Name:

ID Number:

Section TF:

Important Notes:

1. This exam consists of 11 problems on 14 pages, plus this cover sheet, and two pages for scratch work
at the end of the exam.

2. All answers must be written in the spaces provided. Do not write anything in red ink. Answers
written on the back of a page will not be graded. Anything written on the scratch pages will not be
graded.

3. You are allowed to use a set of molecular models for this exam.

Problem Score Problem Score

1. ____________ / 16 7. ____________ / 20

2. ____________ / 16 8. ____________ / 20

3. ____________ / 16 9. ____________ / 20

4. ____________ / 18 10. ____________ / 18

5. ____________ / 20 11. ____________ / 20

6. ____________ / 16
Total Score:

______________
/ 200
Organic Chemistry 2 (CHEM 30) for Bolero 1 Name:

Question 1. Fill in each box with a starting material that would provide the product indicated by the
transformation. (For full credit, you will need to use each of the indicated reagents in a meaningful way.)

1. SOCl2 CbzHN NHBoc

Me
H TiCl4
O OH
(b) Me
Me
Me
(+/-) Me

1. LDA, – 78°C
2. TMSCl
(c)
3. Me
O

HO (+/-)

1. NaOMe, MeOH
2. Me2CuLi
3.
MeO2C
I
SnBu3
(d) 4. LDA, –78 °C MeO2C
5. Tf2O H Me
6. cat. Pd(PPh3)4
7. MeO2C CO2Me (+/-) Me

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Organic Chemistry 2 (CHEM 30) for Bolero 2 Name:

Question 2. Each of the following transformations can be carried out in no more than three steps. Fill in
the reagents required for each step.

O
OH
(a)
OH

S S
(b) O

HO

(c)
Me O Me
HO

H H

(d)
O
O O H H O

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Organic Chemistry 2 (CHEM 30) for Bolero 3 Name:

Question 3. Fill in each box with the major organic product of the indicated transformation. Be sure to
indicate stereochemistry if it is relevant.

O O
(a) Ph H

MeO Me H
N
, HOAc

Me Me
Me Me O
N
O O H
B
(b) Br

cat. Pd(PPh3)4, NaOH

1. NH2OH•HCl
(c)

2. TsCl, Et3N
H2O,

HN 1. H+
(d)
OH
2.

_______ / 16
Organic Chemistry 2 (CHEM 30) for Bolero 4 Name:

Question 4. Alkylation of 1 results in a 99:1 mixture of diastereomeric products 2 and 3.

(a) Fill in the boxes below with the structures of 2 and 3:

O O

Me
1. LDA, -78 °C
O N
2. BnBr
i-Pr

2 3
1 minor major
1 99

(b) In the axes below, draw a free energy diagram of this alkylation. Your diagram should include 2 and 3,
with the enolate derived from 1 in the middle. Clearly indicate the relative energy levels of the transition
states leading each product, and indicate the energy diffence responsible for the diastereoselectivity.

(c) Based on the observed diastereoselectivity and the energy difference you indicated in part (a), estimate
the difference in energy (kcal/mol) between the transition states leading to the major and minor diastereomer.
Organic Chemistry 2 (CHEM 30) for Bolero 5 Name:

Question 5. Many scientists believe that in an early stage in the origin of life, RNA (rather than DNA) was the
polymer which stored genetic information. In 2009, a team of researchers discovered a pathway by which
ribocytidine__one of the four nucleotides found in RNA__might have been synthesized from simple abiotic
precursors (M.W. Powner et al., Nature, 459, 239). In particular, they synthesized the following activated
cyclic phosphate ribocytidine:
NH2
OH
O N N

O
O O
P
O O

activated ribocytidine

You can work through the pathway they reported with some guidance. (Note: Each of the three parts of
this question can be answered independently of each other.)
(a) The pathway begins with 2-aminooxazole, which reacts with glyceraldehyde to form intermediate A.
Provide a complete curved-arrow mechanism for this transformation. You do not need to worry
explicitly about stereochemistry.
OH
OH
N O
HO O cat. H+ N
+
NH2
O NH2
H HO O

Glyceraldehyde 2-aminooxazole Intermediate A

(b) Intermediate A is then treated with a Michael acceptor to form cationic intermediate B. Using the
molecular formula to guide you, provide the structure of the Michael acceptor in the box below, and
then provide a complete curved-arrow mechanism for the transformation of A into B.

OH OH
O O
N N
NH2
NH2 cat. H+ N
HO O O
HO
Intermediate A Intermediate B

Note: There are a number of closely-related mechanics that would be equally acceptable.

(c) One of the hydroxyl groups in intermediate B becomes phosphorylated to form intermediate C (you
need not worry about how this occurs). Finally, intermediate C is converted to the activated
ribocytidine. Draw in the curved arrows for this single-step transformation.
OH NH2
O OH
N O N N
NH2
N
O O
O
O
O O
P
P
O O
O O
Intermediate C Activated ribocytidine

_______ / 20
Organic Chemistry 2 (CHEM 30) for Bolero 7 Name:

Question 6. Consider the following three-component coupling reaction.

Br
MeO2C cat. LnPd0 MeO2C
+ +
Ph
NEt3 H
(+/-) H
(a) Provide a complete mechanism for all steps in this transformation. Annotate each organometallic
transformation precisely and always include the oxidation state of the metal. You do not need
to show curved arrows or draw a catalytic cycle.

(b) The following two-component coupling was attempted under the same reaction conditions. However,
this reaction did not afford 2-phenylnorbornene (illustrated below). Instead, an isolable organopalladium
product was obtained. Predict the structure of this product, and provide mechanistic reasoning to
explain why 2-phenylnorbornene was not observed.
Br
cat. LnPd0
+ (+/-)
NEt3
Ph
2-phenylnorbornene
not observed

_______ / 16
Organic Chemistry 2 (CHEM 30) for Bolero 8 Name:

Question 7. Vitamin D is synthesized in your skin, using sunlight, from 7-dehydrocholesterol, a derivative of
cholesterol. The light-induced transformation affords pre-vitamin D3, which is then converted thermally to
Vitamin D3. Provide the two-step mechanism, classifying in detail both transformations.

h
H

H H

HO

7-dehydrocholesterol Vitamin D3
HO

_______ / 20
Organic Chemistry 2 (CHEM 30) for Bolero 9 Name:

Question 8. You learned in lecture that, unlike aldehydes and ketones, amides are not electrophilic
enough to undergo Wittig reactions. In this problem, we explore two special, more reactive amides which
do undergo Wittig reactions.

(a) Weinreb amides react with phosphonium ylides to produce ketones (J.A. Murphy et al., Org. Lett., 7, 1427).
Provide a complete curved-arrow mechanism for this two-step transformation.

O
O
OMe 1. H2C PPh3
Ph N
2. H3O+ Ph CH3
CH3

(b) In two sentences or less, explain why Weinreb amides are reactive enough to undergo Wittig reactions
whereas normal amides are not.
Organic Chemistry 2 (CHEM 30) for Bolero 10 Name:

(c) The amide shown below also undergoes a Wittig reaction when treated with a phosphonium ylide (A.J.
Kirby et al., Angew. Chem. Int. Ed., 37, 785). Explain why this is the case, and provide a clear drawing to
support your answer.

O
N N
H2C PPh3
H3C CH3 H3C CH3

H3C H3C

_______ / 20
Organic Chemistry 2 (CHEM 30) for Bolero 11 Name:

Question 9.Provide a multistep synthesis forbrevicomin using the indicated starting material and any additional
organic and inorganic reagents. Be sure your synthesis accounts for the relative stereochemistry of the
product. The best answer will require eightor fewer steps.

CH3

CH3

Starting Material

CH3
O
H
O
CH3
H
(+/-)
Brevicomin
Desired Product

_______ / 20
Organic Chemistry 2 (CHEM 30) for Bolero 12 Name:

Question 10. Provide a complete curved-arrow mechanism for the following transformations, and classify
any pericyclic reactions. (Hint: it will be helpful to draw this mechanism in 3-D).

R1
R1 OH
R2 toluene R3
O
R2
Me R3

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Organic Chemistry 2 (CHEM 30) for Bolero 13 Name:

Question 11. In this question, you will work through part of a recent total synthesis of the natrual product
spirotryprostatin A, reported by the Fukuyama lab.

Provide a multistep synthesis of the spirotryprostatin A precursor shown below, using the given starting
materials as your only source of carbon atoms. You may use any other organic and inorganic reagents, and
you do not need to worry about stereochemistry. The best answer will require 7 or fewer steps.

O N
Br
H H

N O
MeO MgCl

Me
OTBS
Starting Materials

O N

H H

N O

N O
H
MeO
spirotryprostatin A
precursor
Organic Chemistry 2 (CHEM 30) for Bolero 14 Name:

(b) Intermediate I was then converted into Intermediate II, which was carried on to the final product
spirotryprostatin A. Fill in the box with the missing reagents for converting Intermediate II to
spirotryprostatin A. You do not need to worry about stereochemistry. The best answer will require 5 or
fewer steps.

O N O N

H H H H

N O N Me O
OH
H
Me
NHBoc

N O
H
MeO
Intermediate I Intermediate II
MeO

O N

H H

N O
O Me

Me
HN

OMe
spirotryprostatin A

_______ / 20