The Journal of Organic Chemistry
Article
0.04 (s, 3H), 0.01 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 178.4 (qC),
148.5 (qC), 144.1 (qC), 143.3 (CH), 130.3 (qC), 129.9 (qC), 129.7
(qC), 127.9 (qC), 126.6 (2 × CH), 125.9−125.8 (2 × CH), 121.8
(qC), 110.5 (CH), 69.8 (CH), 64.8 (CH2), 56.3 (CH), 39.3 (qC),
27.4 (3 × CH3), 26.1 (3 × CH3), 18.7 (qC), −4.4 (CH3), −4.5 (CH3).
HRMS (DART): calcd for C19H19F3N3O3 [M − C5H13O1Si1]+
394.1378; found 394.1374.
Hz), 5.20−5.13 (m, 1H), 4.38 (dd, 1H, J = 7.3, J = 11.2 Hz), 4.12 (dd,
1H, J = 4.9, J = 11.2 Hz), 2.54 (s, 3H), 1.27 (s, 9H), 1.08 (s, 9H), 0.23
(s, 3H), 0.13 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 178.4 (qC),
148.5 (qC), 144.8 (qC), 143.4 (qC), 142.1 (CH), 138.3 (qC), 130.2
(qC), 129.7 (CH), 127.0 (CH), 126.9 (CH), 126.1 (CH), 125.9
(CH), 125.8 (CH), 122.6 (qC), 110.4 (CH), 70.2 (CH), 64.9 (CH2),
49.9 (CH), 39.0 (qC), 27.3 (3 × CH3), 26.1 (3 × CH3), 21.7 (CH3),
18.5 (qC), −4.4 (CH3), −4.5 (CH3). HRMS (DART): calcd for
C32H42F3N1O6S1Si1 [M]+ 653.2454; found 653.2456.
Compound 10c: Yield (400 mg, 76%); oil; Rf = 0.58 (hexane/ethyl
acetate, 98:2); eluent for column chromatography (hexane/ethyl
acetate, 99:1); [α]27 = −13.27 (c 0.10, CHCl3). IR (neat, cm−1):
Compound 11c: Yield (311 mg, 71%); oil; Rf = 0.40 (hexane/ethyl
D
1
2927, 2363, 2110, 1731,1465, 1217. H NMR (CDCl3, 300 MHz): δ
acetate, 96:4); eluent for column chromatography (hexane/ethyl
acetate, 96:4); [α]30 = +17.50 (c 0.10, CHCl3). IR (neat, cm−1):
7.31 (d, 1H, J = 1.6 Hz), 6.31 (d, 1H, J = 1.7 Hz), 4.94 (dd, 1H, J =
4.4, J = 8.9 Hz), 4.69−4.65 (m, 1H), 4.48 (dd, 1H, J = 9.0, J = 11.5
Hz), 4.27 (dd, 1H, J = 4.6, J = 11.5 Hz), 1.69−1.60 (m, 2H), 1.25 (s,
14H), 1.22 (s, 9H), 0.88 (s, 12H), 0.60 (s, 3H) −0.05 (s, 3H). 13C
NMR (CDCl3, 75 MHz): δ 178.3 (qC), 143.7 (qC), 142.9 (CH),
128.9 (qC), 110.5 (CH), 68.1 (CH), 64.8 (CH2), 56.3 (CH), 40.7
(CH2), 39.2 (qC), 32.2 (CH2), 29.9−29.6 (4 × CH2), 27.4 (3 ×
CH3), 26.2 (3 × CH3), 25.6 (CH2), 23.0 (CH2), 18.5 (qC), 14.4
(CH3), −4.2 (CH3), −4.6 (CH3). HRMS (DART): calcd for
C27H50N1O4Si1 [M − N2]+ 480.3509; found 480.3507.
D
1
3274, 2858, 2368, 1724, 1266. H NMR (CDCl3, 300 MHz): δ 7.62
(d, 2H, J = 8.2 Hz), 7.18 (d, 2H, J = 8.2 Hz), 7.09 (d, 1H, J = 1.6 Hz),
6.20 (d, 1H, J = 1.6 Hz), 5.23 (d, 1H, J = 8.2 Hz), 4.95 (d, 1H, J = 6.9,
J = 13.0 Hz), 4.64−4.60 (m, 1H), 4.29 (dd, 1H, J = 7.0, J = 11.2 Hz),
4.07 (dd, 1H, J = 5.0, J = 11.2 Hz), 2.37 (s, 3H), 1.62−1.59 (m, 2H),
1.24 (s, 14H), 1.13 (s, 9H), 0.87 (s, 12H), 0.04 (s, 3H), −0.09 (s, 3H).
13C NMR (CDCl3, 75 MHz): δ 178.5 (qC), 144.4 (qC), 143.4 (CH),
141.6 (CH), 138.4, 129.9 (qC), 129.8 (CH), 127.4, 127.1 (CH), 127.0
(qC), 126.9 (qC), 110.8 (CH), 68.0 (CH), 65.4 (CH2), 49.9 (CH),
42.3 (qC), 40.4 (CH2), 39.1 (qC), 32.2 (CH2), 29.9.0−29.7 (4 ×
CH2), 27.4 (3 × CH3), 26.2 (2 × CH3), 25.7 (CH2), 23.0 (CH2), 21.8
(CH3), 14.5 (CH3), −4.2 (CH3) −4.6 (CH3). HRMS (DART): calcd
for C34H57N1O6S1Si1 [M]+ 635.3675; found 635.3659.
Compound 10d: Yield (1.618 g, 72%); oil; Rf = 0.40 (hexane/ethyl
acetate, 98:2); eluent for column chromatography (hexane/ethyl
acetate, 99:1); [α]31 = −14.76 (c 0.10, CHCl3). IR (neat, cm−1):
D
1
3020, 2361, 2109, 1726, 1216. H NMR (CDCl3, 300 MHz): δ 7.34
(d, 1H, J = 2.6 Hz), 6.30 (d, 1H, J = 2.6 Hz) 5.0 (dd, 1H, J = 8.5, J =
12.2 Hz), 4.63 (s, 2H), 4.43−4.30 (m, 2H), 1.19 (s, 9H), 0.92 (s, 9H),
0.11 (s, 6H). 13C NMR (CDCl3, 75 MHz): δ 177.9 (qC), 144.9 (qC),
142.9 (CH), 124.5 (qC), 111.1 (CH), 64.5 (CH2), 57.7 (CH2), 56.2
(CH), 39.2 (qC), 27.6 (3 × CH3), 26.4 (3 × CH3), 18.8 (qC), −4.8
(2 × CH3). HRMS (DART): calcd for C18H32N3O4Si1 [M + H]+
382.2162; found 382.2159.
Compound 11d: Yield (1.6 g, 75%); oil; Rf = 0.34 (hexane/ethyl
acetate, 85:15); eluent for column chromatography (hexane/ethyl
acetate, 90:10); [α]29 = −2.03 (c 0.10, CHCl3). IR (neat, cm−1):
D
1
3430, 3019, 2363, 1592, 1217. H NMR (CDCl3, 300 MHz): δ 7.57
(d, 2H, J = 8.2 Hz), 7.13 (d, 2H, J = 8.0 Hz), 7.04 (d, 1H, J = 1.6 Hz),
6.03 (d, 1H, J = 1.59 Hz), 5.68 (d, 1H, J = 9.0 Hz), 4.91−4.83 (m,
1H), 4.45−4.41 (m, 1H), 4.34−4.27 (m, 1H), 4.20−4.15 (m, 1H),
2.34 (s, 3H), 1.12 (s, 9H), 0.92 (s, 9H), 0.11 (s, 6H). 13C NMR
(CDCl3, 75 MHz): δ 178.4 (qC), 146.3 (qC), 143.3 (qC), 141.6
(CH), 138.0 (qC), 129.6 (2 × CH), 127.1 (2 × CH), 122.1 (qC),
110.8 (CH), 64.8 (CH2), 57.9 (CH2), 50.2 (CH), 39.1 (qC), 27.4 (3
× CH3), 26.3 (3 × CH3), 21.8 (CH3), 18.7 (qC), −5.0 (2 × CH3).
HRMS (DART): calcd for C25H40N1O6S1Si1 [M + H]+ 510.2345;
found 510.2337.
General Procedure for the Synthesis of Compounds 11a−d
from 10a−d. Compound 11a: To a solution of compound 10a
(900 mg, 1.86 mmol) in CH3OH/CHCl3 (12 mL, 5:1, v/v) were
added 10% Pd−C (150 mg) and Et3SiH (0.69 mL, 4.66 mmol) under
argon, and the reaction mixture was stirred at room temperature for 2
h. It was filtered through a Celite bed and washed with CH3OH. The
solvents were removed under reduced pressure to obtain the crude
product mixture, which was dissolved in dry CH2Cl2 (10 mL), and
then Et3N (0.39 mL, 2.8 mmol) was added to it at 0 °C followed by
dropwise addition of p-TsCl (532 mg, 2.8 mmol) dissolved in dry
CH2Cl2 over a period of 0.5 h. The reaction mixture was now stirred at
room temperature for an additional 2.5 h. On completion of the
reaction (TLC), the reaction was quenched with saturated aqueous
NaHCO3 and extracted with dichloromethane (2 × 5 mL). The
combined organic layers were washed with brine, dried over Na2SO4,
and concentrated under reduced pressure to yield the crude product
mixture. Flash column chromatography gave the pure compound 11a:
yield (797 mg, 70%); oil; Rf = 0.48 (hexane/ethyl acetate, 75:25);
eluent for column chromatography (hexane/ethyl acetate, 98:2);
General Procedure for the Synthesis of Compounds 12a−d
from 11a−d. Compound 12a: NBS (437 mg, 2.45 mmol) was
added in small portions over 0.5 h to solution of p-toluenesulfonyl
amine 11a (750 mg, 1.22 mmol) in THF−H2O (10 mL, 4:1, v/v)
cooled to −5 °C, and the reaction mixture was allowed to warm to
room temperature. After completion of the reaction in about 3.5 h
(TLC), the reaction mixture was diluted with ethyl acetate (10 mL)
and washed successively with a saturated aqueous solution of KI,
Na2S2O3, and NaHCO3. The organic layer was separated, washed with
brine solution, dried over Na2SO4, and concentrated in vacuo at
reduced temperature to furnish the crude mixture, which was subjected
to flash column chromatography to give the pure compound 12a: yield
(507 mg, 66%); oil; Rf = 0.33 (hexane/ethyl acetate, 80:20); eluent for
column chromatography (hexane/ethyl acetate, 90:10); [α]31D = +5.79
[α]25 = +22.43 (c 0.5, MeOH). IR (neat, cm−1): 2960, 2364, 2229,
D
2109, 1729, 1631. 1H NMR (CDCl3, 300 MHz): δ 7.58 (d, 2H, J = 8.2
Hz), 7.54−7.45 (m, 4H), 7.13 (d, 1H, J = 9.0 Hz), 7.06 (d, 1H, J = 1.5
Hz), 6.22 (d, 1H, J = 1.6 Hz), 5.77 (s, 1H), 5.34 (d, 1H J = 8.6 Hz),
5.0−4.93 (m, 1H), 4.16 (dd, 1H J = 7.3, J = 11.3 Hz), 3.93 (dd, 1H J =
4.8, J = 11.3 Hz), 2.36 (s, 3H), 1.08 (s, 9H), 0.87 (s, 9H), 0.02 (s,
3H), −0.06 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 178.3 (qC), 149.7
(qC), 144.9 (qC), 143.4 (qC), 142.5 (CH), 138.3 (qC), 132.6 (2 ×
CH), 129.7 (2 × CH), 127.2 (2 × CH), 126.8 (2 × CH), 125.6 (qC)
118.9 (qC), 111.5 (CN) 110.2 (CH), 69.9 (CH), 64.8 (CH2), 49.8
(CH), 38.9 (qC), 27.2 (3 × CH3), 26.0 (3 × CH3), 21.7 (CH3) 18.4
(qC), −4.5 (2 × CH3). HRMS (DART): calcd for C32H42N2O6S1Si1
[M]+ 610.2532; found 610.2522.
1
(c 0.1, CHCl3). IR (neat, cm−1): 2923, 2357, 1728, 1596, 1216. H
NMR (CDCl3, 300 MHz): δ 7.64 (d, 2H, J = 8.2), 7.54 (d, 2H, J =
8.2), 7.43 (d, 2H, J = 8.2), 7.28−7.26 (m, 2H), 7.05 (d, 1H, J = 3.7),
5.98 (d, 1H, J = 3.6), 5.52 (s, 1H), 4.56−4.52 (m, 1H), 4.27 (dd, 1H J
= 6.0, J = 11.3), 4.1 (dd, 1H J = 6.6, J = 11.3), 2.39 (s, 1H), 0.95 (s,
9H), 0.78 (s, 9H) −0.13 (s, 3H), −0.18 (s, 3H). 13C NMR (CDCl3, 75
MHz): δ 190.7 (CO), 177.9 (qC), 147.3 (qC), 144.7 (qC), 140.3
(qC), 139.1 (CH), 136.7 (qC), 132.5 (2 × CH), 130.5 (2 × CH),
127.6 (2 × CH), 127.0 (2 × CH), 118.9 (qC), 111.9 (CN), 73.9 (CH)
69.3 (CH), 64.8 (CH2), 59.4 (CH), 38.9 (qC), 27.2 (3 × CH3), 25.9
(3 × CH3), 21.8 (CH3), 18.3 (qC), −4.7 (CH3), −4.9 (CH3). HRMS
(DART): calcd for C32H41N2O6S1Si1 [M − OH]+ 609.2454; found
609.2463.
Compound 11b: Yield (380 mg, 68%); oil; Rf = 0.46 (hexane/ethyl
acetate, 85:15); eluent for column chromatography (hexane/ethyl
acetate, 95:5); [α]29D = −13.64 (c 0.1, CHCl3). IR (neat, cm−1): 3449,
Compound 12b: Yield (98 mg, 64%); oil; Rf = 0.46 (hexane/ethyl
acetate, 86:14); eluent for column chromatography (hexane/ethyl
acetate, 95: 5); [α]29D = +7.86 (c 0.2, CHCl3). IR (neat, cm−1): 2921,
1
2933, 1725, 1325. H NMR (CDCl3, 300 MHz): δ 7.76−7.68 (m,
4H), 7.64 (d, 2H, J = 8.2 Hz), 7.32 (d, 2H, J = 8.0 Hz), 7.26 (d, 1H, J
= 1.1 Hz), 6.43 (d, 2H, J = 1.4 Hz), 5.97 (s, 1H), 5.53 (d, 1H, J = 5.8
1
2363, 1732, 1218. H NMR (CDCl3, 300 MHz): δ 7.76−7.70 (m,
8938
dx.doi.org/10.1021/jo201662n|J. Org. Chem. 2011, 76, 8930−8943