Initials______________
Chemistry 634, Fall 2010
Midterm Exam
Prof. Donald Watson
300 points (3 hours)
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•
•
•
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Closed note, closed book. No calculators allowed. You may use a molecular
model set.
Answers should be written in boxes provided. Other markings will not be
considered. Scratch paper can be found at the back of the exam packet.
Please initial each page at the top.
Points will only be awarded for clearly communicated answers.
Please make sure you have all pages of the exam packet.
Name _______________________________________
Question 1: ________/50
Question 2: ________/50
Question 3: ________/25
Question 4: ________/25
Question 5: ________/10
Question 6: ________/15
Question 7: ________/15
Question 8: ________/45
Question 9: ________/15
Question 10: _______/25
Question 11: _______/25
_____________________
Total:_______/300
Page 1/20
Initials______________
1) (50 points, 5 points each) Predict the expected major product for each reaction
sequence after aqueous work-up, drawing your answer in box provided. Denote
stereochemistry where needed. If no reaction is expected, state so.
1) MsCl, Et3N
2) NaN3, DMF
3) BH3•SMe2, TMSOTf
OH
O
O
Et
O
O
Et
C12H21N3O4
OMe
MeO
1) LiAlH4
2) (COCl)2, DMSO, Et3N
O
OEt
MeO
O
i-Pr
EtMgBr, MgBr2
Me
MeO Me
I
i-PrMgBr, –20 °C;
then n-PrCHO
MeO2C
ZnCl
Me
Me
Me
Cl
Pd(t-Bu3P)2
100 °C
THF/NMP
Page 2/20
Initials______________
Question 1 continued
OMe
MeO
OH
DIAD, PPh3, rt
NH2
MeO
Me
OH
1) TPAP, NMO
2) CH2=CHMgBr (1 eq)
OH
OH
OTBS
C19H32O4Si
Me
Ph
O
N
OH Me
LiHAl(OEt)3
Ph
n-Bu
MeO2C
Me
OAc
O
CO2Me
NaH, cat. Pd(PPh3)4
Me
Me
O
NaNH2 (2 eq);
then BnBr (1 eq)
O
_______/50 points
Page 3/20
Initials______________
2) (50 points total, 5 point each) Provide the necessary reagent(s) to provide a high
yielding transformation. Write your answer in the box provided. Be mindful of
stereochemistry, if specified. Note, for each scheme more than one step may be
required (unless otherwise noted). If more than one step is proposed, please indicate
clearly.
O
O
Cl
Cl
O
O
HN
Me
O
Cl
Cl
Cl
Cl
HN
Me
Me
Me
Me
OH
O
Me
O
Me
OMe
Cl
Me
Me
O
OMe
MeO
MeO
H
N
Me
OMe
Me
OMe
NO2
O
H
TBSO
Cl
OH
O
OH
O
O
O
O
NO2
O
H
O
Me
OH
O H
H
O
TBSO
Me
O
Page 4/20
Initials______________
Question 2 continued.
O
O
OH
N
H
Me
HO
OH
NH2
Me
TBDPSO
Ph
NH
O
MeO2C
OH
O
NH
MeO2C
Me
NH
Me
Me
Me
O
OAc
Me
O
Me
O
OTBS
OTBS
OMe
OMe
______/50 points
Page 5/20
Initials______________
3) (25 points) Shown below is a synthetic sequence from taken from Corey’s synthesis
of (±)-Ginkolide B (JACS 1988, 110, 649). In the boxes below, please provide the
missing reagents and intermediates required for making this process viable.
O
O
OMe
O
HCl, reflux
OMe
N
OMe
then HCl
OMe
3 pt
3 pt
3 pt
2 pt
OTMS
OMe
t-Bu
OMe
O
4 pt
3 pt
O
OMe
TiCl4
t-Bu
H
O
O
O
Me
O
O
O
Me
OMe
O
t-Bu
2 pt
5 pt
______/25 points
Page 6/20
Initials______________
4) (25 points) Shown below is a synthetic sequence from taken from Kerr’s recent paper
on the synthesis of (+)-Isatisine A (JOC 2010, 75, 6830). In the boxes below, please
provide the missing reagents and intermediates required to making this process viable.
3 pt
O
5 pt
O
N
Ts
MeO2C CO2Bn
2 pt
PPh3, allyl alcohol
DIAD, THF
3 pt
O
OTBS
N
Ts
MeO2C CO2Bn
2 pt
O
10 pts
OTBS
N
Ts
MeO2C CO2Allyl
O
N
Ts
MeO2C
OTBS
______/25 points
Page 7/20
Initials______________
5) (10 points, 2 points each) Using your knowledge of pka’s, predict the product(s) and
equilibrium constant for each reaction.
BuLi
Br
Keq =
t-BuOK
O
tBuO
Me
Keq =
iPr
BuLi
NH
iPr
Keq =
LDA
O
Ph
Me
Keq =
Et3N
O
Me
OH
Keq =
______/10 points
Page 8/20
Initials______________
6) (15 points) In the spaces below, predict the product of the following reaction. Draw a
detailed mechanism to explain its formation. Label all elementary steps and show
stereochemistry for product and all intermediates, as applicable.
cat. Pd(OAc)2, cat. PPh3
Et3N, rt, MeCN
O
I
product (5 pts)
mechanism (10 pts)
_____/15 points
Page 9/20
Initials______________
7) (15 points) In the spaces below, predict the product of the following reaction. Draw a
detailed mechanism to explain its formation.
H
OH
O
O
Me
1) NaH, CS2; then MeI
2) AIBN, Bu3SnH
O
O
product (5 pts)
mechanism (10 pts)
______/15 points
Page 10/20
Initials______________
8) (45 points, 15 points each) For each of the following and in the spaces provided,
predict the product of the reaction and provide a model to explain the expected
stereoselectivity.
O
Me
LDA (kinetic), THF -78°C; then TBSCl
OMe
product (5 pts)
model (10 pts)
O
Me
LDA (kinetic), THF/HMPA -78°C; then TBSCl
OMe
product (5 pts)
model (10 pts)
Page 11/20
Initials______________
Question 8 continued
OH
Et2BOMe, NaBH4, –78 °C;
then H3O+ workup
O
n-Bu
n-Bu
product (5 pts)
model (10 pts)
____/45 points
9) (15 points) The reduction of α-hydroxyketones with Zn(BH4)2 favors the formation of
1,2-anti diols (as shown below). In the space below, using clearly drawn diagrams and
less than 10 words, please rationalize this result.
OH
Me
iPr
O
Zn(BH4)2
Et2O, 0 °C
OH
Me
iPr
OH
96
OH
+
:
Me
iPr
OH
4
____/15 points
Page 12/20
Initials______________
10) (25 points) Using a maximum of 10 steps, propose a synthesis of 2 using the given
starting material (1) and any other commercial or readily accessible reagents.
Me
Me HO Me
O
Me
OMe
1
Me
Me
Me
(±)–2
______/25 points
Page 13/20
Initials______________
11) (25 points) Using a maximum of 10 steps, propose a synthesis of 5 using the given
starting materials (3 and 4) and any other commercial or readily accessible reagents.
NH2
+
HO
O
3
O
BrMg
OBn
4
MeO
O
5
______/25 points
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Initials______________
This page provided for scratch paper. No answers on this paper will be graded.
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