Nucleophile hydride ion

We ll defer a detailed discussion of the mechanisms of these reductions until Chapter 19. For the moment, we ll simply note that they involve the addition of a nucleophilic hydride ion ( H ) to the positively polarized, electrophilic carbon atom of the carbonyl group. The initial product is an afkoxide ion, which is protonated by addition of H 0+ in a second step to yield the alcohol product. 

Nucleophilic hydride ion replaces selectively the fluorine at the C4 position in perfluoropyridine to give 4//-perfluoropyridine as the sole product from the reaction with lithium aluminum hydride.147 The same position is attacked with this complex hydride in 3-chloro-2,4,5,6-tet-rafluoropyridinc resulting in 3-chloro-2,5,6-trifluoropyridine (9).148... 

Wipf has shown that 4,4-disubstituted cyclohexanones undergo nucleophilic attack where the facial selectivity is determined by dipolar control. Thus, compounds of the type 23 underwent nucleophilic attack anti to the electronegative substituent at C(4), whereas the fluorinated analogue, 24, underwent attack syn to the oxygen, in accordance with the inversion of the dipole moment. They found that the logarithm of the experimentally observed facial selectivity for nucleophilic attack was correlated linearly (R = 0.998) with the calculated dipole moments. The facial selectivities were also shown to depend upon the nature of the nucleophile, hydride ions and alkynyl carbanions being essentially unselective. 

The reactions of complex metal hydrides occur by an attack of the nucleophilic hydride ion on an electrophilic center.1 Aromatic nitrogen heterocycles in which the nitrogen has contributed only one electron to the -system (1) are electrophilic as compared with benzene, and have been shown to undergo reduction by the active reducing agent, lithium aluminum hydride. The nitrogen heterocycles in which the heteroatom has contributed two electrons to the 77-system (2) are electron-rich as compared with benzene and usually do not undergo reaction by reduction with complex metal hydrides.2 A combination of these two structural features, as in oxazoles (3), usually induces sufficient electrophilicity to allow attack by the hydride ion and reduction. 

Nitriles (RCN) can be reduced to primary amines (RCH2HN2) with lithium aluminium hydride that provides the equivalent of a nucleophilic hydride ion. The reaction can be explained by the nucleophilic attack of two hydride ions ... 

On the basis of what we have already learned about the reactions of lithium aluminum hydride with aldehydes and ketones (Chapter 18) and the mechanisms presented so far in this chapter, we can readily predict the product that results when hydride reacts with a carboxylic acid derivative. Consider, for example, the reaction of ethyl benzoate with lithium aluminum hydride. As with all of the reactions in this chapter, this reaction begins with attack of the nucleophile, hydride ion, at the carbon of the carbonyl group, displacing the pi electrons onto the oxygen (see Figure 19.7). Next, these electrons help displace ethoxide from the tetrahedral intermediate. The product of this step is an aldehyde. But recall from Chapter 18 that aldehydes also react with lithium aluminum hydride. Therefore, the product, after workup with acid, is a primary alcohol. 

The mechanisin of alcohol oxidation with NAD has several analoge in laboratory chemistry A base removes the O-TC proton from the alcohol and Keaerates an allcoxide ion, which expels a hydride ion leaving group as in the Cannizzaro reaction tSection 19.13>> The nucleophilic hydride ion dacn adds to the Cs=C-C=N part of NAD in a conjugate addition reaction, much the same as water adds to the C=C-C=0 part of the tt,p-unsaturated acyl CoA in step 2. 

To understand why the hydroboration-oxidation of propene forms 1-propanol, we must look at the mechanism of the reaction. The boron atom of borane is electron deficient, so borane is the electrophile that reacts with the nucleophilic alkene. As boron accepts the rr electrons and forms a bond with one carbon, it donates a hydride ion to the other carbon. In all the addition reactions that we have seen up to this point, the electrophile adds to the alkene in the first step and the nucleophile adds to the positively charged intermediate in the second step. In contrast, the addition of the electrophilic boron and the nucleophilic hydride ion to the alkene take place in one step. Therefore, an intermediate is not formed. 

The alkylborane formed in the first step of the reaction reacts with another molecule of alkene to form a dialkylborane, which then reacts with yet another molecule of alkene to form a trialkylborane. In each of these reactions, boron adds to the sp carbon bonded to the greater number of hydrogens and the nucleophilic hydride ion adds to the other sp carbon. 

Oxiranes are reduced by sodium borohydride to give alcohols [3]. This reaction can be viewed as a ring-opening by the nucleophilic hydride ion ... 

We have seen that NaH is a strong base but a weak nucleophile. In contrast, lithium aluminum hydride (LAH) is a reagent that can serve as a source of nucleophilic hydride ion ... 

In this case, LAH functions as a delivery agent of a nucleophilic hydride ion. We will see this reagent in many upcoming chapters. Explain why LAH is capable of functioning as a strong nucleophile while NaH is not. 

Acid chlorides are the most reactive acyl derivatives toward the nucleophilic hydride ion provided by metal hydrides. Acid chlorides are rapidly reduced to aldehydes. However, hthium aluminum hydride is such a strong reducing agent that the aldehydes produced from acid chlorides are further reduced to primary alcohols under the reaction conditions. 

LAH Lithium aluminum hydride is a somce of nucleophilic hydride ions. It will react with an epoxide in a ring-opening reaction, to attack the less substituted side (it is not possible to use acidic conditiorts and have a hydride ion attack the more substituted side - see the previous section on common mistakes to avoid). 

---