Name………………………………………………………...
Chemistry 730
Autumn 2005
Final Examination
[December 06, 2005, 11:30-1:30 PM]
Total: 120 points
Part I
1. (10 points) (a) Define Hammond postulate. Now answer the following questions (be brief, remember: a
picture is worth a thousand words!):
(b) Use the relative rates of chromic acid oxidation of cis- versus trans- 4-t-butylcyclohexanol to illustrate
the Hammond postulate. For full credit, you should show the major conformations of both starting
materials, and intermediates, and draw schematic energy/reaction progress diagrams and clearly explain the
differences.
(c) The relative rates of acid-catalyzed esterification (acetic anhydride + H+) of the two alcohols do not
follow the same trend. Why?
1
2. (10 points) The stereoselectivity of enolate formation depends on several factors, including temperature,
type of solvent, bulkiness of the base, and size of the R attached to the carbonyl group. Discuss the effect of
the solvent/base in the example shown, providing a clear rationale for your answer.
O
+
Z and E enolates
base/solvent
then TMS-Cl
Base/solvent
Z:E ratio
LDA in THF /23 % HMPA/hexane
Li-TMP in THF / hexane
92:8
18:82
(TMP = 2,2,6,6-tetramethylpiperidide)
2
N
Li
3. (14 points) Draw the most favorable conformation(s) of the following compounds at room temperature in
a nonpolar solvent.
ethyl acetate
OH
CH2(OMe)2
Cl
O
Me
OH
Me
N
H
OTs
Me
OH
H
H
H
OH
H
CO2H
H
OH
cholic acid
4. (6 points) Using transition state models for nucleophilic addition to prochiral carbonyl groups, predict
the structures of the major and minor products in the following reactions. Show the model(s).
Me
O
Ph
H
1. Me -Ti (OPri)3
2. H3O+/H2O
(major)
Transition state:
3
(minor)
5. (5 points) Reaction of 4-t-butylcyclohexanone with the chiral amide shown below, followed by
quenching with TMS-Cl, gives the TMS-enol ether shown in 88 % ee. Label the hydrogen that is removed
in the formation of the major product as pro-R or pro-S.
O
But
1.
OTMS
Ph
N
Li
Ph
o
, THF -90 C
2. TMS-Cl
But
(88 % ee)
6. (12 points) Rank the following compounds using the criteria suggested:
(a) in order of increasing base strength (least basic first):
(a) LDA
(d) cyclohexanone enolate (Li)
(b) n-BuLi
(e) NaOMe
(c) t-BuLi
(f) NaOC(O)CH3
(b) amount of enol content at equilibrium (most amount of enol first):
(a) acetaldehyde
(e) ethyl acetate
(b) cyclohexanone
(c) ethyl acetoacetate
(d) phenol
(c) relative rate of acid-catalyzed H/D exchange of the proton shown in bold (slowest exchange first):
(a) CH3C(O)CH2-H
(b) CH3C(O)CH2CH3
4
(c) CH3C(O)CH2-But
7. (16 points) (Answer any 4) Illustrate the utility of the following reagents in organic synthesis with
‘real’ examples (no X’s or R’s ).
F3C
(i)
OMe
Cl
Ph
(ii)
O
But
OMe
But
+
–
(iv) [Me2N]3S Me3SiF2
(iii)
O
O
O
OSiMe3
But
5
(v)
+
N
I–
Part 2
8. (22 points) (Answer five. You must answer a, b and c; then choose any two others from d-h).
Outline, with solvents, reagents, and approximate reaction conditions, a selective route to each of the
following compounds from the indicated starting materials. If you don’t recall the exact conditions, for
partial credit, show what strategy you would employ or what is the key disconnection in the synthesis.
Me
a.
H
O
O
O
CO2Me
OH
(absolute configuration shown)
• Show the model for stereoselectivity based on the reagent of your choice
O
OOMe
O
OMe
O OMe
OMe
b.
O
O
6
CO2H
c.
from 1,3-dibromopropane
d.
OEt
O
O
OBn
CHO
CHO
CH2Ph
7
O
O
OBn
OBn
e.
O
O
O
O
f.
Cl
(Li-enolate alkylation predominantly leads to elimination; hint: consider the stability of the benzyl cation)
g.
OEt
O
O
Et
O
O
from
O
Et
Part 3
9. (25 points) Provide the products for the reactions shown below. Suggest a reasonable mechanism (show
electron flow or provide a brief explanation) to account for each step, paying attention to stereochemical
details.
O
O
N
a.
a. TiCl4, (i-Pr)2NEt
b. PhCH2OCH2Cl
O
Bn
8
MeS
1. MeO SO2F (methylating agent)
2. KOBut (DME)
b.
0 oC to rt
O
O
NH2+ AcO _
O
O
c.
Me
Me
O
H
d.
H
C6H6, 1 h, 65 oC
1. LDA, THF, CD3I
2. KH, THF, CH3I
3. Li/NH3/t-BuOH
9
t-BuMgBr/ether , workup
O
e.
t
Bu
Na-acetylide/etehr, workup
Bonus Question
(10 points) Provide a reasonable mechanism (arrow-pushing formalism) for the following transformation.
Recall allylsilanes, like allylstannanes we saw in class, are nucleophilic reagents.
Ph
SiMe3
[PhCH 2 –NH3 ]+ CF 3 CO 2 – + H2 C=O
H2 O, 25 oC, 6 h
N
O
OH
10