2^ND YEAR ORGANIC PROBLEM CLASSES 2003/2004

Class 4. Prof. Henry Rzepa Pericyclic Reactions.

Class to be held at 3pm on Monday 19th January 2004 in normal tutors groups

Answers to be handed in to Prof Rzepa's office Rm 169 (C2) before 3 pm on the day of the class. Late scripts will receive no credit.

Please write your own name AND YOUR TUTORS NAME on your script.

Question 1.The following sequence is part of a biomimetic synthesis of propionate derived natural products. The tetraene ester is heated to give the tricyclic core B of the natural system, via a presumed intermediate A. Propose a structure for A (10 marks), mechanisms leading to it and B, including nomenclature (10 marks) and using your knowledge of the predicted stereochemistry of your mechanistic steps, predict what the stereochemistry is of the centre to which the ester group E is attached (5 marks).

Answer

Models

Question 2.The biomimetic synthesis of a potent microtubule-stabilizing agent involves the use of an acyclic precursor C to create the complex pentacyclic chemotherapeutic molecule F, forming seven new stereogenic centres in a fully diastereocontrolled fashion. The step C to D is a conventional macrocyclisation, whilst E to F is a simple lactonisation. Your task is the following;

to propose a mechanism and any nomenclature for the transformation D to E (it may involve more than one step, 12 marks),
to indicate the stereochemistry of the two stereogenic centres shown with a wavy line (2 marks)
to identify the five other new stereogenic centres created (5 marks),
if their stereochemistry is indicated in the diagram, to show it is consistent with the mechanism(s) you propose, giving your reasons (2 marks)
if their stereochemistry is NOT indicated in the diagram above, to complete it (3 marks). A 3D model to help you in this task is shown below.