Pericyclic Reactions
! Classes of pericyclic reactions
SigmatropicRearrangements
ElectrocyclicRearrangements
CycloadditionReactions
!" = ± 2!# = ± 2
!" = ± 1!# = ± 1
!" = 0!# = 0
Pericyclic Reactions
! Classes of pericyclic reactions
SigmatropicRearrangements
ElectrocyclicRearrangements
CycloadditionReactions
!" = ± 2!# = ± 2
!" = ± 1!# = ± 1
!" = 0!# = 0
What is a pericyclic reaction?
Pericyclic Reactions
! Classes of pericyclic reactions
SigmatropicRearrangements
ElectrocyclicRearrangements
CycloadditionReactions
!" = ± 2!# = ± 2
!" = ± 1!# = ± 1
!" = 0!# = 0
! A concerted reaction wherein the transition state ischaracterized as having a cyclic array of interacting orbitals.
What is a pericyclic reaction?
Pericyclic Reactions
! Classes of pericyclic reactions
SigmatropicRearrangements
ElectrocyclicRearrangements
CycloadditionReactions
!" = ± 2!# = ± 2
!" = ± 1!# = ± 1
!" = 0!# = 0
! A concerted reaction wherein the transition state ischaracterized as having a cyclic array of interacting orbitals.
What is a pericyclic reaction?
Pericyclic Reactions
! Classes of pericyclic reactions
SigmatropicRearrangements
ElectrocyclicRearrangements
CycloadditionReactions
!" = ± 2!# = ± 2
!" = ± 1!# = ± 1
!" = 0!# = 0
disrotatoryring-closure
! Basic look at orbital motion:
Electrocyclic Reactions
! What other systems participate in electrocyclic reactions?
R
R R
R
R RR R
R R
RR
Electrocyclic Reactions
! What other systems participate in electrocyclic reactions?
disrotatoryring-closure
disrotatoryring-closure
R
R R
R
R RR R
R R
R R
RR
R R
Electrocyclic Reactions
! What other systems participate in electrocyclic reactions?
R
R R
R
R RR R
R R
RR
Electrocyclic Reactions
! What other systems participate in electrocyclic reactions?
conrotatoryring-closure
conrotatoryring-closure
R
RR
R
RRR R
R R
RR
R
R
R
R
Electrocyclic Reactions
! What other systems participate in electrocyclic reactions?
conrotatoryring-closure
conrotatoryring-closure
! Higher order systems also undergo electrocyclic rearrangement in the same manner
R
RR
R
RRR R
R R
RR
R
R
R
R
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
disrotatoryring-closure
LUMO
HOMO
conrotatoryring-closure
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
disrotatoryring-closure
LUMO
HOMO
conrotatoryring-closure
!
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
disrotatoryring-closure
HOMO
SHOMO
conrotatoryring-closure
hv
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
disrotatoryring-closure
HOMO
SHOMO
conrotatoryring-closure
hv
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
LUMO
HOMO
conrotatoryring-closure
conrotatoryring-closure
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
LUMO
HOMO
conrotatoryring-closure
conrotatoryring-closure
!
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
LUMO
HOMO
conrotatoryring-closure
conrotatoryring-closure
!
Frontier Molecular Orbital Analysis
! Taking a closer look at the electrocyclization
LUMO
HOMO
conrotatoryring-closure
conrotatoryring-closure
!
Frontier Molecular Orbital Analysis
! FMO analysis derived rules for electrocyclization
thermalreaction disrotatory conrotatory
photochemicalreaction disrotatoryconrotatory
R
R R
R
RR RR
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
"con"
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
"con"
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
1 phase inversion
"con"
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
1 phase inversion
Phase inversions:
odd = Möbius
even = Hückel
"con"
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
1 phase inversion
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
"con"
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
1 phase inversion
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"con"
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
1 phase inversion
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"con"
allowed
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
flipped orbital
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
2 phase inversions
"con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
3 phase inversions
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
2 phase inversions
"con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
3 phase inversions
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
2 phase inversions
"con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
allowed
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
0 phase inversions
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
0 phase inversions
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
forbiddenthermally
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis""con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis""con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
0 phase inversions,allowed thermally
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis""con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
0 phase inversions,allowed thermally
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis""con"
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Hückel / Möbius Analysis
! Alternative method for analysis of pericyclic reactions
! Model reaction:
0 phase inversions,allowed thermally
! Aromatic allowed thermally, Anti-aromatic allowed photochemically
"dis""con"
1 phase inversion,allowed photochemically
Phase inversions:
odd = Möbius
even = Hückel
Hückel
Möbius
Aromatic Anti-aromatic
4q+2
4q
4q
4q+2
Nazarov Cyclization through Electrocyclization
! The Nazarov reaction follows typical 4e– electrocyclic behavior
O
Nazarov Cyclization through Electrocyclization
! The Nazarov reaction follows typical 4e– electrocyclic behavior
OHOH+
5 carbons, 4 e–
Nazarov Cyclization through Electrocyclization
! The Nazarov reaction follows typical 4e– electrocyclic behavior
OH OHOH+
O
5 carbons, 4 e–
Nazarov Cyclization through Electrocyclization
! The Nazarov reaction follows typical 4e– electrocyclic behavior
OH OHOH+
OH OH
R R'
R
R'
O
! Conrotatory reactivity for thermal electrocyclic reactions with 4 e–
5 carbons, 4 e–
Nazarov Cyclization through Electrocyclization
! The Nazarov reaction follows typical 4e– electrocyclic behavior
OH OHOH+
OH OH
R R'
R
R'
O
! Conrotatory reactivity for thermal electrocyclic reactions with 4 e–
H HH H5 carbons, 4 e–
Dewar Benzene
! Why does dewar benzene show remarkable stability?
electrocyclicopening (?)
R R RR
RR!
4 e– = conrotatory
Dewar Benzene
! Why does dewar benzene show remarkable stability?
electrocyclicopening (?)
R R RR
RR!
4 e– = conrotatory too unstable!
Dewar Benzene
! Why does dewar benzene show remarkable stability?
electrocyclicopening (?)
R R RR
RR!
4 e– = conrotatory too unstable!
! The alternative, disrotatory opening does occur but is only allowed photochemically
Torquoselectivity in Electrocyclic Reactions
! What is a "torquoselective" reaction?
! Using substituted cyclobutenes as an example, both clockwise and counterclockwiserotation is possible and produces products of different olefin geometry / stereochemistry
Torquoselectivity in Electrocyclic Reactions
! What is a "torquoselective" reaction?
! Using substituted cyclobutenes as an example, both clockwise and counterclockwiserotation is possible and produces products of different olefin geometry / stereochemistry
R
!
"conrotatory"R
R R' R R'
!
"conrotatory"RR'
HR
HH
Torquoselectivity in Electrocyclic Reactions
! What is a "torquoselective" reaction?
! Using substituted cyclobutenes as an example, both clockwise and counterclockwiserotation is possible and produces products of different olefin geometry / stereochemistry
R
!
"conrotatory"
"con" "con"
R
R R' R R'
!
"conrotatory"RR'
HR
HH
Torquoselectivity in Electrocyclic Reactions
! What is a "torquoselective" reaction?
! Using substituted cyclobutenes as an example, both clockwise and counterclockwiserotation is possible and produces products of different olefin geometry / stereochemistry
R
!
"conrotatory"
"con" "con"
R
R R' R R'
!
"conrotatory"
"con" "con"
RR'
HR
HH
Torquoselectivity in Electrocyclic Reactions
! What is a "torquoselective" reaction?
! Using substituted cyclobutenes as an example, both clockwise and counterclockwiserotation is possible and produces products of different olefin geometry / stereochemistry
R
!
"conrotatory"
"con" "con"
R
R R' R R'
!
"conrotatory"
"con" "con"
RR'
How does differential substitution effect the direction of opening?
HR
HH
Torquoselectivity in Electrocyclic Reactions
! Unusual examples of torquoselectivity could not be explained using FMO analysis
Me Me
!
"conrotatory"
<0.2%
only ~1 kcal/mol energy difference
>99.8%
Me
Frey, H. M. Trans. Faraday. Soc., 1964, 60, 83.Curry, M. J., Stevens, I. D. R. J. Chem. Soc., Perkin Trans. 2, 1980, 1391.
Torquoselectivity in Electrocyclic Reactions
! Unusual examples of torquoselectivity could not be explained using FMO analysis
Me Me
!
"conrotatory"
R
!
"conrotatory"R
<0.2%
only ~1 kcal/mol energy difference
>99.8%
Me
MeR
MeMe
65 : 35
Frey, H. M. Trans. Faraday. Soc., 1964, 60, 83.Curry, M. J., Stevens, I. D. R. J. Chem. Soc., Perkin Trans. 2, 1980, 1391.
Et:
i-Pr:
68 : 32
t-Bu: 32 : 68
Ph: 30 : 70
R =
Torquoselectivity in Electrocyclic Reactions
! Unusual examples of torquoselectivity could not be explained using FMO analysis
CF3
F3C
Dolbier, W. R., Koroniak, H., Burton, D., Bailey, A. R., Shaw, G. S., Hansen, S. W. J. Am. Chem. Soc., 1984, 106, 1871.
FF3C CF3
F
F F F F
CF3
FFF
CF3F
FF!
"conrotatory"
(Z,Z) (E,E)
! Thermodynamic analysis of perfluorinated system yields remarkable results:
Torquoselectivity in Electrocyclic Reactions
! Unusual examples of torquoselectivity could not be explained using FMO analysis
CF3
F3C
Dolbier, W. R., Koroniak, H., Burton, D., Bailey, A. R., Shaw, G. S., Hansen, S. W. J. Am. Chem. Soc., 1984, 106, 1871.
FF3C CF3
F
F F F F
CF3
FFF
CF3F
FF!
"conrotatory"
Ea = 30.5 kcal/mol Ea = 49.7 kcal/mol
(Z,Z) (E,E)
kZZ/kEE (at 112 °C): 1.9 x 109
! Thermodynamic analysis of perfluorinated system yields remarkable results:
Torquoselectivity in Electrocyclic Reactions
! Unusual examples of torquoselectivity could not be explained using FMO analysis
CF3
F3C
Dolbier, W. R., Koroniak, H., Burton, D., Bailey, A. R., Shaw, G. S., Hansen, S. W. J. Am. Chem. Soc., 1984, 106, 1871.
FF3C CF3
F
F F F F
CF3
FFF
CF3F
FF!
"conrotatory"
Ea = 30.5 kcal/mol Ea = 49.7 kcal/mol
(Z,Z) (E,E)
kZZ/kEE (at 112 °C): 1.9 x 109
! Thermodynamic analysis of perfluorinated system yields remarkable results:
! Sterics are clearly not the dominant factor in determining direction of rotation
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Substituent preference for outward rotation determined
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Substituent preference for outward rotation determined
Ea (kcal/mol)Substituent Erel (R–H, kcal/mol)
H 32.5 0
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Substituent preference for outward rotation determined
Ea (kcal/mol)Substituent Erel (R–H, kcal/mol)
H
Me
32.5
31.6
0
–0.9
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Substituent preference for outward rotation determined
Ea (kcal/mol)Substituent Erel (R–H, kcal/mol)
H
Me
Cl
OAc
32.5
31.6
29.4
27.8
0
–0.9
–3.1
–4.7
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Substituent preference for outward rotation determined
Ea (kcal/mol)Substituent Erel (R–H, kcal/mol)
H
Me
Cl
OAc
OEt
32.5
31.6
29.4
27.8
23.5
0
–0.9
–3.1
–4.7
–9.0
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
Cl
!
"inward" "outward"
Cl Cl
! Substituent preference for inward rotation determined
XX
X
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
Cl
!
"inward" "outward"
Cl Cl
! Substituent preference for inward rotation determined
Ea (kcal/mol)Substituent Erel (X–H, kcal/mol)
H 29.4 0
XX
X
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
Cl
!
"inward" "outward"
Cl Cl
! Substituent preference for inward rotation determined
Ea (kcal/mol)Substituent Erel (X–H, kcal/mol)
H
Me
Cl
29.4
31.6
35.6
0
+2.2
+6.2
XX
X
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Overall substituent preferences can be determined
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Overall substituent preferences can be determined
inward (kcal/mol)Substituent outward (kcal/mol)
Me
OAc
OR
+3
+6
+5
–1
–3
–5
–9
Cl
Substituent effect on Ea:
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
R
!
"inward" "outward"
R R
! Overall substituent preferences can be determined
inward (kcal/mol)Substituent outward (kcal/mol)
Me
OAc
OR
+3
+6
+5
–1
–3
–5
–9
Cl
Substituent effect on Ea:
Eout – Ein (kcal/mol)
–4
–9
-14
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
F
!
"inward" "outward"
F F
! Overall substituent preferences can be determined
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
F
!
"inward" "outward"
F F
! Overall substituent preferences can be determined
~13 kcal/mol preferencefor outward TS (calculated)
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
F
!
"inward" "outward"
F F
! Overall substituent preferences can be determined
F
!
"inward" "outward"
F FF
FF
~13 kcal/mol preferencefor outward TS (calculated)
Torquoselectivity in Electrocyclic Reactions
! Further thermodymanic analysis towards a rational for torquoselectivity
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
F
!
"inward" "outward"
F F
! Overall substituent preferences can be determined
F
!
"inward" "outward"
F FF
FF
~13 kcal/mol preferencefor outward TS (calculated)
~29 kcal/mol preferencefor outward TS (calculated)
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
inward TS
HH
H
HH
H
HOMO
LUMO
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
inward TS outward TS
HH
H
H
H
H
HH
H
H
H
H
HOMO
LUMO
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
inward TS outward TS
HH
H
H
H
H
HH
H
H
H
H
HOMO
LUMO
Unfavorable 4e– interactionof p-orbital with "
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
inward TS outward TS
HH
H
H
H
H
HH
H
H
H
H
HOMO
LUMOStabilization of TS
through "* / p-orbitaloverlap
Unfavorable 4e– interactionof p-orbital with "
Torquoselectivity in Electrocyclic Reactions
! Unique control arises from torquoselective reactivity
Dolbier, W. R., Koroniak, H., Houk, K. N., Sheu, C. Acc. Chem. Res., 1996, 29, 471.Houk, K. N., Spellmeyer, D. C., Jefford, C. W., Rimbault, C. G., Wang, Y., Miller, R. D. J. Org. Chem., 1988, 53, 2125.
t-Bu!
t-BuMet-Bu Me
Me
30 : 70
Torquoselectivity in Electrocyclic Reactions
! Unique control arises from torquoselective reactivity
Dolbier, W. R., Koroniak, H., Houk, K. N., Sheu, C. Acc. Chem. Res., 1996, 29, 471.Houk, K. N., Spellmeyer, D. C., Jefford, C. W., Rimbault, C. G., Wang, Y., Miller, R. D. J. Org. Chem., 1988, 53, 2125.
t-Bu!
t-BuMet-Bu Me
Me
30 : 70
t-Bu!
t-BuOMet-Bu OMe
MeO
> 99 : 1
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
1 phaseinversion
6 e–, Möbius array
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Kirmse, W., Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1984, 106, 1989.Rondan, N. G., Houk, K. N. J. Am. Chem. Soc., 1985, 107, 2099.
OR
!
OR RO
1 phaseinversion
6 e–, Möbius array
Anti-aromatic, forbidden
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC< 2% observed
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC
inward TS outward TS
HH
H
H
H
H
HH
H
H
H
H
HOMO
LUMO
< 2% observed
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC
inward TS outward TS
HH
H
H
H
H
HH
H
H
H
H
HOMO
LUMO
Favorable 2e– interactionof p-orbital with "
< 2% observed
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC< 2% observed
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC< 2% observed
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC< 2% observed
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC< 2% observed
1 phaseinversion
4 e–, Möbius array
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
Rudolf, K., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1987, 52, 3708.
CHO
!
CHO OHC< 2% observed
1 phaseinversion
4 e–, Möbius array
Aromatic, allowed
Torquoselectivity in Electrocyclic Reactions
! Unique control arises from torquoselective reactivity
Dolbier, W. R., Koroniak, H., Houk, K. N., Sheu, C. Acc. Chem. Res., 1996, 29, 471.Houk, K. N., Spellmeyer, D. C., Jefford, C. W., Rimbault, C. G., Wang, Y., Miller, R. D. J. Org. Chem., 1988, 53, 2125.
H!
HRR
R
! Linear relationship between in-outpreference and Taft substituent parameter for "-donating or accepting ability
Torquoselectivity in Electrocyclic Reactions
! Unique control arises from torquoselective reactivity
Niwayama, S., Houk, K. N. Tetrahedron Lett., 1993, 34, 8, 1251.
!
COCH3
COCH3H3COC
Benzene, !: 66 : 34
Torquoselectivity in Electrocyclic Reactions
! Unique control arises from torquoselective reactivity
Niwayama, S., Houk, K. N. Tetrahedron Lett., 1993, 34, 8, 1251.
!
COCH3
COCH3H3COC
Benzene, !:
ZnI2/Na2CO3, Benzene, !:
66 : 34
17 : 83
! Increasing acceptor strength increases inward torquoselectivity
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Houk, K. N. J. Am. Chem. Soc., 1993, 115, 4165.
!
R
R R
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Houk, K. N. J. Am. Chem. Soc., 1993, 115, 4165.
!
! Octatetraenes adopt a helicalelectrocyclic transition state
R
R R
! Electronic effects in elecrocyclizationare minimal; steric effects dominate
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Houk, K. N. J. Am. Chem. Soc., 1993, 115, 4165.
!
! Octatetraenes adopt a helicalelectrocyclic transition state
R
R R
! Electronic effects in elecrocyclizationare minimal; steric effects dominate
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1995, 60, 7134.
!R
RR
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1995, 60, 7134.
!
! Hexatrienes undergo disrotatorythermal electrocyclization
! Pseudoaxial hydrogens are calculatedto be within van der Waals radii (1.2 Å, H)
R
RR
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1995, 60, 7134.
!
! Hexatrienes undergo disrotatorythermal electrocyclization
! Pseudoaxial hydrogens are calculatedto be within van der Waals radii (1.2 Å, H)
R
RR
Torquoselectivity in Electrocyclic Reactions
! Additional examples of torquoselective effects
Thomas, B. E., Evenseck, J. D., Spellmeyer, D. C., Houk, K. N. J. Org. Chem., 1995, 60, 7134.
!R
RR
inward TS outward TS
HOMO
LUMO ! Additional steric repulsion in inward transition state vs cyclobutene
! Reduced overlap with " bonddecreases electronic contribution
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
MeMeMeMe
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
MeMeMeMe
MeMe
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
MeMeMeMe
MeMe
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
OTs
MeMeMeMe
MeMe
MeMe
MeMe
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
OTs
MeMeMeMe
MeMe
MeMe
MeMe
Me
Me
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
OTs
MeMeMeMe
MeMe
MeMe
MeMe
Me
Me
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
OTs
MeMeMeMe
MeMe
MeMe
MeMe
Me
Me
Rel. Rate
1
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
OTs
MeMeMeMe
MeMe
MeMe
MeMe
Me
Me
Rel. Rate
1
4
Torquoselectivity in Electrocyclic Reactions
! Transition state analysis of torquoselective electrocyclic opening
DePuy, C. H. Acc. Chem. Res., 1968, 1, 33.Faza, O. N., López, C. S., Álvarez, R., de Lera, A. R. Org. Lett., 2004, 6, 905.
OTs
OTs
OTs
MeMeMeMe
MeMe
MeMe
MeMe
Me
Me
Rel. Rate
1
4
18,000
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Denmark, S. E., Wallace, M. A., Walker, C. B. J. Org. Chem., 1990, 55, 5543.
OTMS OH
HH
88% ee 88% ee58% yield
FeCl3
CH2Cl2, -50 °C
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Denmark, S. E., Wallace, M. A., Walker, C. B. J. Org. Chem., 1990, 55, 5543.
OTMS OH
HH
88% ee 88% ee58% yield
FeCl3
CH2Cl2, -50 °C
O[Fe]TMS
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Denmark, S. E., Wallace, M. A., Walker, C. B. J. Org. Chem., 1990, 55, 5543.
OTMS OH
HH
88% ee 88% ee58% yield
FeCl3
CH2Cl2, -50 °C
O[Fe]TMS
axial TMS
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Denmark, S. E., Wallace, M. A., Walker, C. B. J. Org. Chem., 1990, 55, 5543.
OTMS OH
HH
88% ee 88% ee58% yield
FeCl3
CH2Cl2, -50 °C
O[Fe]TMS
equatorial TMS axial TMS
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Hutson, G. E., Türkmen, Y. E., Rawal, V. H. J. Am. Chem. Soc., 2013, 135, 4988.
O
R
Me
55-78% yield80-90% ee
R = Alkyl, Aryl
Cr-Salen (A)
CH2Cl2, rt,
O
Me
R4Å MS
O
N N
O
t-Bu
MesMes
t-Bu
H H
Cr
SbF6
Cr-Salen (A):
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Hutson, G. E., Türkmen, Y. E., Rawal, V. H. J. Am. Chem. Soc., 2013, 135, 4988.
O
R
Me
55-78% yield80-90% ee
R = Alkyl, Aryl
Cr-Salen (A)
CH2Cl2, rt,
O
Me
R4Å MS
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
Pd(PPh3)4 (10 mol%)
THF, reflux
NBoc
NMeO
H
BrMeO2C
NBoc
NMeO
H
MeO2CO
O
MeMe
55% (20:1 dr)
OO
MeMe
ClZn
Remote 1,6-stereoinductionin 6!-electrocyclization
Electrocyclic Reactions
! Additional examples of torquoselective reactivity
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
Pd(PPh3)4 (10 mol%)
THF, reflux
NBoc
NMeO
H
BrMeO2C
NBoc
NMeO
H
MeO2CO
O
MeMe
55% (20:1 dr)
OO
MeMe
ClZn
Remote 1,6-stereoinductionin 6!-electrocyclization
OO
MeMe
MeO2C
Via:
Electrocyclic Reactions
! Studies on differentially 3-substituted electrocyclization substrates
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
xylenes, reflux
NBoc
NH
R
NBoc
NH
RMe Me
Electrocyclic Reactions
! Studies on differentially 3-substituted electrocyclization substrates
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
xylenes, reflux
NBoc
NH
R
NBoc
NH
RMe Me
R
H
A-value
0
Product dr
3.5 : 1
Electrocyclic Reactions
! Studies on differentially 3-substituted electrocyclization substrates
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
xylenes, reflux
NBoc
NH
R
NBoc
NH
RMe Me
R
H
SPh
CO2Me
Me
A-value
0
0.8
1.3
1.7
Product dr
3.5 : 1
6.7 : 1
15.7 : 1
13.3 : 1
Electrocyclic Reactions
! Studies on differentially 3-substituted electrocyclization substrates
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
xylenes, reflux
NBoc
NH
R
NBoc
NH
RMe Me
R
H
SPh
CO2Me
Me
TMS
A-value
0
0.8
1.3
1.7
2.4
Product dr
3.5 : 1
6.7 : 1
15.7 : 1
13.3 : 1
4.3 : 1
Electrocyclic Reactions
! Studies on differentially 3-substituted electrocyclization substrates
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
xylenes, reflux
NBoc
NH
R
NBoc
NH
RMe Me
major product
Electrocyclic Reactions
! Studies on differentially 3-substituted electrocyclization substrates
Barcan, G. A., Patel, A., Houk, K. N., Kwon, O. Org. Lett., 2012, 14, 5388.Ashay, P., Barcan, G. A., Kwon, O., Houk, K. N. J. Am. Chem. Soc., 2013, 135, 4878.
xylenes, reflux
NBoc
NH
R
NBoc
NH
RMe Me
Additional eclipsing and allylic strain
minor product
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
CO2Me
Ph
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
CO2Me
Ph CO2MePh
1. H2, Pd/BaSO4,quinoline
2. toluene, !
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
CO2Me
Ph CO2MePh
CO2MePh
1. H2, Pd/BaSO4,quinoline
2. toluene, !
8"
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
CO2Me
Ph CO2MePh
CO2MePh
CO2MePh
HH
1. H2, Pd/BaSO4,quinoline
2. toluene, !
8"
6"
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
CO2Me
Ph CO2MePh
CO2MePh
CO2MePh
HH
1. H2, Pd/BaSO4,quinoline
2. toluene, !
endiandric acids F and Gmethyl ester
8"
6"
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
CO2MePh
HH
endiandric acid Gmethyl ester
CO2MePh
HH
endiandric acid Fmethyl ester
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
CO2MePh
HH
endiandric acid Gmethyl ester
CO2MePh
HH
endiandric acid Fmethyl ester
CO2Me
Ph
H
H
H
HH
H
endiandric acid Bmethyl ester
[4+2]
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
Electrocyclic Reactions in Synthesis
! Nicolaou's key cascade towards endiandric acids B, C, F and G
Nicolaou, K. C., Zipkin, R. E., Petasis, N. A. J. Am. Chem. Soc., 1982, 104, 5558.Nicolaou, K. C., Petasis, N. A., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5560.
CO2MePh
HH
endiandric acid Gmethyl ester
[4+2]
CO2MePh
HH
endiandric acid Fmethyl ester
MeO2C
Ph
CO2Me
Ph
H
H
H
HH
H
endiandric acid Bmethyl ester
endiandric acid Cmethyl ester
[4+2]
Nicolaou, K. C., Petasis, N. A., Zipkin, R. E., Uenishi, J. J. Am. Chem. Soc., 1982, 104, 5555.Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. J. Am. Chem. Soc., 1982, 104, 5557.
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