Advanced Organic Chemistry: 777380

Questions:

1. Asymmetric Synthesis – Answer ALL parts

• You wish to prepare a sample of compound 1 with the R-stereochemistry at the chiral centre. You have cyclohexanone, the chiral auxiliaries 2 and 3 and benzyl bromide (PhCH2Br) available. Show how you could synthesise compound 1 from cyclohexanone and clearly show factors which are responsible for asymmetric induction. Explain why you could not use the amine 4 to produce a chiral product 1.

(10 Marks)

• Propose reasonable structures for the compounds A, B, C and D indicated below. Take care to show the absolute stereochemistry where relevant. Mechanistic detail is not

(6 Marks)

(c) Suggest a synthesis of EITHER compound 5 from valine OR compound 6 from compound 7.

(4 Marks)

2. Reactive Intermediates – Answer ALL

Identify the products produced in FOUR out of the five of the following reactions, and give a full mechanistic explanation for your reasoning.

3. Pericyclic Reactions – Answer ALL parts

• Indicate the expected product(s) of the following electrocyclic ring-closing reaction, including all stereoisomers that apply. Indicate their stereochemical relationship. Briefly justify your reasoning.

(2 + 2 + 2 marks)

• Indicate the expected product of each of these reactions and indicate with an asterisk each chiral carbon atom (you are NOT asked to specify the absolute configuration of the chiral carbon atoms, nor asked to provide a mechanism of reaction). 

1. i) Claisen rearrangement:

(2 marks)

1. ii) Oxy-Cope rearrangement (specify both tautomers and indicate the most stable of the two):

(2 marks)

• Indicate the expected product(s) of the following Diels-Alder reaction, including all stereoisomers that apply. You are NOT asked to justify your reasoning.

(5 marks)

• Consider the following sigmatropic rearrangement ([1,7]-Hydrogen shift). Test if the antarafacial migration is allowed, then determine the stereochemistry of one of its expected stereoisomer products.

(3 + 2 marks)

reference to the ‘synthon approach’ to Retrosynthetic Analysis – Answer ALL parts 

• Compare and contrast the terms “synthon” and “synthetic equivalent” using a suitable illustrative

example.

(3 marks)

• Diethyl malonate 1 can be used to synthesize long chain carboxylic acids such as 

1. Give a retrosynthetic analysis to show why 2 may be disconnected to starting materials of 1 and propyl iodide.(3 marks)

1. ii) Derive a synthesis based on this retrosynthesis, and give a full mechanism for how it operates.

(4 marks)

• Devise retrosyntheses and syntheses for the molecules shown below. Your syntheses should use starting materials that each contain no more than SEVEN carbon atoms.

Answers:

Answer 3:

1. The cyclization of a 1,3,5-triene (6 Π electron i.e. 4n + 2):

        Stereochemistry-Conrotatory (cis-product)

           I- Claisen rearrangement: This is called aliphatic Claisen rearrangement.

This reaction are called [3,3] sigma tropic rearrangement because the new sigma bond has a 3,3 relationship to the old sigma bond.

    c)

     Diels alder reaction:

1. d) Sigma tropic rearrangement ([1,7]-Hydrogen shift).

• Allowed antarafacial migration. (6 electron i.e. 4n + 2)
• Total = 1 system → Thermally Allowed

Stereochemistry- (E, S).

Question 4:

Answer (a)

 Synthon is a destructural unit within a molecule in retro synthetic analysis.

“Synthon is a fragment usually an ion produced by disconnection”.

Example: In the synthetic of phenyl acetic acid, two synthon are found.

• phCH+group
• COOH-group

Whereas synthetic equivalent is a reagent carrying out the function of synthon which cannot itself be used because it is too unstable.

In this case cyanide anion (CN^–) is synthetic equivalent for COOH^–  synthon and benzyl bromide(PhCH₂Br) is synthetic equivalent for benzyl cation.

Answer (b)

1. i) Retro synthetic analysis of compound 2:

1. ii) Synthesis of compound 2:

• Retro synthesis of compound-