2486 J . Org. Chem., Vol. 63, No. 8, 1998
Uenishi et al.
t, J ) 7.7 Hz), 7.68 (1H, t, J ) 7.7 Hz), 7.50 (1H, d, J ) 7.7
mg), lipase (30 mg), and vinyl acetate (0.2 mL) in dry
diisopropyl ether (20 mL) was stirred vigorously in the
presence of molecular sieves 4A (100 mg). The reaction time,
temperature, and yield are indicated in Table 1. After the
reaction was complete, in which half of the alcohol was
converted to the acetate, the reaction mixture was filtered
through a Celite pad or filtering paper. The filtrate was
condensed, and the residue was purified by column chroma-
tography on silica gel to give the (R)-acetate and a recovery of
the (S)-alcohol. Each enantiomeric purity was determined by
HPLC connected with a chiral column directly or a transfor-
mation to the appropriate derivatives, or alternatively by
Mosher analysis. Physical properties including specific rota-
tion values and spectroscopic data for the (R)-acetates and
physical data and specific rotation values for the recovered
(S)-alcohols are described as follows:
Hz), 7.27 (1H, d, J ) 7.7 Hz), 4.83 (2H, s), 3.80 (1H, br s); 13
C
NMR (100 MHz, CDCl3) δ 158.4, 156.8, 153.2, 141.6, 139.2,
137.7, 128.1, 121.0, 120.2, 119.6, 64.0; IR (KBr) 3420 cm-1
;
MS (EI) m/z (rel intensity) 265 and 263 (M+, base and 93),
237 and 235 (26 and 39), 210 and 208 (4 and 4), 183 (11), 155
(51). Anal. Calcd for C11H9N2OBr: C, 49.84; H,3.42; N, 10.57.
Found: C, 49.76; H, 3.38; N, 10.50. The above alcohol (563
mg, 2.12 mmol) was subjected to the standard Swern oxidation
to give the corresponding aldehyde, which was dissolved in a
mixture of dichloromethnane and ether (15 mL, 2:1).
A
ethereal solution of methylmagnesium bromide (2.76 mL, 0.9
M solution in ether) was added to the aldehyde at 0 °C. The
mixture was stirred for 10 min at the same temperature and
quenched with water (5 mL). The reaction mixture was
extracted with EtOAc (50 mL), washed with water and brine,
and dried over MgSO4. Evaporation of the solvent and
purification of the residue by silica gel column chromatography
eluted with 50% EtOAc to give 2h (417 mg) in 72% yield:
colorless crystals; mp 76-77 °C (hexane), Rf ) 0.58 (50%
EtOAc in hexane; 1H NMR (400 MHz, CDCl3) δ 8.37 (1H, dd,
J ) 7.7, 0.7 Hz), 8.31 (1H, d, J ) 7.9 Hz), 7.81 (1H, t, J ) 7.7
Hz), 7.66 (1H, t, J ) 7.7 Hz), 7.48 (1H, dd, J ) 7.7, 0.7 Hz),
7.30 (1H, d, J ) 7.7 Hz), 4.94 (1H, q, J ) 6.6 Hz), 4.38 (1H, br
s), 1.54 (3H, d, J ) 6.6 Hz); 13C NMR (100 MHz, CDCl3) δ
162.4, 156.7, 152.8, 141.6, 139.1, 137.9, 128.1, 120.5, 120.0,
119.6, 68.7, 24.2; IR (KBr) 3240 cm-1; MS (EI) m/z (rel
intensity) 280 and 278 (M+, 19 and 19), 265 and 263 (82 and
base), 155 (25). Anal. Calcd for C12H11N2OBr: C, 51.64;
H,3.97; N, 10.04. Found: C, 51.74; H, 3.97; N, 10.04.
P r ep a r a tion of P yr id yl Alcoh ol (Meth od B). To an
ethereal solution (186 mL) of 2-pyridinecarboxaldehyde (2 g,
18.7 mmol) was added methyl-, ethyl-, vinyl-, or allylmagne-
sium bromide in ether or THF (24.27 mmol) at 0 °C. The
mixture was stirred for 2 h, quenched with ice-water (5 mL),
and extracted with EtOAc. The extract was washed with
water and brine and dried over MgSO4. The solvent was
removed, and the residue was purified by column chromatog-
raphy on silica gel eluted with 100%, 50%, 50%, and 40%
EtOAc in hexane, respectively, for 2a ,19 2l, 2m , and 2n . The
physical and spectroscopic data for 2l, 2m , and 2n are
described as follows:
(R)-3a : oil; [R]28 +97.4° (c 2.03, CHCl3); 1H NMR (300
D
MHz, CDCl3) δ 8.59 (1H, dm, J ) 4.9 Hz), 7.69 (1H, td, J )
7.7, 1.8 Hz), 7.33 (1H, d, J ) 7.7 Hz), 7.23 (1H, ddm, J ) 7.7,
4.9 Hz), 5.91 (1H, q, J ) 6.7 Hz), 2.13 (3H, s), 1.60 (3H, d, J )
6.7 Hz); 13C NMR (75 MHz, CDCl3) δ 170.1, 160.1, 149.1, 136.6,
122.5, 120.3, 72.9, 21.1, 20.6; IR (film) 1730 cm-1; MS (FAB)
m/z 166 (MH+); HRMS calcd for C9H12NO2 MH+, 166.0868,
found m/z 166.0843. (S)-2a :19 colorless crystals; mp 28-29 °C
(hexane); [R]29 -28.1° (c 2.23, CHCl3).
D
(R)-3b: oil; [R]25 +72.1° (c 2.09, CHCl3); 1H NMR (300
D
MHz, CDCl3) δ 7.55 (1H, t, J ) 7.7 Hz), 7.43 (1H, d, J ) 7.7
Hz), 7.29 (1H, d, J ) 7.7 Hz), 5.86 (1H, q, J ) 6.7 Hz), 2.13
(1H, s), 1.51 (3H, d, J ) 6.7 Hz); 13C NMR (75 MHz, CDCl3) δ
170.0, 161.8, 141.5, 139.0, 127.0, 118.9, 72.3, 21.1, 20.6; IR
(film) 1740 cm-1; MS (FAB) m/z 244 and 246 (MH+) HRMS
calcd for C9H11BrNO2 MH+, 243.9973 and 245.9953, found m/z
243.9981 and 245.9935. (S)-2b:12b oil; [R]25 -11.0° (c 2.15,
D
CHCl3).
(R)-3c: oil; [R]25 +104° (c 2.0, CHCl3); Rf ) 0.63 (50%
D
EtOAc in hexane); 1H NMR (400 MHz, CDCl3) δ 7.56 (1H, t, J
) 7.7 Hz), 7.12 (1H, d, J ) 7.7 Hz), 7.05 (1H, d, J ) 7.7 Hz),
5.87 (1H, q, J ) 6.7 Hz), 2.55 (3H, s), 2.12 (3H, s), 1.58 (3H, d,
J ) 6.7 Hz); 13C NMR (100 MHz, CDCl3) δ 170.2, 159.8, 157.9,
136.8, 122.2, 116.9, 73.3, 24.4, 21.2, 20.9; IR (film) 1730 cm-1
;
MS (EI) m/z (rel intensity) 179 (M+, 6); HRMS calcd for
C10H14NO2 MH+, 180.1025, found m/z 180.1017. (S)-2c: color-
less crystals; mp 43-44 °C (hexane); [R]25 -10.1° (c 1.51,
1-(2-P yr id yl)p r op a n ol (2l).26 oil; Rf ) 0.27 (70% EtOAc
D
1
CHCl3).
in hexane); H NMR (400 MHz, CDCl3) δ 8.52 (1H, dm, J )
(R)-3d : oil; [R]25 +58° (c 0.40, CHCl3); Rf ) 0.50 (20%
4.8 Hz), 7.66 (1H, td, J ) 7.7, 1.7 Hz), 7.24 (1H, d, J ) 7.7
Hz), 7.18 (1H, ddm, J ) 7.7, 4.8 Hz), 4.68 (1H, dd, J ) 7.4, 4.7
Hz), 4.25 (1H, br s), 1.87 (1H, m), 1.71 (1H, dq, J ) 14.1, 7.4
Hz), 0.93 (3H, t, J ) 7.4 Hz); 13C NMR (100 MHz, CDCl3) δ
162.0, 148.1, 136.6, 122.2, 120.4, 73.7, 31.3, 9.4; IR (film) 3400
cm-1; MS (FAB) m/z 138 (MH+); HRMS calcd for C8H12NO
MH+, 138.0919, found m/z 138.0915.
D
EtOAc in hexane); 1H NMR (300 MHz, CDCl3) δ 7.69 (1H, t, J
) 7.7 Hz), 7.42 (1H, d, J ) 7.7 Hz), 7.18 (1H, d, J ) 7.7 Hz),
5.86 (1H, q, J ) 6.7 Hz), 4.83 (2H, s), 2.11 (3H, s), 1.56 (3H, d,
J ) 6.7 Hz), 0.95 (9H, s), 0.12 (6H, s); 13C NMR (100 MHz,
CDCl3) δ 169.9, 160.9, 159.2, 137.1, 118.7, 118.1, 73.0, 66.0,
25.8, 21.1, 20.7, 18.2, -5.5; IR (film) 1738 cm-1; MS (FAB) m/z
310 (MH+, 59); HRMS calcd for C16H28NO3Si MH+, 310.1839,
1-(2-P yr id yl)-2-p r op en -1-ol (2m ): oil; Rf ) 0.30 (60%
EtOAc in hexane); 1H NMR (400 MHz, CDCl3) δ 8.55 (1H, dm,
J ) 4.8 Hz), 7.70 (1H, td, J ) 7.7, 1.6 Hz), 7.30 (1H, d, J ) 7.7
Hz), 7.22 (1H, ddm, J ) 7.7, 4.8 Hz), 5.97 (1H, ddd, J ) 17.0,
10.2, 6.7 Hz), 5.46 (1H, dm, J ) 17.0 Hz), 5.25 (1H, dm, J )
10.2 Hz), 5.19 (1H, d, J ) 6.7 Hz), 4.75 (1H, br s); 13C NMR
(100 MHz, CDCl3) δ 159.9, 148.1, 139.4, 136.8, 122.5, 120.9,
116.5, 74.2; IR (film) 3320 cm-1; MS (FAB) m/z 136 (MH+);
HRMS calcd for C8H10NO MH+, 136.0762, found m/z 136.0741.
1-(2-P yr id yl)-3-bu ten -1-ol (2n ):22 oil; Rf ) 0.27 (40%
EtOAc in hexane); 1H NMR (400 MHz, CDCl3) δ 8.52 (1H, dm,
J ) 4.7 Hz), 7.68 (1H, td, J ) 7.7, 1.7 Hz), 7.31 (1H, d, J ) 7.7
Hz), 7.19 (1H, ddm, J ) 7.7, 4.7 Hz), 5.83 (1H, m), 5.13-5.08
(2H, m), 4.81 (1H, dd, J ) 7.1, 4.9 Hz), 4.26 (1H, br s), 2.63
(1H, m), 2.49 (1H, m); 13C NMR (100 MHz, CDCl3) δ 161.5,
148.2, 136.6, 134.1, 122.3, 120.4, 117.9, 72.3, 42.8; IR (film)
3360 cm-1; MS (FAB) m/z 150 (MH+); HRMS calcd for
C9H12NO MH+, 150.0919, found m/z 150.0933.
found m/z 310.1858. (S)-2d : oil; [R]25 -2.9° (c 1.97, CHCl3).
D
(R)-3e: oil; [R]25 +67° (c 0.73, CHCl3); Rf ) 0.38 (20%
D
EtOAc in hexane); 1H NMR (400 MHz, CDCl3) δ 7.73 (1H, t, J
) 7.6 Hz), 7.69 (1H, d, J ) 7.6 Hz), 7.50 (6H, d, J ) 7.7 Hz),
7.30 (6H, t, J ) 7.7 Hz), 7.23 (3H, tm, J ) 7.7 Hz), 7.19 (1H,
d, J ) 7.6 Hz), 5.82 (1H, q, J ) 6.6 Hz), 4.38 (1H, d, J ) 14.0
Hz), 4.33 (1H, d, J ) 14.0 Hz), 2.08 (3H, s), 1.51 (3H, d, J )
6.6 Hz); 13C NMR (100 MHz, CDCl3) δ 170.2, 159.4, 159.1,
143.9, 137.3, 128.7, 127.9, 127.1, 119.6, 118.4, 87.2, 73.1, 66.9,
21.2, 20.8; IR (film) 1780 cm-1; MS (EI) m/z (rel intensity) 194
(M+ - 243, 17), 407 (4), 360 (19), 243 (base). Anal. Calcd for
C
29H27NO3: C, 79.61; H, 6.22; N, 3.20. Found: C, 79.55; H,
6.32; N, 3.08. (S)-2e: colorless crystals; mp 36-37 °C (hex-
ane); [R]25 +0.2° (c 1.83, CHCl3).
D
(R)-3f: oil; [R]25 +86° (c 1.00, CHCl3); Rf ) 0.27 (10%
D
EtOAc in hexane); 1H NMR (400 MHz, CDCl3) δ 8.01 (2H, dm,
J ) 7.5 Hz), 7.70 (1H, t, J ) 7.6 Hz), 7.60 (1H, d, J ) 7.6 Hz),
7.44 (2H, tm, J ) 7.5 Hz), 7.38 (1H, tm, J ) 7.5 Hz), 7.25 (1H,
d, J ) 7.6 Hz), 6.01 (1H, q, J ) 6.6 Hz), 2.15 (3H, s), 1.66 (3H,
d, J ) 6.7 Hz); 13C NMR (100 MHz, CDCl3) δ 170.1, 160.1,
156.5, 139.1, 137.3, 128.9, 128.6, 126.9, 119.0, 118.3, 73.2, 21.2,
20.6; IR (film) 1740 cm-1; MS (EI) m/z (rel intensity) 241 (M+,
14), 198 (89), 182 (base), 155 (34), 154 (57); HRMS calcd for
Asym m etr ic Acetyla tion of P yr id yl Alcoh ols 2a -n
(Gen er a l P r oced u r e). A mixture of secondary alcohol (100
(26) Brown, H. C.; Vara Prasad, J . V. N.; Zee, S.-H. J . Org. Chem.
1986, 51, 439. Ohno, A.; Nakai, J .; Nakamura, K.; Goto, T.; Oka, S.
Bull. Chem. Soc. J pn. 1981, 54, 3482.