Reaction with Hydride Nucleophiles

From the mechanism it can be seen that it takes two hydride nucleophiles to accomplish this reduction. Therefore, 1 mole of lithium aluminum hydride will reduce 2 moles of the ester. 

What happens if less hydride reagent is used Even though the aldehyde is produced first in the mechanism, the reaction cannot be stopped at the aldehyde stage because the aldehyde is higher on the reactivity scale than the ester. The aldehyde reacts with the hydride nearly as fast as it is formed. If less than 1 mole of hydride per 2 moles of ester is used, a mixture of the ester and the alcohol is produced, along with some of the aldehyde. A reaction that produces a mixture of products like this is not synthetically useful. 

On the basis of this mechanistic reasoning, it is apparent that acyl chlorides and anhydrides should also be reduced to primary alcohols by lithium aluminum hydride. Indeed, this is the case. However, because these compounds are less convenient to work with than esters and offer no advantages in synthesis, they are seldom used as substrates for such reductions. 

Carboxylic acids are also reduced to primary alcohols by lithium aluminum hydride. The first step in the mechanism for this reaction is an acid-base reaction between the 

Q As usual, the hydride nucleophile attacks the carbonyl carbon and displaces the pi electrons onto the oxygen. 

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The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

The elements of H and Nu are added to the carbonyl group. In Chapter 20 you learned about this reaction with hydride (H ) and carbanions (RO as nucleophiles. In Chapter 21. we will discuss similar reactions with other nucleophiles. 

Compared to manganese, little work has been carried out on analogous alkyl complexes of rhenium, although that which has may be divided into the same categories, namely, (1) reaction with transition metal hydrides, for example [CpW(H)(CO>3] (2) reaction with Lewis acids, for example, AlCUEt (3) orthometallation reactions (4) reaction with cationic species, for example, (5) reaction with anionic nucleophiles, for example, BF4" (6) reaction with neutral nucleophiles, for example, PPh3-... 

The ketones and aldehydes have basically two different sites where a reaction with a nucleophile can take place the carbon of the carbonyl group and the hydrogen atom bonded to the a carbon.1,4 If a nucleophile reacts with the carbon of the carbonyl group several products can be formed.1,4 For instance, if the nucleophile is a hydride anion, a reduction of the double bond occurs.52 If a base reacts with the hydrogen atom bonded to the a carbon, the result is an enolate anion.53 Figure 17 summarizes these possibilities. 

Tricyclic furo[2,3-e]pyrido[l,2-fr][l,2,4]triazinium salt 612 underwent ring transformation by reaction with carbon nucleophiles. Thus, the sodium salt of 1 generated from reaction of 1 and sodium hydride in acetonitrile, was treated with 612 to give 7-benzoyl-8,9,10,ll-tetrahydro-9,9-dimethylindenoll,2-eJpyrido[l,2-frJl,2,4-triazin-ll-one (94CB1799), which because of the enhanced delocalization of the n electronic system, it existed in two equilibrium forms 613 and 614 (Scheme 132). 

Aldehydes and ketones undergo nucleophilic addition reactions with hydride ion and with carbon nucleophiles. 

Various aspects of the ring-opening reactions of monosaccharide acetonides with Grignard reagents and with hydride nucleophiles have been discussed in a review article (12 refs.). ... 

Phthalimide is easily deprotonated by potassium hydride, to give the corresponding anion. Alkyl chlorides easily undergo Sfj2 reactions with good nucleophiles, such as the phthalimide anion, and give the amine product. 

In addition to the usual substitution reactions directly on the nitrogen atom of the amino or amido group, there are (as noted earlier, e.g.. Table 7.7) substitution reactions with other nucleophiles that can be converted to the amino (or substituted amino) group. These include incorporation of the azido function (produced by, e.g., a nucleophilic substitution reaction of azide anion [Ns"] on an alkyl halide) and its subsequent reduction (with lithium aluminum hydride, LiALH,) (Equation 10.60) or triphenylphosphine [( 5115)3 ] (Equation 10.61) to the corresponding amine, as well as a similar displacement reaction with isocyanate (0=C=N ) (Equation... 

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