Conjugated Systems

When the p orbitals of double bonds are on adjacent atoms, the double bonds are said to be conjugated

This conjugation leads to differences in the properties of conjugated dienes

Due to the conjugation the electrons can resonate between all conjugated p orbitals

This resonance cannot occur between isolated double bonds

Energy Differences in Conjugated Systems

As seen with other structures that can resonate, the extra resonance forms lead to a more stable system

Conjugated systems are thus more stable than isolated double bonds

stability

Remember from discussion of alkene stability, more substituted double bonds are more stable due to stability offered by hyperconjugation

Therefore the stability of diene isomers can also be predicted due to conjugation and amount of substitution on the double bonds

Can measure stability by hydrogenation

H2catalyst

The energy required for this hydrogenation indicates the stability of the alkene

28.6 Kcal/mol

57.4 Kcal/mol 55.4 Kcal/mol

Almost double in energy

2 Kcal/mol Conjugation stability

Energy Differences in Conjugated Systems

Conjugated systems are thus always lower in energy than isolated double bonds

Structural Differences in Conjugated Systems

Due to the resonance in conjugated double bonds, the bond distances are not strictly “single” or “double” bond lengths

1.53 Å 1.32 Å

1.47 Å

In order for the double bonds to resonate, however, the p orbitals must be aligned

s-trans s-cis

s-trans is more stable due to sterics with hydrogens with the s-cis conformation

H

H

H

HH

H

HH

HH

H H

Allenes

The shortest possible diene system would be propadiene (called “allene”)

H2C C CH2

The two double bonds of allene though are not conjugated

HH

H

H

The central carbon of allene must form a π bond with both adjacent carbons, thus the p orbitals used must be orthogonal

Allenes are thus less stable than either conjugated or isolated double bonds

Alkyne Isomerization using Allenes

When internal alkynes are reacted with strong base, they isomerize to terminal alkynes

NaNH2NH3

The mechanism for this isomerization is first to abstract a hydrogen adjacent to the alkyne which resonates to an allene anion

NaNH2NH3

HC CH2

NH3C CH2

The generated allene can then react again with base to generate another allene anion

NaNH2

C CHHNH3

HNaNH2

The important point is that once the terminal alkyne is formed, it is quantitatively deprotonated with strong base to drive equilibrium

Molecular Orbitals

We can understand, and predict, many properties of conjugated systems by considering the molecular orbitals

Remember when we discussed bonding in organic compounds we formed bonds by combining atomic orbitals

Either sigma (σ) or pi (π) bonds were formed depending upon the symmetry of the resultant bond upon addition of the atomic orbitals

The same process occurs when considering conjugated dienes

Rules for combining orbitals:

1)  Always get the same number of molecular orbitals as number of atomic orbitals used to combine

2) As the number of nodes increase, the energy of the molecular orbital increases

3)  The molecular orbitals obtained are the region of space where the electrons reside (on time average)

Molecular Orbitals

First consider an isolated alkene

Simplest is ethylene

We can separate the sigma and pi framework

With alkenes, we are interested in the pi framework since this is what controls the reactivity

First combine two p orbitals to form a π bond

Each p orbital has two lobes with opposite phase

Upon addition, will obtain two MOs with different energy

Energy

Instead of + and -, often represent phases with color

The molecular orbitals obtained computationally appear same as the approximation used by combining atomic p orbitals

π bond π* bond

Molecular Orbitals

Can draw electronic configuration for the π system

Again consider ethylene Since there are 2 π electrons in this molecule, will place 2 electrons in MO diagram

Always place electrons in lowest energy orbital first, each orbital can accommodate two electrons

Molecular Orbitals

E

Molecular Orbitals

Can obtain molecular orbitals for larger conjugated systems using the same procedure

Consider butadiene, 2 double bonds in conjugation corresponding to overlap of 4 adjacent p orbitals

By combining 4 atomic p orbitals, will obtain 4 molecular orbitals that differ in phase of orbitals

0 nodes 1 node 2 nodes 3 nodes

As the number of nodes increases, the energy of the orbital increases

E

Molecular Orbitals for Butadiene

4 electrons are placed in these molecular orbitals by pairing the lowest energy MO’s until all electrons are placed in orbitals

The molecular orbital that is highest in energy that contains electrons is called the highest occupied molecular orbital (HOMO)

The molecular orbital that is lowest in energy that does not contain electrons is called the lowest unoccupied molecular orbital (LUMO)

Highest occupied MO (HOMO)

Lowest unoccupied MO (LUMO)

Reactivity of Conjugated Systems

The π bonds of conjugated systems can react in similar reactions as isolated alkenes

HBr Br

While the products are similar (H and Br in this case adding to a π bond), the rate is different

When considering a nucleophile adding to an electrophile, the higher in energy the HOMO of the nucleophile, the faster is the rate

As learned in UV-vis spectroscopy, as the conjugation increases the HOMO-LUMO gap is smaller

EDue to the higher energy HOMO of butadiene versus an isolated

alkene, butadiene will react faster in an electrophilic alkene addition

ΔE

Reactivity of Conjugated Systems

The difference in rate between conjugated and isolated alkenes can also be explained by the difference in energy for the intermediate in the rate determining step

HBr

HBr

Br

Br

Br

Br

Secondary cation in resonance

Isolated secondary cation

A cation in resonance is more stable than an isolated cation, therefore the reaction of butadiene will have a lower energy of activation than 1-butene and thus the rate will be faster

Thermodynamic Versus Kinetic Control

Another difference between π reactions of conjugated systems versus isolated alkenes are the possibility of different products

When an isolated alkene reacts, only the product from the most stable carbocation intermediate is formed

HBr BrBr

When conjugated alkenes react, however, the carbocation intermediate can resonate

HBr

Each resonance structure can react to form different products

Br Br

Br

Br1, 2 Product 1, 4 Product

Thermodynamic Versus Kinetic Control

Which product is favored (1, 2 versus 1, 4 product) can be controlled by reaction conditions

In the product isomers, however, the more substituted double bond is more favored

A convenient experimental condition to control thermodynamic product is to run the reaction at higher temperature

The electrophile will first add to the double bond to create a resonance stabilized cation

The resonance forms can react with the nucleophile to generate two transition state structures that have partial positive charges as the new bonds are forming

Br

!+

!+Br

!+

!+In positive charged species, the more substituted form

is more stable The more stable

transition state thus leads to the faster rate (kinetically favored)

Br

Br

The more stable product (thermodynamically

favored)

The kinetic product is favored at lower temperature

1, 2 Product (Kinetic) 1, 4 Product

(Thermodynamic)

Molecular Orbitals for Allylic Systems

An allylic system refers to 3 conjugated p orbitals

Allyl cation Allyl radical Allyl anion

All allylic systems have 3 p orbitals in conjugation, but the number of electrons conjugated changes

With 3 conjugated p orbitals, must obtain 3 molecular orbitals

E

0 nodes

1 node

2 nodes

Depending upon number of π electrons the electronic configuration can be determined

Allyl cation has 2 π electrons

Allyl radical has 3 π electrons Allyl anion has 4 π electrons

Implies that excess negative charge of anion is located on the terminal carbons (size of coefficients correlates with probability of electron density)

Similar to resonance description

Molecular Orbitals for Allylic Systems

(with odd number of carbons, nodes can occur at nucleus

unlike systems with even number of carbons)

Reactions with Allylic Systems

An allyl system is observed as an intermediate or transition state in many reaction mechanisms

Consider an SN1 mechanism:

Cl H2O OH

Generates allyl cation intermediate

The relative rates for this reaction with different structures correspond to the stability of intermediate in reaction mechanism

ClCl

Cl Cl Cl

1˚ cation 2˚ cation 1˚/1˚ cation (resonance)

1˚/2˚ cation (resonance)

1˚/3˚ cation (resonance)

Intermediate:

Relative rate: 1 1.7 14.3 1300 1900000

Reactions with Allylic Systems

Consider an SN2 mechanism:

In an SN2 reaction, there is not an intermediate but rather a transition state structure for the rate-determining step

Cl

NUC

Cl !-

!-

nucleophile NUC

Cl

Cl

NUC

nucleophileWhen reacting an allyl halide, the transition state has an allyl structure

which is more stable

Cl ClCl

Electrophilic carbon in Transition state:

Relative rate: (SN2)

1˚ 1˚ in resonance 2˚ in resonance

1 37 1.9

Relative rate of SN2 reaction with ethoxide:

Reactions with Allylic Systems

Consider pKa for allyl systems:

base

pKa = 50-60

Very unstable anion

base

pKa = 43

Anion stabilized by allyl resonance

Allylic positions are much more acidic than unactivated carbons due to the resonance stabilization

of anion formed after deprotonation

Pericyclic Reactions

Reactions involving concerted bond formation, or bond breakage, with a ring of interacting orbitals

Ring of interacting orbitals -Orbitals must form a continuous loop

Therefore each orbital must be able to interact with the adjacent orbital

Electrons are located in Molecular Orbitals (MO’s)

When two molecules react, a molecular orbital on one molecule interacts with a molecular orbital on the second molecule which causes an energy gain

(if reaction is favorable)

With conjugated π systems we can consider only the π framework

Energy Gain in a Reaction

Remember that these molecular orbitals on two molecules combine to form new orbitals in a reaction

Consider the interaction of HOMO and LUMO orbitals on different molecules

HOMO HOMO

If two HOMO orbitals react then two new MO’s will be obtained

(one lower and one higher in energy)

The 4 electrons will be placed and thus there is no energy gain

LUMOLUMO

If two LUMO orbitals react then also obtain two new MO’s,

but since there are no electrons, there is no change in energy

HOMO LUMOThe only energy gain is when a HOMO from one molecule reacts with a LUMO

from the other molecule

In order for the HOMO of one molecule to interact with the LUMO of another molecule the SYMMETRY of the orbitals must be correct

If the symmetry is wrong, then we cannot have interacting orbitals

Consider butadiene reacting with ethylene

Butadiene HOMO

Ethylene LUMO

The symmetry of the interacting orbitals is correct, therefore butadiene reacting with ethylene is symmetry allowed

Pericyclic Reactions

Ethylene, however, cannot react with itself

The orbitals cannot align themselves with proper symmetry

Therefore this reaction is symmetry forbidden

Ethylene LUMO

Ethylene HOMO

Pericyclic Reactions

Alkenes thus do not react thermally

! No Reaction

E

Excitation

Photolysis (if the energy of light is correct!) can excite an electron to a higher MO

This process changes the symmetry of the HOMO

Therefore a reaction can be made “symmetry allowed” by photolysis

Alkenes, for example, will react under photolysis but not thermally

h!

h!

Similar to process observed in UV-vis

spectroscopy

Diels-Alder reaction is one type of pericyclic reaction

The reaction between butadiene and ethylene is called a Diels-Alder reaction

Obtain cyclohexene functional units after a Diels-Alder reaction

Pericyclic Reactions

-Will always obtain a cyclohexene ring after a Diels-Alder reaction, finding this ring in a product structure will allow proper prediction

of what compounds are needed in a Diels-Alder reaction

Diels-Alder Reaction is favored by a lower HOMO-LUMO energy gap

In addition to requiring the correct symmetry, the energy gap between the HOMO and LUMO orbitals determines the amount of energy gain in a reaction

As the energy gap between the HOMO and LUMO becomes smaller the reaction rate is favored

Pericyclic Reactions

HOMO

LUMO

Energy gain HOMO

LUMO

Energy gain

Adjusting molecular orbital energy levels

Electron withdrawing groups lower the energy of a molecular orbital, Electron donating groups raise the energy of a molecular orbital

Usually the butadiene reacts through the HOMO and ethylene reacts through the LUMO, therefore a Diels-Alder reaction is favored with electron withdrawing groups on ethylene and

electron donating groups on butadiene

Pericyclic Reactions

Methyl groups are donating, thus the diene on the right will have a higher energy HOMO

than butadiene

NO2

Nitro groups are electron withdrawing, thus the alkene on the right will have a lower

energy LUMO than ethylene

Overall therefore with these compounds, the fastest rate will be the Diels-Alder between the methyl substituted diene and the nitro substituted alkene

Reaction Products

Always try to find the cyclohexene unit in the product, this will indicate what was the initial butadiene and ethylene parts

CN CN

O

O

OCH3 O

O

OCH3

When one of the starting materials is already a ring, the product will be a bicyclic compound

(in this case a bridged bicyclic)

O

OH3CO

A bridged bicyclic compound is often best viewed in a perspective drawing to indicate stereochemistry

Break cyclohexene at carbon positions

adjacent to alkene to allow butadiene and ethylene formation

Stereochemistry of Addition

Butadiene must be in a s-cis conformation, not s-trans conformation for a Diels-Alder reaction

Therefore the rate of the reaction will be affected by diene substituents

s-cis (reactive conformer)

s-trans (does not react)

> >

Locked in s-cis Most stable in s-cis, but can convert

to s-trans

Not stable in s-cis, sterics of methyl

groups favor s-trans

Orientation Between the Diene and Alkene

With substituents on the diene and dienophile, the two components can react to form two different stereoproducts

These two products are diastereomers

Which is favored?

Stereochemistry of Addition

NO2 NO2 NO2

Endo Rule

The Diels-Alder reaction favors the endo product

Endo means “inside” the pocket formed by the Diels-Alder reaction, exo is “outside” of this pocket

O2NH

HNO2

When the substituted ethylene approaches the butadiene, the substituent (nitro in this example) could either be pointing towards the sp2 hybridized

carbons of butadiene (endo) or away from these carbons (exo)

Endo orientation

Exo orientation

O2NH

HNO2

As the bonds form in the Diels-Alder reaction, the orientation of the substituents determines the stereochemistry of the product formation

O2NH

H

HNO2

H

NO2

NO2

Endo product

Exo product

=

=

Energetic Basis of Endo Rule

This stereochemical preference is due to ENERGY

In the endo position the orbitals on the electron withdrawing group can favorably interact with the orbitals of the diene

In exo orientation this interaction is not present

NC H

Endo position

CN

In endo position, orbitals on alkene substituents can interact with p orbitals of butadiene

Exo position

Favorable interaction

Regiochemistry of Unsymmetrically Substituted Diels-Alder Products

When a monosubstituted butadiene and a monosubstituted alkene react, different regioproducts can be obtained

Can predict favored product by understanding location of charge in molecules

OCH3 OCH3 OCH3

Consider resonance forms Negative charge is located on C2 and C4

OCH3NO2 !

OCH3NO2

OCH3

NO2

or

123

4

NO

O

Consider resonance forms

NO

O

Positive charge located on C2

12

The negative charge will react preferentially with the positive charge to obtain one regioproduct

Using this analysis we can predict regioproducts

A Diels-Alder reaction can therefore control both regio- and stereochemistry depending upon the structure of the diene and dienophile

Pericyclic Reactions

OCH3NO2

OCH3NO2 Will observe both regio- and

stereocontrol of reaction product

H3CO NO2 H3CO

NO2

Observe regiocontrol, but with only one stereocenter

with this product can not obtain diastereomers

Natural Rubber

Natural rubber is an alkene polymer produced by many sources, the most common being the “rubber” tree

Originally named by Joseph Priestly due to its ability to “rub” out pencil marks, therefore rubber is named due to its eraser properties

Natural rubber is a result of a polymerization from conjugated isoprene units

Natural rubber obtained from tree is called “latex”, it is too soft and is later hardened by a process called vulcanization (heating with sulfur) to cross link the chains

Double bonds in product are key for the rubber to be deformed and return to original shape – they cause kinks in polymer so neighboring chains have difficulty packing

Isoprene 2-methyl-1,3-butadiene

Polyisoprene (has Z alkenes in natural rubber)

Isoprene Rule

Instead of polymerizing a large number of isoprene units to form a polymer, isoprene is a common precursor in naturally occurring materials

Isoprene is first reacted once to create an alcohol,

OH O PO

OO P

O

OOHHO P

O

OO P

O

OOH

and then the alcohol is reacted with diphosphoric acid

The diphosphate compound can then be equilibrated to generate a compound that has the good diphosphate leaving group in an allylic position

OPP enzyme OPP

Isoprene Rule

The allylic diphosphate isoprene compound can react through an SN1 reaction to couple two isoprene units

OPP

OPP OPP OPP

Many naturally occurring compounds are simply multiples of the simple isoprene starting material (called isoprene rule)

Two isoprene units form terpenes, three isoprene units form sesquiterpenes, four isoprene units form diterpenes and so on

O

Limonene Camphor Pinene

Steroids

Isoprenes are also used in biochemical reactions to produce steroid structures

OPP

Two compounds with three isoprene units (Farnesyl-OPP) are coupled in a head-to-tail fashion to create squalene

OPP

Farnesyl-OPP Squalene

O

Steroids

A terminal alkene of the symmetrical squalene molecule is then reacted biochemically to form an epoxide

Realize that the squalene oxide is not in a linear conformation in the enzyme, but rather is folded into a more compact spherical shape

This conformation of the squalene allows the adjacent double bonds to first react with the epoxide and then sequential alkenes react with carbocations to form the 6-6-6-5 ring junction

HO

All steroids have this same 6-6-6-5 ring junction, the substituents can be modified by other enzymes to create “different” steroids