Chem 634 – Fall 2014
Problem Set 2 – Corrected 9/20/14
Due Fri, 9/26/14, 5pm to Mary’s Mailbox in the Mailroom
1) 2-Chloropyridinium iodide (Mukaiyama’s salt), carbonyldiimidazole (CDI) and BOP-Cl are 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
H2NBn
Bn = benzyl = CH2Ph
2) A) As shown in Eq. 1 below, addition of alkylmetal reagents, such as EtMgBr, to esters 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 formation of the ketone
under similar conditions. This is particular to the Weinreb amide. Please explain.
O
O
EtMgBr (1 equiv)
OMe
O
OH
+
OMe
Et
Et
(1)
O
OMe
N
Me
EtMgBr (1 equiv)
Et
(2)
1
3) Predict the product for each of the following transformations and provide a mechanism.
1) BuLi, THF, –50 °C,
then (CH2O)n, –50 °C to rt
2) I2, PPh3, imid
O
O
O
C12H17O3I
Me
O
1) tBuLi (2 equiv),
then CO2
2) HCl
3) MeI,K2CO2
O
C8H10O3
I
Me3Si
F
NO2
N
Na
SiMe3
C17H16N2O2
Me
N
THF, 60 °C
F
O
CF3
CN
NH2
NaH, then HCl
Me
C12H9F3N2O
4) Please provide a mechanism for the following reaction and explain the observed selectivity.
NMe2
NMe2
N
NC
Br
iPrMgBr,–10 °C
then nPrCHO
OH
N
NC
nPr
Br
Br
5) Provide formal oxidation state, d-electron count and valence electron count for each of the following transition metal
complexes. If not given, proposed a reasonable structure.
a)
Ni(cod)2
cod =
O
b)
Cp2Ti
Me
c) CoCl(PCy3)3
d) (MeCN)2PdCl2
e) Rh2(OAc)4
f) OsO4
g) FeCp2
h) CuBr
i)
MesN
Cl
Cl
NMes
Ru
Ph
N
Me
Me
Cp = cyclopentadienyl anion
2
6) Predict the product for the following reactions. If a single enantiomer of product is expected, state so, but do not worry
about which enantiomer is formed from the enantiomer of catalyst used.
Pd2(dba)3
SPhos
K3PO4
Cl
B(OH)2
+
Me
Me
O
Pd2(dba)3
SPhos
NBn
I
I
Pd(PPh3)4
+
SnBu3
H
H
Me
ClMg
Bu
EtO2C
I
+
Ph
B O
O
Pd(PPh3)4
Pd(PPh3)4
+
EtONa
Br
ZnBr
O
NC
Pd(OAc)2/1
NaOtBu
Cl
OTf Me
N
+
PdCl2, PPh3
Et3N
C8H17 NH2
N
O
OAc
N
H
Ph
I
CO2Et
Pd(PPh3)4, NaH
CO2Me
CO2Me
CuI (cat), K3PO4
NHMe
MeHN
(cat)
O
NaCH(CO2Me)2
cat. [Ir(COD)Cl]2
cat 3
OAc
H
PhCCH, 4
Et3N, Zn(OTf)2
Ph
PtBu2
Fe
Me
PCy2
MeO
1
CyPF-tBu Josiphos
Ph
Me
P N
O
Me
PCy2
OMe
Me
O
4
3
SPhos
NMe2
HO
7) Two related reactions from the Grigg group are shown below. A) Please provide a mechanism for each reaction.
B) Rationalize the observed relative stereochemistry for each transformation by providing 3-D drawings of the
possible completing transition states and providing arguments for why one maybe preferred. C) Finally, as you will
see from the correct mechanisms for each, the order of events differs greatly with respect to CO in each of these
reactions. Please discuss what factors might influence how and when CO undergoes reaction in these types of
cyclizations.
O
10% Pd(OAc)2
20 mol% P(2-furyl)3
CO, NaBPh4
anisole, 120 °C
O
Ph
84%
O
I
TfO
10 mol% Pd(OAc)2
20 mol% PR3
Bu3N, CO
morpholine
1,1-dimethylallene
MeCN, 70 °C
Me
CO2R
60%
Me
O
Me
H
Me
O
N
O
CO2R
3
8. Please fill in the missing reagents in the following synthesis. For some boxes, more than 1 step may be required.
OH
OH
SnBu3
TBSO
HO
OH
OPMB
Br
TBSO
HO
Br
9. Please fill in the missing reagents in the following synthesis. For some boxes, more than 1 step may be required.
OPMB
OH
PMBO
OPMB
OH
O
Br
HO
O
Me
Me
Br
O
H
H
Br
H
OH
For the following questions, please work alone. You may use Reaxys, Scifinder or Web of Knowledge for these problems.
10) Using Reaxys or Scifinder, please identify up to 3 major US commercial suppliers (ie Aldrich, Acros, Strem, etc)
for each of the following. If fewer suppliers exist, please state so. (Please see note on the course Syllabus
regarding commercial sources).
OMe
Cl
Li
N
iPr
2·BF4
O
Bu2Mg
N
F
MeO
iPr
PCy2
iPr
O
iPr
1
11) Please identify at least one paper that provides indicated spectral data in the specified solvent. the H NMR
spectra in CDCl3 for the following compounds.
O
PPh3
OMe
1H
in CDCl3
31P
in d6-acetone
Please note: I have not assigned any specific problems from Grossman, Ch. 6, but you are responsible for the information
in this chapter. It is a good resource for extra metal-catalyzed reaction mechanism practice.
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