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4.3.1. Ethyl cis-6-ethoxy-1,2-oxazinane-3-carboxylate
(cis-6). This compound was isolated in 79% yield with IR,
1H and 13C NMR spectra in agreement with those reported
in the literature.8 1H NMR (CDCl3) d 1.27 (t, 3H, JZ
7.1 Hz), 1.29 (t, 3H, JZ7.2 Hz), 1.85 (m, 4H, CH2CH2),
3.71 (dq, 1H, JZ9.7, 7.1 Hz, 1H of CH3CH2O), 3.82 (m,
2H, 3-H and 1H of CH3CH2O), 4.20 (q, 2H, JZ7.2 Hz),
4.73 (dd as t, 1H, JZ2.6 Hz, 6-H), 5.75 (br s, 1H, N–H); 13C
NMR (CDCl3) d 14.1, 15.0, 22.1, 27.8, 58.9, 61.0, 63.7,
97.6, 171.1; HRMS (m/z) calcd for C9H17NO4Na 226.105
(MCCNa), found 226.1053.
7.07 (d, 1H, JZ7.7 Hz), [NH and OH not appeared]; 13C
NMR (CDCl3) d 13.9, 25.4, 33.8, 46.0, 60.0, 61.7, 110.3,
119.0, 122.9, 127.8, 135.9, 150.2, 151.4, 164.2; MS m/z (%)
262 (MC); Anal. Calcd for C14H18N2O3 C, 64.11,H, 6.92,
N, 10.68. Found: C, 64.21,H, 7.10, N, 10.58.
4.3.6. Ethyl anti-6-[(trimethylsilyl)methyl]-1,2-oxazi-
nane-3-carboxylate (28). This compound was isolated in
84% yield. IR (neat) 3350, 1735 cmK1; 1H NMR (CDCl3) d
0.03 (s, 9H, SiMe3), 0.74 (dd, 1H, JZ14.5, 7.2 Hz, 1H of
CH2SiMe3), 0.89 (dd, 1H, JZ14.5, 7.1 Hz, 1H of CH2-
SiMe3), 1.27 (t, 3H, JZ7.2 Hz), 1.43, 1.77 and 2.12 (three
m, 1H, 2H and 1H, CH2CH2), 3.68 (dddd as ddt, JZ11.9,
7.2, 7.1, 2.2 Hz, 6-H), 3.75 (dd, JZ11.2, 3.1 Hz, 3-H), 4.18
(q, 2H, JZ7.2 Hz), 5.11 (br s, 1H, N–H); 13C NMR (CDCl3)
d K0.8, 14.1, 23.4, 27.4, 33.1, 59.4, 60.9, 78.0, 170.6; MS
m/z (%) 245 (MC, 48), 230 (81), 200 (39); HRMS (m/z)
calcd for C11H24NO3Si 246.152 (MCHC), found 246.1532.
4.3.2. Ethyl trans-6-ethoxy-1,2-oxazinane-3-carboxylate
(trans-6). The mixture prepared by NaCNBH3 reduction of
5 (1.20 g, 6 mmol) was chromatographed before the
isomerisation on a silica gel column with hexane/ethyl
acetate 2:1 as the eluent to give cis-6 (625 mg, 51%) as a
1
colorless oil followed by trans-6 (337 mg, 28%) with H
and 13C NMR spectra in agreement with those reported in
the literature.8 Mp 103–105 8C; 1H NMR (CDCl3) d 1.31 (t,
3H, JZ7.1 Hz), 1.33 (t, 3H, JZ7.2 Hz), 1.82, 2.05 and 2.20
(three m, 1H, 2H and 1H, CH2CH2), 3.71 (dq, 1H, JZ9.7,
7.1 Hz, 1H of CH3CH2O), 3.98 (m, 2H, 3-H and 1H of
CH3CH2O), 4.29 (m, 2H), 5.10 (dd as t, 1H, JZ2.0 Hz, 6-
H), 7.25 (br d, 1H, JZ4.3 Hz, N–H); 13C NMR (CDCl3) d
13.8, 14.8, 20.4, 25.1, 62.8, 63.4, 65.6, 99.8, 168.2; Anal.
Calcd for C9H17NO4 C, 53.19,H, 8.43, N, 6.89. Found: C,
53.24,H, 8.36, N, 6.98.
4.3.7. (C)-Ethyl (3R,6S)-6-[(R)-1-phenylbutoxy]-1,2-
oxazinane-3-carboxylate (33). This compound was iso-
lated in 63% yield. [a]DZC141.4 (c 0.3, CHCl3); IR (neat)
1
3350, 1735 cmK1; H NMR (CDCl3) d 0.95 (t, 3H, JZ
7.0 Hz), 1.28 (t, 3H, JZ7.2 Hz), 1.3–2.1 (m, 8H, two
CH2CH2), 3.82 (dd, 1H, JZ11.2, 3.4 Hz, 3-H), 4.21 (q, 2H,
JZ7.2 Hz), 4.55 (t, 1H, JZ2.4 Hz, PhCHO), 4.69 (dd, 1H,
JZ7.9, 5.5 Hz, 6-H), 5.85 (br s, 1H, N–H), 7.3 (m, 5H, Ar–
H); 13C NMR (CDCl3) d 13.9, 14.1, 19.4, 22.1, 27.6, 40.2,
59.0, 61.0, 77.9, 94.2, 126.9, 127.7, 128.5, 141.8, 171.1; MS
m/z (%) 307 (MC, 45), 291 (21), 249 (61), 158 (90), 92
(100); Anal. Calcd for C17H25NO4 C, 66.43,H, 8.20, N,
4.56. Found: C, 66.35,H, 8.05, N, 4.29.
4.3.3. Ethyl (3R*,4aR*,8aS*)-hexahydro-pyrano[3,2-e]-
1,2-oxazine-3-carboxylate (12). This compound was iso-
1
lated in 58% yield. IR (neat) 3350, 1735 cmK1; H NMR
(CDCl3) d 1.27 (t, 3H, JZ7.2 Hz), 1.75 (m, 5H), 2.0 (m,
2H), 3.62 (ddd as dt, 1H, JZ11.6, 3.1 Hz, 7-Haxial), 3.84
(dd, 1H, JZ9.8, 3.0 Hz, 3-H), 4.09 (dd, 1H, JZ11.6,
3.7 Hz, 7-Hequatorial), 4.18 (q, 2H, JZ7.2 Hz), 4.74 (s, 1H,
8a-H), 5.79 (br s, 1H, N–H); 13C NMR (CDCl3) d 14.1, 20.3,
26.3, 27.3, 32.1, 58.8, 61.1, 67.2, 97.5, 170.7; HRMS (m/z)
calcd for C10H18NO4 216.1230 (MCHC), found 216.1229.
4.4. General procedure for the protection of oxazinanes
cis-6, 12, 19, 28 and 33
To a solution of by cis-6, 12, 19, 28 or 33 (2.65 mmol) and
Et3N (0.6 mL) [and DMAP (20 mg) for the case of 33] in
dry CH2Cl2 (10 mL) (Boc)2O (1.16 g, 5.3 mmol) was added
at 0 8C and the mixture was allowed to warm at room
temperature and was then stirred for 12 h. The resulting
solution was washed with aqueous HCl 5% (10 mL), the
aqueous layer was extracted with CH2Cl2 (10 mL) and the
combined organic layer was dried over Na2SO4. The solvent
was subsequently evaporated off and the residue was
chromatographed on a silica gel column with hexane/ethyl
acetate as the eluent to give products cis-7, 13, 20, 29 or 34
as colorless or yellowish oils.
4.3.4. Ethyl (3S*,4aR*,8aS*)-8a-methoxyoctahydro-2H-
benzo[e]-1,2-oxazine-3-carboxylate (cis-19) and ethyl
(3R*,4aR*,8aR*)-8a-methoxyoctahydro-2H-benzo[e]-1,2-
oxazine-3-carboxylate (trans-19). This inseparable mix-
ture of diastereoisomers was isolated in 63% yield. IR (neat)
1
3330, 1735 cmK1; H NMR (CDCl3) d 1.27 (t, 3H, JZ
7.3 Hz), 1.2–2.2 (m, 11H), 3.25 and 3.28 (two s, w1:1, 3H,
OMe), 3.90 (dd, 0.5H, JZ9.8, 3.4 Hz), 4.01 (dd, 0.5H, JZ
12.7, 3.5 Hz), 4.18 (q, 2H, JZ7.3 Hz), 5.57 (br s, 1H, N–H);
13C NMR (CDCl3) d 14.1, 22.6/22.7, 25.1/25.5, 28.1/28.7,
28.8/28.9, 29.4/32.0, 36.6/42.3, 47.3/47.6, 54.3, 60.2/60.9,
98.2/99.3, 170.9/171.7; MS m/z (%) 243 (MC, 56), 212
(81); HRMS (m/z) calcd for C12H21NO4Na 266.1363
(MCCNa), found 266.1360.
4.4.1. 2-(tert-Butyl) 3-ethyl cis-6-ethoxy-1,2-oxazinane-
2,3-dicarboxylate (cis-7). This compound was isolated in
70% yield. IR (neat) 1745, 1710 cmK1; 1H NMR (CDCl3) d
1.25 (t, 3H, JZ7.2 Hz), 1.31 (t, 3H, JZ7.2 Hz), 1.52 (s,
9H), 1.62 and 1.90 (two m, 1 H and 2H, 4-Haxial and 5-CH2),
2.41 (dddd, 1H, JZ11.0, 4.9, 4.3, 1.8 Hz, 4-Hequatorial), 3.69
(dq, 1H, JZ9.7, 7.2 Hz, 1H of CH3CH2O), 4.07 (dq, 1H,
JZ9.7, 7.2 Hz, 1H of CH3CH2O), 4.25 (m, 2H), 4.65 (dd
1H, JZ9.7, 1.8 Hz, 3-H), 4.72 (d, 1H, JZ4.2 Hz, 6-H). 13C
NMR (CDCl3) d 14.1, 15.0, 23.6, 27.3, 28.1, 55.6, 61.5,
65.4, 81.6, 103.7, 154.6, 169.4; HRMS (m/z) calcd for
C14H25NO6Na 326.1574 (MCCNa), found 326.1571.
4.3.5. Ethyl 2-hydroxyimino-3-(3-methyl-2,3-dihydro-
1H-indol-3-yl-propionate (25). This compound was iso-
1
lated in 91% yield. IR (neat) 3350, 3250, 1710 cmK1; H
NMR (CDCl3) d 1.22 (t, 3H, JZ7.2 Hz), 1.37 (s, 3H), 2.96
(d, 1H, JZ12.9 Hz, 1H of 3-CH2), 3.09 (d, 1H, JZ12.9 Hz,
1H of 3-CH2), 3.20 (d, 1H, JZ9.3 Hz, 1H of CH2N), 3.59
(d, 1H, JZ9.3 Hz, 1H of CH2N), 4.10 (m, 2H), 6.65 (d, 1H,
JZ7.7 Hz), 6.73 (t, 1H, JZ7.1 Hz), 7.02 (t, 1H, JZ7.7 Hz),
4.4.2. 2-(tert-Butyl) 3-ethyl (3R*,4aR*,8aS*)-hexahydro-