Chemistry 634: Advanced Organic Chemistry – Synthesis and Reactivity
Fall 2013, University of Delaware
Prof. Donald Watson
Problem Set 2 Due Beginning of Class 9/17/13
You may work in groups, unless otherwise noted. No not try to fit answers on these
pages, use separate paper.
1) Order the following sets (1 being greatest) and explain why:
a) Most electrophilic
O
O
Bu
Bu
OMe
O
NMe2
Bu
Cl
b) Most sterically crowded amine
Me
Me
H2N
NH2
Me
Me
Me
NH2
Me
Me
Me
Me
NH2
Me
Me
c) Most acidic (H2O), provide pKa’s for each
O
O
OH
O
OH
Me2N
OH
F 3C
d) Most acidic (DMSO), provide pKa’s for each
O
O
Me
Bu
Me
O
Me
NBu2
H
H
OBu
H
e) Longest expected C=O bond length.
O
O
Bu
Bu
OMe
O
NMe2
Bu
Cl
2) Predict the products of the following reactions and provide a complete mechanism:
Me
OH
1) TsCl, pyr
2) NaI, Acetone
HO
Me
Me
P(O)Cl3
Et3N
O
Et
SOCl2, pry
then NaCN
OH
HO
Me
SOCl2, py
N
NH2
H
EMO
O
PPh3
DEAD
OH
HO
OBn
Me
Me
Me
O
PhO P
N3
PhO
OH
Me
N
(DBU)
N
3) Provide a mechanism for the following reactions. Be detailed (obey 3-arrow rule).
O
N Cl
O
O
t-Bu
O
O
OSiEt3
O
PPh3, tol, reflux
t-Bu
Cl
O
OSiEt3
Cl
Cl
NaH, THF
OSiEt3
OH
O
Cl
OSiEt3
Cl
4) 2-chloropyridinium iodide (Mukaiyama’s salt), carbonyldiimidazole (CDI) and BOP-Cl
are other reagents often used in acylation reactions. Please provide mechanisms for
each of the following transformations, which employ these reagents.
I
N
Me
Et3SiO
NHBn
+
HO
Cl
Et3SiO
Bn
N
O
O
Me
N
Me
O
N
N
N
N
O
O
Me
Me
OH
O
CO2H
NHBu
BuNH2
O
O
O
P
N
N
O
Cl
(BOP-Cl)
O
NHBn
Et3N
Bn = benzyl = CH2Ph
5) A) As shown in Eq. 1, addition of alkyl-metal reagents, such as EtMgBr, to ester
usually results in a mixture of tertiary alcohol and starting material, not ketone as
might be expected. Please provide a mechanism and explain why this occurs.
B) N-methoxy, N-methyl amides (Weinreb amides), such as shown in Eq. 2, usually
lead to the formation of the ketone product under similar conditions. This is particular
to the Wienreb amide. Please explain.
O
O
EtMgBr (1 equiv)
OMe
O
OH
+
OMe
Et
Et
(1)
O
OMe
N
Me
EtMgBr (1 equiv)
Et
(2)
6) Predict the equilibrium constant for each of the following reactions.
O
O
OH + Et3N
H2O
O Li
+
+
LiOH
O
OMe
OMe
O
Me +
N
H
Me
O
Me
Me
Me
H
N
Me
Me
iPr
iPr
N
Li
+
O
Me
Me
+ Me
Me
Et3NH
+
O
Li
Me +
N
Li
O
OK
Me
Me
Li
N
Me
Me
Bu Li
Me
Me
iPr
N
H
iPr
Me
+ Me
Me
+
OH
Bu H
Me
7) Using reactions from the undergraduate curriculum, please provide a retrosynthesis
of each molecule that disconnects it to starting materials containing no more that 7carbon atoms and 2-heteroatoms (ie not C or H).
O
O
Me
Me
OH
AcO
O
NPr2
O
hex
O
Me
Me
Me
8) Without worrying about the particular reactions needed to accomplish each
transformation, please identify retrosynthetic bond disconnections that would results
in molecules that do not contain bridged-ring systems. In some cases, there are
more than one correct answer, please identify as many as you can. In all cases,
there are single step disconnections that can accomplish the task.
Me
Me
O