Reductive cleavage ethers, sodium cyanoborohydride

The regiochemistry of reductive cleavage of p-methoxybenzylidene acetals depends on the substrate and the reaction conditions. By suitable choice of solvent and electrophile, the distribution of regioisomers can be controlled in some cases. For example, sodium cyanoborohydride cleaved glucose derivative 66.1 [Scheme 3.66] selectively to the 6-0-p-methoxybenzyl ether 663 using trifluoro-acetic add as electrophile and DMF as solvent whereas the 4-Op-methoxy-benzyl ether 663 predominated when chlorotrimethylsilane was used as electrophile in acetonitrile as solvent.115 Note, however, that application of the latter conditions to the p-methoxybenzylidene acetal 67,1 [Scheme 3.67] gave the p-methoxybenzyl ether of the less hindered primary hydroxyl as well as rearrangement of the isopropylidene acetal,116... 

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). 

In contrast to the reductive cleavage of 1-methylcyclohexene epoxide with LiAlH4 or, better, with LiEtjBH to produce 1-methylcyclohexanol, reduction of the epoxide with sodium cyanoborohydride in the presence of boron trifluoride etherate furnishes cE-2-methylcyclohexanol. In this case, complexation of the epoxide oxygen with the Lewis acid BF3 now directs hydride addition to the more substituted carbon, which can better sustain the induced partial positive charge. 

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]. ... 

An efficient new route for the reductive cleavage of acetals to methyl ethers involves sodium cyanoborohydride in acid [equation (12 a)]. ° The same type of process can also be performed on the acetals of aliphatic aldehydes and ketones using what is believed to be a Ti° species [equation (12 )]. ° ... 

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