Nucleophilic addition

Aldehydes and ketones are reactive electrophiles.  When we looked at the preparation of alcohols we introduced you to nucleophilic addition to ketones and aldehydes.

From resonance, we know the "real" structure of ketones and aldehydes is some mixture of the following two resonance structures.  The carbonyl carbon is a region of decreased electron density and has some positive character based on this resonance and the higher electronegativity of O versus C.  Aldehydes, ketones, and carboxylic acid derivatives are susceptible to nucleophilic attack.

Because of the sp2 geometry about the carbonyl carbon, the two R groups and the carbonyl C and O are all in the same plane.

A variety of nucleophiles will attack the carbonyl carbon, including water, alcohols, amines, carbanions and Wittig reagents.

When a nucleophile attacks a carbonyl, the nucleophile approaches at an angle of 107o to the electrophile.  This is referred to as the Bürgi–Dunitz angle or trajectory and it defines the geometry of "attack" of a nucleophile on a ketone, aldehyde, ester, and amide carbonyls.

Recall that if the R groups are different then the aldehyde/ketone has Re and Si faces - i.e. the ketone or aldehyde is prochiral.

There are two typical conditions underwhich nucleophilic addition can occur, acidic and basic conditions.

Nucleophilic Addition under Acidic Conditions

Under acidic conditions such as acidic water, alcohol or HCN, the ketone or aldehyde is first protonated before nucleophile attacks.  This protonation activates the ketone or aldehyde making it a better electrophile.  The carbonyl carbon changes hybridization from sp2 to sp3 and now has a tetrahedral geometry.

Nucleophilic Addition under Basic Conditions

A different pathway occurs under basic conditions as with Grignard reagents, hydride reducing reagents, NaOR, NaOH or NaCN.  In these cases, the strong nucleophile attacks the carbonyl carbon first.  The alkoxide anion is quenched (protonated) with a mild proton source (acid), H-A.  Usually this is H3O+.  Attack of the nucleophile results in a tetradehral product.

Relative Reactivity of Aldehdyes and Ketones

In general, aldehydes are more reactive than ketones.  This can be attributed to steric and electronic effects.


Consider a nucleophile attaching formaldehyde, acetaldehyde and acetone shown below.  Hydrogens are much smaller than alkyl groups, so formaldehyde is the least sterically hindered carbonyl C.  Ketones, like acetone on the other hand have two alkyl groups and would be expected to react slower.


If we look at the resonance structures of aldehdyes versus ketones we see that the carbocation in ketones is more stable "secondary like", while that for aldehydes is "primary like".  Formaldehyde is very reactive, notice how its resonance structure is like a very unstable methyl cation.

Addition to Chiral Aldehydes and Ketones - Cram's Rule

Cram's rule applies to chiral aldehydes and ketones.  For example suppose we have the following aldehyde.  The asymmetric center has three groups other than the formyl group - a big group (Ph), a medium group (CH3) and a small group (H).  The most stable conformation of the aldehyde is such the carbonyl rests between the medium and small groups as follows. The attacking nucleophile would prefer to attack from the side of the small group, resulting in the predominant formation of one diastereomer in the product.

For example addition of phenyl magnesium bromide to the above aldehyde results in the following.