Mind Bending Mechanisms
Baran Lab
Hafensteiner
N
N
Pyrroles are abundant in both natural products and pharmaceuticals. The
Schultz group has demonstrated the following pyrrole synthesis (J. Org.
Chem. 1980, 45, 2040-2041).
N
O
N
O
N
N
[3 + 2]
N
N
OMe
O
O
OMe
- N2
N
N
N
N3 1. D
N
O
O
OMe
2. hn, MeOH
Ph
N
N
N
O
O
O
OMe
O
OMe
CO2Me
retro Diels-Alder
CO2Me
N
PhN
Provide one or more plausible mechanisms for this transformation.
O
MeO
O
Ph
N
N
CO2Me
O
MeOH
Product
Mind Bending Mechanisms
Baran Lab
Hafensteiner
O
H
O
O
O
HO
O
HO
O
Cycloaddittions and rearrangements were the hallmark of Jacobi's synthesis
of (±)-Gnididione and (±)-Isognididione (J. Org. Chem. 1990, 55, 202-209) . It
was postulated that (±)-Gnididione could be synthesized using the following
transformation. This hypothesis was proven in the hood and is shown below.
N
N
[1,3]
O
O
Diels-Alder
O
O
O
O
O
O
D;
HO
O
N
O
O
O
H3O+
O
N
N
O
-HCN
Gnididione
O
Provide one or more plausible mechanisms for this transformation including
a transition state that accounts for stereochemistry.
O
O
O
O
H3O+
O
O
Gnididione
Mind Bending Mechanisms
Baran Lab
Activated Sufur
Et3N + S8
Et3N
O
Sulfur oddities have intrigued chemists from the time the odiferous yellow
compound was discovered. Here is an investigation into elemental sulfur
chemistry by the Purello group of the Universitá di Cantania (Heterocycles,
1993, 36, 223-229).
Ph
Ph
S8
Ph
Et3N
O
S
S
S
6
6
Ph
H
S
Ph
S6
S
O
NEt3
Et3N
Ph
S
Ph
S
S
S
6
O
B
S
O
S S
S
B
S
O
Ph
Ph
S S
Et3N
A
O
S S
Ph
S
Ph BH
Ph
O
S
Ph
S
Hafensteiner
Ph
H
Ph
S
Ph
S
Ph
Sx
S
O
-H2S
S
O
S S
Ph
Ph
S
NEt3
S
Provide one or more plausible mechanisms for this transformation
identifiying all intermediates. Also, identify the active sulfur reagent in the
above process.
Ph
Ph
O
Ph
Ph
SH
SH
O
Mind Bending Mechanisms
Baran Lab
B
Ph
S
H
S
Ph
HS
Sx
S
B
Ph
O
Ph
S
Ph
O
Ph
S
A
Et3N
Ph
S
S
H
Ph
O
S
S
Sx
O
A
S
Ph
NAME
S
S
S
6
S
S
Ph
O
Ph
S
S
O
O
S
Ph
Ph
Ph
S
O
Ph
S
S
O
S S
Ph
S S
Ph
Ph
O
Ph
S
S
SH
Ph
Mind Bending Mechanisms
Baran Lab
H+
O
N
Hafensteiner
H
N
Ph
PhNHNH2
During investigations by Prof. Cook into the synthesis of indoloisoquinolines,
an interesting observation was made (Heterocycles, 1993, 36, 157-189).
EtOH, HCl or
X
Ethylene glycol,
or 360 ºC
O
N
Ph
PhNHNH2
360 ºC
N
N
H
N
Ph
N
Ph
Ph
HN
N
N
N
N
H
N
Ph
N [1,3] H- shift
N
N
N
Ph
H
Ph
-H+
Provide mechanisms for the observed and expected products.
N
H
N
Ph
isomerize
N
N
H
Ph
Ph
Mind Bending Mechanisms
Baran Lab
O
Hafensteiner
H
N
N
Ph
HN
H
N
PhNHNH2
N
N
Ph
During investigations by Prof. Cook into the synthesis of indoloisoquinolines,
an interesting observation was made (Heterocycles, 1993, 36, 157-189).
N
Ph
Ph
[3,3]
H+
H+
EtOH, HCl or
X
Ethylene glycol,
or 360 ºC
O
N
Ph
PhNHNH2
360 ºC
HN
H2N
HN
H2N
NH
HN
NH
N
N
N
N
Ph
Ph
HN
HN
HN
PhNHNH2
[O]
N
N
Ph
Provide mechanisms for the observed and expected products.
Ph
Ph
-NH3
N
N
H
H
N
O
Ph
B
Ph
H
HN
N
H+
N
Ph
N
H
Mind Bending Mechanisms
Baran Lab
Hafensteiner
nuc
nuc
CN
nuc
OEt
N N
nuc
ClO4B
Pyridinium salts (Heterocycles, 1990, 31, 289-304) are reactive to both
electrophiles and nucleophiles, reactivity which was exploited by the
Messmer group of the Hungarian Academy of Sciences. The reactive starting
block B was synthesized from the condensation of A with HC(OEt)3.
HN
CN
CN
O
OEt
N N
N N
ClO4-
ClO4-
N NH
2
A
morpholine
CN
HC(OEt)3
N N
ClO4B
C
D
O
B
CN
OEt
PhCH2NH2
E
N N
N
N
O
ClO4-
NH
CN
N
C
6 p elecrocyclic
ring opening
O
CN
N
N
N
O
N
O
D
O
CN
N N
Propose a structure for C, D, and E. Hint: Identify the electrophilic sites of
molecule B.
ClO4-
OEt
CN
PhCH2NH2
N N
-EtOH
ClO4
NH
Ph
-
NH
B
N
N
N
ClO4E
Ph
Mind Bending Mechanisms
Baran Lab
Hafensteiner
O2N
MeO2C
CHO
O2N
N
Ts
The Harada group has developed an efficient route to the following polycyclic
architecture (Heterocycles, 1993, 36, 449-454).
O2N
O
MeO2C
O
1. HNEt2
O2N
CO2Me
N
Ts
2. TiCl4
TsN
N
N O
N
Ts
CO2Me
H
H
H O CO Me
2
LA
MeO2C
H
O
TsN
N
N
Ts
MeO2C
H
O
N
O
CO2Me
O
N
N
CO2Me
O
CO2Me
N
Ts
O
CO2Me
H
H
H O CO Me
2
CO2Me
H
N
Ts
N
Ts
Propose a plausible mechanism for the formation of the product.
CO2Me
N O
-H2O
LA
CO2Me
CHO
O
H
CO2Me
O
LA