Phosgenation Reactions - Phosgenations - page 479

Swern conditions have been applied in the selective oxidation of primary silyl
ethers, intermediates in the synthesis of natural products [1322]. Thus, primary
trimethylsilyl or triethylsilyl ethers 1868, in the presence of secondary trime-
thylsilyl or triethylsilyl ethers, are selectively oxidized to the corresponding alde-
hydes 1869 under Swern conditions. A short synthesis of key intermediates to-
wards various natural products, e.g. leukotrienes, has been achieved.

OTES

CHO

(COCl) 2 -DMSO

OTES

OTES

1869

1868

The reactivity of trimethylsilyl ethers of primary and secondary alcohols towards
the Swern reagent (oxalyl chloride/DMSO) has been investigated [1336]. Useful
selectivity is possible when the competing ether groups have widely differing de-
grees of steric hindrance. Dimethyl-tert-butylsilyl ethers are unaffected by this re-
agent. Thus, oxidation of octanyl trimethylsilyl ether with the Swern reagent gave
octanal, which was isolated as the 2,4-dinitrophenylhydrazone in 92% yield.
Selective Swern oxidation of the primary alcohol groups of allylamino alcohols,
as a key step in the formation of enantiopure b-amino alcohols with a 3-oxa-2,7-di-
azabicyclo[3.3.0]octane framework, has also been reported [1339].

4.7.5.2 Miscellaneous Methods for the Oxidation of Alcohols

Dicyclohexylcarbodiimide/DMSO
The original discovery of Pfitzner and Moffatt [1390] that alcohols are oxidized to
carbonyl compounds by dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC), and
phosphoric acid at room temperature was immediately recognized as an effective
and mild procedure for sensitive substrates.

Typical procedure. Methyl 2,3-O-isopropylidene-b- d -ribo-pentodialdo-1,4-furanoside 1870
[1391]: A solution of anhydrous crystalline orthophosphoric acid (0.98 g, 10
mmol) in dimethyl sulfoxide (2.0 mL) was added to a solution of methyl-2,3-O-iso-
propylidene-b-d-ribofuranoside (4.08 g, 20 mmol), pyridine (0.8 mL, 10 mmol), and
DCC (12.4 g, 60 mmol) in dimethyl sulfoxide (50 mL). The mixture was kept at
around 25 C for 3 h by occasional ice-cooling, then diluted with ethyl acetate (100
mL), and a solution of oxalic acid dihydrate (5.04 g, 40 mmol) in methanol (10 mL)
was added. The mixture was subsequently poured into saturated sodium chloride
solution (200 mL), filtered, and the aqueous phase was extracted with ethyl acetate
(100 mL). The combined organic phases were washed successively with dilute so-
dium hydrogen carbonate solution (100 mL), saturated sodium chloride solution
(2 100 mL), and iced water (100 mL). The organic phase was dried with magne-

sium sulfate, concentrated under reduced pressure, and the residue was dissolved
in ethyl acetate (25 mL) and filtered to remove residual N,N 0 -dicyclohexylurea. The
solution was concentrated to a syrup (4.7 g), which was purified by sublimation
at 60-70 C (0.1 Torr) to give the product 1870 as a white crystalline solid, 3.23 g