Conjugate additions Flashcards
How does an alkene react with a nucleophile?
Electrophilic addition followed by nucleophilic addition
What affect does having an heteroatom substituent on an alkene do for electrophilic substitution
- It can enhance the nucleophilic states by using LP to mesomerically donate electron density to the alkene
- Results in an increased rate of reaction and can react with a wider range of electrophiles
How do carbonyls react with nucleophiles?
- electron poor sp² carbon accepts LP from Nucleophiles forming a new covalent bond
- Nucleophilic addition
How does a carbonyl compound with a good leaving group react with a nucleophile
- Electron poor sp² carbon accepts a LP from the nucleophile
- This boots of the leaving groups, hence sp² hybridisation remains
- Now a nucleophilic substitution
What are the two biggest factors which come into play in carbonyl chemistry?
- Electronics (the influence of attached functional groups, including resonance)
- Sterics (repulsion of reacting molecules)
Alkenes can be described as ……. nucleophilic
Weakly
When Alkenes react with electrophile, which orbital is used?
The HOMO is used to attack the electrophile
How can sp² hybridisation be returned when an alkene reacts with a nucleophile
- A C-H bond breaks at the tertiary centre, reforming the C=C bond
What affect do electron withdrawing groups have on alkenes?
They lower the LUMO (π’) of the alkene
Which stabilises the anionic intermediate
Name some electron withdrawing groups
- CO₂R
- SO₂R
- CN
- NO₂
How does an alkene react with a nucleophile when it has an electron withdrawing substituent?
- Attack of the sp² carbon by the nucleophile
- Then PT from the Nu to the carbanion
How do the following two compounds react?
- Nu attacks the sp² carbon, breaking C=C bond
- Followed by PT
What is the C=C ¹³C NMR shift for an enone vs an alkene and why?
enone = 143-124ppm
alkene = 132-119
Due to the deshielding effect of the electron withdrawing carbonyl
What is the IR peaks for an enone vs and alkene and why?
enone = 1675 cm‾¹
alkene = 1650 cm‾¹
higher frequency peak for enone due to the electron withdrawing carbonyl
Enones have two electrophilic sites, which ones are they
2 position and the 4 position
How does the 1,2-addition of an enone occur?
- Attack of the carbonyl carbon by Nu
- Breaking of C=O
What are some key features of the 1,2-addition of enones?
- Generally the kinetic product (fastest)
- However reverse reaction dominant if nucleophile is a good leaving group
How does the 1,4-addition of an enone occur?
- Attack by the Nu at the sp² alkene carbon
- Pushes electrons onto adjacent carbon and breaks C=O bond
- Then PT
State key features of the 1,4-addition of enones?
- Generally thermodynamic product (more stable)
- Reversible 1,2-addition allows product of 1,4-addition to accumulate
What is interesting about Cyanide?
It is a good nucleophile and a good leaving group
Why is the thermodynamic product favoured in additions of enones, even though the activitation energy is higher than the kinetic product?
Because the energy of the thermodynamic product is lower and hence more stable
(if we leave this reaction long enough, only the thermodynamic product will be formed)
How does Grignards react with a cyclic enone to form an enol (42% yield)
- Nu addition of Grignards towards carbonyl carbon
- Forms tertairy carbon intermediate, where the oxygen is protonated
How can we affect the reactivity of the reaction of a cyclic enone with grignards?
How is the nucleophile formed? (R = Me)
- Through adding copper chloride (1%)
- Nu addition of Grignards towards Copper, breaking Cu-Cl
- 2nd Nu addition of Grignards
How will the nucleophile formed from Grignards and CuCl react with the cyclic enone?
- Nu addition of methyl at sp² C=C
- Electrons transfer onto adjacent carbon and C=O bond breaks
- Then PT
- Results in a 1,4-addition rather than 1,2-addition
