Cycloadditions Pt4

Question 1

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

Answer 1

• 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

Question 2

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

Answer 2

• 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

Question 3

• Trans- (or E-) dienophiles lead to….
• Cis- (or Z-) dienophiles lead to…

Answer 3

• Trans- (or E-) dienophiles lead to trans-cycloaddition products
• Cis- (or Z-) dienophiles lead to cis-cycloaddition products

Question 4

Why are Diel-Alder cycloadditions stereospecific?

Answer 4

• 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

Question 5

For a successful cycloaddition reaction the diene must be able to adopt a….

Answer 5

s-cis conformation (note: s-cis means single bond-cis)

Question 6

What is the product of this diels alder reaction with a diene and an alkyne?

Answer 6

Question 7

What is the differences between these two diels-alder reactions?

Answer 7

• Large steric clash between phenyl and hydrogen groups for the s-trans favoured
• Differences in speed
• Differences in sterochemistry

Question 8

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

Answer 8

• The hydrazone and alkene are conjugated (simiar to a butadiene)

Question 9

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

Answer 9

• This reaction works as almost an elimination reaction where we lose a dimethylamine
• Results in the formation of a pyridine product

Question 10

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)

Answer 10

• 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

Question 11

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

Answer 11

• Electron deficient heterodiene due to oxygen with an electron rich dienophile (OMe)
• Highly conjugated product is stable - driving force

Question 12

What is the mechansim for acetal hydroloysis?

Answer 12

Question 13

How can lewis acids affect Diels-Alder reactions?

Answer 13

Lewis acids can be added to accelerate a Diel-Alder reaction by modifying the HOMO-LUMO gap of the diene and dienophile

Question 14

Explain the results of this table

Answer 14

• 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

Question 15

What is the intermediate formed when using the Lewis acid

Answer 15

• 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

Question 16

Another develped catalytic method of LUMO lowering involve the use of…

Answer 16

organic molecule catalysts (i.e. organocatalysis)

Question 17

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?

Answer 17

As we can use single enantiomer chiral catalyst, it is possible to obtain enantiomerically enriched products from this process

Question 18

What is the mechanism for the following organocatalysis Diels-Alder reaction

Answer 18

• 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

Question 19

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

Answer 19

• 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)

Question 20

An example of an intramolecular hetero-Diels Alder is hexahydrocannabinol synthesis
What is the product and curly arrows mechaisms

Answer 20

• last step is forming a benzene ring
• Similar mechanisms using sulfoxide which have already learnt