- “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
The Robinson Annulation is one of the longer mechanisms you’ll encounter. It’s a way of taking a ketone and an enone (a.k.a. “alpha,beta unsaturated ketone”) into a six membered ring with a new double bond.
When you’re asked to give out the mechanism of a reaction like this, I’d advise starting in one place.
Wait for it….. I know I sound like a broken record…. “what bonds are formed, and what bonds are broken?” I say this to my students over a dozen times per day. I am not kidding.
In this instance I ask this question because it gives you a Road Map to what your mechanism should look like.
Let’s look closely at the Robinson. I’ve numbered the carbons to make things more clear.
The first point should be obvious. All the bonds that form and break should be accounted for in the mechanism!
This is a good thing. It means that you can rule out certain things. Having constraints helps narrow your focus.
Don’t make things more complicated than they actually are.
Let’s narrow things down a bit more, and analyze the bonds formed/broken one by one. Let’s pay special attention to the electron density on each. You should ask – is this atom electron-rich or electron poor? Or is there something about the reaction conditions that could make it more electron-rich or electron poor?
The first clue to the mechanism is the fact that we are adding base. Remember, “the conjugate base is a better nucleophile”*. That means that we should consider positions that could be deprotonated here as potential nucleophiles. Especially enolates.
OK. Let’s break this Robinson down.
- C3-C4 – C3 is next to ketone (could be from enolate – nucleophilic). C4 is on beta position (electrophilic).
- C2-C7 – C2 is electrophilic (carbonyl carbon) C-7 is next to ketone (potentially from enolate)
- C2-C7 (pi bond). All C-C Pi bonds come from elimination reactions of some kind. We will need a good leaving group on one of these carbons.
- C5-H – This is adjacent to a ketone: could have come from an enolate.
- C3-H Breaking the C-H bond adjacent to the ketone means we are forming an enolate under these conditions (basic).
- C7-H Adjacent to a ketone. Also implies enolate formation.
- C2-O (Pi) – all C-O (pi) bonds are broken through (1,2)-addition reactions. Therefore, a nucleophile must have added to this carbon.
- C2-O (single) – here, we broke a C-O bond. This carbon becomes part of a double bond, so this is the leaving group in the elimination reaction that formed C2-C7 (pi).
We can get all of this information from just examining the bonds! The bonds that form and the bonds that break give you clues about the mechanism.
Here’s some clues, made more clear:
- Every time you break a C-O (pi) bond, it had to happen through addition of a nucleophile to a carbonyl.
- Every time you see a proton adjacent to a carbonyl missing, it is a VERY strong indicator that an enolate formed there.
- Every time you see a C-C (pi) bond being formed, it is the result of an elimination reaction (usually a condensation, where you’re losing water)
- Every time you see a C-C (pi) bond being broken, it is likely the result of a conjugate addition (1,4-addition) especially when it’s adjacent to a carbonyl (C=O).
See how far you can get with this mechanism, based on just that information.
I’ll go through the mechanism tomorrow.
Thanks for reading ! James