4978 J . Org. Chem., Vol. 62, No. 15, 1997
Vidal-Ferran et al.
(d × d, 1H, J ) 10.8, 7.5 Hz), 3.59 (d, 1H, J ) 9.3 Hz), 2.51-
2.53 (br s, 2H), 2.30 (br s, 2H), 1.70 (br s, 1H, OH), 1.51-1.60
(m, 4H), 1.29-1.34 (m, 2H); 13C-NMR (75 MHz, CDCl3) δ 133.2
(C), 129.7 (CH), 128.4 (CH), 128.2 (CH), 75.7 (CH), 67.4 (CH2),
67.1 (CH), 51.6 (CH2), 25.9 (CH2), 23.9 (CH2); IR (KBr) 3544,
3286, 3064, 3029, 2993, 2933, 2852, 2792, 2751, 1451, 1123,
1088, 1063, 1026, 754, 708, 698 cm-1; MS (EI) m/ z 235 (M+,
0.1), 174 (M - C2H5O2+, 100). Anal. Calcd for C14H21NO2: C,
71.46; H, 8.99; N, 5.95. Found: C, 71.48; H, 9.09; N, 5.93.
(2R,3R)-3-Mor p h olin o-3-p h en yl-1,2-p r op a n ed iol (5e).
Compound 1a (250 mg, 1.66 mmol), CH2Cl2 (10 mL), morpho-
line (220 µL, 2.52 mmol), and Ti(OiPr)4 (735 µL, 2.49 mmol)
were treated as described for 5a during 5 h. The reaction
mixture was quenched with a 10% solution of NaOH in brine
(10 mL) as described for 5a to give 345 mg (87%) of 5e as a
(d × d × d, 1H, J ) 9.6, 1.8, 1.8 Hz), 4.20 (br s, 2H, OH), 4.07
(d × d, 1H, J ) 11.7, 1.8 Hz), 3.83 (d, 1H, J ) 9.6 Hz), 3.67 (d
× d, 1H, J ) 11.7, 1.8 Hz), 2.99-3.11 (m, 2H), 2.33 (s, 6H),
2.14-2.45 (m, 4H), 2.05 (s, 3H); 13C-NMR (75 MHz, CDCl3) δ
133.8 (C), 129.7 (CH), 128.1 (CH), 127.5 (CH), 70.8 (CH), 64.2
(CH2), 63.4 (CH), 55.5 (CH2), 50.4 (CH2), 44.2 (CH3), 38.4 (CH3);
IR (film) 3359, 3106, 3087, 3062, 3029, 2942, 2860, 2821, 2794,
1452, 1366, 1102, 1072, 1042, 752, 704 cm-1; MS (EI) m/ z 252
(M+, 0), 191 (M - C2H5O2+, 10), 194 (M - C3H8N+, 100).
Selective p r otection of th e p r im a r y h yd r oxy gr ou p in
5a -h a s a silyl eth er .
(2R,3R)-1-[(ter t-Bu t yld im et h ylsilyl)oxy]-3-p h en yl-3-
(p yr r olid in -1-yl)-2-p r op a n ol (4a ). A solution of 5a (440 mg,
1.99 mmol), tert-butyldimethylsilyl chloride (330 mg, 2.19
mmol), and imidazole (299 mg, 4.39 mmol) in DMF (18 mL)
was heated at 65 °C for 24 h under N2. The reaction mixture
was cooled to room temperature, and Et2O (18 mL) and brine
(18 mL) were added. The aqueous layer was extracted with
Et2O (2 × 25 mL). The combined organic extracts were dried
and concentrated in vacuo. The residual oil was chromato-
graphed using hexane:EtOAc (90:10-80:20) as eluent to give
white solid after recrystallization from hexane:EtOAc (2:1):
1
mp 103 °C; [R]23 ) -23.8 (c ) 1.1 in CHCl3); H-NMR (300
D
MHz, CDCl3) δ 7.24-7.42 (m, 5H), 4.34 (m, 1H), 3.66-3.70
(m, 5H), 3.63 (d × d, 1H, J ) 10.5, 5.1 Hz), 3.49 (d, 1H, J )
7.5 Hz), 2.43-2.55 (m, 4H), 2.02 (br s, 1H, OH), 1.59 (br s,
1H, OH); 13C-NMR (75 MHz, CDCl3) δ 133.6 (C), 129.6 (CH),
128.5 (CH), 128.4 (CH), 73.7 (CH), 68.2 (CH), 66.7 (CH2), 66.2
529 mg (79%) of 4a as a colorless oil: [R]23 ) -19.7 (c ) 1.0
D
1
(CH2), 50.9 (CH2); IR (KBr) 3442, 2815, 1497, 1449, 1117, 872,
in CHCl3); H-NMR (300 MHz, CDCl3) δ 7.27-7.34 (m, 5H),
+
777, 719 cm-1; MS (EI) m/ z 237 (M+, 0.1), 176 (M - C2H5O2
,
4.15 (d × d × d, 1H, J ) 6.6, 6.3, 3.9 Hz), 3.38 (d × d, 1H, J
) 9.9, 6.3 Hz), 3.33 (d, 1H, J ) 3.9 Hz), 3.20 (d × d, 1H, J )
9.9, 6.6 Hz), 3.14 (br s, 1H, OH), 2.60-2.63 (m, 2H), 2.42-
2.46 (m, 2H), 1.74-1.78 (m, 4H), 0.88 (s, 9H), 0.00 (s, 3H),
-0.02 (s, 3H); 13C-NMR (75 MHz, CDCl3) δ 138.0 (C), 129.3
(CH), 127.8 (CH), 127.3 (CH), 71.6 (CH), 71.2 (CH), 64.3 (CH2),
52.4 (CH2), 25.9 (CH3), 23.2 (CH2), 18.2 (C), -5.5 (CH3); IR
100). Anal. Calcd for C13H19NO3‚1/3H2O: C, 64.18; H, 8.15;
N, 5.76. Found: C, 64.12; H, 8.39; N, 5.80.
(2R,3R)-3-(Azep a n -1-yl)-3-p h en yl-1,2-p r op a n ed iol (5f).
Compound 1a (750 mg, 4.99 mmol), CH2Cl2 (25 mL), hexa-
methyleneimine (840 µL, 7.45 mmol), and Ti(OiPr)4 (2.20 mL,
7.46 mmol) were treated as described for 5a during 8 h. The
reaction mixture was quenched with a 10% solution of NaOH
in brine (30 mL) as described for 5a to give 1.13 g (91%) of 5f
as a white solid after recrystallization from Et2O: mp 94 °C;
(film) 3454, 3064, 3031, 2956, 2858, 2804, 1115, 757, 702 cm-1
;
MS (CI, NH3) m/ z 336 (C19H33NO2Si‚H+, 100).
(2R,3R)-1-[(ter t-Bu tyldim eth ylsilyl)oxy]-3-[(2S)-2-(m eth -
oxym eth yl)p yr r olid in -1-yl]-3-p h en yl-2-p r op a n ol (4b). A
solution of 5b (567 mg, 2.14 mmol), tert-butyldimethylsilyl
chloride (354 mg, 2.35 mmol), and imidazole (320 mg, 4.71
mmol) in DMF (20 mL) was heated at 65 °C for 24 h under
N2. A workup identical to the one described for 4a followed
by chromatography using hexane:EtOAc (90:10) as eluent
[R]23 ) +17.5 (c ) 1.0 in CHCl3); 1H-NMR (300 MHz, CDCl3)
D
δ 7.26-7.38 (m, 5H), 4.27 (d × d × d, 1H, J ) 9.0, 6.6, 5.1
Hz), 3.83 (d × d, 1H, J ) 10.9, 5.1 Hz), 3.75 (d × d, 1H, J )
10.9, 6.6 Hz), 3.74 (d, 1H, J ) 9.0 Hz), 2.73 (d × t, 2H, J )
12.7, 6.4 Hz), 2.52 (d × t, 2H, J ) 12.7, 6.4 Hz), 1.80 (br s, 2H,
OH), 1.50-1.61 (m, 8H); 13C-NMR (75 MHz, CDCl3) δ 135.0
(C), 129.3 (CH), 128.3 (CH), 127.9 (CH), 75.2 (CH), 68.0 (CH),
67.5 (CH2), 53.3 (CH2), 28.5 (CH2), 26.3 (CH2); IR (KBr) 3384,
3226, 3087, 3060, 3025, 3002, 2966, 2931, 2885, 2854, 1451,
1059, 1022, 762, 702 cm-1; MS (EI) m/ z 249 (M+, 0), 188 (M
- C2H5O2+, 100). Anal. Calcd for C15H23NO2: C, 72.25; H,
9.30; N, 5.62. Found: C, 72.33; H, 9.41; N, 5.62.
yielded 615 mg (76%) of 4b as a colorless oil: [R]23 ) -42.4
D
1
(c ) 1.1 in CHCl3); H-NMR (300 MHz, CDCl3) δ 7.33-7.35
(m, 5H), 4.19 (d × d × d, 1H, J ) 7.2, 6.3, 6.0 Hz), 3.87 (d, 1H,
J ) 7.2 Hz), 3.53-3.63 (m, 2H), 3.46 (d × d, 1H, J ) 9.3, 6.3
Hz), 3.40 (s, 3H), 3.28 (d × d, 1H, J ) 9.3, 6.0 Hz), 2.76-3.09
(m, 2H), 2.32-2.40 (m, 1H), 1.45-1.76 (m, 4H), 0.91 (s, 9H),
0.05, 0.07 (s, 3H+3H); 13C-NMR (75 MHz, CDCl3) δ 136.3 (C),
130.0 (CH), 127.7 (CH), 127.2 (CH), 76.8 (CH2), 71.0 (CH), 67.0
(CH), 65.0 (CH2), 59.0 (CH + CH3), 49.8 (CH2), 28.0 (CH2), 25.9
(CH3), 23.3 (CH2), 18.3 (C), -5.4 (CH3); IR (film) 3458, 3029,
2929, 2858, 1117, 778, 704 cm-1; MS (CI, NH3) m/ z 380
(C21H37NO3Si‚H+, 100).
(2R,3R)-3-(Diisop r op yla m in o)-3-p h en yl-1,2-p r op a n e-
d iol (5g). Compound 1a (650 mg, 4.33 mmol), CH2Cl2 (20 mL),
diisopropylamine (910 µL, 6.49 mmol), and Ti(OiPr)4 (1.91 mL,
6.47 mmol) were treated as described for 5a during 7 h. The
reaction mixture was quenched with a 10% solution of NaOH
in brine (20 mL) as described for 5a to give 5g as an oil after
chromatography using hexane:EtOAc (20:80-40:60) as eluent.
The oil was recrystallized from hexane:Et2O (10:1) to give 155
(2R,3R)-1-[(ter t-Bu tyldim eth ylsilyl)oxy]-3-[(2R)-2-(m eth -
oxym eth yl)p yr r olid in -1-yl]-3-p h en yl-2-p r op a n ol (4c). A
solution of 5c (425 mg, 1.60 mmol), tert-butyldimethylsilyl
chloride (265 mg, 1.76 mmol), and imidazole (241 mg, 3.54
mmol) in DMF (15 mL) was heated at 65 °C for 24 h under
N2. A workup identical to the one described for 4a followed
by chromatography using hexane:EtOAc (80:20) as eluent
mg (14%) of 5g as a white solid: mp 114 °C; [R]23 ) -51.9 (c
D
1
) 1.0 in CHCl3); H-NMR (300 MHz, CDCl3) δ 7.26-7.38 (m,
5H), 4.16 (d × d × d, 1H, J ) 9.6, 5.7, 5.4 Hz), 3.90 (d, 1H, J
) 9.6 Hz), 3.83 (d × d, 1H, J ) 10.9, 5.4 Hz), 3.74 (d × d, 1H,
J ) 10.9, 5.7 Hz), 3.33 (h, 2H, J ) 6.6 Hz), 1.75 (br s, 2H,
OH), 1.14 (d, 6H, J ) 6.6 Hz), 0.80 (d, 6H, J ) 6.6 Hz); 13C-
NMR (75 MHz, CDCl3) δ 139.7 (C), 129.9 (CH), 128.5 (CH),
127.5 (CH), 70.7 (CH), 65.9 (CH2), 62.6 (CH), 46.4 (CH), 21.4
(CH3), 23.6 (CH3); IR (KBr) 3282, 3195, 3031, 2981, 2966, 2914,
yielded 520 mg (85%) of 4c as a colorless oil: [R]23 ) +9.7 (c
D
1
) 1.1 in CHCl3); H-NMR (300 MHz, CDCl3) δ 7.27-7.39 (m,
5H), 4.18 (d × d × d, 1H, J ) 6.3, 4.2, 3.6 Hz), 3.66 (d, 1H, J
) 4.2 Hz), 3.44 (d × d, 1H, J ) 10.0, 3.6 Hz), 3.27 (d × d, 1H,
J ) 10.0, 6.3 Hz), 3.05-3.18 (m, 2H), 3.12 (s, 3H), 2.95-3.05
(m, 2H), 2.64-2.73 (m, 1H), 1.63-1.74 (m, 4H), 0.86 (s, 9H),
0.02 (s, 3H), -0.05 (s, 3H); 13C-NMR (75 MHz, CDCl3) δ 137.8
(C), 130.1 (CH), 127.8 (CH), 127.5 (CH), 75.9 (CH2), 72.0 (CH),
69.6 (CH), 64.5 (CH2), 59.0 (CH), 58.6 (CH3), 53.6 (CH2), 28.2
(CH2), 25.8 (CH3), 23.5 (CH2), 18.2 (C), -5.5 (CH3); IR (film)
3440, 3029, 2956, 2929, 2858, 1115, 778, 704 cm-1; MS (CI,
NH3) m/ z 380 (C21H37NO3Si‚H+, 100).
2869, 1452, 1395, 1383, 1102, 1082, 1061, 1036, 722, 698 cm-1
;
MS (EI) m/ z 251 (M+, 0), 190 (M - C2H5O2+, 100). Anal.
Calcd for C15H25NO2: C, 71.67; H, 10.25; N, 5.34. Found: C,
71.67; H, 10.02; N, 5.57.
(2R,3R)-3-[[[2-(Dim eth yla m in o)eth yl]m eth yl]a m in o]-3-
p h en yl-1,2-p r op a n ed iol (5h ). Compound 1a (1.0 g, 6.66
mmol), CH2Cl2 (40 mL), N,N,N′-trimethylethylenediamine
(1.27 mL, 9.99 mmol), and Ti(OiPr)4 (2.95 mL, 9.99 mmol) were
treated as described for 5a during 8 h. The reaction mixture
was quenched with a 10% solution of NaOH in brine (40 mL)
as described for 5a to give 1.172 mg (70%) of 5h as an oil after
chromatography using hexane:EtOAc (40:60), EtOAc and
(2R,3R)-1-[(ter t-Bu tyld im eth ylsilyl)oxy]-3-p h en yl-3-p i-
p er id in o-2-p r op a n ol (4d ). A solution of 5d (783 mg, 3.33
mmol), tert-butyldimethylsilyl chloride (551 mg, 3.65 mmol),
and imidazole (500 mg, 7.34 mmol) in DMF (30 mL) was
heated at 65 °C for 14 h under N2. A workup identical to the
one described for 4a followed by chromatography using hexane:
EtOAc:EtOH (90:10) as eluents: [R]23 ) -46.2 (c ) 1.1 in
D
CHCl3); 1H-NMR (300 MHz, CDCl3) δ 7.22-7.37 (m, 5H), 4.22