Nucleophilic Attack on the C=O Bond

The HOMO-LUMO Interaction

We can use the resonance description of the C=O bond to treat nucleophilic attack as a primarily electrostatic phenomenon: attraction of the (negative) electrons on the nucleophile to the positive end of the polarized C=O bond:
C=O resonance structures place a partial positive charge on carbon; this attracts electron density from a nucleophile.
Recognize that this is a simplistic model. A more sophisticated approach is to recognize that this will be driven by a molecular orbital process that involves making a new bonding MO (as well as a new antibonding MO) from two MOs of the reactant: the HOMO of the nucleophile (describing the electrons used to make the bond), and the LUMO of the carbonyl, which describes where and how elections can interact.

A seminal structural study identified the structure of the natural product protopine (right) as a model for the process. The conformation of the large ring holds the nitrogen in close proximity to the carbonyl. We can see the interaction between the nitrogen lone pair and the carbonyl LUMO:

Show the Lone Pair on Nitrogen
Show the LUMO

Background: Black White
Model type: Wireframe Ball-and-stick

Ref: a. Burgi, H. B.; Dunitz, J. D.; Shefter, E. J. Am. Chem. Soc., 1973, 95, 5065. b. Hall, S. R.; Ahmed, F. R., Acta Crystallogr., Sect. B., 1968, 24337.

This is a general principle for all nucleophiles: there is an equilibrium between the carbonyl and the tetrahedral species formed by nucleophilic addition. The trajectory of attack is from above the place of the carbonyl and slightly to the rear, maximizing MO interactions. Where the equilibrium lies depends on the relative strenth of the new bond (vs. the strength of the pi bond--about 420 kJ/mol or 100 kcal/mol) and the leaving group ability of the nucleophile (or of OH^-). Move on to a summary of reactivity to explore this further.