2. Asymmetric autocatalytic reaction of chiral (S,S)-5,5´-(3,3´-bipyridyl)dialkanediol (5a)
S
S
ZnO
S
N
S
OZn
HO
OH
i-Pr2Zn
N
N
N
(S,S)-6a
(S,S)-5a
H+
Asymmetric autocatalyst
OHC
CHO
N
N
4
+
i-Pr2Zn
Asymmetric autocatalyst
Asymmetric autocat. &
Newly formed diol (5a)a
Entry
(5a)
newly formed 5a
E.e./ %b
46.6
E.e./ %b dl / mesob
Yield/ %
5a 34
E.e./ %
18.8
dl / meso
56 / 44
53 / 47
58 / 42
1c 5a >99.5
2d 5a 78.2
3e 5a 98.6
>99.5 / <0.5
65 / 35
48.9
5a 21
5a 29
14.1
85 / 15
75.4
28.9
a
The amounts of the (S,S)- and (R,R)- enantiomers and meso- isomer of the diol used as an initial
asymmetric autocatalyst were subtracted from that of the obtained diol by calculation. b Determined by
c
HPLC analyses using a chiral column (Chiralpak AD).
1.0 : 10. d Molar ratio. (S,S)-5a : 4 : i-Pr2Zn = 0.2 : 1.0 : 10.
Molar ratio. (S,S)-5a : 4 : i-Pr2Zn = 0.1 :
e
Molar ratio. (S,S)-5a : 4 : i-Pr2Zn =
0.4 : 1.0 : 10.

In summary, highly enantiomerically enriched (S,S)-5,5´-(3,3´-bipyridyl)dialkanediols (5a, b) with up to
98.6% e.e. were synthesized by the enantioselective addition of dialkylzincs to 3,3´-bipyridine-5,5´-
dicarbaldehyde (4) using (1S,2R)-N,N-dipropylnorephedrine (DPNE) as a chiral catalyst. Furthermore,
chiral diol ((S,S)-5a) automultiplied in the asymmetric autocatalytic reaction of dialdehyde (4) with
diisopropylzinc.12
EXPERIMENTAL
General. Optical rotations were measured with Jasco DIP-1000 polarimeter. IR spectra were recorded
1
13
with Horiba FT-210 spectrophotometer. H and C NMR spectra were measured with Bruker DPX300
spectrometer using tetramethylsilane as an internal standard. High resolution mass spectra (HRMS) were
obtained with Hitachi M-80B mass spectrometer. Toluene was distilled from calcium hydride and dried
over molecular sieves 4A. All reactions were carried out under an argon atmosphere.
3-Bromo-5-(N-methoxy-N-methylcarbamoyl)pyridine (2). Thionyl chloride (30 mL, 411
mmol) was added to 5-bromonicotinic acid (1) (2.02 g, 10.0 mmol) and the mixture was refluxed for 6 h.
Excess of thionyl chloride was removed by distillation, and then the resulted mixture was evaporated to
dryness under reduced pressure. The residue (acid chloride) was dissolved in dichloromethane (20 mL),
then triethylamine (2.8 mL, 20 mmol) and N,O-dimethylhydroxylamine hydrochloride (975 mg, 10.0
mmol) were added successively at 0 ˚C. The mixture was warmed to rt and stirred for 24 h. The reaction
was quenched by the addition of sat. aq. sodium bicarbonate (20 mL). The reaction mixture was extracted
twice with 20 mL of ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate
and evaporated to dryness under reduced pressure. Purification of the residue by flash column
chromatography on silica gel (hexane : acetone = 7 : 1) afforded Weinreb’s amide (2) as a colorless oil. 2.35
g. Yield 96%. IR (neat) ν/cm-1 = 1647; 1H NMR (300 MHz, CDCl3) δ 3.39 (s, 3H), 3.58 (s, 3H), 8.18 (dd,
13
J = 2.0, 2.0 Hz, 1H), 8.75 (d, J = 2.0 Hz, 1H), 8.88 (d, J = 2.0 Hz, 1H); C NMR (75 MHz, CDCl3) δ
33.0, 61.3, 120.1, 130.9, 138.5, 147.2, 152.3, 165.6; HRMS found m/z 243.9843, calcd for
C8H9N2O2Br: 243.9848.
5,5´-Bis(N-methoxy-N-methylcarbamoyl)-3,3´-bipyridine (3). A suspension of NiCl2 (560
mg, 4.4 mmol), zinc powder (288 mg, 4.4 mmol) and triphenylphosphine (4.63 g, 17.6 mmol) in DMF
(15mL) was heated at 50 ˚C for 1 h, and amide (2) (2.16 g, 8.8 mmol) in DMF (5 mL) was added. After the
reaction mixture was stirred for 5 h at 50 ˚C, the mixture was cooled to rt and poured into 30 mL of 5%
aqueous NH3. The resulted mixture was filtered and the filtrate was extracted with ethyl acetate. The
combined organic layer was dried over anhydrous sodium sulfate and evaporated to dryness under reduced
pressure. Purification of the residue by flash column chromatography on silica gel (hexane : CH2Cl2 :
acetone : MeOH = 12 : 8 : 3 : 1) afforded 3,3´-bipyridine (3). 979 mg. Yield 81.5%. Colorless powder
1
(recrystallized from hexane – ethyl acetate). mp 87.0 – 88.0 ˚C; IR (KBr) ν/cm-1 = 1643; H NMR (300
MHz, CDCl3) δ 3.44 (s, 6H), 3.61 (s, 6H), 8.27 (dd, J = 2.1, 2.1 Hz, 2H), 8.95 (d, J = 2.1 Hz, 2H), 9.02
13
(d, J = 2.1 Hz, 2H); C NMR (75 MHz, CDCl3) δ 33.2, 61.4, 130.1, 132.2, 134.7, 148.9, 149.5, 166.8;
HRMS found m/z 330.1316, calcd for C16H18N4O4: 330.1329;Anal. Calcd for C16H18N4O4: C, 58.17; H,
5.49; N, 16.96. Found: C, 58.50; H, 5.71; N, 16.84.

3,3´-Bipyridine-5,5´-dicarbaldehyde (4). A toluene solution of 1.0 M DIBAL (10 mL, 10.0 mmol)
was added dropwise to a solution of 3,3´-bipyridine (3) (826 mg, 2.5 mmol) in THF (15 mL) at –100 ˚C,
and the mixture was stirred for 1 h. The reaction was quenched by the addition of 15 mL of mixed solvent
[THF : H2O = 1 : 1 (v/v)] at –100 ˚C, and the resulted mixture was warmed to rt. After stirring for 1 h, the
mixture was filtered through Celite and the filtrate was extracted with ethyl acetate. The combined organic
layer was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure.
Purification of the residue by flash column chromatography on silica gel (ethyl acetate : CHCl3 = 1 : 1)
afforded 4. 273 mg. Yield 51%. Colorless powder (recrystallized from hexane – ethyl acetate). mp 219.0 –
1
220.0 ˚C; IR (KBr) ν/cm-1 = 1693; H NMR (300 MHz, CDCl3) δ 8.43 (dd, J = 1.9, 2.2 Hz, 2H), 9.15 (d,
J = 2.2 Hz, 2H), 9.18 (d, J = 1.9 Hz, 2H), 10.25(s, 2H); 13C NMR (75 MHz, CDCl3) δ 131.5, 132.9,
133.9, 152.1, 152.9, 190.0; HRMS found m/z 212.0592, calcd for C12H8N2O2: 212.0586;Anal. Calcd for
C12H8N2O2: C, 67.92; H, 3.80; N, 13.20. Found: C, 67.87; H, 3.89; N, 13.21.
A typical experimental procedure for the enantioselective dialkylation of dialdehyde (4)
using (1S,2R)-N,N-dipropylnorephedrine (DPNE) (Table 2, Entry 2). To a mixture of
(1S,2R)-DPNE (56.5 mg, 0.24 mmol) and dialdehyde (4) (63.7 mg, 0.3 mmol) in toluene (3.0 mL), 1 M
toluene solution of diisopropylzinc (3.0 mL, 3.0 mmol) was added at 0 ˚C. After the mixture was stirred for
51 h at 0 ˚C, the reaction was quenched by the addition of 1 M hydrochloric acid (5 mL) followed by the
addition of sat. aq. sodium bicarbonate (15 mL). The resulted mixture was filtered through Celite and the
filtrate was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium
sulfate and evaporated to dryness under reduced pressure. Purification of the crude residue on silica gel TLC
(developing solvent. CH2Cl2 : MeOH = 10 : 1) gave diol (5a) (46.7 mg, 52%).
(S,S)-(-)-5,5´-Bis(1-hydroxy-2-methylpropyl)-3,3´-bipyridine
(5a).
Colorless
oil.
Enantiomeric excess of (S,S)-5a was determined to be 98.6% e.e. (dl/meso = 85.3/14.7) by HPLC
analysis using a chiral column (Daicel Chiralpak AD: 4 x 250 mm, 254 nm UV detector, rt, eluent: 10% 2-
propanol in hexane, flow rate: 1.0 mL/min, retention time: 16.4 min for the minor isomer, 21.7 min for the
meso- isomer and 30.1 min for the major isomer). Specific optical rotation of (S,S)-5a with >99.5% e.e.
1
(dl/meso = >99.5/<0.5) is shown in ref. 11. IR (neat) ν/cm-1 = 3228; H NMR (300 MHz, CDCl3) δ 0.85
(d, J = 6.7 Hz, 6H), 1.02 (d, J = 6.7 Hz, 6H), 2.01 (dqq, J = 6.5, 6.7, 6.7 Hz, 2H), 4.50 (d, J = 6.5 Hz,
2H), 4.81 (br s, 2H), 7.79 (dd, J = 1.7, 1.7 Hz, 2H), 8.26 (d, J = 1.7 Hz, 2H), 8.40 (d, J = 1.7 Hz, 2H);
13C NMR (75 MHz, CDCl3) δ 18.0, 18.8, 35.2, 76.9, 132.5, 132.7, 140.2, 146.1, 147.7; Anal. Calcd for
C18H24N2O2: C, 71.97; H, 8.05; N, 9.33. Found: C, 71.92; H, 8.10; N, 9.41.
(S,S)-(-)-5,5´-Bis(1-hydroxypropyl)-3,3´-bipyridine
(5b).
Colorless
oil.
Yield
47%.
Enantiomeric excess of (S,S)-5b was determined to be 92.3% e.e. (dl/meso = 71.8/28.2) by HPLC
analysis using a chiral column (Daicel Chiralpak AD: 4 x 250 mm, 254 nm UV detector, rt, eluent: 10% 2-
propanol in hexane, flow rate: 1.0 mL/min, retention time: 16.8 min for the minor isomer, 21.3 min for
meso- isomer and 25.4 min for the major isomer). [α]23 –28.2° (c 0.5, MeOH); IR (neat) ν/cm-1 = 3340;
D
1H NMR (300 MHz, CDCl3) δ 0.94 (t, J = 7.3 Hz, 6H), 1.75 (dq, J = 6.4, 7.3 Hz, 4H), 4.69 (t, J = 6.4
Hz,2H), 4.94 (br s, 2H), 7.83 (br s, 2H), 8.29 (br s, 2H), 8.41 (br s, 2H); 13C NMR (75 MHz, CDCl3) δ
10.0, 31.9, 72.8, 132.3, 133.0, 141.3, 146.0, 147.1; HRMS found m/z 272.1527, calcd for C16H20N2O2:

272.1526.
A typical experimental procedure of the asymmetric autocatalytic reaction using chiral
diol (5a) (Table 2, Entry 3). To a mixture of dialdehyde (4) (63.7 mg, 0.3 mmol) and diol ((S,S)-5a)
(36.0 mg, 0.12 mmol) with 98.6% e.e. (dl/meso = 85.3/14.7) [containing (S,S)-isomer (30.5 mg),
(R,R)-isomer (0.2 mg) and meso isomer (5.3 mg)] in toluene (4.1 mL) was added i-Pr2Zn (3.0 mmol, 3.0
mL of 1 M toluene solution) at 0 ˚C. After the reaction mixture was stirred for 44 h at 0 ˚C, the reaction was
quenched by the addition of 1 M hydrochloric acid (5 mL). After the mixture was neutralized by the addition
of sat. aq. sodium bicarbonate (15 mL), the mixture was filtered through Celite. The filtrate was extracted
with ethyl acetate. The extract was dried over anhydrous sodium sulfate and evaporated under reduced
pressure. Purification of the residue on silica gel TLC (developing solvent. CH2Cl2 : MeOH = 10 : 1) gave
diol (5a) (62.3 mg, 0.207 mmol), which contained the newly formed diol and the initially used diol as an
asymmetric autocatalyst. HPLC analysis using a chiral column (Chiralpak AD, eluent: 10% 2-propanol in
hexane; flow rate: 1.0 mL/min; 254 nm UV detector) showed that the enantiomeric purity of the obtained
diol ((S,S)-(-)-5a) was 75.4% e.e. (dl/meso = 73.7/26.3). Therefore, the obtained diol ((S,S)-5a)
contained (S,S)-isomer (40.3 mg), (R,R)-isomer (5.6 mg) and meso isomer (16.4 mg). The amount of the
newly formed diol (5a) was calculated as 62.3 – 36.0 = 26.3 mg (29% yield), consisting of the major
(S,S)-enantiomer (40.3 – 30.5 = 9.8 mg), the minor (R,R)-enantiomer (5.6 – 0.2 = 5.4 mg) and the meso
isomer (16.4 Å| 5.3 =11.1 mg). As a result, the enantiomeric purity of the newly formed diol ((S,S)-5a)
was calculated as 28.9% e.e. (dl/meso = 57.8/42.2).
ACKNOWLEDGMENT
This work was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education,
Science, Sports, and Culture of Japan. I. S. thanks DaicelAward in Synthetic Organic Chemistry.
REFERENCES AND NOTES
1. Review: J. K. Whitesell, Chem. Rev., 1989, 89, 1581.
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Kenmoku, A. Ahmed, and K. Inomata, Chem. Lett., 1997, 59; (c) K. Ding, A. Ishii, and K. Mikami,
Angew. Chem., Int. Ed. Engl., 1999, 38, 497; (d) D. Seebach, I. M. Lyapkalo, and R. Dahinden, Helv.
Chim. Acta, 1999, 82, 1829.
3. (a) K. Soai, H. Hori, and M. Kawahara, Chem. Commun., 1992, 106; (b) D. Seebach, A. K. Beck, B.
Schmidt, and Y. M. Wang, Tetrahedron, 1994, 50, 4363.
4. (a) K. Soai, T. Shibata, H. Morioka, and K. Choji, Nature, 1995, 378, 767; (b) T. Shibata, H. Morioka,
T. Hayase, K. Choji, and K. Soai, J. Am. Chem. Soc., 1996, 118, 471; (c) T. Shibata, K. Choji, H.
Morioka, T. Hayase, and K. Soai, Chem. Commun., 1996, 751; (d) T. Shibata, S. Yonekubo, and K.
Soai, Angew. Chem., Int. Ed. Engl., 1999, 38, 659.
5. (a) Asymmetric autocatalysis of a chiral diol; K. Soai, T. Hayase, C. Shimada, and K. Isobe, Tetrahedron:
Asymmetry, 1994, 5, 789; (b) cf. Asymmetric autoinduction of a chiral diol; K. Soai, Y. Inoue, T.
Takahashi, and T. Shibata, Tetrahedron, 1996, 42, 13355.

6. (a) T. Shibata, H. Morioka, S. Tanji, T. Hayase, Y. Kodaka, and K. Soai, Tetrahedron Lett., 1996, 37,
8783; (b) K. Soai, S. Niwa, and H. Hori, Chem. Commun., 1990, 982.
7. S. Nahm and S. M. Weinreb, Tetrahedron Lett., 1981, 22, 3815.
8. C. Bolm, M. Ewald, M. Felder, and G. Schlingloff, Chem. Ber., 1992, 125, 1169.
9. (a) K. Soai, T. Hayase, K. Takai, and T. Sugiyama, J. Org. Chem., 1994, 59, 7908; (b) K. Soai, S.
Yokoyama, and T. Hayasaka, J. Org. Chem., 1991, 56, 4264; For reviews on the enantioselective
addition of dialkylzincs to aldehydes: (c) K. Soai and S. Niwa, Chem. Rev., 1992, 92, 833; (d) K. Soai
and T. Hayase, Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem., Jpn.), 1995, 53, 138; (e) R.
Noyori and M. Kitamura, Angew. Chem., Int. Ed. Engl., 1991, 30, 49.
10. Absolute configuration is tentatively assigned based on our previous result that (1S,2R)-DPNE
catalyzes the enantioselective addition of i-Pr2Zn to benzaldehyde to afford (S)-2-methyl-1-phenyl-1-
propanol (ref. 9a).
11. Diol ((S,S)-5a) with >99.5% e.e. (dl/meso = >99.5/<0.5) was synthesized as follows:
Enantioselective isopropylation of 5-bromopyridine-3-carbaldehyde (7), derived from Weinreb’s amide
(2) by the reduction with DIBAL, using 50 mol% of (1S,2R)-DPNE as a chiral catalyst afforded (S)-8 in
the yield of 75% with 87.9% e.e. The e.e. of 8 was increased by recrystallization of the corresponding
camphanic acid ester from petroleum ether, and nickel(0)-mediated homocoupling8 followed by
hydrolysis gave (S,S)-5a with >99.5% e.e. ([α]21D –58.2° (c 0.6, MeOH)).
Ph
Me
HO
N(n-Pr)2
1) (-)-Camphanoyl chloride (quant.)
2) Recrystallization
HO
OH
Br
CHO
+ i-Pr2Zn
Br
(1S,2R)-DPNE
toluene, 0 ˚C
OH
3) NiCl2, Zn, PPh3, DMF (86%)
4) K2CO3, MeOH (93%)
N
N
N
N
7
(S)-8
75%, 87.9% e.e.
(S,S)-5a > 99.5% e.e.,
dl / meso = > 99.5 / < 0.5
(S)-1-{5-bromo(3-pyridyl)}-2-methyl-1-propanol (8). Colorless oil. Enantiomeric excess of
(S)-8 was determined to be 87.9% e.e. by HPLC analysis using a chiral column (Daicel Chiralcel OD-
H: 4 x 250 mm, 254 nm UV detector, rt, eluent: 0.4% 2-propanol in hexane, flow rate: 1.0 mL/min,
retention time: 130 min for the major isomer, 149 min for the minor isomer). [α]22 –58.6° (c 10.5,
D
CHCl3); IR (neat) ν/cm-1 = 3278; 1H NMR (300 MHz, CDCl3) δ 0.83 (d, J = 6.7 Hz, 3H), 0.95 (d, J =
6.7 Hz, 3H), 1.94 (dqq, J = 6.2, 6.7, 6.7 Hz, 1H), 4.39 (d, J = 6.2 Hz, 1H), 4.51 (br s, 1H), 7.85 (dd,
13
J = 2.0, 2.0 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.42 (d, J = 2.0 Hz, 1H); C NMR (75 MHz, CDCl3)
δ 17.6, 18.6, 35.1, 76.1, 120.6, 137.1, 141.4, 145.9, 148.9; HRMS found m/z 229.0111, calcd for
C9H12BrNO: 229.0102.
12. In the reaction of dialkylzinc and 2,2´-bipyridine-5,5´-dicarbaldehyde, unprecedented alkylation to the
pyridine ring occurred. The results will be reported elsewhere.