Chem 634 – Fall 2015
Problem Set 2
Due Tues, 10/13/15
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
Mechanism:
N
Me
O
N
N
N
N
O
O
Me
Me
OH
O
CO2H
O
O
O
P
N
N
O
Cl
(BOP-Cl)
Et3N
H2NBn
+
HO
O
NHBn
Bn = benzyl = CH2Ph
I
N
Me
Et3SiO
NHBn
NHBu
BuNH2
Cl
Et3SiO
Bn
N
O
O
Me
N
Me
O
N
N
N
N
O
O
Me
Me
OH
O
Mechanism:
CO2H
NHBu
BuNH2
O
O
O
P
N
N
O
Cl
(BOP-Cl)
Et3N
H2NBn
O
NHBn
Bn = benzyl = CH2Ph
1
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
Mechanism:
2) 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.
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)
2
3) Predict the product for each of the following transformations and provide a mechanism.
1) nBuLi, THF, –50 °C,
then (CH2O)n, –50 °C to rt
2) I2, PPh3, imidazole
O
O
O
Me
C12H17O3I
Mechanism:
O
1) t-BuLI (2 equiv),
then CO2
2) HCl
3) MeI, K2CO3
O
I
C8H10O3
Mechanism:
3
F
O
NH2
CF3
CN
NaH, then HCl
Me
C12H9F3N2O
Mechanism:
4
5) 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
I
O
SnBu3
H
H
Pd2(dba)3
SPhos
NBn
I
Pd(PPh3)4
+
Me
ClMg
Bu
I
+
EtO2C
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
Pd2(dba)3
SPhos
K3PO4
Cl
B(OH)2
+
O
I
+
H
Fe
Me
Bu
3)4
PtBu
Me
2
H
Me
PCy2
O
Pd(PPh3)4
Me
SnBu3 I
Pd2(dba)3
SPhos
NBn
ClMg
PCy2
MeO
1
EtO2CPh
O
+
B tBu
CyPFJosiphos
Br
O
OMe
I
ZnBr
Pd(PPh
3)4
NC
SPhos
EtONa
OTf Me
N
Pd(PPh3)4
+
Me
P Bu
N
O
Me
SnBu3
H
Me
Ph
B O
O
HO+
Me
O
+
O
I
H
Pd(PPh3)4
Ph
Br
Pd(PPh3)4
NMe2
4
3
Pd(OAc)2/1
NaOtBu
Cl
+
PdCl2, PPh3
Et3N
EtONa
C8H17 NH2
N
O
Pd(OAc)2/1
NaOtBu
Cl
+
C8H17 NH2
N
OAc
N
H
Ph
I
CO2Et
Pd(PPh3)4, NaH
CO2Me
CO2Me
CuI (cat), K3PO4
NHMe
(cat)
MeHN
O
OAc
CO2Me
Pd(PPhOAc
3)4, NaH
NaCH(CO2Me)2
cat. [Ir(COD)Cl]2
cat 3
H
PhCCH, 4
Et3N, Zn(OTf)2
Ph
CO2Me
O
PtBu2
H
Fe
Me
PCy2
1
PhCCH, 4
Et3N, Zn(OTf)2
CyPF-tBu Josiphos
PCy2
OMe
MeO
SPhos
Me
P N
O
Me
Ph
Me
O
3
NMe2
HO
4
6
6) 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
H
Mechanism and 3D Drawing:
TfO
10 mol% Pd(OAc)2
20 mol% PR3
Bu3N, CO
morpholine
1,1-dimethylallene
MeCN, 70 °C
Me
CO2R
Me
O
O
60%
CO2R
10% Pd(OAc)2
20 mol% P(2-furyl)3
CO, NaBPh4
anisole, 120 °C
O
O
Ph
84%
10 mol% Pd(OAc)2
20 mol% PR3
Bu3N, CO
morpholine
1,1-dimethylallene
MeCN, 70 °C
Me
CO2R
60%
O
N
O
I
TfO
Me
Me
Me
O
Me
H
Me
O
N
O
CO2R
Mechanism and 3D Drawing:
7
Me OH
Me OH
Me
HO
Me
O
8. Please fill in the expected products.
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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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