Enolate Chemistry Flashcards
Characteristics of an enolate
- Base with negative charge
- Pos charge on Oxygen
- Neg charge on alpha carbon
- nucleophile
- intermediate in keto-enol tautamerization under basic conditions
What favors a kinetic product?
- low temp
- large bulky base (LDA)
Tautomer definition and how it differs from resonance
- two molecules that can be easily interconverted at equilibrium
- resonance is showing two different forms of charge delocalization
Breakdown what an enol is:
- ene = C=C
- ol = OH group
Acid Catalyzed Keto-enol Tautomerism
- add strong acid, protonate carbonyl O
- goal: now to remove pos charge that discretes
- water (as weak base) removes one of the acidic alpha hydrogens
- electron (formerly bound to hydrogen) forms double bond with carbonyl carbon
- allows electrons in one of carbonyl bonds to be pushed up to oxygen
result: enol with OH
Base Catalyzed keto enol Taut
- strong base attack alpha H directly
- C=C bond between alpha carbon and carbonyl carbon
- carbonyl O is now negative, pulls proton from H to regenerate OH-
Keto vs Enol tautomerism
keto > enol by 99:1
- stabilize enol structure through resonance and H-bond
Outcome of asymmetric ketones: kinetic vs thermodynamic
Kinetic: C=C with less substituted alpha cabon
- form quickly > less stable long term
- low temp
- rapid, irreversible Rx
- strong bulkly base, less likely to go for hydrogen on alpha carbon
Thermodynamic; C=C carbonyl carbon and more substituted alpha carbon
- form slowly > more stable long term
- high temp, weaker less hinder base
- more slowly, promote reversibility
What is an aldol
- combine features of aldehyde (or ketone) and OH alcohol
Base catalyzed aldol condensation
- base removes hydrogen from aldehyde > enolate
- neg charged alpha carbon attacks carbonyl C of another aldehyde C-C
- neg charged oxygen need protonation > aldol
- spont dehydration can occur removing OH group
- strong base removes another H from same alpha carbon > C=C from alpha carbon and C-OH
- forces OH off > alpha, beta unsatured aldehyde
Acid catalyzed aldol condensation
- acid protonates carbonyl O > pos charge
- enol thru keto-enol taut
- 2nd aldehyde protonated by acid to make better nucleophile > pos charge on O
- enol > carbonyl C of activated aldehyde
- C-C alpha C of enol and carbonyl C of activated aldehyde > aldol
- typically break down into alpha, beta unsaturated aldehyde
What happens with asymmetric ketone aldol condensation?
- alpha carbons are no symmetric > two different aldol products based on two different enolates that can be produced
- both can be dehydrated into alpha, beta unsaturated ketones
- possibility of 4 different products > difficult to control
- control: use ketone without hydrogens on other alpha carbon > only one enolate form
What is a cross aldol condensation?
- aldol condensation with two diff ketones/aldehydes or one of each
- start with only one aldehyde/ketone (only hydrogen on one alpha carbon)
- LDA (strong hindered base) > rapid deprotonation > every ketone becomes enolate (neg charge)
- now add 2nd ketone/aldehyde (electrophile)
- produce very specific aldol product
- can even avoid dehydration step
What is a keypoint of enolates including how carbonyls can behave differently?
enolates can act as nucleophiles
carbonyls carbon act as electrophiles
Famous example of retro-aldol condensation?
glycolysis:
- F1,6BP > GAP + DHAP
what two sites on aldols are electrophilic?
what is this due to?
Carbonyl carbon and beta carbon
-resonance: major and minor structure, puts pos charge on beta carbon
Michael addition reaction
Substrates: Enolate and alpha, beta unsaturated aldehyde/ketone
- enolate neg > attacks beta carbon > C=C alpha carbon and carbonyl > neg charge on carbonyl O
- double bond is removed, during protonation which removes carbonyl O neg charge
- 2 carbonyl groups separated by number of carbons
- Michael addition: Alcohol, amine, cynade, beta dicarbonyl are nucleophile
- commonality is nuc addition to beta carbon of alpha, beta unsaturated aldehyde/ketone
Robinsinon annulation is what two reactions
michael addition > aldol condensation
Robinson annulation product
2,6 dicarbonyl of 7 carbon structure
Robinson annulation steps
- starting with end product of michael addition: 1,5 dicarbonyl
- we need an enolate > strong base pull hydrogen from terminal alpha carbon
- neg charge attack carbonyl carbon on other side: C6
- cyclic structure with carbonyl from beginning unchanged, C6 with methyl and hydroxyl
- hydroxyl can be pushed off via dehydration > alpha, beta unsaturated ketone but cyclic
what biological importance does robinson annulation have?
formation of 6 membered ring > similar to ringed structures in hormone synthesis
important takeaways from michael addition and robinson annulation:
- enolates make good nucleophiles
- carbonyl containing compounds can have several electrophilic sites
Base catalyzed keto enol Taut
- base is strong enough to attack alpha hydrogen directly and create C=C bond
- compared to acid hydrolyzed, since it wasnt protonated first this adds neg charge on oxygen
- neg charge pulls proton from water > enol
What is more predominate usu: Keto or enol?
what can stabilize the less predominate species?
Keto by a lot
- resonance and H-bonding
- also solvent, but to less extent as other two
