A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Experimental section
was triturated with water (2 x reaction volume), filtered, triturated with acetone (2 x
reaction volume), filtered and triturated with EtOAc (1 x reaction volume). The
combined washes were reduced under vacuum, transferred to a separating funnel, the
aqueous phase acidified, washed with EtOAc (3 washes, each 2 x reaction volume) and
the organic washes reduced under vacuum to give the amide as a white powder which
was combined with the residue from the filtration.
General Procedure 2: Oxazoline synthesis from aryl amide
Adapted from the method of Linclau, 3 diisopropylcarbodiimide (DIC, 1.0 eq) was
added to a solution of the amide (1.0 eq) and Cu(OTf) 2 (0.06 eq) in cyclic ether (3
cm 3 /mmol) under a nitrogen atmosphere. When heated under reflux, dioxane was used
as solvent, and refluxed for the stated time. When heated under microwave irradiation,
THF was used and the reaction conducted in a closed vial at the stated temperature for
the stated time. Crude reaction mixture was filtered with EtOAc, concentrated under
vacuum, and purified by flash chromatography.
General Procedure 3: Preparation of oxazolines from aryl amide and α-amino
alcohol
Adapted from the method of Meyers 4 to a stirred solution of benzamide (1 eq)
dissolved in anhydrous CH 2 Cl 2 (10 cm 3 /mmol) was added triethyloxonium
tetrafluoroborate (1.2 eq) under an atmosphere of nitrogen. After being stirred at room
temperature for 16 hr, amino alcohol was added (1.3 eq), and solution brought to reflux
for 16 hr. Upon cooling the mixture was washed with water, extracted with CH 2 Cl 2 ,
dried over anhydrous Na 2 SO 4 , and concentrated under vacuum to give a residue which
was purified by flash chromatography.
General Procedure 4: Nucleophilic Addition to Aryl Oxazolines
The organolithium was added drop wise to a stirred solution of oxazoline in the stated
dry solvent (0.05 mmol/cm 3 ) and co-solvent at –78 °C under a nitrogen atmosphere.
After the stated time, the electrophile was added and the reaction mixture allowed to
warm to ambient temperature before addition of excess methanol. The reaction
mixture was reduced under vacuum and passed through a silica plug (1:1 EtOAc:
petrol) and solvent removed before purification by flash chromatography.
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