Transcript
CBMS304/CBMS804; Advanced Organic and Biological Chemistry B, Topic 2 Pericyclic No
Reactions
intermediates No electrophile or nucleophile Rate not dependant on solvent Two or more bonds are broken simultaneously Catalysed by light or heat Are reversible
MAP FOR 331
CONCEPT
2 new -bonds 2 less -bonds
cycloadditions
electrocyclic reactions
thermal
photoc hemi hemicc al
thermal
[4n + 2] electrons
[4n] electrons
conrotatory
HOMO + LUMO sec ondary orbi orbital tal over lap = exo or endo TS regioselec tivit tivity y bas bas ed on electronegativity
ring closing: HOMO of
1 new -bonds 1 less -bonds
photoc hemi hemic c al
disrotatory
ring opening: HOMO of , LUMO of
0 new -bonds bonds shifted sigmatropic rearrangem ents 0 less -bonds rearrangem
photoc hemical
thermal
suprafacial
antarafacial
HOMO of , LUMO of
H-shift C-shift
MAP FOR 331
CONCEPT
2 new -bonds 2 less -bonds
cycloadditions
electrocyclic reactions
thermal
photoc hemi hemicc al
thermal
[4n + 2] electrons
[4n] electrons
conrotatory
HOMO + LUMO sec ondary orbi orbital tal over lap = exo or endo TS regioselec tivit tivity y bas bas ed on electronegativity
ring closing: HOMO of
1 new -bonds 1 less -bonds
photoc hemi hemic c al
disrotatory
ring opening: HOMO of , LUMO of
0 new -bonds bonds shifted sigmatropic rearrangem ents 0 less -bonds rearrangem
photoc hemical
thermal
suprafacial
antarafacial
HOMO of , LUMO of
H-shift C-shift
Bonding in carbon compounds Valence
bond model
Equates Thus
2p
{ 2s
1s
covalent bonds with the sharing of two electrons
H should form 1 bond and O 2 etc.
Lewis
rule of eight Aufbau principle Pauli exclusion principle
Valence Bond Theory Thus
Oxygen should form two bonds And Nitrogen three bonds But why does carbon form four bonds?
H
O
H
H
N
H
Hybridisation Carbon
should form two bonds but it usually forms
four
sp3 H H C
C H
H
Pauling theory of hybridisation Mathematical
combination of s and p orbitals gives
sp3 hybrids This explains four equivalent bonds and tetrahedral geometry
4
+ 3 s
p
sp3
Does H2+ exist? Correlation Diagrams
H:H
•
Rule #1: Conservation of Orbital Number
H.H+ ?
H
H:.H+
H
Why is O2 paramagnetic?
O
O
Rule
#2: Sigma () Orbitals are Always the Lowest Energy [and Sigma* (*) the Highest] Rule #3: pi () Orbitals are Higher in Energy than but pi* (*) are Lower than * •
O
O
•
2p
2p
O
O
H
Ethylene (or is it ethene)?
H C
H
C H
Rule
#2: Sigma () Orbitals are Always the Lowest Energy [and Sigma* (*) the Highest] Rule #3: pi () Orbitals are Higher in Energy than but pi* (*) are Lower than *
LUMO
sp2
sp2 HOMO
Frontier Molecular Orbitals Highest
Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are the orbitals that can either donate or receive electrons from another molecule and thus are the most important The HOMO of one reactant interacts with the LUMO of the other ie a filled orbital of one and an empty orbital of another are the closest in energy
NH3 + H-Cl
NH4Cl
Is
something as simple as the reaction of ammonia with hydrochloric acid describable with a correlation diagram? HOMO sp3
*
LUMO
n
NH3
HCl NH4+
Reaction of ethylene and bromine The
HOMO of ethylene is the -bond The LUMO of Bromine in the * orbital
LUMO
LUMO
HOMO
HOMO
Guidelines to Constructing Molecular Orbitals in Conjugated Systems With n p-orbitals you get n -orbitals (Rule #1) The energy of the -orbital increases with the number of nodes (Rule #5) Nodes MUST be symmetrically placed Bonding () orbitals have energies less than an isolated p-orbital Non-bonding (n) orbitals have the same energy as an isolated porbital Antibonding (*) orbitals have greater energy than an isolated porbital Rotation (or reflection) about the centre of the conjugated system produces an image with phases reversed (A) or the same (S)
The Allyl system Bonds
–2
nodes *
0
n
1
+2
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A
S
A
The Butadiene system C2
mirror
S
A
A
S
S
A
A
S
The Cyclobutadiene System Nodes Bonds 3
–3
2
–1
1
+1
0
+3
Nodes Bonds 4
–4
2
0
0
+4
The Cyclohexatriene System Nodes Bonds –5 5
4
3
Nodes Bonds
A
–3
S
–1
A S
2
+1
1
+3
A
0
+5
S
6
–6
4
–2
2
2
0
6
A
S
A
S
A
S
Pericyclic reactions Concerted E.g.
HO –
SN2 reactions H
H C H
reactions proceed with no intermediate
H
Br
HO
C
H Br
HO
C H
H H
H
Br –
Pericyclic reactions are concerted reactions with a cyclic transition state
Examples
O
O
Cycloadditions
O
+
O
O
O
1,-3-dipolar additions
O
O
Ph
N
N
N
N
Electrocyclic reactions
N O
h
Ph
N H
O
O
Sigmatropic rearrangements O
O
OH
H
Cycloadditions
2 new -bonds 2 less -bonds
cycloadditions
thermal
photoc hemic al
[4n + 2] electrons
[2n + 2] electrons
HOMO + LUMO secondary orbital overlap = exo or endo TS regioselectivity based on electronegativity
Cycloaddition Reactions: Mechanism The simplest example is the photolysis of ethylene: A [2+2]-cycloaddition 1. Arrow pushing
Electrons can go either way
Cycloaddition Reactions: Mechanism
Consider two ethylenes approaching each other and the orbitals slowly become -orbitals
Cycloaddition Reactions: Mechanism
2. Correlations Diagrams 2 -bonds
are converted to two -bonds
A
A
S
S
A
S
S
A
Cycloaddition Reactions: Mechanism
2. Correlations Diagrams Photochemically
allowed: Excited state goes to excited state
Cycloadditions: Mechanism 3.
Frontier Molecular Orbital (FMO) approach
HOMO LUMO
LUMO X
HOMO
Cycloadditions: [4 +2 ]-Cycloaddition Also
known as the Diels-Alder reaction Involves a 4-electron system (diene) and A 2-electron system (dienophile) 3 -bonds become 2 -bonds and one new -bond Need to consider only the orbitals that change.
Cycloadditions: [4 +2 ]-Cycloaddition Also
known as the Diels-Alder reaction
S
A
A
A
S
A
S
S
m1
A
S S
A
Cycloadditions: [4 +2 ]-Cycloaddition FMO
model LUMO
LUMO
HOMO
LUMO HOMO
HOMO
HOMO LUMO
Cycloadditions: [4 +2 ]-Cycloaddition Aromatic Add
TS Rule
up the number of electrons involved in the transition state (TS) If the TS is aromatic then the reaction is thermally allowed (4n+2) electrons is the magic number because it allows electron delocalisation and REDUCTION in overall energy
Secondary Effects: Secondary Orbital Overlap Notice
that in the Diels-Alder reaction the dienophile approaches the diene from one face: Suprafacial.
Qui ckTim e™ and a
GIF decomp res sor are needed to see this pic ture.
Secondary Effects: Secondary Orbital Overlap What happens if the dienophile is more than just an alkene? For the dimerisation of cyclopentadiene, you can have endo or exo attack
exo
endo
Secondary Effects: Secondary Orbital Overlap
The two orientations end up with different stereochemistries
exo H H H H
endo
Secondary Effects: Secondary Orbital Overlap
Frontier molecular orbital analysis
LUMO
exo
HOMO endo
DNA damage; an example of [2 +2 ]cycloaddition
Two thymidine bases can react when one is excited photochemically.
O
O
HN O
O NH
N
N
280 nm O 240 nm
O
HN O
NH N
N H H
O
Not all cycloadditions are endo [6+4]-cycloadditions
Exo O
O
Endo X O
O
Secondary effects: Regioselectivity If
the diene and dienophile are substituted many products are possible OCH3
CHO
OCH3
CHO
OHC OCH3
OCH3
OCH3 CHO
CHO
Secondary effects: Regioselectivity [4+2]-cycloaddition,
therefore thermally allowed Aldehyde has a double bond that is conjugated with the dienophile so it is really a diene too Substituents on the diene and dienophile can polarise the pi-system to favour one orientation over another
Secondary effects: Regioselectivity Resonance
effects can explain the regioselectivity
O H
O H
H
O O H OCH3
OCH3
OCH3
Secondary effects: Regioselectivity
Secondary orbital overlap explains the stereoselectivity
H3CO
H3CO
HOMO H
O
LUMO H
O
Secondary effects: Regioselectivity Only
one product is formed OCH3
OCH3 CHO
CHO
OHC OCH3
OCH3
OCH3 CHO
CHO
1,3-dipolar addition Another
example of [4+2]-cycloaddition
1,3-dipolar addition Correlation
diagram is constructed as usual S
S
A
A n
A S S
S
S
A
1
1,3-dipolar addition FMO
analysis Take the HOMO and LUMO of two reactants See if the orbitals overlap constructively or not anion
cation
HOMO
HOMO
LUMO
LUMO
1,3-dipolar addition Ozonolysis
of an alkene is an example of 1,3-dipolar
addition The malozonide is the product of the addition which quickly rearranges to the ozonide O O
O
O
O O
O
malozonide
O
O
O
O O
Larger rings Explain
the following reaction:
1.
Draw arrows to explain the mechanism 2. Use frontier molecular orbitals to determine if the reaction is allowed or forbidden 3. Identify the HOMO and LUMO of each reactant 4. Does the HOMO of one overlap with the LUMO of the other in a constructive fashion?
Larger rings LUMO
of the hexatriene has 3 nodes HOMO of alkene has none
LUMO HOMO
Larger rings For
larger rings, the ends can be flexible
antarafacial
suprafacial
Summary Cycloadditions involve bonds to two -bonds They
the conversion of two -
can be allowed (thermal) or forbidden (requires electronic excitation of one reactant) Allowed reactions involve [4n+2] electrons Photochemical reactions require [4n] electrons Exo and Endo products are determined by secondary orbital overlap Regiochemistry is determined by electronic effects Reactions are typically suprafacial but larger rings can react in an antarafacial way
Summary Adding two more electrons reverse the rules Catalysing with UV-light reverses the rules Going from suprafacial to antarafacial reverses the rules
Summary
2 new -bonds 2 less -bonds
cycloadditions
thermal
photoc hemic al
[4n + 2] electrons
[2n + 2] electrons
HOMO + LUMO secondary orbital overlap = exo or endo TS regioselectivity based on electronegativity
Electrocyclic
Reactions
electrocyclic reactions
thermal
conrotatory
ring closing: HOMO of
1 new -bonds 1 less -bonds
photoc hemic al
disrotatory
ring opening: HOMO of , LUMO of
Electrocyclic Reactions Involve
the conversion of two -bonds into a -bond and a new -bond What happens if the butadiene is substituted? If this is like the other pericyclic reactions the reaction should go with stereospecificity
Cycloaddition Reactions The
reverse reaction (ring opening) is possible because it is an equilibrium system R
H
R
Conrotatory
H
cis
H
H
R
H
cis
R
R
H H
R
trans
R
cis
R
Disrotatory
Disrotatory vs Conrotatory Look
at the reaction in more detail Disrotation
Conrotation mirror
Disrotatory
Conrotatory
axis of
Conrotatory and Disrotatory
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Disrotatory Correlation Diagram energy R R R H H
H
A R
H A
R
R
H
R H A
H H S
R
R
R
R H H H
S
H A
R R H
R
H
R H
S
R
Thermally forbidden
Conrotatory Correlation Diagram energy R R R H H
R
A R
H S
H
R
H
R H S
R H A
H
R
R
R R H H
A
H S
H R R
R
H
R H
A
H
Thermally allowed
FMO approach R R H
R
H R
H
H H
H R
HOMO
R H H R R H
R R
R
R
LUMO
H HHOMO
Biosynthesis of vitamin D An
example of a biological electrocyclic reaction
H
H
H
HO
HO
ergosterol
lumisterol
h h H HO
H
Biosynthesis of vitamin D Looking
at just the reacting ring
H
H
HOMO
H H
LUMO
H
Biosynthesis of vitamin D
Provitamin D2 is converted spontaneously to vitamin D
H HO
H HO
provitamin D2
vitamin D2
Sigmatropic
Rearrangements
0 new -bonds bonds shifted sigmatropic rearrangem ents 0 less -bonds
photoc hemical
thermal
suprafacial
antarafacial
HOMO of , LUMO of
H-shift C-shift
Sigmatropic Rearrangements Nomenclature
2 2 1
1'
3
2'
3'
1
3
1'
3' 2'
One sigma bond is destroyed and a new one made
Sigmatropic Rearrangements Nomenclature,
[3, 3]-sigmatropic shift
2 2 1
1'
3
2'
3'
1
3
1'
3' 2'
Cope Rearrangement HOMO
LUMO
LUMO
of and LUMO of -bonds
HOMO
Name this reaction
5 6 4 3
1' 2
1
new -bond
HOMO new -bond
LUMO
Charged species Name
this sigmatropic rearrangement
2 1
3
base
O 1'
2'
Ph
O
O Ph
Ph
Biosynthesis of vitamin D
Provitamin D2 is converted spontaneously to vitamin D
H
H HO
H HO
provitamin D2
vitamin D2
[1,7]-migrations should be forbidden So
why does it proceed spontaneously in the biosynthesis of vitamin D?
HOMO
LUMO suprafacial
antarafacial
Last silde many peaks does this compound have in its 1H NMR spectrum?
How
Macquarie University
Where is Macquarie University???
