The Robinson Annulation is a useful reaction for the formation of six-membered rings in polycyclic compounds, such as steroids. It combines two reactions: the Michael Addition and the Aldol Condensation
Mechanism of the Robinson Annulation
The first step in the process is the Michael Addition to an α,β-unsaturated ketone, such as methyl vinyl ketone (ethyl vinyl ketone is shown above):
The newly formed enolate intermediate must first tautomerize for the conversion to continue:
The subsequent cyclization via Aldol Addition is followed by a condensation to form a six-membered ring enone:
The Robinson Annulation can also proceed under acidic catalysis, with the entire process occurring in one pot, as shown below. The use of a precursor of the α,β-unsaturated ketone, such as a β-chloroketone, can reduce the steady-state concentration of enone and decrease the side reaction of polymerization.
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Asymmetric Synthesis of Wieland-Miescher and Hajos-Parrish Ketones Catalyzed by an Amino-Acid-Derived Chiral Primary Amine
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