Synthesis: Walkthrough of A Sample Problem
- “Initial Tails” and “Final Heads”
- 3 Ways To Make OH A Better Leaving Group
- A Simple Formula For 7 Important Aldehyde/Ketone Reactions
- Acetoacetic
- 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
- Amines
- 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
- Conformations
- Conjugate Addition
- Curved Arrow Refresher
- Curved Arrows
- Decarboxylation
- 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
- Enolates
- Epoxides – Basic and Acidic
- Evaluating Resonance Forms
- Figuring Out The Fischer
- Find That Which Is Hidden
- Formal Charge
- Frost Circles
- Gabriel Synthesis
- Grignards
- 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
- Hybridization Shortcut
- Hydroboration
- 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
- Paped
- 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
- Rearrangements
- 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
- Stereochemistry
- Strong Acid Strong Base
- Strong And Weak Oxidants
- Strong and Weak Reductants
- Stronger Donor Wins
- Substitution
- 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
- t-butyl
- Tautomerism
- 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
I recently got an email from a reader with an advanced practice problem they were struggling with.
Here’s the problem. I really hope this wasn’t for a take home exam or anything. I want to show an example of the thought process that goes into solving a synthesis problem by applying the “3 questions” method I teach.
So how do you actually apply the “3 questions” method? Here’s what I wrote back.
The first thing I’d notice is that all the groups on carbons 1 through 4 (that you’ve labelled) are the same. What’s changing is C-5 and C-6.
What’s new?
– new methyl group on C-5
– c-6 attached to an amine (NH2)
– C6 attached to a carboxylic acid.
What reactions do we know that can do each of the following
– form a C-C bond (such as C-CH3)
– form a C-NH2 bond
– form a C- CO2H bond.
Now let’s think:
CO2H can come from hydrolysis of CN
C-NH2 can come from reduction of C=N
[together these 2 steps are called the Strecker synthesis]
C-CH3 can come from alkylation of an enolate
this means C-6 used to be C=O…
because we can easily turn C=O into C=N with NH2 [typo: should have written NH3]
and we can add CN to C=N (this is the Strecker synthesis)
we can also form the enolate of C=O by treating with LDA and then CH3-Br
So we need to turn that C5-C6 double bond so that there’s a C=O at C-6.
This requires anti-markovnikov hydroboration of an alkene (BH3 then H2O2)
Then oxidize that alcohol to an aldehyde (PCC)
Part 3 is putting all those reactions together in the right order.
I’m omitting one final detail: acetone is used here too [any idea why?! ] But this shows the thought process
I hope this helps? James