Grignard addition

A Grignard reagent is one of organic chemistry's most powerful tools for building carbon skeletons: an organomagnesium compound, R-Mg-X, made by reacting an alkyl or aryl halide with magnesium metal in dry ether. The trick is that the carbon bonded to magnesium is polarized the 'wrong' way: because carbon is more electronegative than magnesium, that carbon carries a partial negative charge and behaves like a carbanion, a carbon nucleophile.

When a Grignard reagent meets a carbonyl, the nucleophilic carbon attacks the electron-poor carbonyl carbon, forging a brand-new carbon-carbon bond. The C=O electrons go onto oxygen as an alkoxide (with the magnesium as counterion), and a final aqueous workup protonates it to an alcohol. The pattern of product depends on the carbonyl: formaldehyde gives a primary alcohol, any other aldehyde gives a secondary alcohol, and a ketone gives a tertiary alcohol. Organolithium reagents (R-Li) do the very same chemistry, only more reactively.

Grignard additions are essentially irreversible and go to completion, unlike the gentler equilibrium additions of water or alcohols. That power comes with a strict limitation: the carbanion is also a strong base, so it is destroyed by any acidic proton, including -OH, -NH, and -COOH, and even water in the air. So Grignard chemistry demands scrupulously dry, aprotic conditions, and substrates with no acidic hydrogens (or those groups must be protected first).