A copy of the Level III (FHEQ Level 6) Equation and Data Sheet booklet
is provided.
The use of hand-held, battery-operated, electronic calculators will be
permitted subject to the regulations governing their use which are
displayed outside the examination room.
The type of calculator used must be specified on the cover sheet of your
answer book.
KEELE UNIVERSITY
EXAMINATIONS, 2014/15
LEVEL III (FHEQ LEVEL 6)
Wednesday 14th January, 09:15 – 11:15
CHEMISTRY/MEDICINAL CHEMISTRY
CHE-30039
ADVANCED ORGANIC CHEMISTRY
Section A – Answer ALL questions
Section B – Answer THREE Questions
NOT TO BE REMOVED FROM THE EXAMINATION HALL
CHE-­‐30039 Page 1 of 11 SECTION A – ANSWER ALL QUESTIONS
1. (a) Silicon substituents are often used as protecting groups in synthesis.
Identify three properties of an ideal protecting group.
(3 marks)
(b) A non-expert in organosilicon chemistry drew the following mechanism
to explain the fluoride promoted deprotection of the tertbutyldimethylsilyl (TBS) group in 1:
Using your knowledge of silicon chemistry, explain why this
mechanism is incorrect and draw the correct mechanism for the
conversion of 1 into 2.
(5 marks)
(c) The TBS protecting group proved unstable when 1 was subjected to
concentrated acid. Suggest an alternative silicon protecting group which
would be more stable under acidic conditions, and indicate why your
choice is more suitable.
(2 marks)
CHE-­‐30039 Page 2 of 11 2. Two metal carbenes, 1 and 2, are shown below:
(a) Identify the class of carbenes each belongs to, and in each case, explain
your answer.
(4 marks)
(b) Rhodium carbene 4 can be prepared from the reaction of ethyl
diazoacetate, 3, and Rh2(OAc)4. Draw a mechanism to show how this
occurs - you may use LnRh to abbreviate rhodium and its other ligands.
(3 marks)
(c) Triene 5 was subjected to ring closing metathesis (RCM) using the
Grubbs G2 catalyst. Despite the potential to form more than one
product, a single product was obtained from the reaction. Predict the
structure of the product obtained, explaining your choice – no
mechanism is required.
(3 marks)
CHE-­‐30039 Page 3 of 11 3. (a) Suggest suitable syntheses of both 2 and 3 that begin with the alkene 1,
using any reagents required. No explanations are required.
(5 marks)
(b) An alternative method to prepare 3 is from a ruthenium catalysed
transfer hydrogenation reaction from the ketone 4. Briefly, outline the
advantages and disadvantages that transfer hydrogenations provide over
conventional hydrogenation and suggest two suitable donors that could
be used to reduce 4 into 3.
(5 marks)
CHE-­‐30039 Page 4 of 11 4. (a) Draw structures for the missing intermediates 3 and 4 in the following
synthetic sequence. Your structures should specify relative
stereochemistry.
(4 marks)
(b) Draw structures for the missing intermediates 7, 8 and 9 in the following
synthetic sequence. Your structures should specify relative
stereochemistry.
(6 marks)
CHE-­‐30039 Page 5 of 11 SECTION B – ANSWER THREE QUESTIONS
5. (a) Triphenylphosphine (PPh3) is a much stronger nucleophile than
triphenylamine (NPh3). Using a suitable diagram, explain this
observation.
(4 marks)
(b) The scheme below shows the reactions of sulfur ylides:
(i) Provide suitable reagents 1 and 2 to complete the reactions shown.
(2 marks)
(ii) Identify product 3 and draw a mechanism to show its formation.
(4 marks)
(c) When alkene 4 was subjected to a selenolactonisation reaction with
benzeneselenenyl bromide two products, 5 and 6, are formed. Separately
5 and 6 were each reacted with 1 equivalent of m-CPBA. 5 formed
product 7 with the molecular formula shown, whereas 6 gave two
products, benzeneselenenic acid and a second product, 8, which
contained no selenium.
CHE-­‐30039 Page 6 of 11 (i)
Identify the two selenolactonisation products, 5 and 6, and draw a
mechanism to illustrate the formation of either 5 or 6.
(4 marks)
(ii) Identify products 7 and 8 and fully explain the difference in
reactivity observed.
(6 marks)
CHE-­‐30039 Page 7 of 11 6. (a) When vinylmagnesium bromide, 1, and aryl iodide 2 are reacted in the
presence of a nickel catalyst, a Kumada cross-coupling reaction occurs
to afford the alkene product 3:
(i)
The active catalyst for this reaction, the 14 electron species
(PPh3)2Ni0, is generated by reduction of the pre-catalyst
(PPh3)2NiIICl2 with 1. Show how the active catalyst is generated by
consecutive transmetallation and reductive elimination reactions.
(3 marks)
(ii) The catalytic cycle for the reaction is given below:
Identify the structures of the catalytic intermediates 4 and 5, and
for both species determine: the number of valence electrons, and
the formal oxidation state of the nickel.
(4 marks)
CHE-­‐30039 Page 8 of 11 (iii) For each of the three reactions shown below, identify the structures
of the expected products 6-8 (no further detail is required):
(3 marks)
(b) When phenyl iodide and ethyl (Z)-but-2-enoate are reacted together in
the presence of a palladium catalyst and triethylamine, a Heck reaction
takes place to generate a new alkene 9:
Given that the active catalyst is Pd0(PPh3)2, draw a full catalytic cycle
for this reaction, and thus predict the structure of product 9. Your
answer should also fully account for the regiochemistry and
stereochemistry expected in alkene 9.
(10 marks)
CHE-­‐30039 Page 9 of 11 7. (a) Draw the 4 π molecular orbitals (as combinations of p orbitals) for a
conjugated diene. Identify the HOMO and LUMO orbitals. Based on
your diagram, explain why a [4+4] cycloaddition reaction between two
conjugated dienes is not ‘symmetry allowed’ under thermal conditions.
(4 marks)
(b) Draw the kinetically preferred product of the following reaction (with
stereocentres defined), and provide a Transition-State diagram that
explains your answer. Explain the origin of the predicted
regioselectivity.
(8 marks)
(c) Using appropriate diagrams to illustrate your answer, explain why
electron rich dienes react fastest with electron deficient alkenes
(dienophiles) in the Diels-Alder cycloaddition and why electron
deficient dienes react fastest with electron rich alkenes (dienophiles) in
the Diels-Alder cycloaddition.
(8 marks)
CHE-­‐30039 Page 10 of 11 8. (a) For the following reactions, perform a ‘Woodward-Hoffman rule’
analysis to determine the stereochemistry or double-bond geometry in
the products. You should use suitable diagrams to illustrate your answer.
(2 × 7 marks)
(b) Using a ‘Frontier Molecular Orbital’ approach, with suitable diagrams to
illustrate your answer, explain why a [2+2] cycloaddition reaction
between two diene molecules is not ‘symmetry allowed’ under thermal
conditions but can take place using photochemical activation instead.
(6 marks)
CHE-­‐30039 Page 11 of 11