In our discussion of the oxidation of alcohols, we classified this process as a 1,2-elimination of the "elements of" dihydrogen. The reverse process, the 1,2-addition of the "elements of" dihydrogen to a multiple bond, constitutes a reduction. The reagents used for the 1,2-addition of the "elements of" dihydrogen to a multiple bond depend upon the nature of the multiple bond. For homonuclear multiple bonds, i.e. alkenes and alkynes, the most common method is called catalytic hydrogenation: a solution of the alkene or alkyne is mixed with dihydrogen gas in the presence of a catalytic quantity of a transition metal. For heteronuclear multiple bonds; aldehydes, ketones, nitriles, esters, etc., addition of the "elements of" dihydrogen is genarally accomplished in two steps, addition of hydride ion, :H^-, followed by addition of H⁺. Since the addition of hydride ion is rate determining, these reductions are called hydride ion reductions. We'll take a look at catalytic hydrogenation first.

The catalyst most commonly used to reduce carbon-carbon multiple bonds consists of platinum metal dispersed over the surface of finely divided charcoal (Pt/C). Palladium and rhodium are also used (Pd/C and Rh/C). These reagents are available commercially. The catalyst is mixed with a solution of the alkene or alkyne dissolved in an inert solvent such as ethanol or diethyl ether. Since the reaction mixture is heterogeneous, it is important that the catalyst be dispersed over a large surface area in order to insure adequate contact between the reactants and the catalyst. The charcoal provides the required surface area.

The mechanistic details of catalytic hydrogenations are uncertain because of the difficulties associated with studying heterogeneous reactions. Figure 3 animates the generally accepted view of the process using 2-butyne as an example.

Adsorption onto the catalytic surface brings the reactants into proximity. It also weakens the H-H and the C-C bonds, increasing the reactivity of the reactants. The details of the transfer of the hydrogen atoms from the platinum to the alkyne are uncertain. However, as the animation indicates, both hydrogen atoms add to the same side of the pi bond, leading to the formation of cis-2-butene. In other words, catalytic hydrogenation of alkenes and alkynes involves the syn addition of the "elements of" dihydrogen to the multiple bond. Equation 9 illustrates the syn addition of dihydrogen to (E)-3-chloro-2-phenyl-2-butene. Since the addition occurs to the top and bottom faces of the pi bond with equal probability, the reaction produces a racemic mixture of the two stereoisomers shown.

As reaction 10 indicates, catalytic hydrogenations are not restricted to alkenes and alkynes. Compounds containing multiple bonds between carbon and a heteroatom such as oxygen or nitrogen may also be reduced catalytically.

While the outcome depicted in reaction 10 may be desireable, it would be nice to have a method to hydrogenate heteronuclear multiple bonds while leaving carbon-carbon multiple bonds untouched. Such a method exits. It takes advantage of the fact that, unlike C-C multiple bonds, which are relatively non-polar, heteronuclear multiple bonds have a permanent bond dipole; the carbon is electron deficient while the heteroatom is electron rich. This means that the carbon atom of a heteronuclear multiple bond is inherently reactive toward negatively charged reagents, while the heteroatom is inherently reactive towards positively charged reagents. Figure 4 demonstrates this reality for negatively and positively charged hydrogen atoms.

The net result of the addition of :H^- and H⁺ to the multiple bond is the 1,2-addition of the "elements of" dihydrogen. Since it is not possible to have significant concentrations of :H^- and H⁺ in the same flask at the same time (why?), hydrogenation of heteronuclear multiple bonds is normally a 2-step process; hydride ion adds to the carbon atom in the first step, while a proton adds to the heteroatom in the second. The remainder of this topic will consider different reagents that act as a source of hydride ion.

Reagents that act as hydride ion donors all share one structural feature: They all contain at least one hydrogen atom that is bonded to another atom which is less electronegative than hydrogen. The greater the difference in electronegativity, the more reactive the reagent will be as a hydride donor. The most reactive source of hydride ion is lithium aluminum hydride, LiAlH₄. This material is a grey solid that reacts violently with protic solvents. Most commonly it is used as a suspension in a dry, inert solvent such as diethyl ether or THF. A solution of the compound to be reduced is added to this suspension and stirred vigorously until analysis indicates that all of the starting material has reacted. At this point the mixture is acidified by the careful addition of aqueous acid. Figure 5 illustrates these two steps for the reduction of acetophenone.

Note that all four hydrogen atoms attached to the aluminum in LiAlH₄ are active; one mole of LiAlH₄ will reduce four moles of the ketone.

LiAlH₄ is so reactive that it will reduce almost any type of heteronuclear multiple bond. It will even reduce carboxylic acids and esters to the corresponding primary alcohols as indicated in reactions 11 and 12, and it reduces amides to amines as shown in Equation 13.

Clearly these reactions are more complicated than the mechanism shown in Figure 5 would suggest. Elimination of water as well as reduction must be involved.

Before we consider less reactive hydride donors, let's revisit the reaction of the unsaturated ketone we considered in Equation 10. Figure 6 compares the catalytic hydrogenation of pent-4-en-2-one with its reduction by LiAlH₄.

Because simple, i.e. non-conjugated, double bonds are non-polar, they are non-reactive towards nucleophilic reagents.

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Exercise 3 Why are alkenes non-reactive towards nucleophiles, but react readily with electrophiles?

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While lithium aluminum hydride's high reactivity may be useful, it can also be a disadvantage if you want to selectively reduce one heteronuclear multiple bond in a compound that contains several. In that case it is desireable to have a reagent that is less reactive and more selective. One such reagent is sodium borohydride, NaBH₄. This material is a white solid. It is much less reactive than LiAlH₄. In fact, it is possible to reduce aldehydes, ketones, and esters with NaBH₄ even in protic solvents such as ethanol. It will not reduce carboxylic acids or amides. The mechanism of the reaction is very similar to that shown in Figure 5. Figure 7 compares the results of the reduction of a compound that contains both an ester and an amide group with LiAlH₄ and NaBH₄.

Figure 7

LiAlH₄ vs NaBH₄

Table 1

Hydride Reductions

Reducing Agent	Alkenes	Aldehydes	Ketones	Esters	Amides	Carboxylic Acids
H2, Pt/C	alkanes	1o alcohols	2o alcohols	NR	NR	NR
LiAlH4	NR	1o alcohols	2o alcohols	1o alcohols	amines	1o alcohols
NaBH4	NR	1o alcohols	2o alcohols	1o alcohols	NR	NR
DIBAL	....	1o alcohols	2o alcohols	aldehydes	aldehydes	1o alcohols