Stereodefined Polysubstituted Olefins
J . Org. Chem., Vol. 65, No. 23, 2000 7969
reaction’s progress was deemed complete by TLC analysis,
trimethyltin (50 mg, 0.207 mmol, 1.5 equiv) and LiCl (17.5
mg, 0.41 mmol, 3 equiv) were added directly to the mixture.
The reaction was then warmed to 95 °C, and the progress was
again monitored by TLC analysis. When the reaction was
complete, the solution was cooled to room temperature and
quenched with saturated NH4Cl (1.0 mL). The layers were
separated; the aqueous layer was twice extracted with ether,
and the organic layers were pooled and dried over anhydrous
MgSO4. Solvent removal in vacuo and flash chromatography
(10% ether in pentane) provided 120 mg of 10e (82% yield) as
a yellow oil. IR (thin film): 3081, 1736 cm-1. 1H NMR (CDCl3,
300 MHz): δ 7.28 (m, 5H), 5.26 (s, 1H), 5.10 (s, 1H), 3.74 (s,
6H), 3.16 (s, 2H), 1.31 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ
172.1, 144.5, 141.5, 128.0, 127.4, 126.8, 118.2, 53.4, 52.1, 40.6,
19.9. HRMS m/z (M+) calcd for C15H18O4: 262.1205. Found:
262.1208.
Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 214.9, 171.0, 141.9,
132.4, 131.6, 116.3, 61.5, 60.4, 38.1, 35.1, 32.5, 32.2, 31.4, 22.2,
19.5, 14.0, 13.9. HRMS m/z (M+) calcd for C17H26O3: 278.1882.
Found: 278.1891.
Com p ou n d 12. Into a 100 mL flask was added 240 mg of
sodium hydride (60% mineral oil dispersion, 6.0 mmol, 1.2
equiv) and 35 mL of dry THF. Slow addition of 804 mg of
dimethyl methylmalonate (5.5 mmol, 1.1 equiv) was followed
by the addition of 9.0 mg of tetrakis(triphenylphosphine)-
palladium(0) (0.008 mmol, 0.16%) and 1.0 g of 1,3-dibromo-1-
propene (12) (5.0 mmol, 1.0 equiv, 1.5:1 mixture of geometric
isomers). When complete, the reaction was quenched with 10
mL of water, the layers were separated, and the aqueous layer
was twice extracted with ether. The combined organic layers
were dried over anhydrous MgSO4. Following solvent removal
in vacuo, flash chromatography (5% ethyl acetate in hexanes)
provided 1.31 g of 12 (99% yield) as a clear oil. The spectral
analysis was performed on the mixture of geometric isomers.
IR (thin film): 1734 cm-1. Anal. Calcd for C9H13O4Br: C, 40.77;
H, 4.94. Found: C, 40.55; H, 5.00. 1H NMR (CDCl3, 300 MHz)
δ E isomer: 6.31 (m, 1H), 6.10 (m, 1H), 3.74, (s, 6H), 2.79 (dd,
J ) 6.6, 1.5 Hz, 2H), 1.44 (s, 3H); Z isomer: 6.10 (m, 2H),
3.73 (s, 6H), 2.59 (d, J ) 7.4 Hz, 2H), 1.41 (s, 3H). 13C NMR
(CDCl3, 75 MHz, APT pulse sequence: evens up (+), odds down
(-)) δ E isomer: 171.9(+), 132.1(-), 129.3(-), 53.3(+),
52.5(-), 35.9(+), 20.0(-); Z isomer: 171.8(+), 132.1(-),
129.3(-), 53.1(+), 52.5(-), 39.1(+), 19.9(-).
Com p ou n d 10f. Following the general procedure for the
preparation of 10e, 3.5 mg of NaH (60% mineral oil dispersion,
0.15 mmol, 1.1 equiv), 21.7 mg of ethyl 2-oxocyclopentane
carboxylate (0.14 mmol, 1.05 equiv), 26.4 mg of 7b (0.13 mmol,
1.0 equiv), 4.6 mg of tetrakis(triphenylphosphine)palladium-
(0) (0.004 mmol, 3%), 40 mg of trimethyltin (0.17 mmol, 1.25
equiv), and 17 mg of LiCl (0.40 mmol, 3 equiv) afforded 21 mg
of 10f (59% yield) as a clear oil. IR (thin film): 3081, 1752,
1
1723 cm-1. H NMR (CDCl3, 300 MHz): δ 7.29 (m, 5H), 5.26
(s, 1H), 5.10 (s, 1H), 3.96 (m, 2H), 3.31 (d, J ) 14.0 Hz, 1H),
2.82 (d, J ) 14.0 Hz, 1H), 2.33 (m, 2H), 2.01 (m, 2H), 1.83 (m,
2H), 1.17 (t, J ) 7.4 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ
214.1, 170.1, 145.0, 141.4, 128.1, 127.6, 126.8, 117.1, 61.4, 60.7,
39.1, 37.7, 32.0, 19.4, 13.9. HRMS m/z (M+) calcd for
P r ep a r a tion of 13. Following the general procedure out-
lined for the preparation of 10g, 17.6 mg of sodium hydride
(60% mineral oil dispersion, 0.44 mmol, 1.1 equiv), 58.5 mg of
dimethyl methylmalonate (0.40 mmol, 1.0 equiv), 9.2 mg of
tetrakis(triphenylphosphine)palladium(0) (0.008 mmol, 2%),
80 mg of 1,3-dibromo-1-propene (11) (0.40 mmol, 1.0 equiv),
81.8 mg of hexenylboronic acid (0.64 mmol, 1.6 equiv), and 500
µL of a 2 M KOH solution (1.0 mmol, 2.5 equiv) afforded 69
mg of 13 (64% yield). The spectral analysis was performed on
C
17H20O3: 272.1412. Found: 272.1415
The general procedure for the sequential reaction of 2,3-
dibromo-1-propene (7b ) with stabilized nucleophiles (allylic
substitution) and (E)-1-hexenyl-catecholborane (Suzuki cou-
pling) is outlined below for the preparation of compound 10g.
Com p ou n d 10g. To a 10 mL flask was added 7.0 mg of
NaH (60% mineral oil dispersion, 0.29 mmol, 1.2 equiv) and
2.0 mL of 1,4-dioxane. To this suspension was added 38.9 mg
of dimethyl methylmalonate (0.27 mmol, 1.1 equiv) dropwise,
and the solution was stirred for 15 min at room temperature.
The addition of 5.6 mg of tetrakis(triphenylphosphine)-
palladium(0) (0.005 mmol, 2 mol %) was followed by 48.4 mg
of 7b (0.24 mmol, 1.0 equiv). When the reaction’s progress was
deemed complete by TLC analysis, (E)-1-hexenyl-catecholbo-
rane (54 mg, 0.27 mmol, 1.1 equiv) and 483 µL of a 2 M NaOEt
solution (0.48 mmol, 2 equiv) were quickly added directly to
the mixture. The reaction was then warmed to 55 °C, and the
progress was again monitored by TLC analysis. When the
reaction was complete, the solution was cooled to room
temperature and quenched with saturated NH4Cl (1.0 mL).
The layers were separated, the aqueous layer was twice
extracted with ether, and the organic layers were pooled and
dried over anhydrous MgSO4. Solvent removal in vacuo and
flash chromatography (5% ether in pentane) provided 49 mg
of 10g (76% yield) as a clear oil. IR (neat): 1737 cm-1. 1H NMR
(CDCl3, 300 MHz): δ 5.99 (d, J ) 15.5 Hz, 1H), 5.70 (dt, J )
15.5, 7.4 Hz, 1H), 5.03 (s, 1H), 4.79 (s, 1H), 3.70 (s, 6H), 2.85
(s, 2H), 2.06 (m, 2H), 1.38 (s, 3H), 1.34 (m, 4H), 0.89 (t, J )
7.4 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 172.6, 141.3, 132.3,
131.2, 116.6, 54.0, 52.4, 36.7, 32.5, 31.5, 22.3, 20.2, 13.9. HRMS
m/z (M+) calcd for C15H24O4: 268.1675. Found: 268.1684.
Com p ou n d 10h . Following the general procedure for the
preparation of 10g, 6.3 mg of NaH (60% mineral oil dispersion,
0.26 mmol, 1.05 equiv), 39.3 mg of ethyl 2-oxocyclopentane
carboxylate (0.25 mmol, 1.0 equiv), 50.3 mg of 7b (0.25 mmol,
1.0 equiv), 5.8 mg of tetrakis(triphenylphosphine)palladium-
(0) (0.005 mmol, 2%), 48 mg of (E)-1-hexenylboronic acid (0.38
mmol, 1.5 equiv), and 314 µL of a 2 M KOH solution (0.63
mmol, 2.5 equiv) afforded 36 mg of 10f (51% yield) as a clear
the mixture of geometric isomers. IR (thin film): 1737 cm-1
.
HRMS m/z (M+) calcd for C15H24O4: 268.1675. Found: 268.1674.
1H NMR (CDCl3, 300 MHz) δ E isomer: 6.01 (m, 2H), 5.60
(dt, J ) 14.0, 7.0 Hz, 1H), 5.38 (dt, J ) 14.0, 7.4 Hz, 1H), 3.70
(s, 6H), 2.57 (d, J ) 7.4 Hz, 2H), 2.07 (m, 2H), 1.38 (s, 3H),
1.30 (m, 4H), 0.89 (t, J ) 7.4 Hz, 3H); Z isomer: 6.27 (dd, J )
14.7, 11.0 Hz, 1H), 6.01 (m, 1H), 5.70 (dt, J ) 14.7, 7.0 Hz,
1H), 5.15 (dt, J ) 10.3, 8.1 Hz, 1H), 3.70 (s, 6H), 2.74 (d, J )
8.1 Hz, 2H), 2.07 (m, 2H), 1.40 (s, 3H), 1.30 (m, 4H), 0.90 (t, J
) 7.4 Hz, 3H). 13C NMR (CDCl3, 75 MHz) δ E isomer: 172.4,
134.8, 134.3, 129.7, 124.7, 53.9, 52.4, 39.0, 32.2, 31.37, 22.2,
19.88, 13.87; Z isomer: 172.4, 136.6, 135.2, 125.1, 122.1, 53.8,
52.4, 33.7, 32.5, 31.43, 22.2, 19.79, 14.06.
Com p ou n d 14. Following the general procedure outlined
in the preparation of 10a , 60 mg of 11 (0.30 mmol), 46.0 mg of
dimethyl methylmalonate (0.32 mmol, 1.05 equiv), 13.2 mg of
NaH (60% mineral oil dispersion, 0.33 mmol, 1.1 equiv), 7.0
mg of tetrakis(triphenylphosphine)palladium(0) (0.006 mmol,
2 mol %), 49.3 mg of 1-hexyne (0.60 mmol), 63.9 mg of
piperidine (0.75 mmol, 2.5 equiv), and 1.1 mg of CuI (0.006
mmol, 2 mol %) yielded 76 mg of 10 (95% yield). The spectral
analysis was performed on the mixture of geometric isomers.
IR (thin film): 1783, 1737 cm-1. HRMS m/z (M+) calcd for
1
C
15H22O4: 266.1518. Found: 266.1508. H NMR (CDCl3, 300
MHz) δ E isomer: 5.86 (dt, J ) 15.8, 7.5 Hz, 1H), 5.51 (d, J )
15.8 Hz, 1H), 3.71 (s, 6H), 2.61 (d, J ) 7.5 Hz, 2H), 2.25 (dt,
J ) 7.5, 1.5 Hz, 2H), 1.48 (m, 4H), 1.36 (s, 3H), 0.89 (t, J ) 7.5
Hz, 3H); Z isomer: 5.68 (dt, J ) 11.8, 7.5 Hz, 1H), 5.55 (d, J )
11.8 Hz, 1H), 3.71 (s, 6H), 2.85 (d, J ) 7.5 Hz, 2H), 2.31 (dt,
J ) 7.5, 2.2 Hz, 2H), 1.48 (m, 4H), 1.40 (s, 3H), 0.90 (t, J ) 7.4
Hz, 3H). 13C NMR (CDCl3, 300 MHz, APT pulse sequence:
evens up (+), odds down (-)) δ E isomer: 172.0(+), 136.0(-),
114.4(-), 90.1(+), 76.7(+), 53.5(+), 52.4(-), 39.2(+), 30.7(+),
21.9(+), 19.9(-), 18.9(+), 13.5(-);
Z isomer: 172.2(+),
1
oil. IR (neat): 1753, 1726 cm-1. H NMR (CDCl3, 300 MHz):
135.2(-), 113.4(-), 95.6(+), 78.5(+), 53.6(+), 52.5(-), 36.0(+),
30.8(+), 21.9(+), 19.8(-), 19.1(+), 13.5(-).
δ 6.00 (d, J ) 16.2 Hz, 1H), 5.70 (dt, J ) 16.2, 6.6 Hz, 1H),
4.99 (s, 1H), 4.80 (s, 1H), 4.14 (q, J ) 7.0 Hz, 2H), 2.89 (d, J
) 14.7 Hz, 1H), 2.61 (d, J ) 14.7 Hz, 1H), 2.44 (m, 2H), 2.02
(m, 4H), 1.34 (m, 6H), 1.24 (t, J ) 7.0 Hz, 3H), 0.89 (t, J ) 7.0
Com p ou n d 15. Following the general procedure outlined
for the preparation of 10g, 8.6 mg of sodium hydride (60%
mineral oil dispersion, 0.36 mmol, 1.2 equiv), 43.8 mg of