Nucleophilic Addition

Chapter 17: Aldehydes and Ketones. Nucleophilic Addition to C=O

Nucleophilic addition reactions are an important class of reactions that allow the interconversion of C=O into a range of important functional groups.

What does the term "nucleophilic addition" imply ?

A nucleophile, Nu^-, is an electron rich species that will react with an electron poor species (here the C=O)
An addition implies that two systems combine to a single entity.

There are three fundamental events in a nucleophilic addition reaction:

formation of the new s bond between the nucleophile, Nu, to the electrophilic C of the C=O group
breaking of the p bond to the O resulting in the formation of an intermediate alkoxide
protonation of the intermediate alkoxide to give an alcohol derivative

Depending on the reactivity of the nucleophile, there are two possible general scenarios:

Strong nucleophiles (anionic) add directly to the C=O to form the intermediate alkoxide. The alkoxides are then protonated on work-up with dilute acid.

Addition of strong nucleophiles to aldehydes and ketones

Examples of such nucleophilic systems are : RMgX, RLi, RCºCM, LiAlH₄, NaBH₄

Weaker nucleophiles (neutral) require that the C=O be activated prior to attack of the Nu.

This can be done using a acid catalyst which protonates on the Lewis basic O and makes the system more electrophilic.

Addition of weaker nucelophiles under acidic conditions to aldehydes and ketones

Examples of such nucleophilic systems are : H₂O, ROH, R-NH₂

The protonation of a carbonyl gives a structure that can be redrawn in another resonance form that reveals the electrophilic character of the C since it is a carbocation.

The reactions on the following pages are catalogued based on the nature of the nucleophilic atom involved.
In most cases it is useful to identify the mechanism in each case in terms of the two general schemes presented above.