A R T I C L E S
Huang and Negishi
0.27 g (84% over 2 steps) of the desired product 7a: 1H NMR (300
MHz, CDCl3) δ 0.99 (d, J ) 6.6 Hz, 3H), 1.13 (s, 9H), 1.35 (br, 1H),
1.82 (s, 3H), 1.92 (d, J ) 1.8 Hz, 3H), 2.55-2.65 (m, 1H), 3.52 (d, J
) 6.3 Hz, 2H), 4.05-4.25 (m, 2H), 5.12 (d, J ) 9.9 Hz, 1H), 5.79 (s,
1H), 7.4-7.55 (m, 6H), 7.7-7.8 (m, 4H); 13C NMR (75 MHz, CDCl3)
δ 17.13, 19.35, 20.84, 24.65, 26.93 (3C), 36.22, 62.95, 68.79, 127.07,
127.66 (4C), 129.62 (2C), 131.45, 132.88 (2C), 133.94 (2C), 135.74
(4C). HRMS calcd. for C26H36O2Si, 408.2485; found, 408.2483.
(2Z,4Z,6S)-1-(tert-Butyldimethylsilyloxy)-7-(tert- butyldiphenyl-
silyloxy)-2,4,6-trimethyl-2,4-heptadiene (7b): Representative Pro-
cedure for the Use of (Z)-4-Methyl-2-alkenylzincs Generated from
the Corresponding Alkenyl Iodides (Zn-III Protocol). A solution
of 5a (0.46 g, 1.0 mmol) in ether (2.0 mL) was treated with tBuLi (1.2
mL, 1.7 M in pentane, 2.0 mmol) at -78 °C over 30 min and then
with a solution of dry ZnBr2 (0.23 g, 1.0 mmol) in THF (1.5 mL) at
-78 °C for 10 min. The reaction mixture was warmed to 0 °C over 30
min, treated with Pd(PPh3)4 (23 mg, 0.020 mmol) and (1Z)-3-(tert-
butyldimethylsilyloxy)-1-iodo-2-methyl-1-propene (0.25 g, 0.80 mmol)
in THF (1.5 mL), warmed to 23 °C, and monitored by GLC analysis.
The reaction was complete in 4 h, and the reaction mixture was
quenched with 1 N HCl, extracted with ether, washed successively with
saturated NaHCO3 and brine, dried over MgSO4, filtered, and concen-
trated. Flash chromatography (silica gel, 98/2 hexanes-EtOAc) afforded
0.33 g (78%) of the desired product 7b: 1H NMR (300 MHz, CDCl3)
δ 0.11 (s, 6H), 0.97 (s, 9H), 1.04 (d, J ) 6.4 Hz, 3H), 1.13 (s, 9H),
1.81 (s, 3H), 1.88 (d, J ) 1.2 Hz, 3H), 2.4-2.6 (m, 1H), 3.4-3.6 (m,
2H), 4.12 (s, 2H), 5.11 (d, J ) 10.2 Hz, 1H), 5.72 (s, 1H), 7.4-7.55
(m, 6H), 7.7-7.8 (m, 4H); 13C NMR (75 MHz, CDCl3) δ -5.24 (2C),
17.08, 18.42, 19.38, 20.67, 24.49, 26.0 (3C), 26.93 (3C), 36.14, 62.89,
68.53, 125.72, 127.6 (4C), 129.54 (2C), 131.11, 132.68, 134.14 (2C),
135.71 (4C), 136.19.
(2E,4Z)-2,4-Dimethyl-2,4-nonadien-1-ol (11): Representative Pro-
cedure for the Use of in Situ Generated (Z)-2-Alkenylborons (B-I
Protocol). To a solution of 1-bromo-1-hexyne (80 mg, 0.50 mmol) in
toluene (0.50 mL) was added Br2BH (0.50 mL, 1.0 M in CH2Cl2, 0.50
mmol) at 23 °C, and then the reaction mixture was warmed to 70 °C
and kept at this temperature for 1 h. The resultant mixture was cooled
to -78 °C, and Me2Zn (0.75 mL, 2.0 M in toluene, 1.5 mmol) was
added dropwise. After 10 min at -78 °C, the reaction mixture was
warmed to 0 °C over 30 min, treated with a solution of (1E)-3-(tert-
butyldimethylsilyloxy)-1-iodo-2-methyl-1-propene (0.13 g, 0.42 mmol),
Pd(DPEphos)Cl2 (7.2 mg, 10 µmol), and NaOMe (1.0 mL, 1.0 M in
MeOH, 1.0 mmol) in DMF (3.0 mL), warmed to 60 °C, and monitored
by GLC analysis. The reaction was complete in 10 h, and the reaction
mixture was quenched with 1 N HCl, extracted with ether, washed
successively with saturated NaHCO3 and brine, dried over MgSO4,
filtered, and concentrated. Flash chromatography (silica gel, 95/ 5
hexanes-EtOAc) afforded 51 mg (72%) of the desired product 11: 1H
NMR (300 MHz, CDCl3) δ 0.75-0.95 (m, 3H), 1.2-1.35 (m, 4H),
1.5 (t, J ) 6.0 Hz, 1H), 1.65 (d, J ) 0.9 Hz, 3H), 1.76 (s, 3H), 1.85-
1.95 (m, 2H), 4.07 (d, J ) 5.4 Hz, 2H), 5.25 (t, J ) 7.5 Hz, 1H), 5.89
(s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 15.28, 22.49, 23.9, 28.87,
31.84, 68.79, 124.93, 128.72, 131.84, 136.16. HRMS calcd. for C11H20O
168.1514, found 168.1512.
7a: Representative Procedure for the Use of Isolated (Z)-4-
Methyl-2-alkenyl Iodides (B-II Protocol). A solution of (1Z)-3-(tert-
butyldimethylsilyloxy)-1-iodo-2-methyl-1-propene (0.32 g, 1.0 mmol)
t
in ether (2.0 mL) was treated with BuLi (1.2 mL, 1.7 M in pentane,
2.0 mmol) at -78 °C over 30 min, and B-methoxy-9-BBN (1.0 mL,
1.0 M in hexanes, 1.0 mmol) at -78 °C for 10 min. The reaction
mixture was warmed to 0 °C over 30 min, treated with a solution of
5a (0.37 g, 0.80 mmol), Cs2CO3 (0.65 g, 2.0 mmol), and Pd(DPEphos)-
Cl2 (14 mg, 0.020 mmol) in DMF (1.5 mL), warmed to 60 °C, and
monitored by TLC analysis. The reaction was complete in 14 h, and
the reaction mixture was quenched with 1 N HCl, extracted with ether,
washed successively with saturated NaHCO3 and brine, dried over
MgSO4, filtered, and concentrated to give a viscous oil. To this crude
product in THF (3.5 mL) was added 3 drops of 1 N HCl at 23 °C, and
the resultant mixture was monitored by TLC analysis. After the
complete removal of the TBS group (∼30 min), the mixture was
quenched with aqueous NH4Cl, extracted with ether, washed succes-
sively with saturated NaHCO3 and brine, dried over MgSO4, filtered,
and concentrated. Flash chromatography (silica gel, 95/5 hexanes-
EtOAc) afforded 0.14 g (42% over 2 steps) of the desired product 7a.
7b: Representative Procedure for the Use of (Z)-4-Methyl-2-
alkenylborons Generated from the Corresponding Alkenyl Iodides
(B-III Protocol). A solution of 5a (0.46 g, 1.0 mmol) in ether (2.0
t
mL) was treated with BuLi (1.2 mL, 1.7 M in pentane, 2.0 mmol) at
-78 °C over 30 min, and then with B-methoxy-9-BBN (1.0 mL, 1.0
M in hexanes, 1.0 mmol) at -78 °C for 10 min. The reaction mixture
was warmed to 0 °C over 30 min, treated with a solution of (1Z)-3-
(tert-butyldimethylsilyloxy)-1-iodo-2-methyl-1-propene (0.25 g, 0.80
mmol), Cs2CO3 (0.65 g, 2.0 mmol) and Pd(DPEphos)Cl2 (14 mg, 0.020
mmol) in DMF (1.5 mL), warmed to 60 °C, and monitored by TLC
analysis. The reaction was complete in 16 h, and the reaction mixture
was quenched with 1 N HCl, extracted with ether, washed successively
with saturated NaHCO3 and brine, dried over MgSO4, filtered, and
concentrated. Flash chromatography (silica gel, 98/2 hexanes-EtOAc)
afforded 0.17 g (40%) of the desired product 7b.
Acknowledgment. We thank the National Science Foundation
(CHE-0309613), the National Institutes of Health (GM 36792),
and Purdue University for support of this work.
Supporting Information Available: Detailed experimental
procedures and compound characterization data. This material
JA0772039
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14792 J. AM. CHEM. SOC. VOL. 129, NO. 47, 2007