Pericyclic Reactions: Part–2
D. A. Evans
Chem 206
■ Other Reading Material:
http://www.courses.fas.harvard.edu/~chem206/
Chemistry 206
■ Woodward-Hoffmann Theory
R. B. Woodward and R. Hoffmann, The Conservation of Orbital
Symmetry, Verlag Chemie, Weinheim, 1970.
Advanced Organic Chemistry
■ Frontier Molecular Orbital Theory
I. Fleming, Frontier Orbitals and Organic Chemical Reactions,
John-Wiley and Sons, New York, 1976.
Lecture Number 12
■ Dewar-Zimmerman Theory
T. H. Lowry and K. S. Richardson, Mechanism and Theory in
Organic Chemistry, 3rd Ed., Harper & Row, New York, 1987.
Pericyclic Reactions–2
■ Electrocyclic Reactions
■ Cheletropic Reactions
■ Sigmatropic Rearrangements: [1,2], [1,3], [1,5]
■ General Reference
R. E. Lehr and A. P. Marchand, Orbital Symmetry: A Problem
Solving Approach, Academic Press, New York, 1972.
■ Problems of the Day:
Predict the stereochemical outcome of this reaction.
O
Ph O
Ph
O
■ Reading Assignment for week:
O
❉
O
Carey & Sundberg: Part A; Chapter 11
Concerted Pericyclic Reactions
Ph
❉
heat
Huisgen, TL, 1964, 3381.
O
Ph
Fleming: Chapter 4
Thermal Pericyclic Reactions
Houk, et. al. Acc. Chem. Res. 1996, 29, 471-477.
Houk, et. al. JOC. 1996, 61, 2813-2825.
Matthew D. Shair
Monday,
Columbus Day,
October 14, 2002
Suggest a mechanism for the following reaction.
H
CO2Me
heat
H
MeO2C
CO2Me
Bloomfield, TL, 1969, 3719.
CO2Me
H
H
Electrocyclic Processes-1
Evans, Breit
Electrocyclic Reaction - Selection Rules
Controtation
and
on to the indicated bonding and anti-bonding
orbitals of cyclobutene:
Ground State
(Thermal process)
Excited State
(Photochemical Process)
4n π e(n = 1,2...)
conrotatory
disrotatory
4n+2 π e(n = 0,1,2...)
disrotatory
Examples
Chem 206
LUMO
Con
HOMO
conrotatory
Ground State
Excited State
Conrotatory
Con
LUMO
Disrotatory
HOMO
Disrotatory
Conrotatory
Activation Energy (kcal/mol)
for electrocyclic ring opening
Conrotatory
Disrotatory
42
45
Disrotatory
Conrotatory
29
27
Conrotatory
Disrotatory
H
Activation Energy (kcal/mol)
for electrocyclic ring opening
H
Criegee, Chem. Ber. 1968, 101, 102.
Conrotatory
Disrotatory
Ph O
Disrotatory
Conrotatory
Ph
O
O
Ph
O
O
R
R
Con
R
Ph O
O
O
Ph
O
Ph
O
Con
R
R
R
O
R
R
Sterically favored
Ph
Huisgen, TL, 1964, 3381.
Ph
O
Electrocyclic Processes-2: Torquoselectivity
Evans, Breit
Torquoselectivilty is defined as the predisposition of a given R
substituent for a given conrotatory motion
How do we explain?
Chem 206
Donor substituents prefer con–out mode
Pi acceptor substituents prefer con–in mode
Houk et al. Acc. Chem. Res 1996, 29, 471
R
View the 2 conrotatory modes by looking at
the breaking sigma bond from this perspective
R
R
R
con
con
H
in
H
out
R
Examples:
Donor substituents prefer con–out mode
Pi acceptor substituents prefer con–in mode
R
H
H
Inward Motion
Outward Motion
R
R
con
R
+
H
H
R = Me
R = CHO
H
none
only
only
none
H
H
H
H
H
H
LUMO + p
LUMO + p
CH2OBn
CHO
H H
CH2OBn
con
+
H
H
CH2OBn
H
CHO
CHO
ratio: >20:1
A
H
H
H
H
HOMO + p
Me
CN
con
CN
CN
+
Me
ratio: 4:1
Me
As conrotation begins the energy of
the breaking sigma bond rises
steeply. Hyperconjugation with a pi*
orbital, while possible in both A & B ,
is better in B. (Houk)
H
H
H H
H
HOMO + p
destabilizing 4 electron
interation for donor
substituents
stabilizing 2 electron
interation for acceptor
substituents
B
Electrocyclic Processes-3: 3-Atom Electrocyclizations
Evans, Breit
Three-Atom Electrocyclizations (2 electrons)
A
H
H
Dis??
R
R
R
H
H
A
Does solvolysis proceed via cation 1 followed by rearrangement to 2
(Case 1), or does it proceed directly to 2 (Case 2)?
H
Con??
C
A
H
Solvolysis of Cyclopropyl Derivatives
A
A
Chem 206
A
fast
slow
X
Case 1
H
–X–
1
2
X
Case 2
fast
slow
–
+X–
–X
nonbonding
TsO
TsO
H
H
Ψ1
anion
Me
+
A
R
+
Dis
H
A
Me
LUMO
H
HOMO
R
R
R
X
Dis
Dis
Favored for R = ring
R
H
R
Dis
H
Me
HOMO
Me
X
H
LUMO
Me C
R
Sterically favored
Me
Me
R
R
C
C
Note that there are two disrotatory modes
R
40,000
H
X
H
R
Me
DePuy, Accts. Chem. Res. 1967, 1, 33
C
C
A
H
Me
H
4
H
A
H
H
1
H
TsO
H
relative rate
LUMO
Me
R
H
C
H
HOMO
Me
R
Dis
+
cation
R
X
2
+
Ψ2
X
+X–
fast
Ψ3
Me
H
Electrocyclic Processes-3: 3-Atom Electrocyclizations
Evans, Breit
Solvolysis Summary
dis-in
dis-out
Unfavorable
favorable
TsO
TsO
Me
H
Me
TsO
H
H
1
A
H
H
Dis??
R
Me
H
R
H
Con??
A
H
A
A
C
A
Me
H
relative rate
Three-Atom Electrocyclizations (4 electrons)
H
H
Chem 206
R
H
H
A
40,000
4
Ring-fused Cyclopropyl Systems
Ψ3
When the cis substiltutents on the cyclopropyl ring are tied together
in a ring the following observsations have been made
Ψ2
TsO
TsO
H
H
H
H
H
nonbonding
Ψ1
H
favored
relative rate: > 10
H
R
H
H
TsO
H
CH2
H
disavored
H
Cl
base
O–
H CO2Me
Con
A
H
CO2Me
••
Ar N
•• (–)
MeO2C
Con
Ar N
(+)
3-exo-tet
MeO2C
CO2Me
Ar N
(+)
MeO2C
H CO2Me
products
B C
C
R
••
Ar N
O
–Cl–
disallowed
C
A
dis-in
Cl
Con
B
Observation
Revisiting the Favorski rearrangement: (Carey, Part A, pp 506-8)
O–
A
B
H2C
dis-out
O
C
B
••
A
H2C
TsO
anion
cation
dis-in
+6
H
MeO2C
•• (–)
Electrocyclic Processes-3
Evans, Breit
Chem 206
Five-Atom Electrocyclizations (4 electrons)
The Nazarov Reaction
O
R
R
Dis??
❋
A
A
A
+H+
R
Con??
❋
A
O
OH
❋
A
A
A
A
–H+
A ❇
A
❇ A
A
Denmark, S. E. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5; pp 751.
O
O
nonbonding
+H
+
predict
stereochemistry
❇
❇
Eight-Atom Electrocyclizations (8 electrons)
A
Anion
Cation
Dis??
Pentadienyl Cation
A
A
LUMO
+
Con
●
A
A
A
Con??
A
H
HOMO
C
A
A
C
H
A
Let's use the "Ready" shortcut to find the homo: Nodes will appear at
single bonds
symmetry of homo
Pentadienyl Anion
A
H
●
Dis
●
–
••
C
A
C
A
A
H
Closure should be conrotatory
Cheletropic Processes-1
Evans, Breit
CHELETROPIC REACTIONS: [n+1] Cycloadditions (or Cycloreversions)
Chem 206
2 + 1 CheletropicReaction: Olefins + Singlet Carbene
Concerted processes in which 2 σ-bonds are made (or broken) which terminate at
a single atom.
R
R
C
C
[4+2]
R
R
+
Linear Approach: 2 HOMO-LUMO Interactions
O
O
[4+1]
S
S
+
C
O
O
R
R
C
General
C
R
R
C
Reversion
Y
X
Addition
Z
LUMO
Y
π-system
π-system
HOMO
+
LUMO
HOMO
Nonlinear Approach: 2 HOMO-LUMO Interactions
X
Z
R R
Y
X
C
Z
N N
C O
Singlet-Carbene
Addition (and Reversion)
N N O
SO2
C
C
C
C
Reversion
and Addition
Cycloreversion only
R R
LUMO
Frontier Orbitals
sp2 (filled)
0
2
p (empty)
HOMO
E
ω0
Y
Carry out the analysis of the indicated hypothetical transformation
ω2
X
Me
Z
Me
Y
Y
C
Question: what is orientation of carbene
relative to attacking olefin??
LUMO
HOMO
Z
Z
R
Me
C
C
Me
R
predict approach geometry of carbene
Cheletropic Processes-2
Evans, Breit
Let's now consider SO2 as the one-atom component
Chem 206
Key step in the Ramberg Bäcklund Rearrangement
R1
O
O
O
S
S
S
O
O
X
O
O
R1
4e– in pi system
filled
filled
empty
S
O
Me
O
Me
reactions are:
stereospecific & reversible
S
O
R1
R
O
S
O
S
O
O
O
O–
S
O
O
S
S
O–
empty (LUMO)
O
O
O–
LUMO
filled
R2
SO2
O
HOMO
LUMO
-SO2
2
S
empty (LUMO)
O
R2
Z
O
O
O
O
R1
R1
+
Me
S
R2
Clough, J. M. The Ramberg-Backlund Rearrangement.; Trost, B. M. and Fleming, I.,
Ed.; Pergamon Press: Oxford, 1991; Vol. 3, pp 861.
"The Ramberg-Backlund Rearrangement.", Paquette, L. A. Org. React. (N.Y.) 1977,
25, 1.
O
S
R
2
base
R1
S
Me
-SO2
Analysis of the Suprafacial SO2 Extrusion (nonlinear)
O
suprafacial
HOMO
base
S
O
Me
O
O
O
O
suprafacial
Me
R2
S
Me
Me
R1
E
O
S
S
O
R2
filled
Similar to carbene geometry
S
O–
Sigmatropic Rearrangements-1
D. A. Evans
Sigmatropic rearrangements are those reactions in which a sigma bond
(& associated substituent) interchanges termini on a conjugated pi system
■ Examples:
X
Y:–
R
X
X
∆
H3
C
Retention at carbon
∆
R
antibonding
H
X
■ [1,3] Sigmatropic Rearrangements (H migration)
H
H
Y
X
∆
X
Consider the orbitals needed to contruct
the transition state (TS).
X
‡
Y
H
X
Y
❐ The stereochemical constraints on the suprafacial migration of carbon
with inversion of configuration is highly disfavored on the basis of strain.
Y
[1,3]-Sigmatropic rearrangements are not common
D
no observed scrambling of labels
bonding
H
antibonding
H
X
X
H
H
H
Y
H
Sychronous bonding to both termini
is possible from this geometry
■ Construct TS by uniting an allyl and H radical:
bonding
H
bonding
Suprafacial on allyl fragment
Sychronous bonding to both termini
cannot be achieved from this geometry
H
C
H X
bonding
Suprafacial on allyl fragment
consider the 1,3-migration of H
Y
Inversion at carbon
bonding
X
H
‡
Y
X
C R
H
X
H
Y
❐ Construct TS by uniting an allyl and Me radicals:
R
[1,5] Sigmatropic rearrangement
X
Y
X
∆
[3,3] Sigmatropic rearrangement
CH3
∆
Consider the orbitals needed to contruct
the transition state (TS).
–:X
[2,3] Sigmatropic rearrangement
CH3
consider the 1,3-migration of Carbon
X
R
R
X
■ [1,3] Sigmatropic Rearrangements (C migration)
X
∆
[1,3] Sigmatropic rearrangement
Chem 206
Y
‡
C
Y Ψ2 (allyl HOMO)
1
✻
X
Me
Me
D
∆
✻
Me
1
H
120 °C
H
bonding
Suprafacial Geometry
Antarafacial Geometry
Bridging distance too great for antarafacial migration.
3
1
3
3
These rearrangements are only seen in systems that are highly strained,
an attribute that lowers the activation for rearrangement.
Sigmatropic Rearrangements-2
D. A. Evans
■ [1,5] Sigmatropic Rearrangements (C migration)
SIGMATROPIC REACTIONS - FMO-Analysis
2
4
3
R
2
∆/hν
1
4
5
1
R = H, CR3
5
Chem 206
3
[1s,5s] alkyl shift ⇒ RETENTION
R
■ [1,5] Sigmatropic Rearrangements (H migration)
[1a,5a] alkyl shift ⇒ INVERSION
disfavored
■ [1,5] (C migration): Stereochemical Evaluation
Me
Me
Me
RETENTION
nonbonding
230-280°C
hν
H
[1,5s]C- shift
[1,5s]H- shift
Me
Me
Me
Dewar–Zimmerman Analysis: Retention
thermal
R
photochemical
R
H
R
R
H
R
H
H
H
R
H
suprafacial preferred
R
H
H
View as cycloadditon between following species:
R
H
R
H
H
H
H
H
H
+
0 phase inversions ⇒ Huckel toplogy
6 electrons
therefore, allowed thermally
R
either, or
pentadienyl radical
pentadienyl radical
H
Sigmatropic Rearrangements-3
D. A. Evans
■ [1,2] Sigmatropic Rearrangements: Carbon
The Wittig Rearrangement [1,2]
[1,2] Concerted sigmatropic rearrangements to cationic centers allowed
R
+
R
+
Chem 206
"[2,3]-Wittig Sigmatropic Rearrangements in Organic Synthesis.", Nakai,
T.; Mikami, K. Chem. Rev. 1986, 86, 885.
Marshall, J. A. The Wittig Rearrangement.; Trost, B. M. and Fleming, I.,
Ed.; Pergamon Press: Oxford, 1991; Vol. 3, pp 975.
Li
O
consider as cycloaddition
C–R homoylsis
R
R
O
BuLi
●
R
+
●
●
R●
This 1,2-sigmatropic
rearrangement is
non-concerted
R
●
R
Li
O
O
olefin radical cation
transition state
The Wittig Rearrangement [2,3]
R
Li
[1,2] Concerted sigmatropic rearrangements to carbanionic centers not observed
O
R
●●
stepwise
R
R
●●
C–R homoylsis
consider as cycloaddition
C–R homoylsis
OLi
●
R
●
●●
C
O
●
●●
C
O
R
H
antibonding
●
●
●●
●
●●
ketyl radical
R
R
H
olefin radical anion
transition state
Allyl radical
Allyl radical
Li