S. Florio et al. / Tetrahedron 57 :2001) 6775±6786
6783
1
1H NMR). H NMR 4500 MHz): d0.64 and 0.69 42£d,
1H), 2.83 4dd, J9.4, 2.8 Hz, 1H), 3.00 4s, 3H, CH3O),
3.20±3.40 4br s, 1H, exchanges with D2O), 3.81 4s, 1H,
CHCvO), 3.81±3.88 4m partially overlapping s at 3.81,
1H), 4.81 4d, J4.8 Hz, 1H, CHOH), 6.51 4d, J8.9 Hz,
1H, exchanges slowly with D2O), 7.21±7.52 43m, 15H,
aromatic H). 13C NMR 4125 MHz): d53.6, 58.8, 63.7,
67.2, 72.1, 74.0, 126.1, 126.3, 127.7, 128.1, 128.29,
128.33, 128.4, 135.5, 138.6, 140.8, 166.7 4CvO). FTIR
4KBr, cm21): 3457 4broad), 3417 4sharp), 3062, 2980,
1653 4CvO), 1536, 1450, 1122, 1050, 761, 629. Anal.
Calcd for C25H25NO4: C 74.42, H 6.25, N 3.47. Found C
74.15, H 6.47, N 3.24.
J6.7 Hz, 2£3H, 2£CH3), 1.30±1.40 4m, 1H), 3.73±3.82
4m, 2H), 3.90±3.96 4m, 1H), 4.04 4d, J0.9 Hz, 1H), 7.25±
7.33 4m, 8H, aromatic H), 7.42±7.48 4m, 2H, aromatic H).
13C NMR 4125 MHz): d18.2, 18.6, 32.5, 59.5, 66.5, 70.6,
72.4, 126.8, 127.98, 128.04, 128.3, 128.4, 135.7, 139.0,
161.4. GC-MS 470eV); m/z 4%): 307 410.9, M1), 290
493.5), 278 410.7), 248 412.8), 208 4100.0), 191 425.4),
165 458.0), 105 410.9), 77 47.8). FTIR 4CHCl3, cm21):
2962, 2928, 1680, 1658, 1657, 1602, 1447, 1262, 1098,
1010, 823. Anal. Calcd for C20H21NO2: C 78.15, H 6.89,
N 4.56. Found: C 78.33, H 7.37, N 4.55.
4.2.9. 01S,2R)-02)-2-Chloro-N-02-hydroxy-1-methyl-2-
phenylethyl)acetamide 07a). White solid, mp 113±1148C
4.2.13. General procedure for the lithiation of the chloro-
methyloxazolines 8 and 12 and reaction with Ph2CO in
various solvents 0Tables 1 and 2). A solution of LDA
41.4 equiv.) in the given solvent 41.6 mL mmol21) was
cooled to 21008C with a methanol±liquid nitrogen bath.
A mixture of oxazoline 8 or 12 41 equiv.) and Ph2CO
41.3 equiv.) in the given solvent 41.6 mL mmol21) was
added dropwise and the resulting solution stirred at
21008C for the ®xed time 4see Tables 1 and 2) under N2.
Then, the reaction mixture was quenched with sat. aq.
NH4Cl and extracted with Et2O. The combined organic
layers were dried over Na2SO4 and concentrated in vacuo.
The resulting crude mixture of chlorohydrins 10a and 10b or
14a and 14b was puri®ed by column chromatography 4silica
gel; petroleum ether/AcOEt 9:1) 4see Tables 1 and 2 for
isolated yields) and subsequently cyclized quantitatively to
a diastereomeric mixture of epoxides 11a and 11b or 15a and
15b with NaOH/i-PrOH.32 Diastereomers 11a and 11b could
be separated and characterized as previously described.
These new compounds showed the following data:
1
4hexane). [a]D253.9 4c 1 CHCl3). H NMR 4300 MHz)
4as reported in Ref. 11). GC-MS 470eV); m/z 4rel.int.): 228
40.5, M111), 210 41.5), 134 412.6), 121 476.0), 107 445.4),
86 472.6), 77 461.5), 57 427.6), 44 4100.0). FTIR 4KBr,
cm21): 3308, 1646, 4CvO), 1544 4NH), 1264, 1024, 760,
703, 585. Anal. Calcd for C11H14NO2Cl: C 58.03, H 6.20, N
6.15. Found C 58.43, H 6.45, N 6.02.
4.2.10. 01S,2S)-01)-2-Chloro-N-02-hydroxy-1-methoxy-
methyl-2-phenylethyl)acetamide 07b). White solid, mp
1
114±1168C 4Et2O). [a]D143 4c 5.3 CHCl3). H NMR
4300 MHz): d 1.61 4br s, 1H, exchanges with D2O), 3.37
4s, 3H, CH3O), 3.39±3.49 4br s, 1H, which exchanges with
D2O), 3.54 and 3.59 42£dd, 2H, AB part of an ABMX
2
3
3
system, JAB9.6 Hz, JAM3.4 Hz, JBM4.0Hz, C H2O),
3.92 and 3.98 42H, 2£d, AB system, 2JAB15.3 Hz, CH2Cl),
4.14±4.21 4m, 1H, M part, CHNH), 5.04 4d, 1H, X part,
3JMX3.7 Hz, CHPh), 7.25±7.35 42m, 5H, aromatic H).
13C NMR 4APT, 50.3 MHz): d 42.6 4CH2Cl), 54.9
4CHNH), 59.4 4CH3O), 73.5 4CH2O), 74.3 4CHOH), 125.9
4ArCH), 127.9 4ArCH), 128.4 4ArCH), 140.7 4ArC), 166.3
4CONH). GC-MS 470eV); m/z 4%): 24040.1, M 1217), 121
430.1), 119 4100.0), 84 430.5), 79 423.6), 77 434.7), 74
429.4). FTIR 4KBr, cm21): 3320±3200 4br, OH), 1644
4CvO), 1527 4NH). Anal. Calcd for C12H16NO3Cl: C
55.93, H 6.26, N 5.43. Found C 56.28, H 6.49, N 5.38.
:2S,40S,50S)-2-:3,3-diphenyloxiranyl)-4-methoxymethyl-5-
phenyl-2-oxazoline :major) 415a): Inseparable mixture of
1
diastereomers 41.35±2:1 ratio by H NMR analysis). Oil,
see Table 2 for isolated yields in various solvents. 1H
NMR 4500 MHz): d3.13 4dd, J6.8, 9.7 Hz, 1H,
CHaOCH3 minor), 3.304s, 3H, C H3O minor), 3.36 4s, 3H,
CH3O major), 3.41±3.44 4m, 2H, CHbOCH3 minor1
CHaOCH3 major), 3.52 4dd, J4.3, 9.7 Hz, 1H, CHbOCH3
major), 3.94±4.01 42m, 2H, CHCH2 major1CHCH2
minor), 4.19 4s, 1H, CH epoxide major), 4.23 4s, 1H, CH
epoxide minor), 5.06 4d, J7.5 Hz, 1H, CHPh major), 5.19
4d, J7.7 Hz, 1H, CHPh minor), 6.70±6.72 4m, 2H,
aromatic H minor), 6.92±6.94 4m, 2H, aromatic H major),
7.19±7.39 43m, 22H, 11 aromatic H minor111 aromatic H
major), 7.51±7.57 4m, 4H, 2 aromatic H major12 aromatic
H minor). 13C NMR 4125 MHz): d59.0, 59.07, 59.13,
59.4, 66.61, 66.63, 73.6, 73.7, 74.0, 74.1, 84.0, 84.3,
125.2, 125.8, 126.7, 127.1, 127.81, 127.84, 128.02,
128.05, 128.14, 128.18, 128.28, 128.32, 128.35, 128.4,
128.5, 135.5, 135.6, 138.78, 138.84, 139.5, 139.6, 161.9,
162.2. GC-MS 470eV) 4major); m/z 4%): 385 43.4, M1),
368 49.1), 238 435.6), 208 436.7), 165 482.1), 148 4100.0),
147 499.5), 105 442.1), 77 427.2), 45 456.9). GC-MS 470 eV)
4minor); m/z 4%): 385 45.8, M1), 368 49.9), 238 434.6), 208
435.9), 165 481.4), 148 499.6), 147 4100.0), 105 444.3), 77
431.7), 45 464.9). FTIR 4®lm, cm21) 4major1minor): 3061,
2926, 16604C vN), 1679 4CvN), 1603, 1495, 1435, 1449,
1200, 1127, 977, 912, 758, 699. Anal. Calcd for C25H25NO3:
C 77.90, H 6.01, N 3.63. Found: C 78.28, H 6.22, N 3.65.
4.2.11. 02R,10S,20S)-3,3-Diphenyl-N-02-hydroxy-1-meth-
oxymethyl-2-phenylethyl)oxiranecarboxamide
016a).
White solid, mp 152±1538C 4Et2O). [a]D153.8 4c 0.5
CHCl3). 1H NMR 4300 MHz): d2.00±2.20 4br s, 1H,
exchanges with D2O), 2.85 4dd, J9.7 and 3.3 Hz, 1H),
3.14 4dd, J9.7 and 3.8 Hz, 1H), 3.17 4s, 3H, CH3O), 3.94
4s, 1H, CHCvO), 3.90±3.97 4m partially overlapping s at
3.94, 1H), 4.08 4d, J7.6 Hz, 1H, CHOH), 6.41 4d,
J8.8 Hz, 1H, which exchanges slowly with D2O), 7.07±
7.54 44m, 15H, aromatic H). 13C NMR 450.3 MHz):
d55.4, 59.0, 64.1, 67.6, 71.5, 74.6, 126.5, 127.9, 128.0,
128.4, 128.47, 128.51, 128.7, 129.0, 135.4, 138.6, 140.1,
167.2 4CvO). FTIR 4KBr, cm21): 3415 4sharp), 3252
4broad), 3033, 1651 4CvO), 1529, 1494, 1448, 1124, 949,
704, 552. Anal. Calcd for C25H25NO4: C 74.42, H 6.25, N
3.47. Found C 74.03, H 6.54, N 3.21.
4.2.12. 02S,10S,20S)-3,3-Diphenyl-N-02-hydroxy-1-meth-
oxymethyl-2-phenylethyl)oxiranecarboxamide
016b).
White solid, mp 132±1338C 4Et2O). [a]D129.2 4c 1
1
CHCl3). H NMR 4300 MHz): d2.304dd, J9.4, 4.4 Hz,