Robinson Annulation
Explained

The two starting materials are: (1) a ketone with an α-hydrogen (the Michael donor, e.g. cyclohexanone) and (2) methyl vinyl ketone (MVK), CH₂=CH–CO–CH₃, the Michael acceptor. Under basic conditions they undergo Michael addition then intramolecular aldol condensation to give a cyclohex-2-enone.

Robinson Annulation is a tandem reaction combining a Michael addition and an intramolecular aldol condensation carried out in one pot. It builds a new six-membered carbocyclic ring bearing an α,β-unsaturated ketone (cyclohex-2-enone).

Sir Robert Robinson published the reaction in 1935. He was awarded the 1947 Nobel Prize in Chemistry for his investigations of alkaloids and other natural products. The reaction was later generalised and named in his honour.

Michael Addition is a 1,4-conjugate addition of a nucleophile (Michael donor) to an α,β-unsaturated carbonyl compound (Michael acceptor). In Robinson Annulation, the enolate of the donor ketone adds to the β-carbon of MVK in a Michael-type fashion.

The product is a cyclohex-2-enone — a six-membered carbocyclic ring with a conjugated α,β-unsaturated ketone. When a cyclic ketone is used as the donor, the product is a fused bicyclic enone such as an octalone or the Wieland–Miescher ketone.

It is a workhorse of steroid, terpenoid, and polycyclic natural product synthesis. The six-membered ring with α,β-unsaturated ketone it builds is the fundamental framework of steroids, terpenes, and countless pharmaceutically important compounds. The Wieland–Miescher ketone synthesis uses it as a key step.