a n s w e r s - webhome < main < foswiki · 2013-08-23 · chem 330 final exam p. 3 of 12 2....
TRANSCRIPT
CHEM 330
Final Exam December 11, 2007
Your name:
This a closed-notes, closed-book exam
The use of molecular models is allowed
This exam contains 12 pages
Time: 2h 30 min 1. ________ / 20 2. ________ / 20 3. ________ / 30 4. ________ / 40 5. ________ / 30 6. ________ / 40 7. ________ / 30 8. ________ / 40 TOTAL ________ / 250 = ________ / 100
This exam counts for 45% of your CHEM 330 final grade
A N S W E R S
Chem 330 final exam p. 2 of 12
1. (20 pts.) Write a chemical equation to show an example of the following reactions (do not write mechanisms – just the reactions). a. Baylis-Hillman reaction:
O
H
O
OMe
N
N
cat.
+
O
OMe
OH
b. Prasad Reduction:
O
Ph
OHNaBH4
Et2BOMe
OH
Ph
OH
c. Cannizzaro reaction:
CHOAq. NaOH
(then H+)
CH2OH COOH
+2
d. Mukaiyama aldol reaction:
O
Ph
OSiMe3 OH
Ph
O+
BF3
e. Swern oxidation:
R–CH2–OH R–CHO
DMSO
(COCl)2
thenEt3N
Chem 330 final exam p. 3 of 12
2. (20 pts.) A highly stereoselective reaction ensues when compound A below is treated with 1 equivalent of ZnCl2, followed by cyclopentadiene. The result is product B. (i) Draw the structure of B in the box; (ii) Sketch an approximate transition state structure that accounts for the observed stereoselectivity.
CO–Xc
Me
H
H
ON
O
O
ZnCl2, then
cyclopentadiene
A
B approximate transition state structure:
O
NO
O
Me
H
Cl2Zn
4!s + 2!s endo
H
secondaryorbitalinteraction
Chem 330 final exam p. 4 of 12
3. (30 pts.) Complete the reaction diagram shown below by indicating all missing reagents / products. Each box corresponds to one reagent / product. Note: aqueous workup steps are understood and are not to be included in your answers.
MeO
O 1.
2.MeO
OO
OEt
(together)
MeO
O COOEtCHO
LDA
EtO–CO–CN DBU
CHO
(together)
MeO
O COOEtOH
CN
(together)
N
A
excess
and
N
N
CNMe3SiOTf
MeO
TMSO COOEtOTMS
CN
(together)
and
1. TBAF
COOEt
OMe
OHCN
2.
O
N
O
O
final product
B
heat
COOEt
OMe
OTMS
NC
TMSO
Pr4N RuO4
Chem 330 final exam p. 5 of 12
4. (40 pts) Check the appropriate box to indicate whether the following statements are true or false.
a. The copper atom undergoes reductive elimination in the following reaction:
Me2CuLi + 2 HBr 2 Me–H + LiBr + Cu–Br
true false
b. The following transformation may be induced by the use of MeMgBr:
Cl
O O
true false
c. Treatment of A with Li and tert-BuOH in liquid NH3, followed by allyl bromide, results in formation of B:
O Li, tert-BuOH
liq. NH3, then
CH2=CH-CH2BrA B
O
true false
d. The reaction shown below will give compound C as the major product:
COOEt
COOEt NaH,cat. EtOH
then aq. wrkp.C
O
COOEt
true false
e. The reaction shown below is a retro-Diels-Alder:
H
H
NC
NCNC
NCH
H
HH
true false
Chem 330 final exam p. 6 of 12
f. Treatment of D with NaBH(OAc)3 followed by aqueous workup yields E as the major product:
Ph
OOH
Ph
OHOHNaBH(OAc)3
then aq. wrkp.
D E
true false
g. Reaction of F with NaOMe yields compound G:
H
H
OH
H
O
F G
cat.
NaOMe
O O
true false
h. Compound H may be converted to I as follows:
H
O
H
1. LDA
2. Ph-CH2BrH
O
PhI
true false
i. Substrate and reagent in the reaction shown below are stereochemically matched:
N OMe
O OB
Bu Bu
PhMeO H
CHO
+MeO H
OH
Me
O
Xc
true false
j. Compound J forms when 1,3-cyclohexadiene reacts with maleic anhydride:
J
H
H
O
O
O
OO O
true false
Chem 330 final exam p. 7 of 12
5. (30 pts.) Provide a succinct explanation for the following experimental observations: (a) Benzoquinone A undergoes Diels-Alder reaction with butadiene selectively at the methyl-substituted double bond,
O
O
Me
OMeH
O
O
Me
OMeA
because: the Me-substituted double bond is less electron-rich (= more electron-deficient) than the MeO-substituted double bond (MeO is a more powerful electron-donating substituent than Me) (b) The Noyori copper reagent shown below adds stereoselectively to enone B to form C,
Ph
O
Cu(PBu3)2
then aq. workup
Ph
O
H HH
B C
because: the organo-Cu reagent tends to add axially to the double bond. The Ph group occupies an equatorial position (A-value ≈ 3), and this defines the conformation of the cyclohexenone. (b) Reaction of ketone D with a defect of LDA produces enolate E,
O OLiD E
0.9 equiv. of LDA
because: the initially formed kinetic enolate can equilibrate with the thermodynamic one, because leftover ketone can act as a "proton shuttle".
Chem 330 final exam p. 8 of 12
6. (40 pts) Predict the structure of the major product expected from the following reactions. Notes: (i) it is not necessary to draw mechanisms; (ii) aqueous workups at appropriate stages are understood.
O
OMe
1. LDA, THF
2.
CHO
a. TBSO
TBSO OH
COOMe
ON
OO
Bn
1. LDA
2. CH2=CHCH2Br
3. K2CO3
MeOH
b.
COOMe
1. Cy2BCl Et3N
2.
O
Ph CHO
3. NaBH(OAc)3
cPh
OH OH
O
OEt
1. LDA, THF - HMPA
2.CHO
d.OH
COOEt
Ph
OH
OMe
Xc
O
Ph CHOON
OO
MeO
1. Bu2BOTf, Et3N
2.
Me Ph
e.
Chem 330 final exam p. 9 of 12
1. 9-BBN-OTf
Et3N
2. PhCHO3. NaBH(OAc)3
O
f.
OH
Ph
OH
Og.
1. excess tBuOK, 1 equiv. of EtOOC-COOEt
2.
HN NH2
NH2N
N
COOEt
H2N
H
H
O
h.
1. LDA, then PhSeBr
2.MCPBA, then heat
3. Me2CuLi, then Et3N
and Br
H
H
O
i.
COOEt
COOEt
1. NaH, cat. EtOH
2.O
, cat. DBU
3. tBuOK COOEt
O
1.
2. excess HCHO, aq. NaOH
j.
CHO
OH
OH
Chem 330 final exam p. 10 of 12
7. (30 pts.) Indicate all the reagents that are necessary to effect the following transformations. Provide your answers as a numbered list of reagents, in the correct order, written over/under the reaction arrows, according to the format of question 6 above.
a.
O
O O
COOMeMeOH
cat. MeONa
b.H
O
H
O
Ph
1. H2N–NMe2
2. LDA
3. BnBr
4. O3
c.
O O1. TMS2NH
TMS–I
2. MeLi
3. CH2=CH–CH2Br
d.COOEt
COOEtO
COOEt1. NaH, cat. EtOH
2. MeI
e. COOEt
OHOH
Ph
H
MeH
(racemic)
1. LDA, THF-HMPA2. Ph–CHO
3. MeMgBr
f.O MeOOC
H
H
O
(racemic)
1. TMSOTf, Hüning base
2.
3. TBAF
COOMe
g.COOEt
O1. NaOH, then H+
2. Conc. H2SO4
3. LDA, then PhSeBr
4. MCPBA, then heat
5. Bu2CuLi
Chem 330 final exam p. 11 of 12
8. (40 pts) Propose a method to achieve the enantioselective synthesis of the molecules shown below starting with the indicated building blocks. Be careful about protecting groups and configurations of stereocenters. Assume the availability of all needed reagents, auxiliaries, etc. Present your answer as a flowchart. It is not necessary to draw mechanisms.
MeH
OH
Me
OHH
H
OHH
CHO
a.
from:
CHO
O
N O
Bn
O 1. Bu2BOTf, Et3N
2. MeH
OOHH
Xc
1. TBS-Cl Et3N
2. DIBAL3. Swern
MeH
OTBSOH
H
O Cy2BCl
Et3N
O BCy2
MeH
OHTBSOH
Me
ONaBH(OAc)3
MeH
OHTBSOH
Me
OH
H
HH
H
TBAFPDT .
Chem 330 final exam p. 12 of 12
HO
O OH OTBS O-Si(iPr)3
O-Si(iPr)3I
from:
b.
(cf. J. Org. Chem. 2006, 71, 9853)
N O
O O
Ph
1. LDA
2.O-Si(iPr)3I
Xc
O O-Si(iPr)3 1. DIBAL
2. Swern
H
O O-Si(iPr)3
N O
O O
Ph
BBu Bu
+
O OH O-Si(iPr)3
Xc
1. TBS–Cl
Et3N
2. DIBAL3. Swern
O OTBS O-Si(iPr)3
H
N O
O O
Ph
BBu Bu
+ Xc
O OH OTBS O-Si(iPr)3
LiOH then H+
PDT.
Happy Holidays !