C341/Fall 2011
Chapter 9: Addition Reactions:
Chapter 9: Addition
Reactions of Alkenes
1. Addition vs. Elimination
2. Addition Reactions to Alkenes
A. Addition of HX (hydrohalogenation)
B. Addition of H2O (acid catalyzed hydration)
C. Addition of H2O (oxymercuration‐demercuration)
D. Hydroboration‐Oxidation
E. Catalytic Hydrogenation
F. Addition of X2 (halogenation)
G. Addition of X2/H2O (halohydrin)
H. Anti‐hydroxylation
I. Syn‐hydroxylation
J. Oxidative Cleavage
3. Synthesis Strategies (intro to one‐step and multi‐step syntheses)
It would be BEST if you did ALL the textbook problems, but at the very
least do these:
9.49‐9.55, 9.57, 9.58, 9.60, 9.63‐9.66, 9.68‐9.71, 9.74‐77, 9.79, 9.81, 9.82
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Chapter 9: Addition Reactions:
Addition Reactions:
Try to minimize any memorization and focus on understanding the
mechanisms and learn to understand why reactions occur as they do.
DO NOT JUST MEMORIZE THEM!
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Chapter 9: Addition Reactions:
1. Addition vs. Elimination –
• Addition is the opposite of elimination (a pi bond is converted to a
sigma bond).
• Because an addition is the reverse of an elimination, often the
processes are at equilibrium.
• One must assess the ΔG to determine which side the equilibrium will
favor.
• A pi bond will often act as a Lewis base (i.e. nucleophile or as a
Brønsted‐Lowry base).
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Chapter 9: Addition Reactions:
Thermodynamics of Addition Reactions
• Typical addition reactions have a –ΔH.
• What will the sign (+/‐) be for ΔSsys?
• Predict the sign for ΔG.
What is the driving force of addition reactions to alkenes?
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2.
Chapter 9: Addition Reactions:
Addition Reactions
Alkenes are nucleophiles, so we will react them with electrophilic
reagents. In 1869, Markovnikov made an important observation for all
addition reactions:
Markovnikov addition =
Regioselective reaction =
Syn versus anti addition =
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Chapter 9: Addition Reactions:
A. Hydrohalogenation – Electrophilic Addition of HX
Markovnikov Addition of HBr
Anti‐Markovnikov Addition of HBr
H
Br
ROOR
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Chapter 9: Addition Reactions:
Predict the products for the following reactions:
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Chapter 9: Addition Reactions:
Provide the mechanism explaining the following reaction:
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B.
Chapter 9: Addition Reactions:
Hydration — Acid‐Catalyzed Hydration of Water
What do you observe about this reaction?
Could you use these conditions to make primary alcohols?
Practice drawing products before we try the mechanism:
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Chapter 9: Addition Reactions:
Acid‐catalyzed hydration mechanism:
A catalyzed reaction mechanism always regenerates the catalyst.
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Chapter 9: Addition Reactions:
Acid‐catalyzed hydration (addition) and elimination are in equilibrium
What might one do to shift the equilibrium toward the side you desire?
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Chapter 9: Addition Reactions:
C. Oxymercuration‐demercuration
Alternative that provides products more cleanly with no rearrangements.
Reaction is:
Reagents are:
1. Hg(OAc)2 is:
2. NaBH4 is:
o This reaction is regiospecific
o Markovnikov addition with NO rearrangement.
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Chapter 9: Addition Reactions:
Mechanism?
How would the product be different if the reaction was done in ethanol
instead of water?
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D.
Chapter 9: Addition Reactions:
Hydroboration‐Oxidation (last type of hydration of an alkene)
What do you notice about the addition above?
What is BH3(THF)? BH3 does not exists as a single species, but it exists as
a Lewis acid/Lewis base adduct:
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Chapter 9: Addition Reactions:
1) BH3 THF
2) H2 O2 / NaOH
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Chapter 9: Addition Reactions:
Hydroboration Mechanism:
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Chapter 9: Addition Reactions:
Compare all three hydration reaction conditions:
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Chapter 9: Addition Reactions:
E. Catalytic Hydrogenation
 Most alkenes react
with H2 in the presence
of a late transition
metal catalyst (Pd, Pt,
Ru or N) at high
pressure (ca. 3 atm or
higher).
 Yields are nearly
quantitative (i.e. ca.
99%).
Heterogeneous Catalysis:
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Chapter 9: Addition Reactions:
Homogeneous Catalysis
• In 1968, Knowles modified Wilkinson’s catalyst by using a chiral
phosphine ligand.
• A chiral catalyst can produce one desired enantiomer over another.
• Why would someone want to synthesize one enantiomer rather than a
racemic mixture?
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Chapter 9: Addition Reactions:
Noyori and Knowles shared the 2001 Nobel Prize in Chemistry for
asymmetric catalysis:
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Chapter 9: Addition Reactions:
F. Halogenation—Addition of X2
• Halogenation with Cl2 and Br2 is generally effective, but halogenation
with I2 is too slow, and halogenation with F2 is too violent.
• The reaction can be run “neat” or in an “inert” solvent like CCl4 or
CH2Cl2.
• Halogenation occurs with ANTI addition
Predict the major product(s) for the reactions below.
Br2
CCl4
Br2
H2O
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Chapter 9: Addition Reactions:
Mechanism?
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G.
Chapter 9: Addition Reactions:
Halohydrin Reaction ‐ Addition of X2/H2O
What observation(s) do you notice about how the substituents added?
Mechanism?
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H.
Chapter 9: Addition Reactions:
Anti‐dihydroxylation
 What are peroxy acids? (e.g. mCPBA)
 Replacing the relatively unstable O–O single bond is the
thermodynamic driving force for this process.
 Is there anything unstable about an epoxide?
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Chapter 9: Addition Reactions:
Acid‐catalyzed ring opening mechanism:
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Chapter 9: Addition Reactions:
Note the similarity in all these intermediates:
• Ring strain and a +1 formal charge makes these structures GREAT
electrophiles.
• They also each yield ANTI products because the nucleophile must
attack in an SN2 fashion.
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Chapter 9: Addition Reactions:
I. Syn‐dihydroxylation
• Like other syn additions, SYN dihydroxylation adds across the C=C
double bond in ONE step.
• Because OsO4 is expensive and toxic, conditions have been developed
where the OsO4 is regenerated after reacting, so only catalytic
amounts are needed.
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Chapter 9: Addition Reactions:
I. 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 MnO41‐ is reactive
toward many other functional groups as well.
• The synthetic utility of MnO41‐ is limited.
1. OsO4
2. NaHSO3
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Chapter 9: Addition Reactions:
J. Oxidative Cleavage of Alkenes
o C=C double bonds are also reactive toward oxidative cleavage.
o Oxidative cleavage of an alkene breaks both the  and  bonds of the
double bond to form two carbonyl compounds.
o Cleavage with ozone (O3) is called ozonolysis.
o Reductive workup: Zn (in H2O) or dimethylsulfide (CH3SCH3)
o Oxidative workup: H2O2 in ROH
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Chapter 9: Addition Reactions:
Ozonolysis – cleavage of a C=C bond to form carbonyls
1. O3
2. (CH3)2S
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Chapter 9: Addition Reactions:
3. Synthesis Strategies
A. Analyze the reagents used to determine what groups will be added
across the C=C double bond.
B. Determine the regioselectivity (Markovnikov or anti‐Markovnikov).
C. Determine the stereospecificity (syn or anti addition)
–
Each step can be achieved with minor reagent memorization and a
firm grasp of the mechanistic rational.
–
The more familiar you are with the mechanisms, the easier predicting
products will be.
What type of reaction type is depicted below?
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Chapter 9: Addition Reactions:
Practicing One‐Step Synthesis. Provide correct product(s) for the following
reactions demonstrating correct stereochemistry in your products. If the product
has an enantiomer or diastereomer, then just write +E or +D as necessary. Finally,
circle if the reaction undergoes ANTI or SYN addition (if a mechanism undergoes
both then circle both words). Provide reagents for reactions A and B.
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Chapter 9: Addition Reactions:
Using mechanistic arrows provide step‐by‐step mechanism.
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Chapter 9: Addition Reactions:
Multistep synthesis:
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\
Chapter 9: Addition Reactions:
Multistep synthesis:
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\
Chapter 9: Addition Reactions:
Multistep synthesis:
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