Chemistry 6942 Spring 2004
Final Exam
Name:
200 points
Answer questions as thoroughly as possible and try to be clear with diagrams.
1. (15 pts) Give a complete mechanism for the following conversion from Curran’s Hirsutene synthesis.
H
H
I
n-Bu3SnH,
AIBN (cat)
PhH, reflux
H
H
H
H
(+/-) - Hirsutene
1
2. (30 pts) This question is in two parts relating to the synthesis of compound 5 (next page) from allylic
alcohol 1.
a.
Give a complete mechanistic interpretation for the following sequence of steps.
OH
O
1. n-BuLi, THF, -78 oC
2. BrCH2CO2Na,
then H+ workup
OCH3
O
1
3. CH3OH, DCC, DMAP,
CH2Cl2, 0 oC
2
2
1. LDA, THF, -78 oC
2. CH3CHO, - 78 oC to RT
then H+ workup
O
OCH3
HO
O
3
b. Provide a stepwise mechanism that explains how 3 is converted into 5.
1.
O
OCH3
HO
O
3
H2N
OH , 80 oC
O
N
2. CH3SO2Cl (2 equiv.),
pyridine., CH2Cl2
O
ClCH2CH2Cl,
80 oC
O
O
N
3. Et3N, CH2Cl2, 50 oC
4. NaN(SiMe3)2, THF, RT
4
3
5
3. (15 pts) Give a complete mechanistic interpretation of the following conversions from Woodward’s lysergic
acid synthesis.
O
O
Br
1.
O
O
THF, reflux
NMe
NMe
2. H3O+
BzN
3. NaOEt, EtOH
BzN
4
4. (20 pts) Provide mechanisms for each of the following reaction sequences.
a.
OCH3
H3CO P
OCH3
CH3Br
THF, ∆
O
n-BuLi, THF, -78 oC
H3CO P CH3
OCH3
then PhCHO
b.
O
1.
H
N
H
MeO
2.
PhH, reflux
O
H
O
THF, reflux
3. H3O+
5
CO2Me
5. (20 pts) Give the expected products from each part of the following sequence of steps from Danishefsky’s
Migrastatin 1 synthesis.
1. Dess-Martin periodinane
CH2Cl2, RT
OH
O
2. MeP(O)(OMe)2, n-BuLi
THF, -78oC to RT
O
3. Dess-Martin periodinane
CH2Cl2, RT
TESO
O
HO
O
4.
OTBS
OMe
O
H
NH
O
LiCl, DBU, MeCN, RT
5. [(Ph3P)CuH]6, PhMe, RT
6. HOAc, H2O, THF, RT
6
NH
OTBS
OMe
6. (20 pts) Give the major organic products from each of the following ring-closing metathesis reactions.
a.
Mes N
OBn
OH
N Mes
Ph
Cl
Ru
Cl
PhMe, reflux
PCy
3
N
Boc
b.
Mes N
N Mes
Ph
Cl
Ru
Cl
PhMe, reflux
PCy3
OCH3
N
Ts
O
c.
Mes N
N Mes
Ph
Cl
Ru
Cl
PhMe, reflux
PCy
O
3
O
d.
Mes N
O
N
N
N Mes
Ph
Cl
Ru
Cl
PhMe, reflux
PCy3
O
7
7. (15 pts) Explain the stereochemical outcome of the following reaction from the Woodward reserpine
synthesis.
H
H
H
H
O
O H
O
NaOMe
MeOH
H
H
O
O H
O
Br
8
H
H
OMe
8. (24 pts) Give structures for the organic product formed in each step of the Stork aspidospermine synthesis.
1. HO
OH , p-TsOH, PhH
2. NH4OH
CO2Me 3. LiAlH4, THF then H3O+
4.
O
O
Cl
Cl
N
, pyridine
5. KOtBu, PhH
H
6. HO
O
OH , TsOH, PhH
7. LiAlH4, THF then H3O+
9
H
9. (21 pts) Provide the products from each step of the following portion of Nicolaou’s brevetoxin B synthesis.
1. (COCl2)2, DMSO, CH2Cl2, -78 oC
then Et3N
2. AlMe3, MgBr2.OEt2, CH2Cl2, -50oC
OBn
HO
o
3. O3, CH2Cl2, -78 C, then Me2S, PPh3
H
4.
O
OTPS
MgBr
, THF, 0oC
5. t-BuPh2SiCl, imid., DMF, RT
6. O3, CH2Cl2, -78oC, then Me2S, PPh3
7. Ph3P=CHCO2Me, PhH, RT
8. NaH, THF, RT
10
H
MeO2C
TPSO
H
O
OBn
Me
H
OTPS
10. (20 pts) Provide the major organic product from each step in the following sequence from the Stork
prostaglandin A2 synthesis.
1.
MgCl CH2Cl2/THF
(3 equiv)
2. ClCO2Me, -30 - 0oC
O
HO
0oC
H
H
O
O
Me
Me
3. CH3C(OCH3)3 (excess)
CH3CH2CO2H (0.1 eq)
4. Heat (sigmatropic
rearrangement)
5. 25% AcOH, H2O, 120oC
6. Et3N (1 eq), CH2Cl2, RT
11
MeO2C
OH
HH O
O
O