Reducing Agents

Before understanding hydride-donor reagents, the reactivity of carbonyl compounds needs to be understood. Carbonyl compounds have a slight positive charge on the carbonyl-carbon giving it an electrophilic-character. Thus, carbonyl compounds that have a positive charge are more reactive to different nucleophiles such as a hydride donor. Acyl chlorides have a good leaving group (Cl^-) making it also very electrophilic. Esters and amides are more stable because of the strong resonance structure from the second heteroatom on the carbonyl.

Most reductions of carbonyl compounds are done with reagents that transfer a hydride from boron or aluminum. Two common reagents of this type are sodium borohydride and lithium aluminum hydride. Sodium borohydride is a less reactive donor reagent but is efficient for reducing aldehydes and ketones to alcohols. However, lithium aluminum hydride is much more reactive and can reduce ketones and aldehydes to alcohols but also reduce esters, amides, and carboxylic acids.

To demonstrate the varying degree in reactivity, a reaction with two carbonyl functional groups will be subjected to two sets of conditions with hydride-donating reducing reagents.

Figure 1. Representative IR results for ethyl 3-hydroxybutyrate.

The trends of carbonyl reactivity and hydride donor ability have been reviewed and demonstrated. The visual reactiveness of the two commonly used reagents is apparent and can be appreciated.

The understanding of the reactivity of reagents and functional groups is of high importance when developing new methods for reductions or any other kind of reaction. Controlling the selectivity and reactivity of any reaction is an important factor to consider when deciding on the reagents used for a chemical step. This drives chemists to develop new reagents and new methods.

The review of periodic trends is still important in organic chemistry. For example, when adding potassium metal to water, there is a more violent explosion than when sodium metal is added to water. For that reason, we could extend this analogy to the comparison and reasoning to why LiAlH₄ is more reactive than NaBH₄.

On the entire spectrum of nucleophiles and electrophiles, reactivity matters. A weak nucleophile will not react with a weak electrophile; but a more reactive electrophile might react with the same weak nucleophile. It all depends on their reactivity and the conditions.