Benzylidene sodium cyanoborohydride

In a further synthesis of (345) by Rana and Matta [234], the disaccharide (353), prepared by the action of sodium cyanoborohydride — hydrogen chloride [120, 121] on the benzylidene derivative (352), was condensed with the fucosyl bromide (322) to give the trisaccharide (354) in 82 % yield. 

For sodium cyanoborohydride — hydrogen chloride reagent the direction of the reductive opening of the dioxolane acetals obeys the same rule, it depends on the stereochemistry at the asymetric, benzylidene acetal carbon [168, 169]. Methyl exo-2,3 4,6-di-0-benzylidene-a-D-mannopyranoside is cleaved in oxolane solution to give 50 % of the 3,6-di-O-benzyl derivative, which is also the major product in the reaction of methyl 3-0-benzyl-4,6-0-benzylidene-a-D-mannopyranoside. The 2-O-benzyl isomer (20) was cleaved nonselectively, indicating again the effect of the bulk of the C-3 substituent [169]. A compatibility of this reagent, as well as of borane — tri-... 

During their synthesis of the Dactomelynes, Lee and co-workers employed sodium cyanoborohydride and titanium(IV) chloride95 to accomplish the regiose-lective cleavage of a benzylidene acetal [Scheme 3,57].%... 

Methyl acetals and ketals are rapidly reduced to methyl ethers by sodium cyanoborohydride in methanol with dry HCI at ice temperatures. A dioxolane is completely cleaved to a methyl ether, showing intervention by the solvent at some stage (equation 14), but when an inert solvent such as THF is used only single cleavage occurs this reagent shows interesting selectivity in the reduction of benzylidene acetals in the carbohydrate series (see Section 1.9.3.4). 

Reaction (5.12) shows an example of a reductive opening of a benzylidene. The mixture of the acetal and sodium cyanoborohydride (NaBHjCN) in oxolane is acidified with HCI in ether until no more gas is emitted. The reaction, which appears to be general (Garegg et al. 1982), is completed in 5 min at room temperature in 87% yield. This can be interpreted as resulting from regioselective protonation at 0-4 of the sugar, followed by displacement of oxonium by a hydride. 

With strong protic acids, the regiochemistry of the reductive cleavage reverses to give the benzyl ether of the less hindered alcohol. One of the few metal hydrides that can withstand the harshly acidic conditions of the reaction is sodium cyanoborohydride. When used in large excess, it will reduce benzylidene acetals in the presence of anhydrous HG [Scheme 3.61] -or trifluoro-methanesulfonic acid. The excess is required because the sodium cyanoborohydride is consumed under the reaction conditions at an appreciable rate. More convenient reaction conditions were described by DeNinno and co-workers in which the benzylidene acetal is reductively cleaved using triethylsilane in the presence of trifluoroacetic acid [Scheme 3.62]. ... 

Reductive cleavage of the acetal groups in some methyl 4,6-Q-benzylidene-a-D-hexopyranosides with sodium cyanoborohydride has been shown to depend upon subtle structural features as illustrated in Scheme 21. in the first two examples, the products shown were the only ones isolated. 

The reductive opening of the dioxane ring in the 4,6-Q-ben dene acetal (8) with sodium cyanoborohydride in the presence of hydrochloric add was accompanied by deojygenation at the anomeric centre giving the products (11) and (14) in 3 2 ratio as outlined in Scheme 2. In the case of benzylidene derivatives (9) and (10) the 1,6-anhydroalditols (12) and (13) respectively were the only products isolated. ... 

Reductive cleavage of benzylidene acetals has been further examined. Using sodium cyanoborohydride-hydrogen chloride, 4,6-0 -benzylldene derivatives of hexopyranosides are opened selectively... 

---