Reaction of Π Bonds Remember Discussion of Reaction of Alkenes Using Orbital Analysis, Π Bonds Are Far More Reactive

Home , Hyperconjugation, Resonance (chemistry)

Reaction of π Bonds Remember discussion of reaction of alkenes using orbital analysis, π bonds are far more reactive than σ bonds and they generally react as the nucleophile * σ C-C * π C-C

C (p) C (p) C (sp3) C (sp3)

π C-C σ C-C Atomic p orbital is higher in energy than sp3 C-C single bonds are relatively unreactive (less s character) and the overlap for p orbitals due to large overlap of sp3 hybridized is much less to form π bond orbital and energy match, therefore very Therefore orbitals do not mix as well for π bond low HOMO and high LUMO energy and thus HOMO does not lower in energy nor LUMO raise in energy as much as σ bond (already had seen this with weaker π bond)

C-C π bond will thus be far more reactive, and it will react preferentially as the nucleophile due to higher HOMO level Electrophilic Addition to Alkenes

Alkenes generally react in an addition mechanism (addition – two new species add to a molecule and none leave) If hydrogen halides react, then a H and Cl add to the two ends of the double bond !+ !- Cl CH3 H Cl CH3 H3C H3C H Since H-Cl is polarized, the H will be partially positively charged and Cl partially negative The alkene is thus the nucleophile and the proton is the electrophile The reaction is thus a two step reaction The ﬁrst step will generate a carbocation as a reactive intermediate

!+ !- Cl Cl CH3 H Cl CH3 CH3 H3C H3C H3C H H And the second step will have the carbocation react with the chloride to yield the product (the chloride is the nucleophile and the carbocation is the electrophile) Since the carbocation is the most unstable structure, the ﬁrst step is the rate determining step for this reaction Regiochemistry of Alkene Additions

When E-2-butene was reacted with HCl, only one product can be obtained

!+ !- Cl Cl CH3 H Cl CH3 CH3 H3C H3C H3C H H

When an unsymmetrical alkene, however, like propene is reacted, two possible products are obtained (2-chloropropane or 1-chloropropane) (resulting from H and Cl adding to different ends of alkene) Cl Cl !+ !- H3C H3C H Cl H C 3 Cl Cl H3C H3C

Since the carbocation is the high energy structure along the reaction coordinate, the energy of activation will be determined by the stability of the possible carbocations in the ﬁrst step

Since 2˚ carbocations are more stable than 1˚, 2-chloropropane is the only product obtained Regiochemistry of Alkene Additions

Hammond postulate is used to predict the relative rates of propene addition, because the cation is the high energy structure along the reaction coordinate the transition state for this reaction closely resembles the cation structure, thus has a high amount of positive charge on the carbon !- Cl !+ !- H H Cl !+ H3C H3C

H3C

Reaction Coordinate Similar to a 2˚ cation is more stable than a 1˚ cation, a partial positive charge on a 2˚ carbon is more stable than a partial positive charge on a 1˚ carbon Regiochemistry of Alkene Additions

The hydrogen halide reactions with alkenes follow “Markovnikov” addition

Markovnikov addition – in an electrophilic addition, the heavier atom adds to the more substituted carbon

The physical meaning behind the Markovnikov addition is the electrophile adds in such a way to generate the most stable intermediate

What does this imply for a hydrogen halide reaction? (remember that the ﬁrst step is the creation of a carbocation)

Cl Cl Markovnikov product !+ !- H3C H3C H Cl H C 3 Cl Cl Anti-Markovnikov H3C H3C product Regiochemistry of Alkene Additions

When considering an addition to an alkene, need to look at the two possible intermediate structures and compare their energies (the more stable one will therefore react with a faster rate)

Some factors that could inﬂuence stability:

Resonance effects

We have observed previously that especially with charged species, structures that can resonate the charge onto multiple atoms are more stable than compounds that isolate the charge on a single atom

pKa H2 ~16 C H3C O

O O 4.8 H3C O H3C O Regiochemistry of Alkene Additions

The same effect can be observed in the carbocation intermediates for alkene additions

CH3 H3C Cl H Cl or Which is favored? CH3 H3C Cl Cl CH2CH3 CH3 CH3 Cl H3C H3C CH3

The chlorine atom has lone pair of electrons which can delocalize into empty p orbital of cation for resonance stabilization

The reaction of Z-2-butene with HCl thus only yields 2,2-dichlorobutane

Cl Cl H Cl Cl Cl CH3 CH3 CH3 H3C H3C H3C Regiochemistry of Alkene Additions

Any atom with lone pair of electrons adjacent to empty p orbital can stabilize cation through resonance, realize though that resonance can only occur with orbital alignment between adjacent atoms

OH H+ H2O OCH3 OCH3 OCH3

OCH3 The proton adds in the ﬁrst step to generate the carbocation adjacent to the oxygen due to resonance from the lone pair stabilizing the cation, thus directing the regiochemistry Because the cation is more stable with resonance, the relative rate compared to alkenes without the possibility of resonance is higher Relative Rate (25˚C) OH H+/H O 2 5 x 1014 OCH3 OCH3

H+/H2O OH 1 Regiochemistry of Alkene Additions

Resonance can also occur with extended p orbitals on adjacent carbon atoms

We observed the reaction of butadiene in discussing kinetic versus thermodynamic reactions

Isolated 1˚ cation

H+ or !+ OH2 OH

!+ H2O 2˚ cation in resonance !+ OH2 OH !+ Partial charge on 2˚ carbon More substituted double more stable than 1˚ carbon, bond is more stable, therefore top pathway is the therefore bottom pathway is kinetic pathway the thermodynamic pathway

In practice, kinetic pathway is favored at low temperatures and thermodynamic pathway is favored at high temperatures Effect of Hyperconjugation on Carbocation Stability

We have already observed that cations with more alkyl substituents are more stable than cations with less alkyl substituents

CH3 H H H

H3C CH3 H3C CH3 H3C H H H

Stability The reason is due to a type of resonance with the neighboring C-H bond called “hyperconjugation” H H H C CH3 H H H 2 CH H H H H 3 H The electrons in the neighboring C-H bond stabilize the empty p orbital by The interaction is similar, but donating electron density different, than the interaction between two p orbitals in an alkene This effect can only occur with a (less interaction due to further neighboring carbon, distance in hyperconjugation) therefore 3˚ > 2˚ > 1˚ > methyl cation Inductive Effects on Carbocation Stability

In addition to resonance and hyperconjugation, inductive effects can alter carbocation stability

Inductive means “through bond”

Both resonance and hyperconjugation occur through overlap of orbitals, not through the σ bond

H -Cl H H H ! H H H H H H!+ H H H

Overlap of p Hyperconjugation Inductive orbitals

Inductive effects, therefore, are due to dipoles caused by differences in electronegativity Inductive Effects on Carbocation Stability

Inductive effects can either stabilize a carbocation (if electron donating towards cation) or destabilize a carbocation (if electron withdrawing from a cation)

Consider the electrophilic reaction of an allyl chloride

Cl HCl Cl Cl Cl !+ The dipole of C-Cl bond causes a partial positive charge to be placed adjacent to carbocation, therefore destabilizing the cation

Relative Rates (25 ˚C) Cl CH3 OCH3 Cl 1 2 x 106 5 x 1014 1 x 10-4 Faster than 1

hyperconjugation resonance inductive resonance

Resonance effect outweighs the inductive effect for these examples Rearrangements in Alkene Additions

Rearrangements can occur whenever a carbocation is formed as an intermediate in a reaction

We observed carbocation intermediates in both E1 and SN1 reactions

Electrophilic addition of HX or H+/H20 to alkenes also form carbocation intermediates and thus rearrangements may occur if a more stable carbocation can be formed after rearrangement

CH3 H3C CH3 H3C CH3 H3C Cl HCl CH CH3 H C 3 CH3 H3C H3C 3 H3C CH 3 CH3

As with all rearrangements, whether a hydride shift or alkyl shift, the orbitals must be aligned to allow the rearrangement to occur

CH3 H CH3 H H3C H H3C No overlap of orbitals, rearrangement cannot occur Rearrangements in Alkene Additions

In addition to the energy gain from going to a more substituted carbocation through rearrangements, a shift could be energetic driven by formation of a more stable ring system

OH H+, H2O

4-membered ring 5-membered ring (more stable)

Can also observe rearrangements to form smaller rings (would need some other energy driving force)

OH OH OH O H+, H2O

OH Resonance stabilized Need to have a vicinal diol (called Pinacol rearrangement) Hydroboration of Alkenes

We have already observed that alkenes can be converted to alcohols by reacting with acidic water

OH H+, H2O H3C H3C CH3 H3C CH3

A carbocation is formed as an intermediate which drives the reaction to Markovnikov product

Alcohols can also be formed from alkenes using a hydroboration route

Boron is less electronegative than carbon and thus can react as an electrophile

1) BH3•THF 2) H2O2, NaOH OH H3C H3C

The reaction yields a different regioproduct (Anti-Markovnikov) Hydroboration of Alkenes

Boron is to the left of carbon in the periodic table

B C N O F

*therefore boron is electropositive compared to carbon

The neutral form of boron, BH3, is unstable (it only has 6 electrons in the outer shell)

Boron often is complexed with an oxygen containing species to offer stability

O BH3 !+ !- O BH3 Tetrahydrofuran BH3•THF (THF) Hydroboration of Alkenes

Due to the electropositive character of BH3, it will act as an electrophile in alkene reactions

H !- H BH3•THF BH BH2 H C H C 3 + BH2 3 3 H3C ! H3C

A free carbocation is not formed however as the reaction never rearranges regardless of structure of the alkene

A cyclic transition state occurs instead where one of the B-H bonds is transferred to the carbon, this process stabilizes the structure as the carbon never bears a full positive charge

The regiochemistry occurs which places the partial positive charge on the carbon better able to stabilize the charge, after the transition state is passed and the hydrogen has been transferred, the boron is located on the least substituted carbon and the hydrogen on the more

1) BH3•THF H3C CH3 H3C CH3 2) H2O2, NaOH H3C H3C OH Hydroboration of Alkenes

The boron can then be removed in a second step with basic hydrogen peroxide

OH H H O BH H3C BR OOH OBR H C 2 H C 2 BR2 H C 2 3 3 H3C 3 The boron can react 2 more times with alkene

The oxidized boron then rearranges to a boronic ester [B(OR)3]

The boronic ester becomes hydrolyzed under the same basic aqueous conditions to generate the Anti-Markovnikov alcohol

NaOH OBR2 OH H3C H3C H2O Hydroboration of Alkenes

Due to the boron and hydrogen adding in a cyclic transition state, both must attach to the same side of the double bond (SYN addition)

BH2 BH •THF 3 H

Upon oxidation, the alcohol replaces the boron in the same stereochemical position, therefore the alcohol and the H added in the ﬁrst step are in a SYN orientation

BH2 OH H2O2, NaOH H H Formation of Alcohols from Alkenes

The methods shown can create different regio- and stereoproducts from alkenes

H+, H O 2 OH

Acidic aqueous conditions forms the Markovnikov product, carbocation is formed which can rearrange if possible

1) BH3•THF H 2) H2O2, NaOH OH

Hydroboration/Oxidation conditions forms the Anti-Markovnikov product, no free carbocation is formed and addition occurs in a SYN manner Methanol versus Ethanol Biochemically

Ethanol (which is known to lower inhibitions and cause a lightheadedness) is oxidized biochemically to acetaldehyde

alcohol O aldehyde O dehydrogenase dehydrogenase H O H OH

The physiological side effects of consuming ethanol are due to the buildup of acetaldehyde (causes nausea, dizziness, sweating, headaches, lower blood pressure)

The acetaldehyde is then oxidized biochemically to acetic acid

Some people have a nonfunctioning aldehyde dehydrogenase enzyme -these people experience the side effects of acetaldehyde with low ethanol consumption Methanol versus Ethanol Biochemically

Methanol also gets oxidized by the same enzyme

alcohol O dehydrogenase H O H H

But due to one less carbon, this oxidation creates formaldehyde not acetaldehyde

Formaldehyde is toxic to the body because it disrupts other essential enzymes form working properly

Ethanol is consumed ~25 times faster than methanol by this enzyme Cationic Polymerization

Alkenes can also react to form polymers (sufﬁx –mer comes from Greek word meros, meaning “part”)

CH3 CH3 CH H C 3 CH3 H3C CH3CH3 3 H+ H3C H3C H3C CH3 H3C CH3 n Polyisobutylene Initially form most stable carbocation If neither nucleophile The 3˚ cation of the or base are present, dimer structure can This carbocation could react carbocation can react continue to react with

with nucleophiles (SN1) with another alkene to alkenes to form a or have a hydrogen form a “dimer” polymer structure abstracted with base (E1)

Polymerization will continue until the concentration of alkene becomes low

and competes with either SN1 or E1 which will terminate the polymerization