哈佛大学高等有机化学讲义Lecture12

Torquoselectivilty is defined as the predisposition of a given R substituent for a given conrotatory motion Houk et al. Acc. Chem. Res 1996, 29, 471
R
con in
Ph
O
Suggest a mechanism for the following reaction.
H CO2Me MeO2C CO2Me H
heat
H CO2Me
Matthew D. Shair
H
Bloomfield, TL, 1969, 3719.
Evans, Breit
Electrocyclic Reaction - Selection Rules Ground State (Thermal process) 4n π e(n = 1,2...) 4n+2 π e(n = 0,1,2...) conrotatory
TsO H H H H
+6
Ψ2
nonbonding
TsO H
H
Ψ1 cation anion
favored
relative rate: > 10 H TsO H H TsO H
dis-in
H2C H H H2C CH2
A
R
••
Con R
B C B C C A A
C A B
B
disavored
dis-out
Observation
•• Ar N
H CO2Me Con H CO2Me Ar N (+) MeO2C MeO2C Con Ar N (+) H MeO2C
CO2Me •• (–)
Revisiting the Favorski rearrangement: (Carey, Part A, pp 506-8)
s Woodward-Hoffmann Theory R. B. Woodward and R. Hoffmann, The Conservation of Orbital Symmetry, Verlag Chemie, Weinheim, 1970. s Frontier Molecular Orbital Theory I. Fleming, Frontier Orbitals and Organic Chemical Reactions, John-Wiley and Sons, New York, 1976. s Dewar-Zimmerman Theory T. H. Lowry and K. S. Richardson, Mechanism and Theory in Organic Chemistry, 3rd Ed., Harper & Row, New York, 1987. s General Reference R. E. Lehr and A. P. Marchand, Orbital Symmetry: A Problem Solving Approach, Academic Press, New York, 1972.
Evans, Breit
Electrocyclic Processes-2: Torquoselectivity
How do we explain?
R R R
Chem 206
Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode
D. A. Evans
Pericyclic Reactions: Part–2
s Other Reading Material:
Chem 206
http://www.courses.fas.harvard.edu/~chem206/
Chemistry 206 Advanced Organic Chemistry
View the 2 conrotatory modes by looking at the breaking sigma bond from this perspective
H
con
H
out
R R H H
Examples:
Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode
The Nazarov Reaction
O OH +H+ A A A A f f A –H+ A O R Con?? A A
p
Chem 206
R
p
R Dis?? A A
p
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 +H
Solvolysis of Cyclopropyl Derivatives
A Con?? A H H R H A Case 1 X slow –X– 1 fast H 2 fast slow –X
–
Chem 206
Three-Atom Electrocyclizations (2 electrons)
Lecture Number 12
Pericyclic Reactions–2
s Electrocyclic Reactions s Cheletropic Reactions s Sigmatropic Rearrangements: [1,2], [1,3], [1,5]
s Problems of the Day:
destabilizing 4 electron interation for donor substituents stabilizing 2 electron interation for acceptor substituents
Evans, Breit
Electrocyclic Processes-3: 3-Atom Electrocyclizations
27
Disrotatory
O Ph
Conrotatory
Disrotatory
Ph O
O
O O
Disrotatory
Conrotatory
Ph Ph O O O
R Con R R R R
R
Con
R
Ph O
O
O
Ph
R Sterically favored
Ph Huisgen, TL, 1964, 3381. Ph O
Electrocyclic Processes-1
Chem 206
Controtation and on to the indicated bonding and anti-bonding orbitals of cyclobutene:
LUMO
Excited State (Photochemical Process) disrotatory conrotatory
Predict the stereochemical outcome of this reaction.
Ph O O O Ph
h
O O
s Reading Assignment for week: Carey & Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Fleming: Chapter 4 Thermal Pericyclic Reactions
Houk, et. al. Acc. Chem. Res. 1996, 29, 471-477. Houk, et. al. JOC. 1996, 61, 2813-2825. Monday, Columbus Day, October 14, 2002
Ph
heat
h
Huisgen, TL, 1964, 3381.
ratio: >20:1
Me CN CN CN
H H
H H HOMO + p
H H H
Biblioteka Baidu
B
con
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)
R R
Outward Motion +
R H H H
Inward Motion
con
H
R = Me R = CHO
CH2OBn CHO H H
only none
CH2OBn
none only
H H LUMO + p
H H
H H H LUMO + p
con +
CHO
CH2OBn H CHO
A
H H HOMO + p
dis-out
favorable H Me R A
Three-Atom Electrocyclizations (4 electrons)
H H A H A Dis?? R C H A Con?? R H A A H
relative rate
1
4
40,000
Ψ3
Ring-fused Cyclopropyl Systems When the cis substiltutents on the cyclopropyl ring are tied together in a ring the following observsations have been made
O Cl base O– Cl –Cl– 3-exo-tet disallowed O– O
dis-in
•• Ar N
H CO2Me
MeO2C products
•• (–)
Evans, Breit
Five-Atom Electrocyclizations (4 electrons)
Electrocyclic Processes-3
HOMO Dis
C
Note that there are two disrotatory modes
R R X Dis R X R R Dis R Sterically favored R Favored for R = ring R R LUMO
X
Me H Me C C H
HOMO Dis
+
H
R
+
A H R A H Dis?? R C H A
Does solvolysis proceed via cation 1 followed by rearrangement to 2 (Case 1), or does it proceed directly to 2 (Case 2)?
Ψ3 fast +X– 2 Me H H Case 2 Ψ2 nonbonding X
+X–
X
TsO Ψ1 cation anion H
TsO H
Me
TsO H
H Me
H Me
relative rate 1
LUMO
4
DePuy, Accts. Chem. Res. 1967, 1, 33
40,000
+
R
H A H A
R Dis
+
H A C H C A
HOMO
X
LUMO
H Me H C Me Me
Con
HOMO
disrotatory
Examples
Ground State Conrotatory
Excited State Disrotatory
Con
LUMO
HOMO
Disrotatory
Conrotatory
Activation Energy (kcal/mol) for electrocyclic ring opening
Me H
R
R
H H
Me Me
Evans, Breit
Solvolysis Summary
TsO H TsO
Electrocyclic Processes-3: 3-Atom Electrocyclizations
dis-in
Unfavorable Me H H Me H TsO H H Me
Chem 206
Activation Energy (kcal/mol) for electrocyclic ring opening
Conrotatory
Disrotatory
42
45
Disrotatory Conrotatory
Conrotatory
H
29
H Criegee, Chem. Ber. 1968, 101, 102.