Dioxolane, benzylidene acetals

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-... 

TTie most common methods generally used to prepare benzylidene acetals involve (a) reaction of a diol with benzaldehyde in the presence of p-toluenesul-fonic acid or a Lewis acid (usually zinc chloride)144 145 — a reaction that is accelerated by ultrasonication146 — or (b) reaction of the diol with benzaldehyde dimethyl acetal (a,a-dimethoxytoluene) in the presence of camphorsuifonic acid or p-toluenesulfonic acid as shown in Scheme 3.79.147 Both 1,3-dioxolanes or 1,3-dioxanes can be formed under these conditions. Yields may be improved by running the reactions under reduced pressure to remove the methanol as it is formed.88-148... 

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). 

Acetals, however, are easily regioselectively introduced (Schemes 3.11 and 3.12) [9]. Benzylidene acetals are preferentially formed as six-membered dioxane-type acetals (i.e., hexopyranosides form 4,6-0-benzylidene derivatives), whereas isopropylidene acetals are more stable as five-membered dioxolane acetals formed on vicinal cw-diols. However, the selectivity is not complete and methyl mannoside, for example, produces mixtures of the mono- and di-acetal compounds. The use of methyl propenyl ether yields mainly the kinetic product (the 4,6-0-isopropylidene acetal). Complementary to these traditional acetals is a rather recently developed acetal — the BDA-acetal [21]. In contrast to other acetals, this exclusively forms acetals between... 

Relative to their deprotection, it should be emphasized, that the selective removal of one acetal in the presence of the same (or different) type of acetal, at distinct positions in the same molecule, is possible and has been observed quite often [138]. Several well-established observations can be summarized as follows (i) 1,3-dioxanes are hydrolyzed more easily than the corresponding 1,3-dioxolane, (ii) implication of the anomeric center renders the acetal function more stable, (iii) cw-fused 1,3-dioxolanes in a furanose or pyranose ring are more stable than the ones that involve a side chain, and (iv) trows-fused benzylidene acetals of hexopyra-noses are hydrolyzed faster than the corresponding cw-fused acetals [123]. Some examples are shown in Scheme 19. 

Many of the earlier claims for the isolation of diastereoisomers have not been substantiated. However, studies of the chemical shifts of the benzylic proton in various substituted 1,3-dioxanes and dioxolanes, using proton magnetic resonance have made it possible to assign absolute configurations to the two 2,3 4,6-di-0-benzylidene acetals of methyl a-n-mannopyranoside and to the two 2-benzoates of methyl 3,4-0-benzylidene-iS-L-arabinopyranoside, thus establishing their diastereoisomeric relationship. In both cases, the isomerism arose from the five-membered ring. The method has also been used to demonstrate that several of the products... 

Oxidative cleavage of arylmethylene acetals offers another method for the transformation of an arylmethylene acetal to a mono-protected diol. For example, benzylidene acetals of 1,2- and 1,3-diols undergo ozonolytic cleavage rapidly at -78 °C at rates that compete with cleavage of alkenes to give a benzoate ester [Scheme 3.71]. The reaction is not restricted to benzylidene acetals since ethyli-dene and /erf-butylmethylidene acetals also cleave rapidly. The reaction was creatively exploited by Stork and Rychnovsky in the closing stages of their synthesis of dihydroerythronolide A when it was used to unmask a 1,2-diol protected as a 2-methyl-l,3-dioxolane in the presence of a 2-methyl-l,3-dioxane. It is noteworthy that a 1,3-dioxane function cleaved very much slower [Scheme 3.72). 

TiCU was used by Manittoa to mediate the reduction of both syn- and anti-(4S,5S)-2-aryl-4-methyl-5-trifluoromethyl-l,3-dioxolanes with Et3SiD, furnishing monodeuterated hydroxy ethers in high yields and good to excellent diastere-oselectivities [289]. Deuteride addition to the benzylidene acetal and removal of... 

Butyl lithium in THF at temperatures methyl pyranosides or to 1,5-anhydroalditols while 6-membered benzylidene acetals are left intact (Scheme 5). The reaction involves preferential abstraction of a quasi-axial... 

Dioxolane-type ndo-benzylidene acetals were the main products in the kinetically controlled reactions of several hexopyranosides carrying 2,3- or 3,4-cis-hydroxyl groups with dimethoxytoluene and p-tolenesulfonic acid without added solvent. It was noted that endo-exo isomerization was faster for derivatives with unprotected hydroxyl groups vicinal to the acetal thus, methyl a-L-ihanuiopyranoside gave a 1 1 mixture of 14 and 15, while from the 4-0-benzylated starting conqx>und the endo-product 16 was formed stereospecifically. ... 

Ozone oxidation of the trans-decal in di of benzylidene 133 has been carried out (71). Under kinetically controlled conditions, it produces the axial benzoate 134 in preference to the more stable equatorial benzoate 135. Similar results were obtained with an analogous case derived from cholestane-2e,3e-diol. These results are essentially identical to those obtained by King and Allbutt (60, 62) in their study on the hydrolysis of dioxolane orthoesters and dioxolenium salts (cf. p. 82), and can therefore be explained in the same manner. These results further confirm that the oxidation of acetals by ozone produces an intermediate which behaves like the hemiorthoester tetrahedral intermediate which is formed in the hydrolysis of orthoesters. 

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