Synthesis: Working Backwards
- “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
Let’s start talking about synthesis. Guess where I’m going to start? You might think, “what bonds form, and what bonds break?”.
Well… yes, but first, let’s start with arithmetic.
Back in first grade, your teacher might have given you questions like this:
4+ 2 = ?
3 + 5 = ?
And you got more and more comfortable with answering those questions. But then, one day, your teacher threw you a curveball.
3 + ? = 9
The first time you saw this it might have looked weird. But then you learned that you could solve them by moving the 3 over to the right hand part of the equation (making it negative) and then solving it that way.
? = 9 – 3
Believe it or not, we can apply this lesson to organic chemistry questions.
NOW we start with “what bonds break, what bonds form?” (it’s inevitable, I know).
Every time they learn a new reaction, I tell my students to ask themselves what the “pattern” of bonds forming and bonds breaking for a given reaction is. Here’s the Wittig reaction, for instance. (The same pattern applies for every Wittig reaction)
Now there’s a reason why I tell my students to focus on “bonds formed” and “bonds broken” a lot. I do it not only because it’s a simplifying way of looking at reactions, but it also works in the reverse direction.
So once you’ve learned a reaction in the forward direction, reverse that pattern. This is how you’d go “backwards” from a product, to give you back the starting material. Every “bond formed” becomes a “bond broken” and vice versa.
Next, try apply this pattern to different products. In the example of the Wittig reaction provided below, try drawing different alkenes, and applying the “pattern” of the Wittig to give you back different ylides and aldehydes (or ketones).
The more you practice, the better you’ll get.
Getting comfortable with thinking about reactions in the backwards direction is going to be a really valuable skill for doing synthesis.
P.S. You might have noticed that there’s more than one way that the alkenes above could be made using the Wittig reaction. Make a note of these reactions for which this is true; it will come in handy when planning a synthesis.