Hydrides reducing agents

So-called hydride reducing agents can transform carbonyl groups into alcohols, but their reducing ability depends on the nature of the hydride reagent. 

Compare atomic charges for sodium borohydride and lithium aluminum hydride. Which ion contains the most electron-rich hydride The least electron-rich hydride Based on these results alone, which hydride reagent should be the better reducing agent Explain. Obtain atomic charges for free borohydride and aluminum hydride anions. What changes, if any, does the counterion produce  

Next consider the energetics of reduction. Calculate AH for the first step in the reduction process using free reagents (BHT and AlHT). Energies for formaldehyde, and for the two intermediate adducts are provided at left. Which reduction is thermodynamically more favorable Are these results consistent with the predictions made using atomic charges  

Chemists generally rank reducing agent power as LiAlHj NaBH4. Is this ranking consistent with the reaction energetics and atomic charges  

Interestingly, true hydrides, such as NaH and KH, do not reduce carbonyl groups. Using energies of hydride and methoxide (at left), calculate AH xn for the reduction of formaldehyde by H. Is this reaction more or less favorable than those based on ZH4 Can the low reactivity of NaH and KH be attributed to thermodynamic factors, or must kinetic factors be responsible  

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For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride... 

A few reductions using typical hydride reducing agents have been reported for azafulvaleiies. Tlius, lithium aluminium hydride reduces A-methyl-... 

Reaction with water to yield a carboxylic acid Reaction with an alcohol to yield an ester Reaction with ammonia or an amine to yield an amide Reaction with a hydride reducing agent to yield an aldehyde or an alcohol... 

E.R.H. Walker, The Functional Group Selectivity of Complex Hydride Reducing Agents, Soc. Reviews 5, 23 (1976). 

The other way of reducing nitriles to aldehydes involves using a metal hydride reducing agent to add 1 mol of hydrogen and hydrolysis, in situ, of the resulting imine (which is undoubtedly coordinated to the metal). This has been carried out with LiAlH4, LiAlH(OEt)3, LiAlH(NR2)3, and DIBAL-H. The metal hydride method is useful for aliphatic and aromatic nitriles. 

One study showed that the Cram s mle product predominates with metal hydride reducing agents, but the other product with Bouveault-Blanc and dissolving metal reductions Yamamoto, Y. Matsuoka, K. Nemoto, H. J. Am. Chem. Soc., 1988, 110, 4475. 

Sulphoxides are reduced by the more powerful metal hydride reducing agents, but the less reactive reagents such as sodium borohydride are ineffective. Recently, Yoon has... 

For more complete discussion of functional group selectivity of hydride reducing agents, see E. R. H. Walter, Chem. Soc. Rev., 5, 23 (1976). 

The electrophilicity of alane is the basis for its selective reaction with the amide group. Alane is also useful for reducing azetidinones to azetidines. Most nucleophilic hydride reducing agents lead to ring-opened products. DiBAlH, A1H2C1, and A1HC12 can also reduce azetinones to azetidines.100... 

Other compounds that can be readily derived from amides that are more reactive toward hydride reducing agents are a-alkylthioimmonium ions103 and a-chloroimmonium ions.104... 

The effect of the steric bulk of the hydride reducing agent has been examined in the case of 3-benzyloxy-2-butanone.135 The ratio of chelation-controlled product increased with the steric bulk of the reductant. This is presumably due to amplification of the steric effect of the methyl group in the chelated TS as the reductant becomes more sterically demanding. In these reactions, the degree of chelation control was also enhanced by use of CH2C12 as a cosolvent. 

The presence of transition metal ions has a catalytic effect on reduction of halides and tosylates by LiAlH4.166 Various copper hydride reducing agents are effective for removal of halide and tosylate groups.167 The primary synthetic value of these reductions is for the removal of a hydroxy function after conversion to a halide or tosylate. 

The stereochemistry of addition of organometallic reagents to chiral carbonyl compounds parallels the behavior of the hydride reducing agents, as discussed in Section 5.3.2. Organometallic compounds were included in the early studies that established the preference for addition according to Cram s rule.118... 

The electrochemical reduction of aliphatic amides in dilute hydrochloric acid will tolerate other functional group.s active towards the alternative hydride reducing agents. With aliphatic amides the electrochemical step generally leads to the aldehyde because the intermediate imine is rapidly hydrolysed under the conditions... 

Another approach to reduction of an amide group in the presence of more easily reduced groups is to convert the amide to a more reactive species. One such method is conversion of the amide to an O-alkyl imidate with a positive charge on nitrogen.63 This method has proven successful for tertiary and secondary, but not primary, amides. Other compounds which can be readily derived from amides and that are more reactive than amides toward hydride reducing agents are a-alkylthioimmonium ions64 and a-chloroim-monium ions.65... 

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