Cycloadditions Pt4 Flashcards
Resonances forms can be used as a simple way to identify where the largest orbital coefficients will be in the diene and dienophile
Draw the resonances forms for the following dienophile and work out the largest coefficient
- The ketone is an electron withdrawing group
- The resonance forms show that atom 2 accommodaes a cation, and atom 1 remains neutral, therefore 2 has largest coefficient in the LUMO
Resonances forms can be used as a simple way to identify where the largest orbital coefficients will be in the diene and dienophile
Draw the resonance forms for the following diene and work out the largest coefficient
- OMe is electron donating
- Resonance forms show that atom 3 accommodates an anion, and atom 6 remains neutral, therefore atom 3 has the largest coefficient in the HOMO
- Trans- (or E-) dienophiles lead to….
- Cis- (or Z-) dienophiles lead to…
- Trans- (or E-) dienophiles lead to trans-cycloaddition products
- Cis- (or Z-) dienophiles lead to cis-cycloaddition products
Why are Diel-Alder cycloadditions stereospecific?
- Because the reaction is concerted, i.e. breaking and making bonds at the same time
- Meaning there are no intermediates
- All reactions like this are sterospecific with respect to the relative configuration of the centres
For a successful cycloaddition reaction the diene must be able to adopt a….
s-cis conformation (note: s-cis means single bond-cis)
What is the product of this diels alder reaction with a diene and an alkyne?
What is the differences between these two diels-alder reactions?
- Large steric clash between phenyl and hydrogen groups for the s-trans favoured
- Differences in speed
- Differences in sterochemistry
It is also possible to perform very sucessful hetero-Diels alder reactions by incorporating heteroatoms into the diene and/or dienophile
Drawn the curly arrows and product of this reactions
- The hydrazone and alkene are conjugated (simiar to a butadiene)
It is also possible to perform very sucessful hetero-Diels alder reactions by incorporating heteroatoms into the diene and/or dienophile
Draw the curly arrows and product of this reaction
- This reaction works as almost an elimination reaction where we lose a dimethylamine
- Results in the formation of a pyridine product
It is also possible to perform very sucessful hetero-Diels alder reactions by incorporating heteroatoms into the diene and/or dienophile
Draw the curly arrows and product of this reaction
(note BF₃.OEt₂ is a lewis acid)
- Heteroatoms on the alkene component
- EDG OMe + OSiMe₃ on the diene
- Results in carbon 1 having largest orbital co-efficient
- Then treating the silyenolether into a ketone by treating it with acid
- Product is highly stable due to resonance
It is also possible to perform very sucessful hetero-Diels alder reactions by incorporating heteroatoms into the diene and/or dienophile
Draw the curly arrows and product of this reaction
- Electron deficient heterodiene due to oxygen with an electron rich dienophile (OMe)
- Highly conjugated product is stable - driving force
How can lewis acids affect Diels-Alder reactions?
Lewis acids can be added to accelerate a Diel-Alder reaction by modifying the HOMO-LUMO gap of the diene and dienophile
Explain the results of this table
- The methyl group effect of the relative orbitals coefficients of the two ends favours the para product (this is much weaker than the methoxy group)
- Hence only modest regioselectivity
- But when we add a lewis acid, you can accelerate this reaction with increased selectivity - it has decreased the HOMO-LUMO gap
What is the intermediate formed when using the Lewis acid
- The overall effect is to increase the contribution of the allyl cation to the orbital coefficient sizes AND lowers the energy of the LUMO
- Effectively increased the strength of the electron withdrawing group by adding a lewis acid
- These resonance forms provide a large contribution to the overall resonance hybrid
Another develped catalytic method of LUMO lowering involve the use of…
organic molecule catalysts (i.e. organocatalysis)
This method of organocatalysis involves the insitu preparation of iminium species via reaction of secondary amine catalyst with a carbonyl comound
Explain the sterochemistry of the product?
As we can use single enantiomer chiral catalyst, it is possible to obtain enantiomerically enriched products from this process
What is the mechanism for the following organocatalysis Diels-Alder reaction
- The diene reacts with the iminium ion on its least hindered face
- In the example shown this is the ‘back’ face as the front face is shielded by the benzyl (PhCH₂) group
Hint: ΔG‡ = ΔH‡ - TΔS‡
How can intramolecular reactions allow you to ‘order’ the transition state?
Why does the “endo rule” not apply in this case
- Intramolecular reactions allow you to “order” the transition state without costing too much in ΔS‡ terms
- This means that intramolecular cycloadditions can be performed on “unfavourable” substrates
- The “endo rule” does not apply as the strain energy (in ΔH‡ term) is too much to allow an endo-transition state to be favoured)
An example of an intramolecular hetero-Diels Alder is hexahydrocannabinol synthesis
What is the product and curly arrows mechaisms
- last step is forming a benzene ring
- Similar mechanisms using sulfoxide which have already learnt
