Pyridinium tosylate-catalyzed a&al exchange between benxaldehyde dimethyl acetal and 6-O-(tert-butyldiphenylsilyl)-l,2-O-isopropylidene-a-D-glucofuranose was investigated as an alternative to the original procedure of Brigl and Grtiner (condensation of a D-glucose trio1 with benxaldehyde under zinc halide catalysis) for synthesis of 3 ,!I-0-benzylidene-1,2-O-isopropylidene-a-D-glucofuranose. The two routes afford opposite benzylidene diastereoisomers: the traditional procedure leads to the thermodynamically favored isomer (phenyl and C-6 trans), whereas the new sequence gives the cis compound. The orientations and conformations of these isomers were determined after conversion into the corresponding 6-iodides 5 and 7. X-Ray crystallography revealed that the 1,3dioxane ring of the tiuns isomer 7 exists in the expected chair, "O-inside" conformation. In contrast, a combination of n.m.r. spectroscopy and molecular-mechanics calculations demonstrated that the same ring of cis diastereomer 5 does not adopt the alternative chair, "H-inside" conformation; instead, it exists in a specific twist form.
INTRODUCIION
In connection with a program directed toward the synthesis of a series of 6substituted D-glucose analogs, we required a reliable source of the protected Dglucose derivative, 3,5-O-benzylidene-l,2-O-isopropylidene-cr-D-glucofuranose. We found the traditional, zinc halide-catalyzed acetalationl of the D-glucose acetal 1 to be capricious, and for this reason,.we explored an alternative sequence. 1,2-O-Isopropylidenea-D-glucofuranose2 is silylated selectively on the primary hydroxyl group by using tert-butylchlorodiphenylsilane3 to give the ether 2. This compound undergoes transacetalation with benzaldehyde dimethyl acetal under pyridinium p-toluenesulfonate catalysis at 40", and the resulting a&al (3) is deprotected with tetrabutylammonium fluoride, to afford 4 in 75% overall yield from acetal 1.