Robinson Annulation Mech
- “Initial Tails” and “Final Heads”
- 3 Ways To Make OH A Better Leaving Group
- A Simple Formula For 7 Important Aldehyde/Ketone Reactions
- Acids (Again!)
- Activating and Deactivating
- Actors In Every Acid Base Reaction
- Addition – Elimination
- Addition Pattern 1 – Carbocations
- Addition pattern 2 – 3 membered rings
- Addition Reactions
- Aldehydes And Ketones – Addition
- Alkene Pattern #3 – The “Concerted” Pathway
- Alkyl Rearrangements
- Alkynes – 3 Patterns
- Alkynes: Deprotonation and SN2
- Aromaticity: Lone Pairs
- Avoid These Resonance Mistakes
- Best Way To Form Amines
- Bulky Bases
- Carbocation Stability
- Carbocation Stability Revisited
- Carboxylic Acids are Acids
- Chair Flips
- Cis and Trans
- Conjugate Addition
- Curved Arrow Refresher
- Curved Arrows
- Determining Aromaticity
- Diels Alder Reaction – 1
- Dipoles: Polar vs. Covalent Bonding
- E2 Reactions
- Electronegativity Is Greed For Electrons
- Electrophilic Aromatic Substitution – Directing Groups
- Elimination Reactions
- Enantiocats and Diastereocats
- Epoxides – Basic and Acidic
- Evaluating Resonance Forms
- Figuring Out The Fischer
- Find That Which Is Hidden
- Formal Charge
- Frost Circles
- Gabriel Synthesis
- Hofmann Elimination
- How Acidity and Basicity Are Related
- How Are These Molecules Related?
- How Stereochemistry matters
- How To Stabilize Negative Charge
- How To Tell Enantiomers From Diastereomers
- Hybridization Shortcut
- Imines and Enamines
- Importance of Stereochemistry
- Intermolecular Forces
- Intro to Resonance
- Ketones on Acid
- Kinetic Thermodynamic
- Making Alcohols Into Good Leaving Groups
- Markovnikov’s rule
- Mechanisms Like Chords
- Mish Mashamine
- More On The E2
- Newman Projections
- Nucleophiles & Electrophiles
- Nucleophilic Aromatic Substitution
- Nucleophilic Aromatic Substitution 2
- Order of Operations!
- Oxidation And Reduction
- Oxidative Cleavage
- Pi Donation
- Pointers on Free Radical Reactions
- Protecting Groups
- Protecting Groups
- Proton Transfer
- Putting it together (1)
- Putting it together (2)
- Putting it together (3)
- Putting the Newman into ACTION
- Reaction Maps
- Recognizing Endo and Exo
- Redraw / Modify
- Robinson Annulation
- Robinson Annulation Mech
- Sigma and Pi Bonding
- SN1 vs SN2
- sn1/sn2 – Putting It Together
- sn1/sn2/e1/e2 – Exceptions
- sn1/sn2/e1/e2 – Nucleophile
- sn1/sn2/e1/e2 – Solvent
- sn1/sn2/e1/e2 – Substrate
- sn1/sn2/e1/e2 – Temperature
- Strong Acid Strong Base
- Strong And Weak Oxidants
- Strong and Weak Reductants
- Stronger Donor Wins
- Sugars (2)
- Synthesis (1) – “What’s Different?”
- Synthesis (2) – What Reactions?
- Synthesis (3) – Figuring Out The Order
- Synthesis Part 1
- Synthesis Study Buddy
- Synthesis: Walkthrough of A Sample Problem
- Synthesis: Working Backwards
- The 4 Actors In Every Acid-Base Reaction
- The Claisen Condensation
- The E1 Reaction
- The Inflection Point
- The Meso Trap
- The Michael Reaction
- The Nucleophile Adds Twice (to the ester)
- The One-Sentence Summary Of Chemistry
- The Second Most Important Carbonyl Mechanism
- The Single Swap Rule
- The SN1 Reaction
- The SN2 Reaction
- The Wittig Reaction
- Three Exam Tips
- Tips On Building Molecular Orbitals
- Top 10 Skills
- Try The Acid-Base Reaction First
- Two Key Reactions of Enolates
- What makes a good leaving group?
- What Makes A Good Nucleophile?
- What to expect in Org 2
- Work Backwards
- Zaitsev’s Rule
OK. As I said yesterday, the Robinson Annulation is a reaction that takes a ketone and an alpha,beta unsaturated ketone (sometimes called an “enone”) and transforms into a six-membered ring.
Of all the reactions you learn, the mechanism for this one is one of the longest.
But my aim for this post is to try and help to condense it down into a short formula that you could recall readily if asked.
The Robinson is a two step sequence consisting of reactions you’ve learned by now: the Michael reaction and then the Aldol Condensation.
First, the Michael Reaction: this proceeds in 3 steps.
- Deprotonation (making an enolate)
- Conjugate addition (1,4-addition) of the enolate to the end of the alkene
To summarize: D, A(14), P.
However, if this product from the Michael reaction is heated in base, something interesting happens. Base can remove another proton – from C1 or C7, although C7 is shown here – and the resulting enolate can add to the ketone 6 bonds away, in an addition reaction.*
Here, like a snake biting its own tail, the enolate nucleophile adds to the ketone, forming a ring. Make sure you can see this – we’re forming a bond between C2 and C7.
Then, we protonate (P) the oxygen, and then deprotonate (D) carbon 7 again. This forms an enolate, which then leads to elimination of water. Note here that elimination is a different kind then I’ve been talking about – it’s 1,4- elimination (E14), the opposite of 1,4-addition, and it leads to formation of a new C-C Pi bond.
So the pattern is: D, A(12), P, D, E(14).
That’s eight steps. Quite a lot to remember – but if you’re given the starting material and the product, and are armed with the abbreviations for each of the steps, it shouldn’t be *too* hard to attack it. Think of it like a big puzzle. There’s a logic to how things piece together.
Tomorrow: another combination reaction, one that takes two reactions we’ve already learned and smushes them together.
Thanks for reading! James
P.S. *Hold on! Why didn’t this happen earlier – like at the end of the Michael reaction?
Well, it didn’t happen because in organic chemistry, 3 and 4-membered rings are tough to form. Remember ring strain?
On the other hand – 5 and 6 membered rings form quite readily.