Stereocontrolled
Nucleophilic Additions of Lithiated Heterocycles to Nitrones. Synthesis
and Structural Characterization of Novel Chiral (Hydroxyamino)methyl HeterocyclesGeneral Procedure: Method A. Without Lewis acid. A cooled solution (-90°C) of the corresponding lithiated heterocycle (15 mmol, 3.0 equiv) in THF (prepared as described[1]) was treated with a solution of BIGN (1.18 g, 5 mmol, 1.0 equiv) in THF (30 mL) added drop by drop. The rate of the addition was adjusted so as to keep the internal temperature below -80°C. The reaction mixture was stirred for 1 h at -80 °C and then quenched with saturated aqueous ammonium chloride (25 mL). The mixture was stirred at ambient temperature for 5 min and diluted with diethyl ether (25 mL). The organic layer was separated, and the aqueous layer was extracted with diethyl ether (3 x 25 ml). The combined organic extracts were washed with brine and dried over magnesium sulfate, and the solvent was evaportaed under reduced pressure to give the crude hydroxylamines which were purified by column chromatography on silica gel.
Method B. With diethyl aluminum chloride. A 1.0 M solution of
diethyl aluminum chloride in hexane (5 mL, 5 mmol) was added via syringe
under stirring to a solution of BIGN (1.18 g, 5 mmol, 1.0 equiv) in diethyl
ether (50 mL) mbient temperature. The mixture was stirred at this temperature
for 5 min, transferred under argon atmosphere into a dropping funnel, and
slowly added to a cooled (-90 °C) solution of the corresponding lithiated
heterocycle in diethyl ether (or THF), prepared as described[1].
The rate of the addition was adjusted so as to keep the internal temperature
below -80°C. The reaction mixture was stirred for 2 h at -80 °C
and then quenched with 1.0 M aqueous sodium hydroxyde (25 mL). The mixture
was stirred at ambient temperature for 15 min and diluted with diethyl
ether (25 mL). The organic layer was separated, and the aqueous layer was
extracted with diethyl ether (3 x 25 ml). The combined organic extracts
were washed with brine and dried over magnesium sulfate, and the solvent
was evaportaed under reduced pressure to give the crude hydroxylamines
which were purified by column chromatography on silica gel.
[1] Brandsma, L.; Verkruijsse,
H. Preparative Polar Organometallic Chemistry Springer-Verlag, Berlin,
1987.
