Sodium borohydride toward

Sodium borohydride is not normally used to reduce esters because the reaction is very slow. Because of this lower reactivity of sodium borohydride toward esfers, if is possible to reduce the carbonyl group of an aldehyde or a ketone to a hydroxyl group with this reagent without reducing an ester or carboxyl group in the same molecule. 

The final stages of the successful drive towards amphotericin B (1) are presented in Scheme 19. Thus, compound 9 is obtained stereoselectively by sodium borohydride reduction of heptaenone 6a as previously described. The formation of the desired glycosida-tion product 81 could be achieved in dilute hexane solution in the presence of a catalytic amount PPTS. The by-product ortho ester 85 was also obtained in approximately an equimolar amount. Deacetylation of 81 at C-2, followed sequentially by oxidation and reduction leads, stereoselectively, to the desired hydroxy compound 83 via ketone 82. The configuration of each of the two hydroxylbearing stereocenters generated by reduction of carbonyls as shown in Scheme 19 (6—>9 and 82->83) were confirmed by conversion of 83 to amphotericin B derivative 5 and comparison with an... 

Sulfonamides are very difficult to hydrolyze. However, a photoactivated reductive method for desulfonylation has been developed.240 Sodium borohydride is used in conjunction with 1,2- or 1,4-dimethoxybenzene or 1,5-dimethoxynaphthalene. The photoexcited aromatic serves as an electron donor toward the sulfonyl group, which then fragments to give the deprotected amine. The NaBH4 reduces the radical cation and the sulfonyl radical. 

B. (3-Bromo-3,3-difluoropropyl)trimethylsilane. A 1-L, four-necked flask is equipped with a mechanical stirrer, thermometer, Claisen adapter, septum inlet, reflux condenser (the top of which is connected to a calcium chloride drying tube), and a solid addition funnel. The flask is charged with (1,3-dibromo-3,3-difluoropropyl)trimethylsilane (78.3 g, 0.25 mol), and anhydrous dimethyl sulfoxide (200 mL), and the solid addition funnel is charged with sodium borohydride (11.5 g, 0.30 mol) (Notes 7 and 8). The stirred solution is warmed to 80°C, and sodium borohydride is added at a rate sufficient to maintain a reaction temperature of 80-90°C (Note 9). Toward the end of the addition, an additional portion of dimethyl sulfoxide (200 mL) is added via syringe to lower the viscosity of the reaction mixture. After the addition is complete, the mixture is cooled in an ice-water bath, diluted with 100 mL of pentane, and cautiously quenched with 12 M hydrochloric acid until no further gas evolution occurs. The mixture is transferred to a separatory funnel and washed with three, 100-mL portions of 5% brine. The pentane extract is dried over calcium chloride and the solvent removed through a 15-cm Vigreux column. Further fractionation yields 41.5 g (72%) of 3-bromo-3,3-difluoropropyltrimethylsilane, bp 139-141 °C (Note 10). 

The 2,3-, 2,5- and 3,4-dihydropyridines all contain a highly polarized carbon-nitrogen double bond and should be reactive toward nucleophilic reagents. From the limited information in the literature, this appears to be the situation. The 2,3-dihydropyridine is readily reduced by sodium borohydride (equation 58) (64JHC13). Hydride addition occurs in a 1,2 rather than 1,4 sense. 

Treatment of the irradiated isoxazolo[5,4- ]pyridine 95 with sodium borohydride, a reagent which is also thermally inert toward 95, traps the spiroazirine intermediate giving diastereoisomeric spiroaziridines 99 and 100 (Scheme 1). 

Carboxylic acids are considerably less reactive than acid chlorides, aldehydes and ketones towards reduction. They cannot be reduced by catalytic hydrogenation or sodium borohydride (NaBH4) reduction. They require the use of a powerful reducing agent, e.g. LiAlH4. The reaction needs two hydrides (H ) from LiAlITj, since the reaction proceeds through an aldehyde, but it cannot be stopped at that stage. Aldehydes are more easily reduced than the carboxylic acids, and LiAltLj reduces all the way back to 1° alcohols. 

Explain the higher reactivity of acetone (propanone) compared to methyl acetate (CH3CO2CH3) toward reduction by sodium borohydride. 

One drawback, however, is that the products 5 are unstable during extended storage towards racemization. This can be circumvented by converting the aldehydes 5 in situ into derivatives. Depending on the reaction conditions amino alcohols 6 or oxazolidinones 7 are obtained these also are valuable intermediates. The two types of reductive modification are shown in Schemes 7.5 and 7.6, respectively. Such in situ reductions are performed by treatment with sodium borohydride. 

The authors were unable to carry out any transformation of staphinine and staphimine to staphisine and staphidine, respectively, because of the instability of these alkaloids toward various mild reducing agents (e.g., sodium borohydride, sodium cyanoborohydride). Staphimine and staphinine occur in extremely small amounts in the seeds of D. staphisagria. It has been suggested that the imine-containing alkaloids may be biogenetic precursors of staphisine and staphidine. 

The pyridinium salts have been shown to have electrophilic positions at the 2-, 4-, and 6-carbon atoms. Of these, the 2- and 6-positions should be the more positive because of the proximity to the quaternary nitrogen. From the ultraviolet absorption spectra of the reaction mixtures during the reduction and of the isolated products, it can be demonstrated that the predominant attack of the hydride ion from sodium borohydride occurs at these two positions.5,6 The 1,6-dihydro-pyridine (such as 5) formed from the reduction of a 1,3-disubstituted pyridinium ion appears to be stable toward further reduction, for a number of such compounds have been isolated from sodium borohydride reductions containing sufficient borohydride to complete the reduction to the tetrahydro-state.7"10 Since 1,4-dihydropyridines having a 3-substituent which is electron-withdrawing have also been... 

Of the various heterocycles discussed in this chapter, the pyridofuroxans show the least aromatic character. In Section 7.10.5.4, subtle differences in aromaticity between the [l,2,5]thiadiazolo[3,4-c]pyridines and the [l,2,5]oxadiazolo[3,4-c]pyridines are apparent from their dissimilar reactivity towards various reducing agents. In contrast to the former where desulfurization of the thiadiazole ring or substituent reduction occur, the latter heterocycles undergo initial reduction of the C=N bond to form the 4,5-dihydro[l,2,5]oxadiazolo[3,4-c]pyridines (120) with sodium borohydride at ambient temperature (Scheme 19). However, at 80 °C, the oxadiazole moiety is preferentially reduced... 

The extreme sensitivity of tellurols to oxygen make the isolation of these tellurium compounds difficult. Therefore, tellurols are almost always used in situ. In the literature, tellurols are sometimes claimed to be the product of the reduction of diaryl ditelluriums in ethanol as the reaction medium. Tellurols are probably present under these conditions in equilibrium with the tellurolates. Whether the tellurols or the tellurolates are the reactive species, for instance, in addition reactions to carbon-carbon multiple bonds, cannot be decided without additional studies. Benzenetellurol, formed in situ by methanolysis of phenyl trimethylsilyl tellurium, was much less reactive towards acetylenes than the tellurium compound obtained by reduction of diphenyl ditellurium with sodium borohydride in ethanol5. 

Sodium borohydride is selective it usually does not react with carbonyl groups that are less reactive than ketones and aldehydes. For example, carboxylic acids and esters are unreactive toward borohydride reduction. Thus, sodium borohydride can reduce a ketone or an aldehyde in the presence of an acid or an ester. 

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