Robinson annulation
/ ROB-in-son an-yoo-LAY-shun /
The Robinson annulation is a two-reactions-in-one sequence that builds a fresh six-membered ring onto an existing ketone. 'Annulation' just means ring-forming. It chains together two reactions you already know: a Michael addition followed by an intramolecular aldol condensation. Each step forms one new carbon-carbon bond, and together they close a new cyclohexenone ring — a six-membered ring carrying a conjugated enone.
Here is the choreography. First, a ketone enolate does a Michael (conjugate) addition onto an alpha,beta-unsaturated ketone — methyl vinyl ketone is the classic partner — joining the two pieces. The new compound is a 1,5-diketone. Second, base deprotonates the alpha-carbon of one ketone, and that enolate reaches across to the other ketone in an intramolecular aldol; dehydration of the resulting beta-hydroxy ketone gives the conjugated cyclohexenone. Two C-C bonds, one new ring, one enone.
Why is it a capstone of alpha-carbon chemistry? Because it assembles a substituted six-membered ring — the backbone of countless natural products, especially steroids and terpenes — from two simple, open-chain carbonyls in one operation. It is the showcase of how enolate nucleophiles, conjugate addition, and aldol condensation work in concert to construct real molecular architecture.
A cyclohexanone-type ketone plus methyl vinyl ketone (MVK), CH2=CH-CO-CH3, with base: a Michael addition gives a 1,5-diketone, then intramolecular aldol condensation closes and dehydrates to a fused bicyclic cyclohexenone — the kind of ring fusion central to steroid synthesis.
Michael addition then intramolecular aldol condensation = one new cyclohexenone ring.
Remember it as two familiar steps, not a new mechanism: Michael addition (forms the 1,5-diketone) then intramolecular aldol condensation (closes the ring and dehydrates). The product ring is always six-membered, carrying a conjugated enone.