1,3 dicarbonyl relationship Flashcards
malonates and enones
What are malonates?
Derivatives of malonic acid (1,3 dicarboxylic acid)
What does the acidity of the protons in 1,3 species mean for base catalysed enolation
Weaker bases that will only catalyse enolation of monofunctional carbonyls will fully enolise 1,3 dicarbonyl species
Outline the conditions and mechanism for the alkylation of a malonate
weak basic conditions, see notes for mechanism
Outline the decarboxylation reaction of the alkylation product from the malonate
Acidic conditions and heated. See notes for mechanism
What makes dialkylation possible for 1,3 dicarbonyl species
The fact there are two carbonyl groups and treatment of the initial product with further base to enolise the second C=O group
Outline the mechanism and reaction for ring synthesis
Occurs in di-halide alkanes. Requires two equivalents of base (ethoxide). Mechanism in notes
What are control groups in this context?
Groups that help to acidify the alpha proton position
Examples of controls groups in this context?
Esters, nitriles or halides
What is an enone
an alpha, beta unsaturated carbonyl compound
Which named reaction forms enones from formaldehyde
Mannich reaction
Outline the reactivity of enones
Both the carbon of the carbonyl group and the terminal carbon of the alkene are electrophilic. Electrons can conjugate from the alkene to the carbonyl hence the electrophilicity of the terminal carbon. The alpha carbon is not at all electrophilic
What are the two kinds of attacks possible for enones. What do they involve
1, 2 addition/direct attack. Attack of the carbon of the carbonyl functionality. And 1,4 addition/conjugate attack/Micheal addition. Attack of the terminal carbon of the double bond.
Methods of enone attack and the thermodynamic and kinetic product?
The direct addition product is often the kinetic product whereas the conjugated product is the thermodynamic. The charge of the intermediate of the conjugated attack is delocalised across the enolate, whereas in the direct attack intermediate, charge is localised. The carbonyl product is also more energetically favourable than the alcohol kinetic product that forms when the energy of the nucleophile is too great for it to be ‘kicked’ out.
Which are more stable, C=O or C=C relative to their single bond counterparts
C=O is more stable than two C-O bonds whereas C=C is less stable than two single C-C bonds.
Which reagents tend to give mixtures of the thermal and kinetic product
Grignard
Ideal nucleophiles for Micheal attack
No charge/stabilised charge. Generally quite weak nucleophiles (SOFT)
Ideal nucleophiles for direct attack
More reactive nucleophiles with non-stabilised charge (HARD)
Which organometallic reagent ensures only the 1,4 mechanism occurs
Secondary cuprates
Outline the formation of secondary cuprates
Uses a lithium alkyl and Cu(I) salts
What do cuprates do when reacting with enones?
They alkylate the enone. Act similarly to a Grignard
What is a Michael acceptor
Species with less electrophilic carbonyls that make better substrates for Michael addition
Which cyclic compounds are particularly good Michael acceptors? Draw one
Exo-methylene compounds
Storage of reactive enones
Sone enones are so reactive they cannot be stored. As a result, other carbonyl species are added to the reaction mixuture with base, to allow for enone formation which then goes on to react with the other reagent species
Outline the reduction of enones and give the mechanism
Li/liquid NH3. Proton source (NH4Cl or +BuOH). Mechansim in notes
Why would an enone be reduced in the presence of an alkyl halide
To produce an alkylated mono-carbonyl via an enolate intermediate
What makes a good Michael acceptor
Low electrophilicity of the carbonyl, conjugation of charge across the whole species
