1. Answer ALL parts. MW CH3B) OLD COURSE 2010 exam questions.

(a) Illustrate the frontier orbitals, in each molecule, which are involved in the cycloaddition reactions shown below.

(i) A [2+2] cycloaddition.

PhPh

Ph Ph

Ph

Ph

+

Ph

Phirradiation (hυ)

Ph

Ph

Ph

PhLUMO(ground state)

HOMO(excited state)

1 mark per molecule

[10%]

(ii) A [4+2] cycloaddition. OO

+heat

OHOMOLUMO (or alternative HOMO/LUMO

combination)

1 mark per molecule

[10%]

(b) The conversion of 1 into 2 may be achieved in a two step process. The use of photochemical irradiation results in formation of a reactive intermediate 3, which subsequently rearranges to 2 under non-photochemical conditions.

HO

Me

H

1

Photochemicalirradiation (hυ)

3HO

2

OHOHnon-

photochemical

(i) Identify the structure of intermediate 3.

HO

Me

3

OH

2 marks

[10%]

(ii) Write a mechanism for each step of the reaction above, and describe the type of pericyclic reaction that is taking place.

HO

Me

H

1

Photochemicalirradiation (hυ)

3HO

2

OHOHnon-

photochemical

HO

Me

H

1

Photochemicalirradiation (hυ)

HO2

OH

OHnon-photochemical

HO3

OH

antarafacial6 e process

H

antarafacial, 8 e process

1 mark for each mechanism and 1 for each process description.

[20%]

(c) Provide a mechanism for the following reaction and identify the product 4.

i) Et3N (a base)

ii)O

ClCl

ClH4

O

ClCl

ClH

Et3N

OCCl

Cl

OClCl

H

H

OCCl

Cl [4+2] cyclisation favoured because two pi systems on the ketene are involved.(covered in detail in lectures)

1 mark for step 1, 2 marks for step 2, 2 marks for explanation.

[25%]

(d) Account for the stereochemistry of the product 5 formed in the sigmatropic rearrangement shown below. Your answer should include an illustration of the transition state of the reaction.

PhO

Phheat O

Ph

Ph5

PhO

Ph

via

OPh

Ph5

OPh

Ph

OPh

Ph

OPh

Ph

[25%]

2. Answer ALL parts.

(a) The synthesis of the alkaloid Pulimiotoxin C may be achieved through the reaction sequence illustrated below, which proceeds via the formation of intermediate 6.

O

heat+

NH

OBn

ONH

H

O

BnO O6

stepsPumiliotoxin C.

(i) Account for the control of the regiochemistry of 6 in the cycloaddition.

O

NH

OBn

Oδ−

δ−

δ+ δ+

The electron donating N group and electronwithdrawing C=O create complimentary areasof positive and negative electron density.

2 marks for diagram , 1 mark for explanation.

[15%]

(ii) Draw a transition state for the cycloaddition reaction, and thus predict the relatively configurations of the three chiral centres in 6.

O

NH

BnO

O

LUMO of dienophile alignswith HOMO of diene.Endo transition state due to secondary orbital overlap.

CHO

NHCO2Bn

3 marks for diagram, 2 for explanation.

[25%]

(iii) The use of a Lewis acid increase the rate of the cycloaddition reaction. With aid of appropriate energy level diagrams, explain why?

O Lewis acid co-ordinates to C=O, lowering LUMO energy and giving better overlap with diene HOMO

LAdiene HOMO

LUMO+LA

LUMO no LA

2 marks for energy level diagram, 2 marks for explanation.

[20%]

(b) The reaction of hydroxylamine 7 with aldehyde 8 results in the formation of a reactive intermediate 9. Intermediate 9 subsequently undergoes a reaction with styrene 10 to give the product 11.

NH

OHPh +

7

OPh

8

9Ph

NOPh

Ph

Ph

1110 (i) Propose a structure for 9, and provide a mechanism for its formation.

NO

Ph

Ph

N attacks C=O and then elimination of water.

1 for product and 2 for mechanism.

[15%]

(ii) Illustrate the mechanism of the reaction of 9 with 10 to form 11.

(iii)

NOPh

Ph

Ph

11

NOPh

Ph

Ph 2 mark for mechanism.

[10%]

(c) Explain why the reaction below fails under basic conditions, but gives a product in 100% yield under acidic conditions. Provide a mechanism for the successful cyclisation.

O

O

OMe

HO

O

OMe

Using NaOH; 0% yield.

Using HCl; 100% yield.

The base catalysed process requires a disfavoured 5-endo-trig reaction (2 marks) whilst the acid catalysed reaction involves protonation of the C=O and rearrangement to structure below, which cyclises via a favoured 5-exo-trig cyclisation (3 marks), the mechanism of which should be illustrated.

HO

OH

OMe [25%]

3. Answer ALL parts.

(a) Propose a synthesis of trisaccharide 12 from the three reagents 13, 14 and 15, paying particular attention to the stereocontrol of formation of each anomeric centre. Reagents should be given for each step, together with a mechanism for each step.

[80%]

OO

OH

OOHO

O

O

OMeHO

OH

OHO

OHO

O

O

O

OO

O

O

Br

Ph

Bn

HO

O

TBDMSO

OMeBnO

OBn

TBDMS=Si(tBu)Me2Bn=CH2Ph

Br

OO

OBnO

O PhTBDPS

TBDPS=Si(tBu)Ph2

Ph

Ph

12

13 14 15

O

O

OO

O

O

Br

Ph

Bn

13

Ag

Ag

O

O

OO

O

O

Ph

Bn

O

O

OO

O

O

Ph

Bn

HO

O

TBDMSO

OMeBnO

OBn

14

O

OAc

OO

O

Ph

BnO

O

TBDMSO

OMeBnO

OBn

Neighbouring group participation.

remove TBDMS with TBAF (1 mark) O

OAc

OO

O

Ph

BnO

O

O

OMeBnO

OBn

Br

OO

OBnO

O PhTBDPS15

Ag

OO

OBnO

O PhTBDPS

AgO

OAc

OO

O

Ph

BnO

O

O

OMeBnO

OBn

OO

OBnO

O PhTBDPS

TBAF to remove TBDPSthen hydrogenation to remove Bn groups

12

2 marks

2 marks (mechanism)

2 marks 2 marks (mechanism)

2 marks

Anomeric control

1 mark

2 marks forexplanation ofanomeric control

2 marks for explanation of anomeric control.

(b) Predict the structure of the product X from the cycloaddition reaction shown below, and give a mechanism for its formation.

[20%]

N+ EtO2C CO2Et heat

X

N

EtO2C CO2Et X

N

EtO2C CO2Et

H H

2 marks for product and 2 for mechanism.

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