Addition of Gilman Reagents to Acyl Halides
Addition of Gilman Reagents to Acyl Halides: A Gilman reagent (R₂CuLi) reacts with an acyl halide to form a ketone.
What happens
A Gilman reagent (R₂CuLi) reacts with an acyl halide to form a ketone. One R group from the Gilman reagent replaces the halogen on the acyl halide, creating a new C–C bond.
Reaction summary
Acyl halide + Gilman reagent (R₂CuLi) → ketone
Reagents and conditions
- Starting material: Acetyl chloride (acyl halide)
- Reagents: Lithium diphenylcuprate (Ph₂CuLi, a Gilman reagent)
- Conditions: 1) Ph₂CuLi, −78 °C; 2) H₂O
- Products: Acetophenone (ketone)
Mechanism
- Nucleophilic Attack: An R group from the Gilman reagent attacks the carbonyl carbon of the acyl halide, and the C=O π bond opens onto oxygen.
- Tetrahedral Intermediate: The C=O π bond has opened, forming a tetrahedral intermediate.
- Carbonyl Reforms, Halide Leaves: The C=O reforms and the halide leaves.
- Product: The final ketone is formed: a new C–C bond has replaced the C–Cl bond.
Selectivity
- Chemoselectivity: Gilman reagents are less reactive than Grignard reagents, so under the usual reaction conditions they convert an acyl halide into a ketone without normally adding again to the ketone: acyl halide → ketone → stop. That makes them useful when the ketone itself is the product you want.
Memory trick
Gilman swaps Cl for carbon: R–CO–Cl → R–CO–R′. Acyl chloride + Gilman = ketone. Cl OUT → Carbon IN → STOP.