Notes
2-(1H-Ben zotr iazol-1-yl)-2-(m eth ylth io)-3-(tr im eth ylsilyl)-
J . Org. Chem., Vol. 64, No. 16, 1999 6083
give an oil. Purification by flash chromatography on silica gel
(hexanes/Et2O gradient) afforded 5 as a colorless solid (32 mg,
89%): mp 113.5-113.6 °C; 1H NMR δ 2.33 (s, 3H), 2.40 (m, 1H),
2.60 (dd, J ) 6.6, 15.3 Hz, 1H), 2.91 (ddd, J ) 2.0, 6.9, 18.4 Hz,
1H), 3.23 (dd, J ) 1.8 , 15.2 Hz, 1H), 3.32 (brt d, J ) 2.1, 7.1
Hz, 1H), 3.40 (brt d, J ) 2.2, 6.8 Hz, 1H), 6.16 (brt, J ) 3.2 Hz,
1H), 7.11-7.15 (m, 4H), 7.26 (d, J ) 8.0 Hz, 2H), 7.32-7.41 (m,
3H); 13C NMR δ -21.1, 25.2, 27.6, 39.5, 40.1, 122.2, 125.4, 126.4,
128.5, 129.1, 129.2, 132.0, 137.3, 137.5, 139.9, 178.9, 179.1;
HRMS (EI) calcd for C21H20NO2 (M + 1) 318.1494, found
318.1540. Anal. Calcd for C21H19NO2: N, 4.41. Found: N, 4.75.
Gen er a l P r oced u r e for t h e Syn t h esis of Com p ou n d s
6a -c. Compounds 2 (0.001 mol) were dissolved in THF (100 mL)
and cooled to -78 °C. The appropriate Grignard reagent in THF
(0.004 mol) was added, and the mixture was stirred at -78 °C
for 2 h. The mixture was allowed to reach rt over 16 h. Brine
was added (30 mL), and the aqueous layer was extracted with
ethyl ether (2 × 30 mL). The combined organic layers were dried
(Na2SO4), and the solvent was removed. The obtained residue
was purified by flash chromatography to afford the desired
compound.
3-(1H-Ben zotr ia zol-1-yl)-3-(4-m eth ylp h en yl)-4-(tr im eth -
ylsilyl)bu ta n -2-ol (6a ): white solid (81% yield); mixture of
diastereomers A/B ) 3:1; mp 121.3-122.3 °C; 1H NMR δ -0.52
(s, 9H, A), -0.47 (s, 9H, B), 0.90 (d, J ) 6.3 Hz, 3H, B), 0.97 (d,
J ) 6.4 Hz, 3H, A), 1.82 (s, 2H, A + B), 2.17 (s, 3H, A+B), 4.91
(q, J ) 6.3 Hz, 1H, B), 5.19 (q, J ) 6.1 Hz, 1H, A), 6.53 (d, J )
8.2 Hz, 1H, A), 6.65 (d, J ) 8.2 Hz, 1H, B), 6.84 (m, 2H, A + B),
6.96 (m, 2H, A + B), 7.03 (brt, J ) 7.8 Hz, 1H, A + B), 7.13 (m,
1H, A + B), 7.90 (d, J ) 8.1 Hz, 1H, A + B); 13C NMR δ -0.7
[0.1], 17.0, 21.0, 25.8, 70.0, 73.5 [74.4], 112.7, 119.9 [120.0], 123.9
[124.0], 126.5, 126.9 [127.0], 128.0, 128.5, 129.3, 132.7, 136.4,
137.6. Anal. Calcd for C20H27N3OSi: C, 67.94; H, 7.71; N, 11.89.
Found: C, 67.61; H, 8.08; N, 12.15.
p r op a n a l (2g): white prisms (84% yield); mp 80.4-81.4 °C
(hexanes); 1H NMR δ -0.38 (s, 9H), 1.75 (d, J ) 14.6 Hz, 1H),
1.90 (s, 3H), 1.96 (d, J ) 14.6 Hz, 1H), 7.41 (t, J ) 7.4 Hz, 1H),
7.51 (t, J ) 6.2 Hz, 1H), 7.94 (d, J ) 7.5 Hz, 1H), 8.08 (d, J )
8.2 Hz, 1H), 9.85 (s, 1H); 13C NMR δ -1.1, 12.5, 22.8, 74.8, 112.0,
120.3, 124.5, 127.7, 132.2, 146.4, 184.0. Anal. Calcd for C13H19N3-
OSSi: C, 53.21; H, 6.53; N, 14.32. Found: C, 53.38; H, 6.82; N,
14.34.
2-(1H-Ben zotr iazol-1-yl)-2-(5-m eth ylth ioph en -2-yl)-3-(tr i-
m eth ylsilyl)p r op a n a l (2h ): light yellow prisms (86% yield);
mp 131.7-132.7 °C (hexanes); 1H NMR δ -0.36 (s, 9H), 1.94 (d,
J ) 14.6 Hz, 1H), 2.35 (d, J ) 14.5 Hz, 1H), 2.47 (s, 3H), 6.65-
6.68 (m, 2H), 6.98 (d, J ) 8.6 Hz, 1H), 7.31-7.37 (m, 2H), 8.09
(d, J ) 6.9 Hz, 1H), 10.12 (s, 1H); 13C NMR δ -1.1, 15.3, 24.3,
72.8, 111.4, 120.2, 124.2, 126.0, 127.4, 132.2, 137.3, 142.9, 146.3,
188.8. Anal. Calcd for C17H21N3OSSi: C, 59.44; H, 6.16; N, 12.23.
Found: C, 59.76; H, 6.30; N, 12.30.
3-(1H-Ben zotr ia zol-1-yl)-3-(4-m eth ylp h en yl)-1,4-bis(tr i-
m eth ylsilyl)bu ta n -2-ol (3). 2-(1H-Benzotriazol-1-yl)-2-(4-meth-
ylphenyl)-3-(trimethylsilyl)propanal 2b (0.337 g, 0.001 mol) was
dissolved in THF (100 mL) and cooled to -78 °C. Me3SiCH2-
MgCl in THF (1.0M, 4.0 mL, 0.004 mol) was added and the
mixture stirred at -78 °C for 2 h. The mixture was allowed to
reach rt in 16 h. Brine was added (30 mL), and the aqueous
layer was extracted with ethyl ether (2 × 30 mL). The combined
organic layers were dried (Na2SO4), and the solvent was removed
to give the pure product (yield 96%): white solid; mp 191.0-
1
191.4 °C (hexanes); H NMR δ -0.28 (s, 9H), 0.17 (s, 9H), 0.55
(d, J ) 14.0 Hz, 1H), 0.90 (d, J ) 14.0 Hz, 1H), 2.09 (dd, J )
24.0, 15.0 Hz, 2H), 2.45 (s, 3H), 4.03 (brs, 1H), 5.42-5.46 (m,
1H), 6.74 (d, J ) 8.3 Hz, 1H), 7.12 (d, J ) 7.9 Hz, 2H), 7.20 (d,
J ) 7.9 Hz, 2H), 7.27 (t, J ) 8.0 Hz, 1H), 7.39 (t, J ) 8.0 Hz,
1H), 8.16 (d, J ) 8.3 Hz, 1H); 13C NMR δ -0.6, -0.4, 18.4, 21.0,
26.2, 72.2, 75.4, 112.8, 119.9, 123.8, 126.8, 128.3, 133.0, 137.0,
137.3, 146.4. Anal. Calcd for C23H35N3OSi2: C, 64.88; H, 8.30;
N, 9.87. Found: C, 64.98; H, 8.35; N, 9.94.
2-(1H-Ben zotr ia zol-1-yl)-2-(4-m eth ylp h en yl)-1-p h en yl-3-
(tr im eth ylsilyl)p r op a n -1-ol (6b): colorless oil (94% yield);
mixture of diastereomers A/B ) 1:2; 1H NMR δ -0.34 (s, 9H,
A), -0.31 (s, 9H, B), 1.80 (d, J ) 14.8 Hz, 1H, A + B), 2.08 (d,
1H, J ) 14.8 Hz, A + B), 2.30 (s, 3H, B), 2.34 (s, 3H, A), 4.50
(brs, OH, A + B), 6.01 (s, 1H, B), 6.31 (s, 1H, A), 6.58 (d, J ) 8.3
Hz, 1H, A), 6.73-6.97 (m, 4H, A+B), 6.98 (d, J ) 7.8 Hz, 2H, A
+ B), 7.07-7.31 (m, 5H, A + B), 8.06 (d, J ) 8.3 Hz, 1H, A + B);
13C NMR δ -0.3 [0.1], 21.0, 26.4, 74.0 [75.7], 76.5 [80.2], 113.0
[113.5], 115.5, 119.7 [119.8], 124.0 [124.2], 126.8, 127.0, 127.2,
127.6, 127.9, 128.3, 128.9 [129.1], 129.5, 136.1, 137.7 [137.8],
138.9, 146.2; HRMS (EI) calcd for C25H30N3OSi (M + 1) 416.2158,
found 416.2113.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
4a ,b. 2-(1H-Benzotriazol-1-yl)-2-(4-fluorophenyl)-3-(trimethyl-
silyl)propanal 2d (0.341 g, 0.001 mol) was dissolved in THF (100
mL) and cooled to -78 °C. The appropriate lithiating reagent
(0.0011 mol) was added, and the mixture was stirred at -78
°C for 2 h. The mixture was allowed to reach rt in 16 h. Brine
was added (30 mL), the aqueous layers were extracted with
ethyl ether (2 × 30 mL), the combined organic layer was dried
(Na2SO4), and the solvent was removed to give a residue. The
residue was distilled under vacuum (4 mmHg) to afford the pure
product as the first fraction.
2-(1H-Ben zotr ia zol-1-yl)-2-(2-ch lor op h en yl)-1-p h en yl-3-
(tr im eth ylsilyl)p r op a n -1-ol (6c): white prisms (86% yield); mp
[1-Bu tyl-2-(4-flu or op h en yl)p r op -2-en yl]oxy(tr im eth yl)-
1
1
sila n e (4a ): colorless oil (98% yield); bp 105 °C (4 mmHg); H
208.7-210.1 °C; H NMR δ -0.14 (s, 9H), 1.89 (d, J ) 15.0 Hz,
NMR δ -0.14 (s, 9H), 0.54 (t, J ) 6.9 Hz, 3H), 0.93-1.13 (m,
6H), 4.19 (t, J ) 5.9 Hz, 1H), 4.89 (s, 1H), 4.99 (s, 1H), 6.70 (t,
J ) 8.6 Hz, 2H), 7.07 (t, J ) 8.6 Hz, 2H); 13C NMR δ -0.4, 14.0,
22.5, 28.0, 36.7, 75.2, 113.1, 114.9 (d, J ) 12.0 Hz), 128.7 (d, J
) 7.5 Hz), 136.3, 151.0, 162.3 (d, J ) 244.5 Hz). Anal. Calcd for
C16H25FOSi: C, 68.52; H, 9.00. Found: C, 68.31; H, 9.28.
[2-(4-F lu or op h en yl)-1-(1-m eth ylp r op yl)p r op -2-en yl]oxy-
(tr im eth yl)sila n e (4b): colorless oil (51% yield), mixture of
diastereomers A/B ) 1:2; bp 125 °C (4 mmHg); 1H NMR δ -0.16
(s, 9H), 0.73-0.84 (m, 6H), 0.97-1.20 (m, 1H), 1.20-1.42 (m,
2H), 4.43 (m, 1H), 5.24-5.26 (m, 2H), 6.99 (t, J ) 9.0 Hz, 2H),
7.32-7.37 (m, 1H), 7.40-7.45 (m, 1H); 13C NMR δ 0.2 (A + B,
2C), 11.5 (A), 11.8 (B), 12.9 (B), 15.8 (A), 23.7 (A), 26.6 (B), 38.1
(B), 38.4 (A), 77.9 (B), 80.6 (A), 114.1 (A + B), 114.8 (d, J ) 9.0
Hz, A), 115.1 (d, J ) 9.0 Hz, B), 128.6 (d, J ) 7.5 Hz, A), 129.0
(d, J ) 8.3 Hz, B), 136.8 (A + B), 149.8 (d, J ) 15.0 Hz, A + B),
162.3 (d, J ) 247.5 Hz, A + B). Anal. Calcd for C16H25FOSi: C,
68.52; H, 9.00. Found: C, 68.42; H, 9.34.
1H), 2.53 (d, J ) 15.0 Hz, 1H), 5.80 (s, 1H), 6.13 (s, 1H), 6.44 (d,
J ) 6.0 Hz, 2H), 6.84 (d, J ) 8.1 Hz, 1H), 7.10-7.26 (m, 6H),
7.42 (t, J ) 7.2 Hz, 1H), 7.63 (t, J ) 7.2 Hz, 1H), 7.96 (d, J ) 7.8
Hz, 1H), 8.27 (d, J ) 7.2 Hz, 1H); 13C NMR δ -0.3, 24.5, 72.3,
76.2, 114.7, 118.4, 122.8, 125.2, 127.0, 127.3, 127.8, 128.5, 129.7,
130.5, 131.9, 133.8, 134.9, 136.6, 140.0, 145.8. Anal. Calcd for
C24H26ClN3OSi: C, 66.11; H, 6.02; N, 9.64. Found: C, 66.06; H,
6.23; N, 9.69.
Gen er a l P r oced u r e for t h e Syn t h esis of Com p ou n d s
7a ,b. The corresponding 6 (0.30 mmol) were dissolved in dry
THF (3 mL), and a 1 M solution of tetrabutylammonium fluoride
in THF (450 µL, 0.45 mmol) was added. The resulting mixtures
were allowed to react until complete conversion of the starting
material as verified by TLC, and the solvent was removed. The
residue obtained was purified by flash chromatography on silica
gel (hexanes/Et2O gradient) to afford 7 as pure product.
3-(4-Meth ylp h en yl)bu t-3-en -2-ol (7a ): colorless oil (94%
1
yield); H NMR δ 1.31 (d, J ) 6.5 Hz, 3H), 1.90 (d, J ) 4.1 Hz,
5-(4-Met h ylp h en yl)-2-p h en yl-3a ,4,7,7a -t et r a h yd r o-1H -
isoin d ole-1,3(2H )-d ion e (5). 3-(1H-Benzotriazol-1-yl)-3-(4-
methylphenyl)-1,4-bis(trimethylsilyl)butan-2-ol 3 (50 mg, 0.114
mmol) and N-phenylmaleimide (78 mg, 0.455 mmol) were
dissolved in dry CH2Cl2 (1 mL). Trifluoroacetic acid (26 µL, 0.341
mmol) was added slowly under vigorous stirring. After 10 min,
aqueous 5% NaOH solution (1 mL) was introduced, and the
mixture was extracted with CH2Cl2 (3 × 3 mL). The combined
organic layers were dried (MgSO4), and solvent was removed to
1H), 2.34 (s, 3H), 4.81 (qd, J ) 6.5, 4.1 Hz, 1H), 5.25 (s, 1H),
5.32 (s, 1H), 7.14 (d, J ) 8.0 Hz, 2H), 7.28 (d, J ) 8.0 Hz, 2H);
13C NMR δ 21.1, 22.6, 69.5, 110.8, 126.7, 129.1, 136.9, 137.4,
152.9; HRMS (EI) calcd for C11H14O 162.1045, found 162.1033.
2-(4-Meth ylp h en yl)-1-p h en ylp r op -2-en -1-ol (7b): colorless
oil (85% yield); 1H NMR δ 2.28 (s, 3H), 5.42 (s, 1H), 5.47 (s, 1H),
5.67 (s, 1H), 7.04 (d, J ) 8.0 Hz, 2H), 7.20 (d, J ) 8.3 Hz, 2H),
7.23-7.25 (m, 1H), 7.29 (t, J ) 6.9 Hz, 2H), 7.38 (d, J ) 7.1 Hz,
2H); 13C NMR δ 21.1, 75.9, 113.2, 126.8, 127.0, 127.7, 128.4,