7604 J. Am. Chem. Soc., Vol. 121, No. 33, 1999
Han et al.
60 mL). The combined organic layers were dried over Na2SO4 and
concentrated to a residue that was chromatographed (1:30 EtOAc/
hexanes containing 1% Et3N as eluent) to give 11 (2.10 g, 84% yield)
as a colorless liquid identical with that previously reported:5c (R)-11
of the coupling as monitored by TLC, the reaction mixture was cooled,
diluted with Et2O (30 mL), and washed with a mixture of brine (40
mL) and 5% aqueous NH4OH (8 mL). The aqueous layer was further
extracted with Et2O (2 × 15 mL), and the combined organic layers
were washed with water (2 × 40 mL) then brine (2 × 40 mL), dried
over Na2SO4, and concentrated to a residue that was purified as stated
below.
[R]23 -2.2 (c 1.0, CHCl3).
D
2-(Tri-n-butylstannyl)-1-buten-3-ol (13). 1-Butyn-3-ol (0.16 mL,
2.0 mmol) was converted to 2-bromo-1-buten-3-ol (with complete
position selectivity) by the method of Marshall18c and used as a crude
oil in the following step. To a cooled (-78 °C) solution of crude
2-bromo-1-buten-3-ol in Et2O (6 mL) was added t-BuLi (1.7 M in
pentane, 4.0 mL, 6.8 mmol) dropwise over 15 min. The reaction mixture
was stirred at -78 °C for 30 min, then -40 °C for 2.5 h. Bu3SnCl
(1.09 mL, 4.0 mmol) was added over 6 min and the reaction mixture
stirred for 1.5 h. The reaction mixture was quenched by the addition
of a mixture of pH 7.0 buffer solution (6 mL) and water (6 mL) at
-40 °C, and allowed to warm to room temperature. The mixture was
extracted with Et2O (3 × 15 mL). The combined organic layers were
dried over Na2SO4 and concentrated to a residue that was chromato-
graphed (1:15 EtOAc/hexanes containing 1% Et3N as eluent) to give
13 (0.43 g, 60% yield for two steps) as a colorless liquid identical
with that previously reported.5c
Alcohol (R)-12. Purification by flash chromatography (1:20 EtOAc/
hexanes eluent) gave (R)-12 (60 mg, 95% yield from 10b) as a colorless
oil of 93% ee (determined by HPLC): [R]23 -26.8 (c 1.2, CHCl3);
D
1
FTIR (film) 3390, 2930, 2858 cm-1; H NMR (500 MHz, CDCl3) δ
7.11 (dd, J ) 7.9, 1.8 Hz, 1H), 7.09 (s, 1H), 7.03 (d, J ) 7.9 Hz, 1H),
5.28 (s, 1H), 5.26 (s, 1H), 4.61-4.58 (m, 1H), 2.77 (br s, 4H), 1.82-
1.78 (m, 4H), 1.68-1.57 (m, 2H), 1.53-1.42 (m, 2H), 1.39-1.20 (m,
4H), 0.86 (t, J ) 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 152.2,
137.2, 137.0, 136.7, 129.0, 127.5, 124.0, 111.5, 73.8, 36.1, 31.7, 29.5,
29.1, 25.4, 23.2 (2 C), 22.6, 14.0; HRMS (CI) for [C18H26O + H]+,
m/z calcd 259.2062, found 259.2056; HPLC (chiral) Chiralcel OD at
23 °C, λ ) 254 nm (99:1 hexane/2-propanol eluent) retention times
12.24 (S) and 17.53 (R) min at 1 mL/min flow rate.
Alcohol 14. Purification by flash chromatography (1:15 EtOAc/
hexanes eluent) gave 14 (47 mg, 94% yield from 10a) as a colorless
2-(Tri-n-butylstannyl)-3-benzyloxyl-1-butene (15). A solution of
alcohol 13 (1.05 g, 2.91 mmol) in DMF (25 mL) at 0 °C was treated
portionwise with NaH (60% suspension, 0.58 g, 14.6 mmol). The
resulting suspension was stirred at 0 °C for 2 min, the cooling bath
was removed, and the reaction mixture was treated with BnBr (0.86
mL, 7.3 mmol) and Bu4NI (1.18 g, 3.2 mmol). After the mixture was
stirred at room temperature for 16 h, it was diluted with Et2O (75 mL)
and water (75 mL). The layers were separated and the aqueous layer
further extracted with Et2O (2 × 50 mL). The combined organic layers
were dried over Na2SO4 and concentrated to a residue that was subjected
to column chromatography (1:60 EtOAc/hexanes containing 1% Et3N
as eluent) to give 15 (1.15 g, 88% yield) as a colorless liquid: FTIR
1
oil: FTIR (film) 3390, 2929, 2858, 1683 cm-1; H NMR (400 MHz,
CDCl3) δ 7.12 (dd, J ) 7.8, 1.8 Hz, 1H), 7.10 (s, 1H), 7.04 (d, J ) 7.9
Hz, 1H), 5.30 (app t, J ) 1.2 Hz, 1H), 5.25 (s, 1H), 4.81 (q, J ) 6.4
Hz, 1H), 2.77 (br s, 4H), 1.83-1.78 (m, 4H), 1.69 (s, 1H), 1.34 (d, J
) 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 153.1, 137.0, 136.8,
129.1 (2 C), 127.4, 123.9, 110.6, 69.4, 29.5, 29.1, 23.2 (2 C), 22.6;
HRMS (EI) for [C14H18O]+, m/z calcd 202.1358, found 202.1353.
Ether 16. Purification by flash chromatography (1:60 EtOAc/hexanes
eluent) gave 16 (66 mg, 91% yield from 10a) as a colorless oil: FTIR
1
(film) 3030, 2929 cm-1; H NMR (400 MHz, CDCl3) δ 7.39-7.34
(m, 4H), 7.31-7.29 (m, 1H), 7.19 (dd, J ) 7.9, 1.9 Hz, 1H), 7.16 (s,
1H), 7.03 (d, J ) 7.9 Hz, 1H), 5.39 (d, J ) 1.6 Hz, 1H), 5.32 (dd, J
) 1.4, 0.9 Hz, 1H), 4.70 (d, J ) 11.9 Hz, 1H), 4.45 (d, J ) 11.8 Hz,
1H), 4.39 (qd, J ) 6.5, 0.6 Hz, 1H), 2.78 (app t, J ) 6.4 Hz, 4H),
1.82-1.79 (m, 4H), 1.34 (d, J ) 6.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 149.5, 138.9, 137.0, 136.7, 129.1, 128.4 (2 C), 127.8, 127.5,
127.5, 124.1, 113.2, 77.6, 70.2, 29.5, 29.2, 23.2 (2 C), 21.7; HRMS
(CI) for [C21H24O + NH4]+, m/z calcd 310.2171, found 310.2159.
Alcohol 18. Purification by flash chromatography (1:9 EtOAc/
hexanes eluent) gave 18 (41 mg, 87% yield from 10a) as a colorless
oil: FTIR (film) 3346, 3017, 2928 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.18 (dd, J ) 7.9, 1.8 Hz, 1H), 7.15 (s, 1H), 7.06 (d, J ) 7.9 Hz,
1H), 5.42 (s, 1H), 5.29 (app q, J ) 1.3 Hz, 1H), 4.53 (s, 2H), 2.78
(app d, J ) 5.5 Hz, 4H), 1.82-1.79 (m, 4H), 1.59 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 147.3, 137.2, 137.1, 129.3, 126.7 (2 C), 123.3,
111.7, 65.1, 29.5, 29.1, 23.2 (2 C); HRMS (EI) for [C13H16O]+, m/z
calcd 188.1201, found 188.1203.
Alcohol 20. Purification by flash chromatography (1:5 EtOAc/
hexanes eluent) gave 20 (76 mg, 92% yield from 10a) as a colorless
oil: FTIR (film) 3459, 2928, 2882 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.12 (dd, J ) 7.8, 1.9 Hz, 1H), 7.10 (s, 1H), 7.03 (d, J ) 7.8 Hz,
1H), 5.38 (app t, J ) 1.5 Hz, 1H), 5.26 (app t, J ) 0.7 Hz, 1H), 4.70-
4.66 (m, 1H), 4.63 (q, J ) 6.7 Hz, 2H), 4.16 (d, J ) 10.5 Hz, 1H),
3.84 (d, J ) 10.5 Hz, 1H), 3.39 (s, 3H), 3.17 (d, J ) 4.2 Hz, 1H), 2.77
(br s, 4H), 2.44 (dd, J ) 13.9, 10.1 Hz, 1H), 2.18 (d, J ) 13.9 Hz,
1H), 1.81-1.78 (m, 4H), 1.78 (s, 3H), 1.74 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 152.2, 137.4, 137.0, 136.5, 132.5, 129.1, 128.3, 127.4,
123.9, 111.1, 95.5, 70.7, 68.0, 55.4, 41.9, 29.5, 29.1, 23.2 (2 C), 18.7,
18.2; HRMS (CI) for [C21H30O3 + NH4]+, m/z calcd 348.2539, found
348.2533.
1
(film) 3042, 2928 cm-1; H NMR (400 MHz, CDCl3) δ 7.27-7.24
(m, 1H), 7.34-7.30 (m, 4H), 5.81 (dd, J ) 2.4, 1.0 Hz, JSnH ) 64.8
Hz, 1H), 5.28 (dd, J ) 2.4, 0.9 Hz, JSnH ) 30.8 Hz, 1H), 4.50 (d, J )
12.1 Hz, 1H), 4.34 (d, J ) 12.1 Hz, 1H), 4.03 (q, J ) 6.4 Hz, 1H),
1.56-1.43 (m, 6H), 1.35-1.24 (m 6H), 1.25 (d, J ) 6.4 Hz, 3H), 0.97-
0.86 (m, 6H), 0.88 (t, J ) 7.3 Hz, 9H); 13C NMR (100 MHz, CDCl3)
δ 158.7, 139.0, 128.2, 127.5, 127.2, 125.1, 82.4, 69.9, 29.7, 27.4, 22.3,
13.7, 10.1; HRMS (EI) for C19H31OSn [M - C4H9]+, m/z calcd
395.1397, found 395.1396.
Stannane 19. 7-Methoxymethoxy-5,6-dimethylhept-5-en-1-yn-3-ol
(410 mg, 2.07 mmol, see Supporting Information) was treated with
RhCl(PPh3)3 (20 mg, 0.05 mmol) followed by Bu3SnH (835 µL, 3.1
mmol) in a dropwise fashion over 10 min. The resulting dark solution
was stirred for 20 h, diluted with Et2O (10 mL), and filtered through
SiO2. The filtrate was evaporated and purified by flash chromatography
(hexane f 10:1 hexane/EtOAc eluent) to provide stannane 19 (506
mg, 49% yield) as a slightly yellow oil: FTIR (film) 3478, 2928 cm-1
;
1H NMR (400 MHz, CDCl3) δ 5.83 (app t, J ) 1.8 Hz, JSnH ) 66.4
Hz, 1H), 5.21 (app t, J ) 1.6 Hz, JSnH ) 30.2 Hz, 1H), 4.63 (q, J )
6.6 Hz, 2H), 4.27 (dm, J ) 10.4 Hz, 1H), 4.12 (d, J ) 10.5 Hz, 1H),
3.97 (d, J ) 10.5 Hz, 1H), 3.39 (s, 3H), 2.64 (d, J ) 3.2 Hz, 1H), 2.49
(dd, J ) 13.6, 10.4 Hz, 1H), 2.06 (d, J ) 14.0 Hz, 1H), 1.79 (s, 3H),
1.77 (s, 3H), 1.46-1.56 (m, 6H), 1.36-1.27 (m, 6H), 0.95-0.89 (m,
6H), 0.91 (t, J ) 7.3 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ 159.9,
131.9, 128.4, 122.7, 95.5, 75.3, 67.9, 55.3, 43.4, 29.1, 27.4, 19.0, 18.0,
13.7, 10.2; HRMS (EI) for C19H37O3Sn [M - C4H9]+, m/z calcd
433.1765, found 433.1766.
General Procedure for the Stille Coupling Reactions. A Schlenck
tube (25 mL, ChemGlass-air free) was charged with LiCl (64 mg, 1.5
mmol) and flame dried under high vacuum. Upon cooling, Pd(PPh3)4
(29 mg, 0.025 mmol) and CuCl (124 mg, 1.25 mmol) were added, and
the mixture was degassed (4×) under high vacuum with an Ar purge.
DMSO (2.0 mL) was introduced with concomitant stirring, followed
by the addition of an ArX (0.25 mmol) and a vinyltin compound (0.30
mmol). The resulting mixture was rigorously degassed (4 ×) by the
freeze-thaw process (-78 f 25 °C, Ar). The reaction mixture was
stirred at room temperature for 1 h, then heated to 60 °C for the
necessary period of time (see Table 1 and text). Following completion
2-Phenyloct-1-en-3-ol. Purification by flash chromatography (1:20
EtOAc/hexanes eluent) gave 2-phenyloct-1-en-3-ol (46 mg, 90% yield
from PhI) as a colorless oil identical with that reported in the literature.28
(25) Ensley, H. E.; Buescher, R. R.; Lee, K. J. Org. Chem. 1982, 47,
404.
(26) (a) Subramanian, L. R.; Martinez, A. G.; Fernandez, A. H.; Alvarez,
R. M. Synthesis 1984, 481. (b) Chambers, M. R. I.; Widdowson, D. A. J.
Chem. Soc., Perkin Trans. 1 1989, 1365.
(27) Coulson, D. R. In Inorg. Synth. 1972, 13, 121.