Stereoselective Synthesis of (-)-Siphonodiol
NMR (100 MHz, CDCl3) δ -1.6 (4 × CH3), 15.8 (2 × CH2),
20.5 (2 × CH2), 20.7 (2 × CH2), 28.7 (2 × CH2), 29.0 (2 × CH2),
30.5 (2 × CH2), 96.3 (2 × C), 103.4 (2 × C), 108.8 (2 × CH),
119.6 (2 × C), 145.90 (2 × CH) ppm. IR (CsI) ν 2245 (CtN),
2146 (CtC) cm-1. MS (CI) m/z (%) 437 (MH+, 100), 421 (21),
394 (11), 297 (7), 269 (8), 126 (5). HRMS (EI) calcd for
C26H40N2Si2 436.2730, found 436.2728.
SO4, and concentrated. Purification by flash chromatography
(hexane/ethyl acetate 98:2) afforded the title compound as a
yellow oil (0.29 g, 94% yield). 1H NMR (500 MHz, CDCl3) δ
1.0-1.1 (21H, m), 1.75 (2H, q, J ) 7.0 Hz), 1.95 (1H, t, J )
2.5 Hz), 2.31 (2H, dt, J ) 2.5, 7.0 Hz), 2.41 (2H, t, J ) 7.0 Hz)
ppm. 13C NMR (126 MHz, CDCl3) δ 11.2 (3 × CH), 17.6 (CH2),
18.2 (CH2), 18.5 (6 × CH3), 27.0 (CH2), 66.5 (C), 69.1 (CH),
77.3 (C), 80.3 (C), 82.9 (C), 89.9 (C) ppm. IR (CsI) ν 3309
(tC-H), 2225, 2105 (CtC) cm-1. MS (EI) m/z (%) 272 (M+,
8), 229 (95), 187 (21), 159 (100), 145 (67). HRMS (EI) calcd for
C18H28Si 272.1960, found 272.1961.
(R)-11-[(3′-Cyanopropyl)dimethylsilyl]undeca-3,5,10-
triyne-1,2-diol (28). To a solution of (R)-4-iodobut-3-yne-1,2-
diol (21) (0.23 g, 1.08 mmol) and 1-[(3′-cyanopropyl)dimethyl-
silyl]hepta-1,6-diyne (23) (0.58 g, 2.67 mmol)) in degassed
piperidine (27 mL), cooled on an ice-water bath, was added
CuI (0.05 g, 0.26 mmol), and the mixture was allowed to react
for 1 h at room temperature. The mixture was poured in
aqueous saturated solution of NH4Cl (25 mL), and the organic
layer was extracted with CH2Cl2 (3 × 20 mL), washed with
brine (2 × 60 mL), dried over anhydrous Na2SO4, and
concentrated. Purification by flash chromatography (hexane/
(R)-13-Triisopropylsilyltrideca-3,5,10,12-tetrayne-1,2-
diol (30). Following the same procedure described for 28,
treatment of (R)-4-iodobut-3-yne-1,2-diol (21) (0.05 g, 0.24
mmol) and 1-triisopropylsilylnona-1,3,8-triyne (27) (0.17 g, 0.62
mmol) in degassed piperidine (5 mL) with CuI (0.01 g, 0.05
mmol) for 6 h at room temperature afforded, after purification
by flash chromatography (CH2Cl2/ethyl acetate 95:5), the title
compound as a light brown oil (0.07 g, 83% yield). [R]20D -14.8°
ethyl acetate 90:10) afforded the title compound as a yellow
1
1
oil (0.24 g, 74% yield). [R]20 -32.1° (c 0.61, CHCl3). H NMR
(c 1.28, CHCl3). H NMR (300 MHz, CDCl3) δ 1.0-1.1 (21H,
D
(250 MHz, CHCl3) δ 0.15 (6H, s), 0.7-0.8 (2H, m), 1.7-1.8 (4H,
m), 2.3-2.4 (6H, m), 3.7-3.8 (2H, m), 4.4-4.5 (1H, m) ppm.
13C NMR (75 MHz, CDCl3) δ -1.8 (2 × CH3), 15.8 (CH2), 18.2
(CH2), 18.8 (CH2), 20.3 (CH2), 20.5 (CH2), 26.8 (CH2), 63.4 (CH),
64.9 (C), 66.1 (CH2), 70.7 (C), 73.6 (C), 80.5 (C), 83.6 (C), 107.1
(C), 119.7 (C) ppm. IR (CsI) ν 3406 (O-H), 2253 (CtN), 2172
(CtC) cm-1. MS (CI) m/z (%) 302 (MH+, 4), 281 (41), 256 (33),
159 (14), 126 (100). HRMS (EI) calcd for C17H23NO2Si 301.1491,
found 301.1498.
(R)-Undeca-3,5,10-triyne-1,2-diol (29). To a solution of
(R)-11-[(3′-cyanopropyl)dimethylsilyl]undeca-3,5,10-triyne-1,2-
diol (28) (0.17 g, 0.56 mmol) in dry THF (11 mL) was added
n-Bu4NF (1.0 M solution in THF, 1.68 mL, 1.68 mmol), and
the mixture was allowed to react at room temperature for 5
h. The mixture was diluted with ether (10 mL), washed with
brine (3 × 12 mL), dried over anhydrous Na2SO4, and
concentrated. Purification by flash chromatography (CH2Cl2/
ethyl acetate, 50:50) afforded the title compound as a light
brown solid (0. 08 g, 84% yield). [R]20D -43.8° (c 1.16, CHCl3).
Mp 58-60 °C (dec). 1H NMR (300 MHz, CDCl3) δ 1.7-1.8 (2H,
m), 1.96 (1H, s), 2.3-2.5 (4H, m), 3.6-3.7 (2H, m), 4.4-4.5
(1H, m) ppm. 13C NMR (75 MHz, CDCl3) δ 17.5 (CH2), 18.2
(CH2), 26.9 (CH2), 63.5 (CH), 64.9 (C), 66.2 (CH2), 69.3 (CH),
70.8 (C), 73.4 (C), 80.7 (C), 82.9 (C) ppm. IR (CsI) ν 3385 (O-
H), 3300 (tC-H), 2256 (CtC) cm-1. MS (CI) m/z (%) 176 (M+,
1), 159 (54), 129 (98), 116 (77), 91 (100). Anal. Calcd for
C11H12O2: C, 74.98; H, 6.86. Found: C, 74.66; H, 6.96.
9-[(3′-Cyanopropyl)dimethylsilyl]-1-triisopropylsilyl-
nona-1,3,8-triyne (26). Following the same procedure de-
scribed for 28, treatment of 2-iodo-1-triisopropylsilylacetylene
(25) (0.25 g, 0.81 mmol) and 1-[(3′-cyanopropyl)dimethylsilyl]-
hepta-1,6-diyne (23) (0.40 g, 1.84 mmol) in degassed piperidine
(25 mL) with CuI (0.03 g, 0.20 mmol) for 1 h at room
temperature afforded, after purification by flash chromatog-
raphy (hexane/ethyl acetate 90:10), the title compound as a
yellow oil (0.24 g, 74% yield). 1H NMR (250 MHz, CDCl3) δ
0.15 (6H, s), 0.7-0.8 (2H, m), 1.0-1.1 (21H, m), 1.7-1.8 (4H,
m), 2.3-2.4 (6H, m) ppm. 13C NMR (75 MHz, CDCl3) δ -1.6
(2 × CH3), 11.3 (3 × CH), 15.9 (CH2), 18.4 (CH2), 18.6 (6 ×
CH3), 19.1 (CH2), 20.5 (CH2), 20.7 (CH2), 27.2 (CH2), 66.5 (C),
77.4 (C), 80.5 (C), 83.5 (C), 89.8 (C), 107.2 (C), 119.6 (C) ppm.
IR (CsI) ν 2246 (CtN), 2224, 2174 (CtC) cm-1. MS (EI) m/z
(%) 397 (M+, <1), 354 (100), 242 (3), 183 (3), 157 (3), 105 (2).
HRMS (EI) calcd for C24H39NSi2 397.2621, found 397.2617.
1-Triisopropylsilylnona-1,3,8-triyne (27). To a solution
of 9-[(3′-cyanopropyl)dimethylsilyl]-1-triisopropylsilylnona-
1,3,8-triyne (26) (0.45 g, 1.13 mmol) in a 1:1 THF/MeOH
mixture (22 mL) was added anhydrous K2CO3 (0.64 g, 4.63
mmol), and the suspension was allowed to react for 1 h at room
temperature. The mixture was diluted in a 1:2 ether/H2O
mixture (24 mL), and the organic phase was washed with H2O
(2 × 10 mL) and brine (3 × 10 mL), dried over anhydrous Na2-
m), 1.79 (2H, q, J ) 6.9 Hz), 2.4-2.5 (4H, m), 3.7-3.8 (2H,
m), 4.50 (1H, t, J ) 5.0 Hz). 13C NMR (75 MHz, CDCl3) δ 11.3
(3 × CH), 18.4 (2 × CH2), 18.6 (6 × CH3), 26.7 (CH2), 63.5
(CH), 65.1 (C), 66.2 (CH2), 66.7 (C), 70.8 (C), 73.6 (C), 76.9
(C), 80.4 (C), 80.7 (C), 89.7 (C). IR (CsI) ν 3372 (O-H), 2224
(CtC) cm-1. MS (EI) m/z (%) 356 (M+, 21), 325 (36), 295 (9),
225 (100), 197 (58), 179 (58), 165 (89). HRMS (EI) calcd for
C22H32SiO2 356.2171, found 356.2180.
(R)-Trideca-3,5,10,12-tetrayne-1,2-diol (31). Following
the same procedure described for 29, treatment of a solution
of (R)-13-triisopropylsilyltrideca-3,5,10,12-tetrayne-1,2-diol (30)
(0.16 g, 0.45 mmol) in dry THF (5 mL) with n-Bu4NF (1.0 M
solution in THF, 1.35 mL, 1.35 mmol) for 6 h afforded, after
purification by flash chromatography (hexane), the title com-
pound as a light brown solid (0.09 g, quantitative yield). [R]20
D
-33.2° (c 0.45, CHCl3). Mp: 83-85 °C (CH2Cl2). 1H NMR (300
MHz, CDCl3) δ 1.75 (2H, q, J ) 7.0 Hz), 1.96 (1H, t, J ) 1.0
Hz), 2.38 (2H, dt, J ) 7.0, 1.0 Hz), 2.44 (2H, t, J ) 7.0 Hz),
3.6-3.7 (2H, m), 4.4-4.5 (1H, m) ppm. 13C NMR (75 MHz,
CDCl3) δ 18.3 (CH2), 18.5 (CH2), 26.6 (CH2), 63.6 (CH), 65.1
(CH), 65.2 (C), 65.7 (C), 66.3 (CH2), 68.2 (C), 71.0 (C), 73.5
(C), 76.6 (C), 80.3 (C) ppm. IR (CsI) ν 3273 (tC-H, O-H),
2224 (CtC) cm-1. MS (CI) m/z (%) 201 (MH+, 3), 200 (M+, 2),
153 (100). Anal. Calcd for C13H12O2: C, 77.98; H, 6.04. Found:
C, 77.76; H, 6.35.
(2R,14Z,20Z)-23-[(3′-Cyanopropyl)dimethylsilyl]tricosa-
14,20-diene-3,5,10,12,22-pentayne-1,2-diol (32). Following
the same procedure described for 12, treatment of (3Z,9Z)-10-
bromo-1-[(3′-cyanopropyl)dimethylsilyl]deca-3,9-dien-1-yne (12)
(0.025 g, 0.074 mmol), PdCl2(PPh3)2 (0.006 g, 0.009 mmol), and
CuI (0.002 g, 0.011 mmol), in degassed pyrrolidine (2 mL), with
a solution of (R)-trideca-3,5,10,12-tetrayne-1,2-diol (31) (0.030
g, 0.150 mmol) in degassed pyrrolidine (1 mL) for 3 h afforded,
after purification by flash chromatography (hexane/ethyl
acetate 90:10), the title compound as a highly unstable yellow
oil (0.023 g, 68% yield), which was used immediately in the
1
next step. H NMR (250 MHz, CDCl3) δ 0.22 (6H, s), 0.7-0.8
(2H, m), 1.4-1.5 (4H, m), 1.7-1.9 (4H, m), 2.3-2.5 (10H, m),
3.7-3.8 (2H, m), 4.5-4.6 (1H, m), 5.49 (2H, d, J ) 10.8 Hz),
5.98 (1H, dt, J ) 10.8, 7.5 Hz), 6.05 (1H, dt, J ) 10.8, 7.5 Hz)
ppm. 13C NMR (75 MHz, CDCl3) δ -1.6 (2 × CH3), 15.9 (CH2),
18.4 (CH2), 18.7 (CH2), 20.6 (CH2), 20.8 (CH2), 26.9 (CH2), 28.2
(CH2), 28.4 (CH2), 30.2 (CH2), 30.6 (CH2), 63.6 (CH), 66.3 (CH2),
66.6 (C), 66.8 (C), 70.9 (C), 72.5 (C), 73.6 (C), 77.9 (C), 80.6
(C), 83.1 (C), 96.6 (C), 103.3 (C), 108.2 (CH), 109.1 (CH), 119.6
(C), 145.5 (CH), 147.6 (CH) ppm.
(2R,12Z,20Z)-23-[(3′-Cyanopropyl)dimethylsilyl]tricosa-
12,20-diene-3,5,10,22-tetrayne-1,2-diol (33). Following the
same procedure described for 12, treatment of (3Z,11Z)-12-
bromo-1-[(3′-cyanopropyl)dimethylsilyl]dodeca-3,11-dien-1-
yne (13)(0.16 g, 0.44 mmol), PdCl2(PPh3)2 (0.03 g, 0.04 mmol),
and CuI (0.01 g, 0.05 mmol), in degassed piperidine (5 mL),
J. Org. Chem, Vol. 70, No. 16, 2005 6351