Robinson Annulation

Robinson annulation is a reaction between an enolate and an alpha, beta-unsaturated ketone that forms a ring. 

Robinson annulation mechanism 

The very first part of Robinson annulation is basically a base-catalyzed Michael reaction, in which an enolate attacks a conjugated ketone or aldehyde. Let's check it out! To be clear, we're not looking at the actual Robinson annulation just yet. 

Michael-addition

Michael addition

Okay, let's get to the heart of this post: Robinson annulation. Let’s take a look at the mechanism. The very first step is the addition of base to remove the alpha proton to form the enolate. Once the enolate is formed, it can can attack the electrophilic enone. We’ll use an alkoxide as our base in this example. 


Enolate-formation-and-conjugate-addition

Enolate formation and conjugate addition


Second-enone-formation

Second enone formation


From there, another enone is formed. That enol is actually deprotonated, but there’s something to keep in mind: the enolate that forms is the one that actually forms the ring, so we need to count the number of atoms from the enolate to the carbonyl. The most stable ring-size is 6, so we want to get as close to that as possible.  


enolate-formation-and-nucleophilic-addition

Enolate formation and nucleophilic addition


The green alpha-hydrogen is deprotonated, and it then attacks the carbonyl leaving us with an alcohol. 

Ring-formation-and-dehydration

Ring formation and dehydration

That alcohol undergoes dehydration through an E1cB mechanism, which is a special kind of elimination, and we end up with yet another enone! Notice that the alcohol dehydrated “toward” the ketone. Why? Resonance! Conjugated molecules are more stable, so the enone is favored over the isolated double bond. 

Here's the whole mechanism in one piece to see it in all its glory: 

Full-mechanismFull mechanism

Heads up: applications for the Robinson annulation include building molecules like steroids—you know, since they’ve got so many rings.