In an N2-atmosphere
glovebox, a 10 mL round-bottom flask was charged with cesium carbonate
(3.1 mg, 0.010 mmol, 10 mol %), catalyst5b (6.0 mg,
0.010 mmol, 10 mol %), and a PTFE-coated magnetic stir bar. Di-tert-butyl malonate (22 μL, 0.10 mmol, 1.0 equiv)
and anhydrous cyclohexane (2.0 mL) were then added. The flask was
sealed, removed from the glovebox, and stirred (750 rpm) for 12 h
at 23 °C over which time the reaction mixture became uniformly
turbid. After 12 h, the reaction flask was cooled to 10 °C in
a cryogenic cooling bath, and a stock solution of the desired substrate
in anhydrous cyclohexane (2.0 mL, 50 mM, 0.10 mmol, 1.0 equiv) was
injected directly into the precooled reaction mixture. The septum
was quickly sealed with electrical tape and plastic paraffin film,
and the reaction was maintained at 10 °C in the cooling bath
with rapid stirring. After the indicated time, the reaction was quenched
with the addition of 1 M aqueous hydrochloric acid (1.0 mL), diluted
with ethyl ether and allowed to warm to ambient temperature. The layers
were partitioned, and the aqueous layer was extracted with additional
ethyl ether. The organic extracts were filtered through sodium sulfate
and concentrated. The yield was determined from integration of the 1H NMR spectrum of the crude reaction mixture relative to an
internal standard added after workup. The homoallylic alcohol product,2 , was purified by silica gel chromatography (on a pipet column),
eluting with an appropriate ethyl ether/dichloromethane/pentane solvent
mixture, and the enantiomeric excess was determined by chiral stationary
phase–high performance liquid chromatographic (CSP-HPLC) analysis
or chiral stationary phase–gas chromatographic (CSP-GC) analysis.
The absolute configuration of2c was determined by X-ray
crystallographic analysis, and the configurations of all other products
were assigned by analogy.
glovebox, a 10 mL round-bottom flask was charged with cesium carbonate
(3.1 mg, 0.010 mmol, 10 mol %), catalyst
0.010 mmol, 10 mol %), and a PTFE-coated magnetic stir bar. Di-tert-butyl malonate (22 μL, 0.10 mmol, 1.0 equiv)
and anhydrous cyclohexane (2.0 mL) were then added. The flask was
sealed, removed from the glovebox, and stirred (750 rpm) for 12 h
at 23 °C over which time the reaction mixture became uniformly
turbid. After 12 h, the reaction flask was cooled to 10 °C in
a cryogenic cooling bath, and a stock solution of the desired substrate
in anhydrous cyclohexane (2.0 mL, 50 mM, 0.10 mmol, 1.0 equiv) was
injected directly into the precooled reaction mixture. The septum
was quickly sealed with electrical tape and plastic paraffin film,
and the reaction was maintained at 10 °C in the cooling bath
with rapid stirring. After the indicated time, the reaction was quenched
with the addition of 1 M aqueous hydrochloric acid (1.0 mL), diluted
with ethyl ether and allowed to warm to ambient temperature. The layers
were partitioned, and the aqueous layer was extracted with additional
ethyl ether. The organic extracts were filtered through sodium sulfate
and concentrated. The yield was determined from integration of the 1H NMR spectrum of the crude reaction mixture relative to an
internal standard added after workup. The homoallylic alcohol product,
eluting with an appropriate ethyl ether/dichloromethane/pentane solvent
mixture, and the enantiomeric excess was determined by chiral stationary
phase–high performance liquid chromatographic (CSP-HPLC) analysis
or chiral stationary phase–gas chromatographic (CSP-GC) analysis.
The absolute configuration of
crystallographic analysis, and the configurations of all other products
were assigned by analogy.
