Nucleophilic addition

A nucleophilic addition forms a bond by attack of a nucleophile on an electrophilic multiple bond, reducing its bond order. A common case is attack on the carbon of a carbonyl group, with its pi electrons displaced toward oxygen.

Protonation of the resulting oxygen-centered intermediate can give an alcohol. Unlike nucleophilic substitution, the basic addition step does not expel a leaving group from the attacked carbon. Carbonyl polarization and orbital geometry explain both why carbon is attacked and why the incoming bond follows a preferred approach direction.

A Grignard reaction uses an organomagnesium reagent, conventionally written $\mathrm{RMgX}$, as a carbon-based nucleophile or base. Addition to an aldehyde or ketone, followed by protonation of the alkoxide product, forms an alcohol with a new carbon-carbon bond.

The reagent is not simply a free carbanion: its bonding, aggregation, and coordination depend on its environment. Proton donors can consume it by an acid-base reaction instead of the intended carbonyl addition. This competition makes functional-group compatibility central to understanding its synthetic role.^[ref]

Two organomagnesium additions to a suitable ester give a tertiary alcohol after work-up. The first addition–elimination produces a ketone, which accepts the second carbon substituent.

Addition of an organomagnesium reagent to carbon dioxide followed by protonation gives a carboxylic acid with one additional carbon. A free acid cannot remain present during a subsequent Grignard addition without consuming reagent.

The Bürgi-Dunitz angle describes the oblique approach of a nucleophile toward a carbonyl carbon, conventionally measured relative to C=O. A typical trajectory is near $107^{\circ }$, with the optimum depending on the system.

The Bürgi-Dunitz trajectory describes the preferred approach of a nucleophile toward a carbonyl carbon, usually at an obtuse angle to the carbon-oxygen bond, often near $107^{\circ }$. It is a geometrical trend, not a fixed angle obeyed by every reacting system.

An oblique approach balances favorable interaction with the carbonyl antibonding orbital against repulsion from occupied orbitals. Crystallographic observations of close contacts motivated this picture, linking static molecular structures with a possible path of nucleophilic addition. Steric constraints and the other substituents can modify the accessible trajectory.