This track introduces the first fully reliable way to form a new carbon–carbon bond, and it works by flipping carbon's usual role: instead of being the electrophile (as in substitution chemistry) or the nucleophile's target (as in a carbonyl addition), carbon itself becomes the nucleophile.

Organometallic reagents are compounds with a carbon directly bonded to a metal. Because carbon is more electronegative than most metals, that bond is polarized so the carbon end is δ− — effectively a carbanion. Grignard reagents (RMgX, made by reacting an alkyl or aryl halide with magnesium metal in dry ether) and organolithium reagents (RLi, made similarly with lithium metal) are the two workhorses, and both behave as strong, essentially unselective carbon nucleophiles and strong bases.

That dual nature — powerful nucleophile and powerful base — dictates the handling rules. Because the carbanion is such a strong base, it is instantly destroyed by any acidic proton: water, alcohols, amines, or carboxylic acids in the substrate or solvent will protonate it before it can do any useful chemistry (R–MgX + H₂O → R–H). So these reactions must run under strictly anhydrous conditions, and the substrate must be free of –OH, –NH, or –COOH groups (or those groups must first be protected).

Used as a nucleophile, R–MgX (or R–Li) adds to an electrophilic carbon — most commonly the carbonyl carbon of an aldehyde, ketone, ester, or CO₂ — forging a new C–C bond. The result, after an aqueous acidic workup to quench the intermediate alkoxide, is a new alcohol (or, from CO₂, a new carboxylic acid, adding one carbon to the chain). This carbon-nucleophile role is exactly what the upcoming carbonyl-addition track builds on: Grignard and organolithium reagents are simply the most general and powerful members of that nucleophile family.

"Build the Bond"