Monofunctional carbonyls Flashcards
Enols, enolates, alkylation, aldols and claisen reactions
What is in enol
Form of a ketone/aldehyde. Carbonyl compounds are more stable and so are favoured over their enol and enolate forms however, they do technically exist in equilibrium
Draw the mechanism for the formation of enols under acidic and basic conditions
Check notes
Proof of the existence of enols
If a ketone sits in deuterated acid or base, the protons alpha to the carbonyl are exchanged for D
Origin of stabilisation of enolates including diagram
Enolates are four electron, three atom systems. There is a delocalisation of charge across the two terminal atoms p orbitals. Check notes for diagram
Outline the orbital image of enolates
Oxygen atom is electronegative. The HOMO is then focused on the carbon which is why reaction occurs at the terminal carbon. Check notes for wavefunction images.
What is a requirement for an aldehyde or ketone to enolise
There HAS to be an alpha proton. This proton is acidic and hence without one, the species cannot enolize.
Outline the bromination of carbonyl species
Occurs in acid, generally weak
Give the mechanism for the bromination of carbonyl species in acid
Check notes
What happens if the bromination of a carbonyl occurs under basic conditions. Give the visual equation
The initial bromination is triple and this then forms an acid in bromoform as the final product. Check notes for equation
Draw the structure for LDA
check notes
Properties of silyl enol ethers that make them useful and one drawback
They are very stable and can be easily distilled off. They are less reactive than enolates
Draw the mechanism for the formation of a lithium enolate
Check notes, uses LDA
Draw the mechanism for the formation of a silyl enol ether using a mild base
Check notes
Difference in the reactivity of a carbonyl and its enolate
The carbonyl acts as an electrophile whereas the enolate will act as a nucleophile
How do you form a non-equilibrating enolate
By adding a STRONG base
Outline the alkylation of lithium enolates
Addition of LDA to form the lithium enolate, and then the attack by the enolate on an alkyl halide. The mechanism is SN2 and so only works with primary halides due to steric hinderance
Temperature conditions for the alkylation of lithium enolates
LDA is added at -78 C and then the alkyl halide is added to 0 C
Why do aldehydes not alkylate using lithium enolates
Aldehydes are so reactive that they will begin to react with their enolate as soon as it forms. Cannot be prevented using reverse addition
How can you use LDA to overcome the ‘aldehyde’ problem. Include mechanism
You cannot just form the lithium enolate of the aldehyde, the same issue will occur. However, LDA can be added to an ester, this species then alkylated and the final ester reduced to give the aldehyde product. Check notes for mechanism
Formation of enamines
Carbonyl species and a secondary amine. Mechanism in AL notes.
Outline the mechanism for the of an enamine to alkylate a carbonyl
Check notes
When are enamines used most often?
To alkylate aldehydes. This method prevents the aldehyde enolate from reacting with itself
Why would you use equilibrating conditions over non-equilibrating conditions when forming an enolate
If there is more than one possible alpha proton position, more than one enolate can form. Under non-equilibrating conditions with a STRONG base, the least substituted enolate will form (kinetic control). If the system is allowed to equilibrate by using a WEAK base, the more stable, more substituted enolate is likely to form
How are silyl enol ethers used to gain thermodynamic control
The formation of lithium enolates required LDA, a STRONG base. This will provide the kinetic product under non-equilibrating conditions. By first creating a silyl enol ether under equilibrating conditions, and then converting to a lithium enolate, the thermodynamic enolate can be formed
Reagent for the conversion between silyl enol ethers and lithium enolates
MeLi. Forms the lithium enolate and SiMe4. SiMe3Cl when added to a lithium enolate will form the silyl enol ether
How do you undergo the addition of tertiary halides?
Friedel Crafts acylation. Can only be done using silyl enol ethers
Mechanism for an Friedel crafts acylation with a silyl enol ether and a tertiary halide
Check notes
Outline the mechanism for acid catalysed ketone condensation
Check notes
Outline the mechanism for base catalysed ketone condensation
Check notes
What is the difference in mechanism between acid and base catalysed ketone condensation
acid is an E1 mechanism, base is a E1cb mechanism
Conditions for uncontrolled cross condensation
Acid catalyst, only one reagent that can enolise, the reagent that does not enolise must be the more electrophilic of the two
Mannich reaction outline
Allows for the cross condensation between a ketone and formaldehyde.
Mannich Reaction mechanism
Check notes
Methods of controlled cross condensation
Using lithium enolates, silyl enol ethers and enamines
What do Claisen reactions involve
The reaction between an enolate and an ester as supposed to between an enolate and an aldehyde/ketone
Provide the conditions and mechanism for the self condensation of an ester
A full equivalent of base is required, acidic workup is also required as the acidic alpha proton is lost by to the EtO group. Check notes for mechanism
Why is acidic workup necessary in the condensation of an ester
The product is a beta ketone system with a very acidic alpha proton. This is easily removed by the oxide lost during the mechanism to reform an enolate. Acidic workup forms the final product
Explain anion driven regioselectivity
In esters with two possible enolates, in some instances, one of the enolates will give a product with no alpha protons. In this instance, the system will remain in equilibrium and instead, the other enolate that gives a product with alpha protons will form. The only product will be the product of the enolate that gives a system with alpha protons
Outline the Dieckmann reaction
Intramolecular cross condensation between ester groups. Reagent is treated with ethoxide
Draw the mechanism for the Dieckmann reaction
Check notes
How can you interchange between aldol and Claisen products
Both have 1,3 functionality and so, Claisen can be reduced into aldol (NaBH4) and aldol can be oxidised into Claisen
