You should allow yourself

exactly 135 minutes to take this exam.

Last Name:

SOLUTIONS

First Name:
Section TF:
Important Notes:
1. This exam consists of 12 problems on 12 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 page will not be graded.
3. You are allowed to use a set of molecular models for this exam, but NO calculators.

Name:

1. For each of the reactions shown below, predict the single major product and determine which mechanism,
SN1, SN2, E1, or E2, is operative. Be sure to indicate stereochemistry if it is relevant.

OEt

EtOH

(a)
Cl

(+/-)

Mechanism:

Br

(b)

SN 1

NaOH

Mechanism:

E2

OMe

ONa

MeI

(c)

Mechanism: SN 2

conc. H2SO4

(d)
OH

Mechanism:

E1

Name:

2. Fill in each box with the single major product of the indicated transformation. Be sure to indicate
stereochemistry clearly if it is relevant.

OAc

NaOAc

(a)

AcOH
OEt

OEt

(+/-)

Br

1. Li0 (2 equiv.), Et2O

(b)
2. H2O

(c)

1. HBr
2.

SNa

OH

(d)

H2O
H+ cat.
(+/-)

Name:

3. Provide a multistep synthesis for the desired product from homoallyl bromide, shown below. You may use
any additional organic or inorganic reagents. The best answer will require four or fewer steps.

Br

homoallyl bromide
Starting Material

NaOEt
EtO

HBr

Br
EtO

(+/-)

NaCN

CN
EtO

(+/-)
Desired Product

Name:

4. For each of the following species, provide a complete Lewis structure, showing all atoms, bonds, and
lone pairs. Then, using skeletal structures, draw the best alternate resonance structure in the other box.
Include all nonzero formal charges.
Complete Lewis Structure:

a)

Best Alternate Resonance Structure:

H
H2C

H2C

b)

Complete Lewis Structure:

Best Alternate Resonance Structure:

O
O

O
H

C
C

C
H

Complete Lewis Structure:

H
H

c)

H
B
OCH3

Best Alternate Resonance Structure:

C
H

CH3

HC

C
B

B
H

O
C
H

OCH3

Name:

5. Consider the structure shown below.

Cl

a. Provide the best possible systematic name for this compound.

3-chloro-5-methylhept-1-ene
or
3-chloro-5-methyl-1-heptene

b. Use a Newman Projection to show the lowest energy conformation of the compound around the bond
indicated in bold below. Draw your Newman projection from the vantage shown by the "eyeball" below. If
there is more than one conformation of lowest energy, draw all such conformations.

Cl

CH3

You may represent the rest of the

molecule using the "R" notation:

H3C

H
R

Name:

6. Consider the following compound, related to the chemotherapeutic drug epothilone B:

O
H2N

(E)

(R)

(S)
(R)
O

(S)

OH

a) Circle all stereogenic carbons in the molecule above, and then assign R/S and E/Z configurations
wherever necessary.
b) Identify each of the following pairs of structures as structural isomers, enantiomers, diastereomers,
identical, or none. You do not have to explain your choice.

and

MeO

OMe
OH

OH

The above molecules are:

structural
isomers

enantiomers

diastereomers

identical

none

enantiomers

diastereomers

identical

none

enantiomers

diastereomers

identical

none

and
O
O

The above molecules are:

structural
isomers

H
O

and

O
O

The above molecules are:

O
H

structural
isomers

Name:

7. Cordycepic acid, isolated from fungal growths on arthropods, is a component of traditional Chinese herbal
remedies. Naturally isolated samples were shown to have the specific rotation [ ]D = +40.3o
a) Cordecypic acid was originally reported to have the structure shown below. Why must this structure be incorrect?
CO2H
HO

OH
HO

OH

cordycepic acid
HO

Although the molecule has stereogenic centers, it

contains an internal mirror plane of symmetry as
shown and is thus achiral and meso. T his means
that the optical rotation must be 0o and the
structure that was initially reported is wrong.

CO2H

HO

OH
HO

The specific rotation, [ ]D, of an ammonium salt of myoinositol-1-phosphate (structure shown below) is +4.5o.
OH
O
HO
3
4

HO

1
6

O
P
O

OH

OH
myoinositol-1-phosphate
[ ]D = +4.5o
b) What is the specific rotation of the ammonium salt of myoinositol-2-phosphate? (Hint: Use the numbering
scheme shown above, exchanging an OH group for a phosphate group as necessary.)
HO

myoinositol-2-phosphate:

OH

HO

O
P
HO

O
OH

O
meso!
O

Myoinositol-2-phosphate contains an
internal mirror plane of symmetry as
shown and is thus achiral and meso.
T his means that the optical rotation is
0 o.

c) What is the specific rotation of the ammonium salt of myoinositol-3-phosphate?

enantiomer s!

O
P
O

OH

OH
O

OH

HO

HO

OH

HO

OH

OH
myoinositol-3-phosphate

O
P

OH
myoinositol-1-phosphate

Myoinositol-3-phosphate
is the enantiomer of
myoinositol-1-phosphate,
so it has the same
magnitude of optical
rotation, but the opposite
sign, so [ ] D = _4.5o

Name:

8. The compound below, called dihydropyran, reacts with methanol in the presence of strong mineral acid to
form Compound A. The other possible product, Compound B, is not formed at all.
OMe

MeOH
H+ cat.

dihydropyran

OMe

Compound A

Compound B
(not formed)

a) Draw a complete curved-arrow mechanism for the putative formation of Compound B.

Me
O

H
Me
Me
H

O
H

Me

H
O

OMe

b) Explain why in this case Compound A is the only product actually formed. You must provide both a
resonance explanation and an explanation in terms of the molecular orbitals involved in the intermediates.

Resonance Explanation:
Compound A results f rom reaction via a resonancestabilized carbocation, and lowering the energy of the
intermediate thus results in the pref erred reaction
pathway.

Frontier Molecular Orbital Explanation:

Compound A results f rom reaction through a
carbocation intermediate that is stabilized by a f illedempty orbital interaction with the adjacent oxygen lone
pairs:
nO 2pC
O

T he other possible carbocation intermediate lacks

any such stabilization and thus is a disf avored
pathway leading to no product.

T he carbocation intermediate leading to Compound B

can only be stabilized by hyperconjugation with the
adjacent CH bonds, which are signif icantly poorer
donors than lone pairs and thus cannot suf f iciently
stabilize the carbocation to f avor this pathway.

Name:

9. It is observed that Compounds A and B below react with potassium iodide quite readily by the same
mechanism to yield the corresponding alkyl iodides. However, Compound A reacts many times faster than
Compound B.
O
Cl

KI

O
Cl

I many times faster than

KI

Compound B

Compound A

a) Provide a curved-arrow mechanism for the reaction of Compound A with potassium iodide.
O

O
Cl

:I

b) What will happen to the rate of reaction in both cases if the concentration of KI is tripled?
T his is an SN2 reaction, which is f irst-order in both reactants, so the rate of the reaction will triple.

c) Explain briefly why Compound A reacts so rapidly by this mechanism. For full credit, you will need to illustrate
your explanation using "cartoon" orbital sketches. (Hint: consider the transition state for the reaction!)
In the SN2 transition state f or reaction of Compound A, the electrophilic carbon approaches an sp2 hybridization,
and thus possesses a vacant 2p orbital. Since overlap of f illed and empty orbitals is stabilizing, overlap of the
adjacent f illed CO orbital with the 2p orbital on carbon lowers the energy of the transition state relative to that of
Compound B, thus speeding the reaction.

O
C
I

C
H

Cl
H

10

Name:

10. You likely recall that anions of the type OH- and OR- are extremely poor leaving groups. Contrary to this
generalization, the following reaction proceeds rapidly and in excellent yield.

NaN3

O2N

N3

N3

O2N

a) Draw a curved-arrow mechanism to account for the above reaction.

O
N N N

O2N

O2N

b) Briefly explain why the reaction above proceeds so readily. For full credit, your answer should include clearly
drawn resonance structures.
Normally good leaving groups are conjugate bases of strong acids, which means that they are stable and weak
bases. T he leaving group here, although technically an alkoxide like EtO- or MeO-, is exceptionally resonancestabilized (see structures below), so its conjugate acid is actually quite strong, making it a good leaving group.

O
O

N
O

O
O

N
O

O
O

N
O

O
O

N
O

N
O

11

Name:

11. Consider the following questions.

a) In the box provided at right, provide a
complete energy-level diagram for the
molecular orbitals of the molecule A, below.

a) Energy-level diagram for the molecular

orbitals of molecule A:

H3C
S

A:

CH2

H3C

b) Molecule A reacts with an aldehyde to yield the

product shown below. In the box, add curved arrows
to show how you get from reactants to products in
each step. Draw lone pairs when necessary.
b)

____

____

____

____

____

____

____

____

____
O

H3C
S

CH2
H

H3C

CH3

CH3

*C-S+

____

*CS+

____

nC-

____

nS+

____

____

____

____

____

____

____

C-H

CH

S
H3C

CH3

____

(step 2)

____

C-S+

____

CS+

S
H3C

*CH

____

____

(step 1)

*C-H

CH3
CH3

c) The reaction shown in part (b) above takes place in two steps. For each step, identify the donor and acceptor
orbitals by name (e.g. *C-H).
Step 1:
Donor:

Step 2:

nC*CO

Acceptor:

Donor:

nO
*CS+

Donor:

d) Please draw the shapes of the HOMO and LUMO of the aldehyde in the above reaction.
HOMO:

LUMO:
H3C
O
H

H3C
H

12

Name:

12. Provide a complete curved-arrow mechanism for the following transformation.

HO
OH

conc. H2SO4

H+
HO

H2O
OH

OH

OH

:sol
H
O

OH