Ch 09- Addition Reactions.pdf

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Chapter 9

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9.1 Addition Reactions

• Addition is the

opposite of elimination • A pi bond is

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9.1 Addition Reactions

• A pi bond will often act as a Lewis base (as a nucleophile or as a Brønsted-Lowry base)

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9.2 Addition / Elimination Equilibria

• Because an addition is the reverse of an elimination, often the processes are at equilibrium

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9.2 Addition / Elimination Equilibria

• Typical addition reactions have a –ΔH

• Will heat be absorbed by or released into the surroundings?

• What will the sign (+/-) be for ΔS_surr?

• Will the enthalpy term favor the reactants or products? • The heat change (ΔH) will remain roughly constant

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• Having a –ΔH (or a +ΔS_surr) favors the addition reaction rather than the elimination reaction

• To get ΔG (or ΔS_tot) and make a complete assessment, we must also consider the entropy of the system (ΔS_sys) • What will the sign (+/-) be for ΔS_sys? WHY?

• What will the sign (+/-) be for -TΔS_sys?

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9.2 Addition / Elimination Equilibria

• Plugging into the formula gives…

• To favor addition, a –ΔG (or a +ΔS_tot) is needed

• How can the temperature be adjusted to favor addition? • To favor elimination (the reverse reaction in this

example), a +ΔG (or a –ΔS_tot) is needed

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9.3 Hydrohalogenation

• Note the temperature used in this addition reaction

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• Regiochemistry becomes important for asymmetrical alkenes

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9.3 Hydrohalogenation

• Markovnikov’s rule could also be stated by saying that in general, halogen atoms tend to add to the carbon that is more substituted with other carbon groups

• This is a regioselective reaction, because one

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• Anti-Markovnikov products are observed when

reactions are performed in the presence of peroxides such as H₂O₂

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9.3 Hydrohalogenation Mechanism

• The mechanism is a two step process

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9.3 Hydrohalogenation Mechanism

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9.3 Stereochemical Aspects

• In many addition reactions, chirality centers are formed

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9.3 Stereochemical Aspects

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9.3 Rearrangements

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9.3 Rearrangements

• A mixture of products limits synthetic utility

• With an INTRAmolecular rearrangement, WHY isn’t the rearrangement product an even greater percentage?

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9.3 Hydrohalogenation Example

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9.4 Hydration

• The components of water (-H and –OH) are added across a C=C double bond

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• Given the data below, do you think the acid catalyzed hydration goes through a mechanism that involves a carbocation?

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9.4 Hydration Mechanism

• Why does the hydrogen add to this carbon of the alkene?

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9.4 Hydration Mechanism

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9.4 Hydration Thermodynamics

• Similar to Hydrohalogenation, hydration reactions are also at equilibrium

• Explain HOW and WHY temperature could be used to shift the equilibrium to the right or left

Addition

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9.4 Hydration Thermodynamics

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9.4 Hydration Thermodynamics

• Similar to Hydrohalogenation, the stereochemistry of hydration reactions is controlled by the geometry of the carbocation

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9.4 Hydrations

• Ethanol is mostly produced from fermentation of sugar using yeast, but industrial synthesis is also used to

produce ethanol through a hydration reaction

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9.5 Oxymercuration-Demercuration

• Because rearrangements often produce a mixture of

products, the synthetic utility of Markovnikov hydration reactions is somewhat limited

• Oxymercuration-demercuration is an alternative

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9.5 Oxymercuration-Demercuration

• Oxymercuration begins with mercuric acetate

• How would you classify the mercuric cation? – As a nucleophile or an electrophile?

– As a Lewis acid or Lewis base?

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9.5 Oxymercuration-Demercuration

• Similar to how we saw the alkene attack a proton previously, it can also attack the mercuric cation

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9.5 Oxymercuration-Demercuration

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9.6 Hydroboration-Oxidation

• To achieve anti-Markovnikov hydration, Hydroboration-Oxidation is often used

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• Hydroboration-Oxidation reactions achieve syn addition

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• Let’s examine how this new set of reagents might react • The BH₃ molecule is similar to a carbocation but not as

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9.6 Hydroboration-Oxidation

• Because of their broken octet, BH₃ molecules undergo intermolecular resonance to help fulfill their octets

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• In the hydroboration reaction, BH₃•THF is used.

BH₃•THF is formed when borane is stabilized with THF (tetrahydrofuran)

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• What evidence is there for a concerted addition of the B-H bond across the C=C double bond?

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9.6 Hydroboration-Oxidation

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Start Here

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9.6 Hydroboration-Oxidation

• When ONE chirality center is formed, a racemic mixture results

• WHY? What is the geometry of the alkene as the borane attacks?

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• When TWO chirality centers are formed, a racemic mixture results

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9.7 Catalytic Hydrogenation

• The addition of H₂ across a C=C double bond

• If a chirality center is formed, syn addition is observed

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9.7 Catalytic Hydrogenation

• Analyze the energy diagram below

• Why is a catalyst necessary?

• Does the catalyst affect the spontaneity of the process?

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• The metal catalyst is believed to both adsorb the H atoms and coordinate the alkene

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• Draw product(s) for the reaction below. Pay close attention to stereochemistry

• How many chirality centers are there in the alkene reactant above?

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9.7 Catalytic Hydrogenation

• If catalysis takes place on the surface of a solid

surrounded by solution, the catalyst is heterogeneous. WHY?

• Homogeneous catalysts also exist

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9.7 Asymmetric Hydrogenation

• In 1968, Knowles modified Wilkinson’s catalyst by using a chiral phosphine ligand

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• A chiral catalyst allows one enantiomer to be formed more frequently in the reaction mixture • Some chiral catalysts

give better

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9.7 Asymmetric Hydrogenation

• BINAP is a chiral ligand that gives pronounced enantioselectivity

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9.8 Halogenation

• Halogenation involves adding two halogen atoms across a C=C double bond

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9.8 Halogenation

• Halogenation with Cl₂ and Br₂is generally effective, but halogenation with I₂ is too slow and halogenation with F₂ is too violent

• Halogenation occurs with anti addition

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9.8 Halogenation

• Let’s look at the reactivity of Br₂. Cl₂ is similar • It is nonpolar, but it is polarizable. WHY?

• What type of attraction exists between the

Nuc:1- _{and Br} 2?

• Does the Br₂

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• We know alkenes can act as nucleophiles

• Imagine an alkene attacking Br₂. You might imagine the formation of a carbocation

9.8 Halogenation

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9.8 Halogenation

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9.8 Halogenation

• Only anti addition is observed. WHY?

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9.8 Halogenation

• Only anti addition is observed

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9.8 Halogenation

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9.8 Halohydrin Formation

• Halohydrins are formed when halogens (Cl₂ or Br₂) are added to an alkene with WATER as the solvent

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9.8 Halohydrin Formation

• A proton transfer completes the mechanism producing a neutral halohydrin product

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9.8 Halohydrin Regioselectivity

• The –OH group adds to the more substituted carbon

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9.8 Halohydrin Regioselectivity

• When water attacks the bromonium ion, it will attack the side that goes through the lower energy transition state

• Water is a small molecule that can easily access the more sterically hindered site

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9.8 Halohydrin Regioselectivity

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9.9

Anti

Dihydroxylation

• Dihydroxylation occurs when two –OH groups are added across a C=C double bond

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9.9

Anti

Dihydroxylation

• First, an epoxide is formed

• Replacing the relatively unstable O-O single bond is the thermodynamic driving force for this process

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9.9

Anti

Dihydroxylation

• Water is a poor

nucleophile, so the

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9.9

Anti

Dihydroxylation

• Note the similarities between three key intermediates

• Ring strain and a +1 formal charge makes these structures GREAT electrophiles

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9.10

Syn

Dihydroxylation

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9.10

Syn

Dihydroxylation

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9.10

Syn

Dihydroxylation

• MnO₄1- is similar to OsO₄ but more reactive

• Syn dihydroxylation can be achieved with KMnO₄ but only under mild conditions (cold temperatures)

• Diols are often further oxidized by MnO₄1-_{, and MnO}

41- is

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9.11 Oxidative Cleavage with O

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• C=C double bonds are also reactive toward oxidative cleavage

• Ozonolysis is one such process

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• Common reducing agents include dimethyl sulfide and

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9.11 Oxidative Cleavage with O

3

• Predict the major product(s) for the reaction below

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9.12 Predicting Addition Products

1. Analyze the reagents used to determine what groups will be added across the C=C double bond

2. Determine the regioselectivity (Markovnikov or anti -Markovnikov)

3. Determine the stereospecificity (syn or anti addition) • Each step can be achieved with minor reagent

memorization and a firm grasp of the mechanistic rational

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9.12 Predicting Addition Products

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9.13 One Step Syntheses

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9.13 One Step Syntheses

• To set up a synthesis, assess the reactants and products to see what changes need to be made

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9.13 Multi-Step Syntheses

• Multistep syntheses are more challenging, but the same strategy applies

• This is not a simple substitution, addition or

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9.13 Multi-Step Syntheses

• For the strategy to work, the regioselectivty must be correct

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• For the strategy to work, the regioselectivty must be correct

• Will the

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• Multistep syntheses are more challenging, but the same strategy applies

• This is not a simple substitution, addition or

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9.13 Multi-Step Syntheses

• How can the alcohol be eliminated to give the less stable Hoffmann product?

• H₃O+ will give the Zaitsev product

• OH- _{is too poor of a leaving group to use the bulky}

base, t-BuOK

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• In the last step, –H and –OH must be added across the C=C double bond

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-9.13 Multi-Step Syntheses

• Use reagents that give anti-Markovnikov products

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• Solve the multistep syntheses below

• Again, two processes must be combined

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Additional Practice Problems

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• How and why will the concentration of acid affect

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Additional Practice Problems

• Give an example reaction for Markovnikov hydration without the possibility of rearrangement.

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• Should a halogenation reaction be overall first or

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