Notes
J . Org. Chem., Vol. 63, No. 9, 1998 3115
1b (3.49 g, 29.8 mmol), and acetic acid (30 µL, 2 mol %) gave
3.65 g (87%) of 3b after distillation as a colorless liquid: bp 76-
of 2-alkyl and 2-phenyl derivatives, which are obtained
in essentially quantitative yield.
78 °C/52 Torr; [R]27 -67.0° (c 3.32, THF).
D
(4S)-4-Ben zyl-2-m eth yl-2-oxa zolin e (3c). According to the
general procedure (method A), (S)-(-)-2c (3.02 g, 20.0 mmol) was
allowed to react with 1a (3.89 g, 24.0 mmol) in the presence of
acetic acid (50 µL, 4 mol %). Kugelrohr distillation (63-65 °C,
120 mTorr) afforded the title compound (3.27 g, 93%) as a
colorless oil: [R]25 -49.3° (c 2.83, CHCl3) [lit.18 [R]24 -50.7° (c
Exp er im en ta l Section
Gen er a l. 1H (400 MHz) and 13C (100 MHz) NMR spectra
were measured in CDCl3 with TMS as an internal standard.
Wherever necessary, NMR assignments were made with the aid
of COSY and DEPT experiments. 1,2-Dichloroethane was stored
over 4 A molecular sieves prior to use. All other reagents and
solvents obtained from commercial sources were used without
further purification. Amino alcohols, 2a -c, were prepared
according to the general literature procedure:13a 2a ; mp 76.0-
D
D
2.83, CHCl3); lit.3 [R]23 -47.9° (c 1.70, MeOH)]; IR (neat) 1676
D
cm-1 [lit.18 IR 1675 cm-1; lit.3 IR 1670 cm-1]; H NMR (CDCl3)
1
δ 1.96 (d, 3H, J ) 1.46 Hz), 2.64 (dd, 1H, J ) 8.30, 13.7 Hz),
3.08 (dd, 1H, J ) 5.37, 13.7 Hz), 3.92 (dd, 1H, J ) 7.33, 8.30
Hz), 4.16 (t, 1H, J ) 8.30 Hz), 4.31-4.39 (m, 1H), 7.18-7.31
(m, 5H); 13C NMR (CDCl3) δ 13.9, 41.8, 67.4, 71.8, 126.4, 127.8,
128.5, 129.2, 138.0, 165.0. Anal. Calcd for C11H13NO: C, 75.40;
H, 7.48; N, 7.99. Found: C, 75.14; H, 7.67; N, 7.92.
76.5 °C; [R]22D -26.1° (c 5.36, MeOH) [lit.14 mp 75-78 °C; [R]20
D
-27.1° (c 5.36, MeOH)], 2b; bp 88-90 °C/12 Torr; [R]22 +36.6°
D
(c 1.45, EtOH) [lit.15 mp 33-35 °C; [R]26 +37° (c 1.5, EtOH)],
D
2c; mp 95-96 °C; [R]25 -24.1° (c 1.37, EtOH) [lit.16 mp 91-93
D
°C; [R]22D -25.7° (c 1.37, EtOH)]. (1R,2S)-(-)-Norephedrine and
(1S,2S)-(+)-2-amino-3-methoxy-1-phenyl-1-propanol were pur-
chased from Aldrich. All reactions were carried out under a dry
atmosphere of argon except for one without an acid catalyst.
Glassware were generally oven-dried.
(4S,5R)-2,4-Dim eth yl-5-p h en yl-2-oxa zolin e (3d ). Follow-
ing the general procedure (method B), (1R,2S)-(-)-2d (3.02 g,
20.0 mmol), 1b (4.30 g, 35.8 mmol), and acetic acid (50 µL, 4
mol %) gave 3.17 g (91%) of 3d after Kugelrohr distillation (48-
50 °C, 50 mTorr) as a colorless liquid: [R]24 -247° (c 3.43,
D
CHCl3); IR (neat) 1678 cm-1; H NMR (CDCl3) δ 0.76 (d, 3H, J
1
Gen er a l P r oced u r e for th e P r ep a r a tion of 2-Meth yl-2-
oxa zolin es. Meth od A: Usin g Tr ieth yl Or th oa ceta te (1a )
a n d Acetic Acid a s a Ca ta lyst. A solution of amino alcohol
(1.0 equiv), 1a (1.2 equiv), and acetic acid (2-4 mol %) in 1,2-
dichloroethane (2 mL/mmol) was heated at reflux for 2 h under
argon. After cooling to ambient temperature, the volatiles were
removed by rotary evaporation, and the residual oil was treated
with hexane (25-30 mL/g) and dried over anhydrous MgSO4.
Filtration followed by rotary evaporation afforded the crude
product which was distilled or subjected to Kugelrohr distillation
under reduced pressure to give the pure compound.
Meth od B: Usin g Tr im eth yl Or th oa ceta te (1b) a n d
Acetic Acid a s a Ca ta lyst. The procedure is the same as that
described in method A except for 1b (1.2 equiv) was used instead
of 1a .
Meth od C: Usin g Tr ieth yl Or th oa ceta te w ith ou t Ca ta -
lyst. A solution of amino alcohol (1.0 equiv), and 1a (1.2 equiv)
in 1,2-dichloroethane (2 mL/mmol) was heated at reflux for 6 h
under argon. The reaction mixture was worked up as described
in method A to yield a pure product.
) 7.33 Hz), 2.10 (d, 3H, J ) 1.46 Hz), 4.37-4.45 (m, 1H), 5.57
(d, 1H, J ) 9.77 Hz), 7.17-7.20 (m, 2H), 7.26-7.37 (m, 3H); 13
C
NMR (CDCl3) δ 14.1, 17.8, 65.0, 84.0, 126.1, 127.8, 128.3, 137.1,
164.0. Anal. Calcd for C11H13NO: C, 75.40; H, 7.48; N, 7.99.
Found: C, 74.97; H, 7.66; N, 7.77.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2-Eth yl-2-
oxa zolin es. Meth od D: Usin g Tr ieth yl Or th op r op ion a te
(1c) a n d Acetic Acid a s a Ca ta lyst. A solution of amino
alcohol (1.0 equiv), 1c (1.2 equiv), and acetic acid (4-6 mol %)
in 1,2-dichloroethane (2 mL/mmol) was heated at reflux for 2 h
under argon. After cooling to ambient temperature, the volatiles
were removed by rotary evaporation, and the residual oil was
treated with hexane (30-35 mL/g) and dried over anhydrous
MgSO4. Filtration followed by rotary evaporation afforded the
crude product which was subjected to Kugelrohr distillation
under reduced pressure to give the pure compound.
(4R)-2-E t h yl-4-p h en yl-2-oxa zolin e (4a ). Following the
general procedure (method D), (R)-(-)-2a (2.06 g, 15.0 mmol),
1c (3.17 g, 18.0 mmol), and acetic acid (50 µL, 6 mol %) gave
2.60 g (99%) of 4a after Kugelrohr distillation (65 °C, 150 mTorr)
(4R)-2-Meth yl-4-p h en yl-2-oxa zolin e (3a ). According to the
general procedure (method A), (R)-(-)-2a (2.74 g, 20.0 mmol)
was allowed to react with 1a (3.89 g, 24.0 mmol) in the presence
of acetic acid (50 µL, 4 mol %). Kugelrohr distillation (53-54
°C, 120 mTorr) afforded the title compound (3.09 g, 96%) as a
colorless oil: [R]23 +101.7° (c 3.72, CHCl3) [lit.3 [R]23 +107.9°
as a colorless oil: [R]23 +86.5° (c 3.37, CHCl3); IR (neat) 1666
D
cm-1; 1H NMR (CDCl3) δ 1.26 (t, 3H, J ) 7.81 Hz), 2.40 (dq, 2H,
J ) 0.98, 7.81 Hz), 4.06 (dd, 1H, J ) 7.81, 8.30 Hz), 4.58 (dd,
1H, J ) 8.30, 10.3 Hz), 5.15 (m, 1H), 7.22-7.28 (m, 3H), 7.31-
7.35 (m, 2H); 13C NMR (CDCl3) δ 10.5, 21.5, 69.8, 74.6, 126.5,
127.5, 128.6, 142.6, 169.9. Anal. Calcd for C11H13NO: C, 75.40;
H, 7.48; N, 7.99. Found: C, 75.38; H, 7.62; N, 7.97.
D
D
(c 3.75, CHCl3)]; IR (neat) 1672 cm-1
;
1H NMR (CDCl3) δ 2.09
(d, 3H, J ) 1.46 Hz), 4.08 (t, 1H, J ) 8.30 Hz), 4.60 (dd, 1H, J
) 8.30, 10.3 Hz), 5.16 (m, 1H), 7.23-7.36 (m, 5H); 13C NMR
(CDCl3) δ 13.9, 69.8, 74.6, 126.5, 127.5, 128.7, 142.4, 165.7. Anal.
Calcd for C10H11NO: C, 74.51; H, 6.88; N, 8.69. Found: C, 74.40;
H, 6.97; N, 8.62.
(4S)-4-Ben zyl-2-eth yl-2-oxa zolin e (4b). Following the gen-
eral procedure (method D), (S)-(-)-2c (1.36 g, 9.0 mmol), 1c (1.90
g, 10.8 mmol), and acetic acid (20 µL, 4 mol %) gave 1.67 g (98%)
of 4b after Kugelrohr distillation (65 °C, 70 mTorr) as a colorless
oil: [R]25 -35.9° (c 2.34, CHCl3) [lit.18 [R]24 -37.0° (c 2.29,
D
D
(4S)-4-ter t-Bu tyl-2-m eth yl-2-oxa zolin e (3b). A. Following
the above procedure (method B), (S)-(+)-2b (10.40 g, 88.7 mmol),
1b (11.73 g, 97.6 mmol), and acetic acid (150 µL, 3 mol %)
furnished 9.89 g (79%) of 3b as a colorless liquid after distillation
under reduced pressure: bp 78-79 °C/55 Torr (lit.17 bp 140-
CHCl3)]; IR (neat) 1666 cm-1; 1H NMR (CDCl3) δ 1.18 (t, 3H, J
) 7.33 Hz), 2.27 (dq, 2H, J ) 0.98, 7.33 Hz), 2.63 (dd, 1H, J )
8.79, 13.7 Hz), 3.10 (dd, 1H, J ) 4.88, 13.7 Hz), 3.94 (dd, 1H, J
) 7.33, 8.30 Hz), 4.14 (br t, 1H), 4.36 (m, 1H), 7.19-7.26 (m,
3H), 7.27-7.31 (m, 2H); 13C NMR (CDCl3) δ 10.3, 21.5, 41.7, 67.1,
71.5, 126.4, 128.4, 129.2, 137.9, 169.1. Anal. Calcd for
145 °C); [R]23 -100.5° (c 3.95, THF) [lit.17 [R]D -99.7° (c 3.0,
D
THF)]; IR (neat) 1680 cm-1
;
1H NMR (CDCl3) δ 0.89 (s, 9H),
C
12H15NO: C, 76.16; H, 7.99; N, 7.40. Found: C, 75.91; H, 8.12;
N, 7.31.
(4S,5R)-2-Eth yl-4-m eth yl-5-p h en yl-2-oxa zolin e (4c). Fol-
1.97 (d, 3H, J ) 1.46 Hz), 3.79-3.85 (m, 1H), 4.01 (t, 1H, J )
8.30 Hz), 4.15 (dd, 1H, J ) 8.30, 10.3 Hz); 13C NMR (CDCl3) δ
14.0, 26.0, 33.7, 68.8, 76.2, 164.4. Anal. Calcd for C8H15NO:
C, 68.04; H, 10.71; N, 9.92. Found: C, 67.78; H, 10.81; N, 9.72.
B. By the same procedure, (S)-(+)-2b (3.49 g, 29.8 mmol),
prepared by reduction13b of tert-leucine with lower optical purity,
lowing the general procedure (method D), (1R,2S)-(-)-2d (3.02
g, 20.0 mmol), 1c (4.23 g, 24.0 mmol), and acetic acid (50 µL, 4
mol %) gave 3.71 g (98%) of 4c after Kugelrohr distillation (68-
70 °C, 130 mTorr, lit.8a bp 95-97 °C, 2 Torr) as a colorless oil:
[R]25 -223° (c 10.5, ethanol) [lit.8a [R]24 +220.9° (c 10.48,
D
D
(13) (a) Dickman, D. A.; Meyers, A. I.; Smith, G. A.; Gawley, R. E.
Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 530.
(b) Abiko, A.; Masamune, S. Tetrahedron Lett. 1992, 33, 5517.
(14) Meyers, A. I.; Poindexter, G. S.; Brich, Z. J . Org. Chem. 1978,
43, 892.
(15) Aldrich Chemical Catalog, 1996-1997.
(16) Itsuno, S.; Hirao, A.; Nakahama, S.; Yamazaki, N. J . Chem.
Soc., Perkin Trans. 1 1983, 867.
ethanol) for (4R,5S)-isomer]; IR (neat) 1672 cm-1 1H NMR
;
(CDCl3) δ 0.76 (d, 3H, J ) 6.84 Hz), 1.28 (t, 3H, J ) 7.32 Hz),
2.42 (q, 2H, J ) 7.32 Hz), 4.42 (m, 1H), 5.56 (d, 1H, J ) 9.77
Hz), 7.18 (d, 2H, J ) 7.81 Hz), 7.26-7.36 (m, 3H); 13C NMR
(CDCl3) δ 10.4, 17.8, 21.6, 64.8, 83.7, 126.0, 127.7, 128.2, 137.2,
(17) Meyers, A. I.; Shipman, M. J . Org. Chem. 1991, 56, 7098.
(18) Bates, G. S.; Varelas, M. A. Can. J . Chem. 1980, 58, 2562.