9430
J.-Y. Kim et al. / Tetrahedron 67 (2011) 9426e9432
crude product. Purification of this material by silica gel chroma-
tography gave mixtures of anti,syn/anti,anti-oxazines.
3H), 0.87 (s, 9H), 3.39 (s, 3H), 3.64 (q, J¼4.0, 6.5 Hz, 1H), 3.78 (dd,
J¼5.5, 10.5 Hz, 1H), 3.99 (dd, J¼3.5, 10.5 Hz, 1H), 4.11 (t, J¼3.5,
4.5 Hz, 1H), 4.68 (d, J¼7.0 Hz, 1H), 4.77 (d, J¼7.0 Hz, 1H), 4.91 (ddd,
J¼2.0, 3.5, 3.5 Hz, 1H), 5.36 (dt, J¼1.5, 11.0 Hz, 1H), 5.45 (dt, J¼1.5,
17.0 Hz, 1H), 6.10 (ddd, J¼5.0, 10.5, 17.5 Hz, 1H), 7.34e7.43 (m, 3H),
4.3.1. (4R,5R,6R)-4-((tert-Butyldimethylsilyloxy)methyl)-5-methoxy-
2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine (3a). Colorless oil;
Rf¼0.51 (ethyl acetate/hexane¼1/6); ½a D25
ꢁ
þ35.2 (c 0.9, CHCl3); IR
7.96e7.97 (m, 2H); 13C NMR (CDCl3, 125 MHz)
d
ꢂ5.13, ꢂ5.05, 18.43,
(neat) nmax: 3867, 3356, 2946, 2834, 1659, 1454, 1114, 1028, 838,
26.03, 56.06, 57.58, 64.59, 70.85, 74.89, 76.96, 96.36, 117.99, 127.61,
128.17, 130.68, 133.59, 133.76, 155.10; HRMS (FABþ) (MþþH) m/z
calcd for C21H33NO3Si 392.2257 found 392.2261.
780, 672, 498, 453 cmꢂ1; 1H NMR (CDCl3, 500 MHz)
d 0.05 (s, 3H),
0.09 (s, 3H), 0.88 (s, 9H), 3.44 (s, 3H), 3.64e3.74 (m, 3H), 3.99 (dd,
J¼3.5, 10.5 Hz, 1H), 4.84 (ddd, J¼3.0, 4.5, 7.0 Hz, 1H), 5.36 (dt, J¼1.5,
11.0 Hz, 1H), 5.43 (dt, J¼1.5, 17.0 Hz, 1H), 6.10 (ddd, J¼5.5, 10.5,
17.5 Hz, 1H), 7.33e7.43 (m, 3H), 7.95e7.98 (m, 2H); 13C NMR (CDCl3,
4.3.6. (4R,5R,6S)-4-((tert-Butyldimethylsilyloxy)methyl)-5-(methox-
ymethoxy)-2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine
125 MHz)
d
ꢂ5.06, ꢂ4.30, 18.45, 26.05, 56.60, 57.89, 64.70, 74.26,
(3c0). Colorless oil; Rf¼0.45 (ethyl acetate/hexane¼1/6); ½a 2D5
ꢂ1.7
ꢁ
74.52, 116.40, 116.54, 117.94, 125.06, 127.61, 128.16, 130.65, 133.61,
133.76, 155.13; HRMS (FABþ) (MþþH) m/z calcd for C20H31NO3Si
362.2151 found 362.2147.
(c 1.0, CHCl3); IR (neat) nmax: 3358, 2947, 2834, 1664, 1454, 1111,
1030, 836, 780, 672, 498, 453 cmꢂ1 1H NMR (CDCl3, 500 MHz)
;
d
0.05 (s, 3H), 0.10 (s, 3H), 0.86 (s, 9H), 3.41 (s, 3H), 3.54 (q, J¼4.0 Hz,
1H), 3.84 (t, J¼7.5, 8.0 Hz, 1H), 3.92 (dd, J¼4.0, 6.0 Hz, 1H), 3.97 (dd,
J¼4.0, 6.0 Hz, 1H), 4.53 (dd, J¼6.5, 8.0 Hz,1H), 4.71 (d, J¼6.5 Hz, 1H),
4.77 (d, J¼6.5 Hz, 1H), 5.38 (dt, J¼1.0, 10.5 Hz, 1H), 5.52 (dt, J¼1.5,
17.0 Hz, 1H), 6.05 (ddd, J¼6.5, 10.5, 17.0 Hz, 1H), 7.34e7.43 (m, 3H),
4.3.2. (4R,5R,6S)-4-((tert-Butyldimethylsilyloxy)methyl)-5-methoxy-
2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine (3a0). Colorless oil;
Rf¼0.63 (ethyl acetate/hexane¼1/6); ½a D25
þ15.1 (c 1.0, CHCl3); IR
ꢁ
(neat) nmax: 3867, 3357, 2946, 2834, 1666, 1453, 1115, 1028, 671, 497,
7.95e7.97 (m, 2H); 13C NMR (CDCl3, 125 MHz)
d
ꢂ5.08, ꢂ4.93, 18.50,
453 cmꢂ1; 1H NMR (CDCl3, 500 MHz)
d
0.05 (s, 3H), 0.11 (s, 3H), 0.87
26.06, 58.43, 60.81, 63.69, 71.71, 77.96, 97.53, 119.04, 127.70, 128.19,
130.72, 133.21, 134.75, 154.80; HRMS (FABþ) (MþþH) m/z calcd for
C21H33NO3Si 392.2257 found 392.2259.
(s, 9H), 3.39 (t, J¼8.0, 8.5 Hz, 1H), 3.47 (m, 1H), 3.51 (s, 1H), 3.96
(ddd, J¼3.3, 10.3, 18.5 Hz, 2H), 4.48 (ddt, J¼1.0, 4.5, 7.5 Hz, 1H), 5.38
(dt, J¼1.0, 9.5 Hz, 1H), 5.55 (dt, J¼1.5, 17.5 Hz, 1H), 6.07 (ddd, J¼5.8,
10.8, 17.3 Hz, 1H), 7.34e7.43 (m, 3H), 7.95e7.97 (m, 2H); 13C NMR
4.3.7. (4R,5R,6R)-5-(tert-Butyldimethylsilyloxy)-4-((tert-butyldime-
thylsilyloxy)methyl)-2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine
(CDCl3, 125 MHz)
d
ꢂ5.06, ꢂ4.89, 0.20, 18.52, 31.15, 60.17, 60.66,
63.95, 75.29, 77.79, 118.42, 127.70, 128.16, 130.66, 133.29, 134.76,
154.65; HRMS (FABþ) (MþþH) m/z calcd for C20H31NO3Si 362.2151
found 362.2155.
(3d). Colorless oil; Rf¼0.5 (ethyl acetate/hexane¼1/30); ½a D25
þ3.84
ꢁ
(c 1.0, CHCl3); IR (neat) nmax: 2929, 2360, 1661, 1471, 1254, 1115, 836,
777 cmꢂ1
; d 0.08e0.20 (m, 12H),
1H NMR (CDCl3, 300 MHz)
0.88e0.96 (m, 18H), 3.47 (dd, J¼3.0, 5.0, 8.0 Hz, 1H), 3.83 (dd, J¼5.0,
10.0 Hz, 1H), 4.02 (dd, J¼3.0, 10.0 Hz, 1H), 4.21 (dd, J¼4.0, 7.0 Hz,
1H), 4.80 (ddd, J¼2.0, 4.0, 7.0 Hz, 1H), 5.35 (ddd, J¼1.0, 2.0, 7.0 Hz,
1H), 5.40 (ddd, J¼1.0, 2.0,13.0 Hz,1H), 6.10 (ddd, J¼5.0,10.5,17.0 Hz,
1H), 7.38e7.47 (m, 3H), 8.01e8.04 (m, 2H); 13C NMR (CDCl3,
4.3.3. (4R,5R,6R)-5-(Benzyloxy)-4-((tert-dimethylsilyloxy)methyl)-2-
phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine
(3b). Colorless
þ38.1 (c 0.5, CHCl3); IR
oil;
Rf¼0.53 (ethyl acetate/hexane¼1/6); ½a D25
ꢁ
(neat) nmax: 3841, 3381, 2948, 2835,1660, 1452,1112,1029, 837, 780,
698 cmꢂ1
;
1H NMR (CDCl3, 500 MHz)
d
0.04 (s, 3H), 0.08 (s, 3H),
125 MHz)
d
ꢂ5.04, ꢂ4.99, ꢂ4.51, ꢂ4.35, 18.27, 18.55, 26.00, 26.13,
0.87 (s, 9H), 3.67 (q, J¼5.0, 8.5 Hz, 1H), 3.76 (dd, J¼5.5, 10.0 Hz, 1H),
3.92 (dd, J¼4.0, 5.0 Hz, 1H), 4.00 (dd, J¼3.5, 10.5 Hz, 1H), 4.60 (d,
J¼12.0 Hz, 1H), 4.70 (d, J¼12.0 Hz, 1H), 6.10 (ddd, J¼1.5, 3.5, 3.5 Hz,
1H), 5.33 (dt, J¼1.5, 10.5 Hz, 1H), 5.38 (dt, J¼1.5, 17.5 Hz, 1H), 6.10
(ddd, J¼5.5, 11.0, 17.5 Hz, 1H), 7.27e7.43 (m, 8H), 7.97 (m, 2H); 13C
26.27, 59.62, 64.13, 65.35, 75.93, 117.54, 127.62, 128.21, 130.59,
133.72, 133.79, 154.43; HRMS (FABþ) (MþþH) m/z calcd for
C25H44NO3Si2 462.2860 found 462.2857.
4.3.8. (4R,5R,6S)-5-(tert-Butyldimethylsilyloxy)-4-((tert-butyldime-
thylsilyloxy)methyl)-2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine
NMR (CDCl3, 125 MHz)
d
ꢂ5.07, ꢂ5.02, 0.20, 18.49, 26.10, 56.96,
64.62, 71.91, 72.07, 74.51, 76.96, 117.86, 127.62, 128.00, 128.16,
128.18, 128.59, 130.65, 133.61, 133.76, 138.32, 154.92; HRMS (FABþ)
(MþþH) m/z calcd for C26H35NO3Si 438.2464 found 438.2466.
(3d0). Colorless oil; Rf¼0.5 (ethyl acetate/hexane¼1/20); ½a 2D5
ꢂ5.3
ꢁ
(c 1.0, CHCl3); IR (neat) nmax: 3356, 2946, 2833,1663,1451,1030, 836,
780, 671 cmꢂ1; 1H NMR (CDCl3, 300 MHz)
d 0.05 (s, 3H), 0.11 (s, 3H),
0.12 (s, 3H), 0.17 (s, 3H), 0.87 (s, 9H), 0.93 (s, 9H), 3.43 (dd, J¼2.85,
2.85, 8.55 Hz, 1H), 3.90 (t, J¼8.55 Hz, 1H), 3.94e4.02 (m, 2H), 4.40
(dd, J¼6.5, 8.5 Hz, 1H), 5.38 (dt, J¼1.5, 10.5 Hz, 1H), 5.53 (dt, J¼1.5,
17.5 Hz, 1H), 6.03 (ddd, J¼6.5, 10.5, 17.5 Hz, 1H), 7.33e7.42 (m, 3H),
4.3.4. (4R,5R,6S)-5-(Benzyloxy)-4-((tert-dimethylsilyloxy)methyl)-2-
phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine (3b0). Colorless oil;
Rf¼0.57 (ethyl acetate/hexane¼1/6); ½a D25
þ5.0 (c 0.7, CHCl3); IR
ꢁ
(neat) nmax: 3841, 3381, 2947, 2834, 1662, 1452, 1039, 671 cmꢂ1; 1H
7.97e8.01 (m, 2H); 13C NMR (CDCl3,125 MHz)
ꢂ3.40, 18.39, 18.15, 26.05, 26.20, 62.80, 63.10, 66.28, 79.39, 119.10,
127.70, 128.19, 130.60, 133.21, 135.19, 154.70; HRMS (FABþ) (MþþH)
m/z calcd for C25H44NO3Si2 462.2860 found 462.2861.
d
ꢂ5.05, ꢂ4.90, ꢂ4.20,
NMR (CDCl3, 500 MHz)
d
0.05 (s, 3H), 0.11 (s, 3H), 0.87 (s, 9H), 3.56
(dt, J¼3.0, 8.0 Hz, 1H), 3.70 (t, J¼8.5, 9.0 Hz, 1H), 3.97 (dd, J¼3.0,
5.0 Hz, 1H), 4.02 (dd J¼3.0, 5.0 Hz, 1H), 4.55 (ddt, J¼1.0, 6.0, 9.0 Hz,
1H), 4.66 (d, J¼6.0 Hz, 1H), 4.70 (d, J¼6.0 Hz, 1H), 5.38 (dt, J¼1.3,
10.5 Hz, 1H), 5.57 (dt, J¼1.5, 17.0 Hz, 1H), 6.07 (ddd, J¼1.0, 5.5,
6.5 Hz, 1H), 7.29e7.44 (m, 8H), 7.96e7.98 (m, 2H); 13C NMR (CDCl3,
4.3.9. (3R,4R,5R)-5-(Benzyloxycarbonylamino)-4,6-bis(tert-butyldi-
methylsilyloxy)hex-1-en-3-ylbenzoate (9). To a solution of oxazine
3d (71 mg, 0.15 mmol) in CH2Cl2 (1.0 mL) was added a solution of
NaHCO3 (52 mg, 0.62 mmol) in water (1.0 mL), and the mixture was
cooled in an ice bath. To this solution was added dropwise a solu-
tion of benzyl chloroformate (0.044 mL, 0.31 mmol). The mixture
was stirred at room temperature for 24 h. Then benzyl chlor-
oformate (0.044 mL, 0.31 mmol) was added. The mixture was
continued stirring (24 h) until TLC indicate that complete reaction.
The organic layer was separated, and the aqueous layer was
extracted with CH2Cl2 (2ꢃ2 mL). The combined organic layer was
washed with water, dried (MgSO4), and concentrated in vacuo.
125 MHz)
d
ꢂ5.01, ꢂ4.84, 0.21, 18.55, 26.11, 50.83, 63.83, 73.40,
74.52, 78.05, 118.76, 127.72, 128.12, 128.17, 128.30, 128.66, 130.67,
133.24, 134.83, 138.23, 154.72; HRMS (FABþ) (MþþH) m/z calcd for
C26H35NO3Si 438.2464 found 438.2461.
4.3.5. (4R,5R,6R)-4-((tert-Butyldimethylsilyloxy)methyl)-5-(methox-
ymethoxy)-2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazine
(3c). Colorless oil; Rf¼0.38 (ethyl acetate/hexane¼1/6); ½a D25
þ18.6
ꢁ
(c 1.0, CHCl3); IR (neat) nmax: 3357, 2946, 2833, 1655, 1452, 1113,
1029, 673 cmꢂ1 1H NMR (CDCl3, 500 MHz)
; d 0.04 (s, 3H), 0.09 (s,