Ethers sodium cyanoborohydride

Sodium cyanoborohydride is the most commonly used reagent for reduction of oximes and oxime ethers. Although this reaction is highly versatile, and does not interfere with a majority of functional groups, careful control of reaction conditions is necessary. A considerable problem in the reduction, especially for aldoximes 80 (equation 57), is the reaction of initially formed A-alkylhydroxylamine 81 with the starting oxime 80. The obtained nitrone 82 is subsequently reduced to A,A-dialkylhydroxylamine 83, which was found to be a major reaction product at pH = 4 and above. This side reaction can be avoided by adjusting the pH of the reaction mixture to 3 or below. 

MacrocycBc lactams. Two key steps in a synthesis of the polyamine alkaloid dihydroperiphylline (4) involve ring expansion of the cyclic imino ether 1 by reaction with the /3-lactam 2 to form 3. Sodium cyanoborohydride in acetic acid reduces 3 in high yield to 4, probably by way of intermediates a and b.2... 

Hydrogen chloride in diethyl ether at room temperature was added to a mixture of 7 [34] (1.00 g, 2.16 mmol) and sodium cyanoborohydride (1.70 g, 27.0 mmol) in tetrahydrofuran (30 mL, distilled from LiAlH ) containing 3-A molecular sieves, until the evolution of gas biased. Use of TLC [silica gel, light petroleum (bp 40-60°)/ethyl acetate 5 1] after 5 min, PrHcated complete reaction. The mixture was diluted with CHjClj (50 mL) and water, [filtered, and the solution was extracted with water and then with saturated aqueous... 

To a solution of the disaccharide 28 (500 mg, 0.55 mmol) and sodium cyanoborohydride (230 mg, 3.70 mmol) in tetrahydrofnran (25 mL) was added powdered 4-A MS (1 g). The solution was stirred for 20 min at 0°C, then a solution of hydrogen chloride saturated in ether (2 mL) was added dropwise. Stirling was continued for 3 h at 0°C, and the course of the reaction was monitored by TLC. The suspension was filtered through Celite, and the filtrate was processed as usnal. Purification by flash chromatography on silica gel with hexane-EtOAc (3 1) afforded the desired product 29 (300 mg, 60%). 

This rationalization indicates that internal delivery of a hydride is not a requisite for the observed stereospecificity. Reduction of the oxonium ion with an external hydride reagent should also give equatorially oriented bicyclic ether only. Accordingly (112), reduction of tricyclic spiroketal 145 with sodium cyanoborohydride at pH =3-4 yields only the equatorial bicyclic ether alcohol (J47, CHO=CH2OH). Eliel and co-workers (113) have previously suggested that the orientation of the electron pairs of oxygen atoms influence the course of the reduction of 2-alkoxytetrahydropyran with lithium aluminium hydride-aluminium trichloride. 

The 2-propenylidene acetals of hexopyranosides, such as 3, are selectively reduced by acidic sodium cyanoborohydride to 6-0-2-propenyl ethers (eg., 4).3... 

ACETALS Sodium cyanoborohydride. DIMETHYLHYDRAZONES Boron trifluoride etherate. 

Cyclohexanone (202) was converted to compound (203) whose transformation to cyclohexanone (204) was accomplished in three steps. It underwent cyclialkylation with boron trifluoride etherate affording the cyclized product (205) (R=R,=OMe) in 64% yield along with naphthalene (206) (R=Ri= H,H). Compound (205) on heating under reflux with DDQ in benzene produced ketone (207) whose tosylhydrazone on treatment with sodium cyanoborohydride afforded reduced product (208). Deprotection of the aryl methyl ethers and oxidation with ceric ammonium nitrate led to the formation of miltirone (197). 

The Step 2 product dissolved in 20 ml methyl alcohol was treated with 2.78 ml 1 M ZnCl2 in diethyl ether, then stirred 30 minutes at ambient temperature, and treated with solid ammonium formate (167 mmol). The mixture was stirred an additional 60 minutes and solid sodium cyanoborohydride (27.8 mmol) was added in portions. After stirring overnight at ambient temperature, the mixture was quenched with 5 ml water and then partitioned between 10 ml 5M NaOH and 20 ml CHC13. The aqueous layer was extracted with 20 ml CHC13, then dried with Na2S04, filtered, and concentrated. The product consisted of yellow gum as 90 10 mixture of cis and trans amines, respectively. 

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... 

The product from Step 2 (1.5 g), sodium cyanoborohydride (1.1 g), 45 ml ethyl alcohol and 1.7 ml HO Ac were mixed then heated to 80 °C 1 hour. Thereafter the solvent was removed and 3 M HCl dissolved in diethyl ether added. The aqueous layer was basified and extracted with diethyl ether and dried. The solvent was removed, the residue re-dissolved in ethyl alcohol, malonic acid (0.5 g) added, and the mixture warmed until a clear solution was obtained. After cooling to —20°C overnight, the product was isolated as white crystals, mp = 169-170 °C. 

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). 

Sodium cyanoborohydride (NaBHsCN) or tetrabutylammonium cyanoborohydride in acidic methanol or acidic HMPA reduces a,p-unsaturated aldehydes and ketones to the corresponding allylic alcohols. This system is limited to enones in which the double bond is not further conjugated, in which case the allylic hydrocarbon is formed in substantial amounts. Thus, reduction of chalcone gives mainly 1,3-di-phenylpropene (48%) as well as 26% of the allylic ether. Cyclic enones are also not good substrates, as competing 1,4-addition gives large fractions of saturated alcohols. ... 

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