3332 J. Am. Chem. Soc., Vol. 121, No. 14, 1999
Ooi et al.
1
The crude amino alcohol (983 mg, 5.0 mmol) obtained above was
dissolved into pyridine (10 mL) and tosyl chloride (1.43 g, 7.5 mmol)
was added at 0 °C under argon. The reaction mixture was stirred at
room temperature for 7 h. This was then poured into saturated NaHCO3
and extracted with ether. The organic extracts were dried over Na2-
SO4. Evaporation of solvents and purification by column chromatog-
raphy on silica gel (EtOAc/hexane ) 1:1 as eluant) afforded hydroxy
tosylamide as an orange crystal (1.26 g, 3.6 mmol) in 72% yield: 1H
NMR (CDCl3) δ 7.72 (2H, d, J ) 8.4 Hz, Ts), 7.26-7.37 (9H, m, Ts
and Ph), 5.14 (1H, t, J ) 6.6 Hz, NH), 4.48 (2H, s, PhCH2), 3.85-
3.96 (1H, m, CHOH), 3.55-3.72 (2H, m, CH2OBn), 3.34 (1H, s, OH),
2.98-3.11 (1H, m, CH-N), 2.80-2.91 (1H, m, CH-N), 2.41 (3H, s,
ArCH3), 1.63-1.87 (2H, m, CH2).
Homopropargyl alcohol 18 (R′ ) CtCPh): H NMR (CDCl3) δ
7.26-7.40 (10H, m, 2Ph), 4.60 (2H, s, PhCH2O), 4.01-4.10 (1H, m,
CHOH), 3.69 (1H, dd, J ) 3.9, 9.6 Hz, OCH), 3.58 (1H, dd, J ) 6.6,
9.6 Hz, OCH), 2.72 (1H, dd, J ) 6.3, 16.8 Hz, CHCtC), 2.66 (1H,
dd, J ) 6.6, 16.8 Hz, CHCtC), 2.48 (1H, d, J ) 4.8 Hz, OH); IR
(liquid film) 3433, 3063, 3032, 2910, 2804, 1599, 1491, 1454, 1117,
1028, 756, 692 cm-1. Anal. Calcd for C18H18O2: C, 81.17; H, 6.81.
Found: C, 81.21; H, 6.91.
Homopropargyl alcohol 18 (R′ ) CtCSiMe3): 1H NMR (CDCl3)
δ 7.27-7.42 (5H, m, Ph), 4.58 (2H, s, PhCH2O), 3.92-4.00 (1H, m,
CHOH), 3.61 (1H, dd, J ) 3.9, 9.6 Hz, OCH), 3.50 (1H, dd, J ) 6.6,
9.6 Hz, OCH), 2.53 (1H, dd, J ) 6.0, 16.8 Hz, CHCtC), 2.46 (1H,
dd, J ) 6.6, 16.8 Hz, CHCtC), 2.39 (1H, d, J ) 4.8 Hz, OH), 0.14
(9H, s, 3CH3); IR (liquid film) 3443, 2959, 2901, 2864, 2176, 1454,
1250, 1117, 1030, 843, 760, 698 cm-1. Anal. Calcd for C15H22OSi: C,
68.65; H, 8.45. Found: C, 68.62; H, 8.40.
To a solution of the tosylamide (990 mg, 2.8 mmol) in THF (14
mL) was added a 1.59 M hexane solution of BuLi (3.56 mL, 5.66 mmol)
at 0 °C followed by the addition of tosyl chloride (648 mg, 3.40 mmol).
The mixture was then allowed to warm to room temperature and stirred
there for 1 h. The solution was poured into water and extracted with
ether. The ethereal extracts were dried over Na2SO4 and concentrated.
The residual oil was purified by column chromatography on silica gel
(ether/hexane/dichloromethane ) 1:8:8 as eluant) to give the desired
tosyl aziridine 9 as a colorless oil (728 mg, 2.2 mmol) in 78% yield:
1H NMR (CDCl3) δ 7.82 (2H, d, J ) 8.7 Hz, Ts), 7.19-7.41 (7H, m,
Ts and Ph), 4.37 (2H, s, PhCH2), 3.41-3.48 (1H, m, CHOBn), 3.29-
3.66 (1H, m, CHOBn), 2.87-2.95 (1H, m, CH-N), 2.68 (1H, d, J )
6.9 Hz, N-CH), 2.44 (3H, s, ArCH3), 2.13 (1H, d, J ) 4.5 Hz, N-CH),
1.87-1.98 (1H, m, CH), 1.51-1.62 (1H, m, CH). IR (liquid film) 3030,
1
Homopropargyl alcohol 19: H NMR (CDCl3) δ 7.24-7.44 (5H,
m, Ph), 4.53 (2H, s, PhCH2), 3.80-3.90 (1H, m, CHOH), 3.52-3.56
(2H, m, CH2OBn), 2.76 (1H, brs, OH), 2.61 (2H, dd, J ) 1.2, 3.0 Hz,
CH2CtC), 1.74-1.86 (2H, m, CH2), 1.60-1.70 (2H, m, CH2); IR
(liquid film) 3416, 3063, 3030, 2922, 2860, 2363, 1599, 1491, 1454,
1364, 1097, 1072, 1028, 758, 737, 694 cm-1. MS: m/z 294 (M+), 276,
257, 247, 233, 220, 91 (100). Anal. Calcd for C20H22O2: C, 81.60; H,
7.53. Found: C, 81.41; H, 7.69.
1
Homopropargyl alcohol 20: H NMR (CDCl3) δ 7.24-7.45 (5H,
m, Ph), 4.51 (2H, s, PhCH2), 3.80-3.86 (1H, m, CHOH), 3.50 (2H, t,
J ) 6.3 Hz, OCH2), 2.65 (1H, dd, J ) 5.0, 16.8 Hz, CHCtC), 2.55
(1H, dd, J ) 6.8, 16.8 Hz, CHCtC), 2.02 (1H, brs, OH), 1.55-1.70
(4H, m, 2CH2); IR (liquid film) 3417, 3063, 3030, 2937, 2862, 1599,
1491, 1454, 1362, 1101, 1028, 758, 737, 694 cm-1. MS: m/z 308 (M+),
290, 261, 247, 231, 205, 91 (100). Anal. Calcd for C21H24O2: C, 81.78;
H, 7.84. Found: C, 81.77; H, 7.94.
2924, 2864, 1597, 1454, 1325, 1163, 1096, 930, 818, 716, 698 cm-1
.
MS: m/z 331 (M+), 305, 281, 184, 44 (100). Anal. Calcd for C18H21-
NO3S: C, 65.23; H, 6.39; N, 4.23. Found: C, 65.05; H, 6.43; N, 4.16.
General Method of Me3Al-Catalyzed Cleavage of Epoxide with
Alkynyllithiums. To a solution of phenylacetylene (54 µL, 0.48 mmol)
in freshly distilled toluene (4 mL) was added a 1.56 M hexane solution
of BuLi (282 µL, 0.44 mmol) dropwise at 0 °C under argon. The
suspension was stirred for 30 min and then cooled to -78 °C. Epoxy
ether (0.4 mmol) was added dropwise followed by the addition of a
0.5 M hexane solution of Me3Al (80 µL, 0.04 mmol) at the same
temperature. The resulting mixture was allowed to warm to 0 °C and
stirred there for 5 h. The solution was then poured into 1 N HCl and
extractive workup was performed with ether. The combined organic
extracts were washed with brine and dried over Na2SO4. Evaporation
of solvents and purification of the residual oil by column chromatog-
raphy on silica gel (ether/hexane as eluant) gave the corresponding
homopropargyl alcohol.
Homopropargyl alcohol 21: The complete structural assignment
has been performed after conversion to the corresponding acetate. H
1
NMR (CDCl3) δ 7.38-7.42 (2H, m, Ph), 7.27-7.30 (3H, m, Ph), 5.16-
5.25 (1H, m, CH-OAc), 3.92-3.98 (1H, m, CH-O), 3.32-3.43 (2H,
m, O-CH2), 2.63-2.83 (2H, m, CH2CtC), 2.08 and 2.09 (3H, s,
COCH3), 1.78-2.00 (3H, m, CH2 and CH), 1.46-1.67 (4H, m, 2CH2),
1.26-1.35 (1H, m, CH); IR (liquid film) 2936, 2847, 1732, 1491, 1441,
1373, 1244, 1092, 1047, 1030, 758, 692 cm-1. Anal. Calcd for
C18H22O3: C, 75.50; H, 7.74. Found: C, 75.04; H, 7.77.
Homopropargyl alcohol 22: 1H NMR (CDCl3) δ 7.26-7.41 (15H,
m, 3Ph), 5.02 (1H, t, J ) 5.4 Hz, CH(OBn)2), 4.74 (1H, d, J ) 11.7
Hz, PhCH), 4.72 (1H, d, J ) 11.7 Hz, PhCH), 4.62 (1H, d, J ) 11.7
Hz, PhCH), 4.60 (1H, d, J ) 11.7 Hz, PhCH), 4.04-4.13 (1H, m,
CHOH), 3.00 (1H, d, J ) 3.3 Hz, OH), 2.65 (1H, dd, J ) 5.4, 16.5,
Hz, CHCtC), 2.58 (1H, dd, J ) 6.6, 16.5 Hz, CHCtC), 2.16 (1H,
ddd, J ) 2.7, 5.4, 14.1 Hz, CH), 2.03 (1H, ddd, J ) 5.4, 9.3, 14.1 Hz,
CH); IR (liquid film) 3446, 3032, 2929, 1491, 1456, 1207, 1126, 1057,
1026, 756, 737, 695 cm-1. Anal. Calcd for C26H26O3: C, 80.80; H,
6.78. Found: C, 80.75; H, 6.92.
Homopropargyl alcohol 23: 1H NMR (CDCl3) δ 7.29-7.39 (15H,
m, 3Ph), 4.54-4.64 (4H, m, 2PhCH2O), 4.16 (1H, dq, J ) 3.0, 6.0
Hz, CH-OH), 3.83 (1H, dd, J ) 7.8, 9.3 Hz, OCH), 3.75 (1H, dd, J )
5.4, 9.3 Hz, OCH), 3.69 (1H, dd, J ) 6.3, 9.3 Hz, OCH), 3.65 (1H,
dd, J ) 5.7, 9.3 Hz, OCH), 3.17 (1H, ddd, J ) 3.0, 5.4, 7.8 Hz, CH-
CtC), 2.60 (1H, d, J ) 6.0 Hz, OH); IR (liquid film) 3452, 3063,
3030, 2914, 2864, 2361, 2341, 1599, 1491, 1454, 1364, 1207, 1101,
1028, 912, 758, 739, 696 cm-1. MS: m/z 386 (M+), 311, 236, 128,
105, 91 (100). HRMS Calcd for C26H26O3: 386.1883 (M+). Found:
386.1900 (M+).
1
Homopropargyl alcohol 2 (R ) Ph): H NMR (CDCl3) δ 7.25-
7.41 (10H, m, 2Ph), 4.54 (2H, s, PhCH2O), 4.01-4.11 (1H, m, CHOH),
3.66-3.81 (2H, m, OCH2), 3.10 (1H, d, J ) 3.6 Hz, OH), 2.67 (1H,
dd, J ) 6.0, 16.8 Hz, CHCtC), 2.60 (1H, dd, J ) 6.3, 16.8 Hz, CHCt
C), 1.85-2.05 (2H, m, CH2); IR (liquid film) 3451, 3032, 2920, 2884,
1491, 1454, 1364, 1099, 1028, 756, 692 cm-1. Anal. Calcd for
C19H20O2: C, 81.40; H, 7.19. Found: C, 81.41; H, 7.25.
Homopropargyl alcohol 2 (R ) SiMe3): 1H NMR (CDCl3) δ 7.29-
7.38 (5H, m, Ph), 4.53 (2H, s, PhCH2O), 3.92-4.02 (1H, m, CHOH),
3.63-3.78 (2H, m, OCH2), 3.01 (1H, d, J ) 3.6 Hz, OH), 2.48 (1H,
dd, J ) 6.0, 16.8 Hz, CHCtC), 2.41 (1H, dd, J ) 6.3, 16.8 Hz, CHCt
C), 1.77-1.97 (2H, m, CH2), 0.15 (9H, s, 3CH3); IR (liquid film) 3443,
3032, 2959, 2862, 2176, 1454, 1420, 1364, 1250, 1099, 1030, 843,
760, 698, 648 cm-1. Anal. Calcd for C16H24O2Si: C, 69.51; H, 8.75.
Found: C, 69.71; H, 8.85.
1
Homopropargyl alcohol 4: H NMR (CDCl3) δ 7.26-7.42 (10H,
m, 2Ph), 4.44-4.67 (2H, m, PhCH2), 4.05-4.09 (0.2H, m, CHOH),
3.90-4.03 (0.8H, m, CHOH), 3.64-3.81 (1H, m, CHOBn), 3.71 (1H,
s, OH), 3.08-3.11 (0.2H, m, CCHO), 2.87-2.92 (0.8H, m, CCHO),
2.72-2.76 (0.8H, m, CH-O), 2.63-2.68 (0.2H, m, CH-O), 2.44-2.63
(3H, m, CH2CtC and CH-O), 2.46 (1H, dd, J ) 2.4, 2.7 Hz, CH-O),
1.20-1.95 (18H, m, 9CH2); IR (liquid film) 3489, 3034, 2930, 2856,
1491, 1456, 1094, 1074, 1028, 758, 694 cm-1. MS: m/z 434 (M+),
391, 369, 301, 43 (100). Anal. Calcd for C29H38O3: C, 80.14; H, 8.81.
Found: C, 79.88; H, 8.92. After debenzylation, the diol can be
converted to its acetonide, which confirms the regiochemistry of the
selective alkynylation.
1
Tosylamide 8: H NMR (CDCl3) δ 7.75 (2H, d, J ) 8.4 Hz, Ts),
7.21-7.34 (12H, m, Ts and Ph), 5.01 (1H, d, J ) 7.8 Hz, NH), 4.45
(2H, s, PhCH2), 3.56-3.66 (2H, m, OCH and CH-N), 3.41-3.45 (1H,
m, OCH), 2.72 (1H, dd, J ) 5.1, 16.8 Hz, CHCtC), 2.62 (1H, dd, J
) 7.2, 16.8 Hz, CHCtC), 2.39 (3H, s, ArCH3); IR (liquid film) 3375,
3033, 2924, 2868, 1599, 1491, 1414, 1339, 1161, 1090, 814 cm-1
.
MS: m/z 419 (M+), 344, 304, 155, 115, 91 (100), 65. HRMS Calcd
for C25H25NO3S: 419.1557 (M+). Found: 419.1570 (M+).