An organolithium is made the same way a Grignard is — a halide plus the metal, in a dry ether or hydrocarbon solvent — except that it takes two equivalents of lithium, because each lithium carries one electron and one of them leaves as LiBr:
R–Br + 2 Li → R–Li + LiBr
Everything a Grignard does, an organolithium also does. The reason to reach for one is that lithium is more electropositive than magnesium, so the carbon carries more negative charge, and the reagent is both a stronger nucleophile and a stronger base. Sometimes that extra reactivity is what you need; more often it is what you have to manage.
Where RLi succeeds and RMgX does not
Two cases come up repeatedly.
A hindered ketone. A Grignard approaching a very crowded carbonyl often gives enolization — it acts as a base on the α hydrogen instead of adding — or reduction by hydride transfer from its own β carbon. An organolithium, being smaller and more reactive, adds cleanly where the Grignard stalls.
A carboxylic acid straight to a ketone. This one looks impossible. A carboxylic acid has an O–H, so the first equivalent of RLi is spent deprotonating it. But the carboxylate that results is a poor electrophile with a full negative charge, and an organolithium is reactive enough to add to it anyway, giving a doubly charged intermediate that cannot collapse. Collapsing would mean expelling O²⁻, which is no leaving group at all, and would pile a third negative charge onto a center that already carries two. So it sits there until the acidic workup, and only then does it lose water to give the ketone.
Deprotonation as the goal
Because RLi reagents are extremely strong bases, several of the ones you will meet exist to remove a proton rather than to form a C–C bond:
| Reagent | Used for |
|---|---|
| n-BuLi | General-purpose strong base; deprotonating terminal alkynes and heteroaromatics |
| t-BuLi | The same but far more so; also the standard reagent for lithium–halogen exchange |
| LDA (from n-BuLi and diisopropylamine) | The classic enolate base: very strong, too bulky to add to a carbonyl |
LDA is the one worth tracing back. It is made by using n-BuLi as a base on an amine, and its whole point is the combination it achieves: strong enough to deprotonate a ketone completely, yet too hindered to attack the carbonyl. That pairing of high basicity with low nucleophilicity is not something a Grignard can offer, and it is what makes controlled enolate chemistry possible.
Acetylides, the cheapest carbon nucleophile
A terminal alkyne has a pKa of about 25 — acidic for a C–H, because the carbanion sits in an sp orbital with high s character. NaNH2 or n-BuLi removes that proton to give an acetylide, which is a genuine carbon nucleophile made without any transition metal.
An acetylide will do SN2 on a methyl or primary halide, and it adds to aldehydes and ketones. The SN2 is the useful half, and it is worth noting that an ordinary sp³ organometallic and an alkyl halide do not generally do this, because elimination and self-coupling get there first. The contrast is between an sp carbanion and an sp³ one rather than between reagent families — an acetylide is often a magnesium or lithium salt itself.
What carries forward
An organolithium is a Grignard with the volume turned up: same reactions, more reactivity, less selectivity. Use it where a Grignard stalls on a hindered ketone or where you want a ketone from a carboxylic acid, and recognize it in its other role as the base behind LDA and the acetylides. The next section goes the opposite way and turns the reactivity down, which turns out to buy more than turning it up ever does.