12472 J. Am. Chem. Soc., Vol. 120, No. 48, 1998
Wenglowsky and Hegedus
The imine was hydrolyzed with 30.0 mL of 2:1 THF/1 N HCl, and the
diastereomeric amino aldehydes were isolated by radial chromatography
(SiO2, 2 mm plate/4:1:1 hexanes/CH2Cl2/Et2O), giving 168 mg (62%)
of the major diastereomeric amino aldehyde 2c and 19 mg (7%) of the
minor.
(m, 3H); 13C NMR δ 198.3, 157.8, 136.5, 133.8, 128.2, 128.1, 127.7,
127.6, 125.7, 80.9, 66.1, 63.0, 33.8, 25.3, 22.6, 18.6, 13.4. Anal. Calcd
for C22H25NO3: C, 75.19; H, 7.17; N, 3.99. Found: C, 74.96; H, 7.03;
1
N, 4.10. Minor diastereomer: IR (CH2Cl2, cm-1) 1747 (s); H NMR
δ 9.67 (s, 1H), 7.06-7.11 (m, 10H), 6.00 (d, J ) 7.6 Hz, 1H), 5.07 (d,
J ) 7.6 Hz, 1H), 1.87-1.97 (m, 1H), 1.71-1.81 (m, 1H), 1.34-1.36
(m, 4H), 1.09 (s, 3H), 0.91-0.95 (m, 3H); 13C NMR δ 199.5, 157.6,
136.1, 133.6, 128.5, 128.3, 127.9, 127.5, 125.8, 81.1, 65.6, 64.0, 34.0,
25.3, 22.9, 18.7, 13.8.
6: IR (CH2Cl2, cm-1) 3323 (m), 1660 (s), 1633 (s); 1H NMR δ 7.12-
7.26 (m, 7H), 6.98-7.01 (m, 2H), 6.91-6.92 (m, 1H), 5.96 (s, 1H),
5.68 (s, 1H), 4.86 (d, J ) 2.4 Hz, 1H), 4.00-4.07 (m, 1H), 1.66-1.97
(m, 8H), 1.81 (s, 3H) 1.48-1.66 (m, 4H), 1.11-1.20 (m, 1H); 13C
NMR δ 152.9, 141.3, 135.8, 128.5, 127.5, 127.3, 127.2, 127.0, 126.3,
118.9, 104.1, 73.9, 66.8, 51.6, 32.4, 32.3, 25.3, 25.1, 10.6; HRMS m/z
377.2221 (M+ + 1) (calcd for C24H28N2O2 377.2229).
2c: mp 127-129 °C (EtOAc/hexanes); IR (CH2Cl2, cm-1) 1749 (s);
1H NMR δ 9.66 (s, 1H), 7.04-7.10 (m, 10H), 6.01 (d, J ) 8.1 Hz,
1H), 5.63 (dddd, J ) 7.2, 7.2, 9.9, 17.1 Hz, 1H), 5.20 (d, J ) 7.8 Hz,
1H), 5.04 (d, J ) 9.9 Hz, 1H), 4.95 (d, J ) 17.1 Hz, 1H), 2.44 (d, J
) 7.2 Hz, 2H), 1.40 (s, 3H); 13C NMR δ 198.3, 157.7, 136.1, 133.8,
131.3, 128.3, 128.2, 127.7, 127.6, 125.8, 119.5, 80.9, 65.5, 63.3, 38.4,
18.8. Anal. Calcd for C21H21NO3: C, 75.20; H, 6.31; N, 4.18.
Found: C, 75.38; H, 6.47; N, 4.07. Minor diastereomer: IR (CH2Cl2,
1
cm-1) 1748 (s); H NMR δ 9.75 (s, 1H), 7.00-7.11 (m, 10H), 5.84-
6.01 (m, 1H), 5.93 (d, J ) 7.8 Hz, 1H), 5.31 (d, J ) 9.3 Hz, 1H), 5.30
(d, J ) 18.3 Hz, 1H), 5.03 (d, J ) 7.8 Hz, 1H), 2.86 (dd, J ) 7.8, 14.1
Hz, 1H), 2.55 (dd, J ) 7.2, 14.1 Hz, 1H), 1.05 (s, 3H); 13C NMR δ
199.1, 157.8, 136.5, 133.6, 131.6, 128.4, 128.3, 128.1, 128.0, 127.9,
127.3, 125.9, 120.5, 81.1, 65.4, 63.9, 38.3, 19.0.
11. Benzyl 2-aminoisobutyrate‚HCl (92 mg, 0.4 mmol) was
dissolved in 10% NaHCO3 and extracted with CH2Cl2 (3×). The
solvent was removed by rotary evaporation. The resulting oil and 2a
(96 mg, 0.25 mmol) were dissolved in 6 mL of benzene, 4-Å molecular
seives were added, and the mixture was heated to reflux for 26 h. The
solution was filtered through Celite, and the solvent was removed by
rotary evaporation to give 11 as a clear oil which was used in the next
step without further purification: IR (film, cm-1) 1745 (s), 1729 (s),
2d. According to the general procedure, R-amino imine 1 was
prepared from 1.00 g (3.25 mmol) of allylic oxazolidinone 5, 3.25 mL
of Me2S (1 mL/5 mmol), and 0.41 mL (0.89 mmol) of cyclohexylamine.
Imine 1 was alkylated with 3.74 mL (0.89 mmol) of 1-iodo-2-
methylpropane in 20.0 mL of THF and 1.80 mL (1.98 mmol) of 1.10
M KHMDS. The imine was hydrolyzed with 120 mL of 2:1 THF/1 N
HCl, and the diastereomeric amino aldehydes were isolated by column
chromatography (SiO2/4:1:1 hexanes/CH2Cl2/Et2O), giving 709 mg
(62%) of the major diastereomeric amino aldehyde 2d and 68 mg (6%)
of the minor.
1
1668 (m); H NMR δ 7.61 (s, 1H), 7.24-7.35 (m, 11H), 6.80-7.00
(m, 7H), 6.60 (bs, 2H), 5.49 (d, J ) 8.2 Hz, 1H), 5.13 (s, 1H), 4.70 (d,
J ) 8.2 Hz, 1H), 3.63 (d, J ) 13.4 Hz, 1H), 3.36 (d, J ) 13.4 Hz,
1H), 1.37 (s, 3H), 1.33 (s, 3H), 1.31 (s, 3H); 13C NMR δ 173.9, 162.1,
158.1, 137.0, 136.6, 135.9, 134.5, 131.1, 128.5, 128.3, 128.2, 128.1,
128.0, 127.8, 127.6, 127.5, 127.3, 126.7, 126.1, 79.8, 66.6, 65.1, 65.0,
63.5, 41.5, 25.9, 24.9, 23.1.
2d: mp 127-129 °C (Et2O/hexanes); [R]20 -73.6 (c 1, CH2Cl2);
D
1
IR (CH2Cl2, cm-1) 1747 (s); H NMR δ 9.64 (s, 1H), 7.08-7.11 (m,
7H), 7.01-7.03 (m, 3H), 5.94 (d, J ) 7.8 Hz, 1H), 5.14 (d, J ) 7.8
Hz, 1H), 1.53-1.68 (m 3H), 1.44 (s, 3H), 0.86 (d, J ) 6.0 Hz, 3H),
0.70 (d, J ) 6.0 Hz, 3H); 13C NMR δ 198.8, 157.8, 136.5, 133.9, 128.4,
128.3, 127.8, 127.6, 125.9, 81.1, 66.5, 63.5, 43.0, 24.4, 24.2, 23.6, 19.4.
Anal. Calcd for C22H25NO3: C, 75.19; H, 7.17; N, 3.99. Found: C,
74.92; H, 7.20; N, 4.01. Minor diastereomer: IR (CH2Cl2, cm-1) 1746
(s); 1H NMR δ 9.72 (s, 1H), 7.03-7.12 (m, 10H), 5.98 (d, J ) 7.4 Hz,
1H), 5.07 (d, J ) 7.4 Hz, 1H), 1.74-1.91 (m, 3H), 1.11 (s, 3H), 1.02
(d, J ) 6.0 Hz, 1H), 0.98 (d, J ) 6.0 Hz, 1H); 13C NMR δ 199.7,
157.6, 136.1, 133.6, 128.6, 128.4, 128.0, 127.9, 127.8, 125.9, 81.0,
66.0, 64.4, 43.0, 24.8, 24.4, 23.5, 19.3.
12. As described above for 11, 88 mg of 2f (0.25 mmol) gave imine
1
12 as a clear oil: IR (film, cm-1) 1747 (s), 1732 (s), 1668 (m); H
NMR δ 7.61 (s, 1H), 7.33 (s, 5H), 6.94-7.01 (m, 10H). 5.82 (d, J )
7.8 Hz, 1H), 5.14 (s, 2H), 4.97 (d, J ) 7.8 Hz, 1H), 2.05-2.12 (m,
1H), 1.78-1.85 (m, 1H), 1.14 (s, 3H), 1.23-1.41 (m, 4H), 1.36 (s,
3H), 1.20 (s, 3H), 0.82-0.86 (m, 3H); 13C NMR δ 174.0, 162.8, 157.5,
137.1, 135.8, 134.4, 128.4, 128.1, 128.0, 127.8, 127.7, 127.5, 127.4,
125.9, 79.9, 66.4, 64.7, 64.3, 62.7, 35.9, 25.8, 25.6, 24.9, 22.7, 21.8,
13.8.
15. A slurry of m-CPBA (94 mg, ∼0.38 mmol) in 10% NaHCO3
was extracted with CH2Cl2 (3×), and the solvent was removed by rotary
evaporation. The resulting white solid was dissolved in 2.00 mL of
toluene and cooled to -78 °C. To this solution was added a solution
of imine 11 in 2.00 mL of toluene under air. The reaction was stirred
at -78 °C for 30 min and warmed to room temperature for 15 min.
The reaction was washed with 10% Na2S2O3 (1×), NaHCO3 (1×), and
brine (1×) and dried over Na2SO4. The solvent was removed by rotary
evaporation, giving a 1:1 mixture of diastereomeric oxazolidinones 13
as a clear oil. In a quartz tube, this oil was dissolved in 4.00 mL of
benzene and degassed for 45 min by bubbling argon through the
solution. The quartz tube containing the oxaziridine was photolyzed
at 254 nm for 2.5 h. The solvent was removed by rotary evaporation,
and purification by radial chromatography (10:1:1 hexanes/CH2Cl2/
Et2O) gave 50 mg (35%) of 15 as a white solid: mp 157-158 °C;
[R]20D +35.0 (c 1, CH2Cl2); IR (film, cm-1) 3383 (w), 1737 (s), 1667
2e. According to the general procedure, R-amino imine 1 was
prepared from 250 mg (0.81 mmol) of allylic oxazolidinone 5, 0.81
mL of Me2S (1 mL/5 mmol), and 0.10 mL (0.89 mmol) of cyclohexyl-
amine. Imine 1 was alkylated with 0.81 mL (8.13 mmol) of
2-iodopropane in 5.00 mL of THF and 1.80 mL (1.98 mmol) of 1.10
M KHMDS. The imine was hydrolyzed with 30.0 mL of 2:1 THF/1
N HCl, and the diastereomeric amino aldehydes were isolated by radial
chromatography (SiO2, 2 mm plate/4:1:1 hexanes/CH2Cl2/Et2O), giving
132 mg (48%) of the major diastereomeric amino aldehyde 2e: mp
133-140 °C (EtOAc/hexanes); [R]20 -48.8 (c 1, CH2Cl2); IR (film,
D
cm-1) 1743 (s); 1H NMR δ 9.63 (s, 1H), 7.01-7.09 (m, 10H), 5.94 (d,
J ) 8.1 Hz, 1H), 5.10 (d, J ) 8.1 Hz, 1H), 2.68 (m, 1H), 1.34 (s, 3H),
0.97 (d, J ) 6.9 Hz, 3H), 0.84 (d, J ) 6.9 Hz, 3H); 13C NMR δ 199.0,
158.0, 136.3, 134.0, 128.3, 128.1, 127.9, 127.8, 127.7, 125.8, 80.6,
69.5, 64.0, 31.1, 17.6, 17.5, 15.6. Anal. Calcd for C21H23NO3: C,
74.75; H, 6.87; N, 4.15. Found: C, 74.61; H, 6.92; N, 4.15.
1
(m); H NMR δ 7.33-7.38 (m, 5H), 7.21-7.26 (m, 5H), 7.06 (bs,
1H), 7.00-7.04 (m, 3H), 6.78-6.94 (m, 4H), 6.43 (d, J ) 6.0 Hz,
2H), 5.72 (d, J ) 8.3 Hz, 1H), 5.23 (d, J ) 6.6 Hz, 1H), 5.21 (d, J )
8.3 Hz, 1H), 5.19 (d, J ) 6.6 Hz, 1H), 3.90 (d, J ) 13.2 Hz, 1H), 3.20
(d, J ) 13.2 Hz, 1H), 1.62 (s, 3H), 1.61 (s, 3H), 1.20 (s, 3H); 13C
NMR δ 174.3, 172.2, 159.2, 136.8, 135.7, 134.5, 131.1, 128.5, 128.3,
128.1, 127.8, 127.6, 127.5, 127.4, 127.2, 126.9, 126.1, 80.1, 67.2, 65.1,
64.8, 57.0, 41.6, 24.6, 24.4, 22.6. Anal. Calcd for C36H36N2O5: C,
74.98; H, 6.29; N, 4.86. Found: C, 74.87; H, 6.33; N, 4.98.
2f. According to the general procedure, R-amino imine 1 was
prepared from 500 mg (1.63 mmol) allylic oxazolidinone 5, 1.63 mL
Me2S (1 mL/5 mmol), and 0.21 mL (1.79 mmol) cyclohexylamine.
Imine 1 was alkylated with 1.85 mL (1.79 mmol) 1-iodobutane in 10.0
mL THF and 3.60 mL (3.96 mmol) 1.10 M KHMDS. The imine was
hydrolyzed with 60.0 mL of 2:1 THF:1 N HCl and the diastereomeric
amino aldehydes were isolated by column chromatography (SiO2/4:
2:1 hexanes:CH2Cl2:Et2O) giving 369 mg (73%) of the major diaster-
eomeric amino aldehyde 2f and 38 mg (9%) of the minor.
16. As described above for 15, imine 12 was oxidized with 94 mg
(∼0.38 mmol) of m-CPBA to give 14 as a clear oil. Photolysis at 254
nm for 6 h and purification by radial chromatography (SiO2, 2 mm
plate/6:1:1 hexanes/CH2Cl2/Et2O) gave 50 mg (37%) of 16 as a clear
oil: [R]20D -39.2 (c 2.2, CH2Cl2); IR (film, cm-1) 3350 (w), 1739 (s),
2f: mp 116.5-118.5 °C; [R]20 -62.7 (c 1, CH2Cl2); IR (CH2Cl2-
D
CH2Cl2, cm-1) 1749 (s); 1H NMR δ 9.61 (s, 1H), 7.02-7.10 (m, 10H),
5.98 (d, J ) 8.1 Hz, 1H), 5.14 (d, J ) 8.1 Hz, 1H), 1.57-1.72 (m,
1H), 1.40-1.49 (m, 1H), 1.49 (s, 3H), 0.99-1.25 (m, 4H), 0.71-0.76
1
1673 (m); H NMR δ 7.35-7.37 (m, 5H), 7.23 (bs, 1H), 7.04-7.08