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

Experimental section
General Procedure 5: Modified Upjohn Dihydroxylation
Adapted from the methods of the Upjohn Company 5 and Nelson 6 , osmium tetroxide
(0.01 eq, 2.5% solution w/w in t-BuOH) was added to a vigorously stirred solution of
the olefin (1 eq) and N-methylmorpholine N-oxide (2 eq, NMO) in the stated solvent,
and the reaction monitored by TLC. When judged complete, an aqueous solution of
sodium sulfite or sodium metabisulfite (c. 5 eq) was added to the solution and stirred
for 2 hr, all solvent removed under vacuum, and the resulting emulsion dried onto
celite before being passed through a silica plug (EtOAc), and solvent again removed
under vacuum, before final purification by flash chromatography.
General Procedure 6: Oxazoline alkylation-reduction
Adapted from the method of Meyers 7 methyl trifluoromethanesulfonate (2.0 eq) was
added drop wise to a stirred solution of oxazoline in CH 2 Cl 2 (0.1M) under a nitrogen
atmosphere at room temperature. After the stated time, the reaction was cooled to 0 °C
and a cooled solution of sodium borohydride (2 eq) in dry THF-methanol (4:1) was
added over 10 min, resulting in a white foam. The reaction was warmed to room
temperature, and ammonium chloride (1 x reaction volume) was added and solvent
removed under vacuum. The reaction mixture was extracted with CH 2 Cl 2, dried over
anhydrous Na 2 SO 4 and concentrated under vacuum to give the crude oxazolidine.
General Procedure 7: Oxazolidine hydrolysis-reduction
Adapted from the method of Meyers 7 oxalic acid (5 eq) was added to a solution of
oxazolidine in 4:1 THF:water (0.1M) and stirred at the stated temperature. When
judged complete by TLC, the solvent was removed, the aqueous layer washed with
EtOAc and the combined organic phases dried over anhydrous MgSO 4 . The resulting
aldehyde was dissolved in methanol (0.1M), cooled to 0 °C and sodium borohydride (2
eq) added in a single portion. When judged complete by TLC, acetic acid was added
until effervescence ceased and the solvent removed under vacuum. The resultant oil
was partitioned between water and EtOAc, and the aqueous layer washed with EtOAc
until no further organic compound was extracted (TLC). The combined organic
washes were dried over anhydrous MgSO 4 and solvent removed under vacuum to give
the crude alcohol.
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