Transcript Document

Chapter 8: Addition Reactions
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Addition Reactions to Alkenes (Section 8.1)
Markovnikov’s Rule (Section 8.2)
Stereochemistry of Ionic Addition to Alkenes (Section 8.3)
H2SO4 Additions to Alkenes (Section 8.4)
H2O Additions to Alkenes (Section 8.5)
Oxymercuration/Demurcuration (Section 8.6)
Hydroboration/Oxidation (Section 8.7)
Addition of Br2 and Cl2 to Alkenes (Section 8.12)
Stereochemistry of Dihalide Additions (Section 8.13)
Halohydrin Formation [Net Addition of X-OH] (Section 8.14)
Divalent Carbon Compounds: Carbenes (Section 8.15)
Oxidations of Alkenes (Sections 8.16-8.17)
Additions to Alkynes (Sections 8.18-8.19)
Oxidative Cleavage of Alkynes (Section 8.20)
Applications in Synthesis (Section 8.21)
Chapter 8 Relevant Text: Pages 328-376
Addition Reactions: Addition to Alkenes
C
C
A
B
Addition
A
C
C
B
• Have Already Looked at Addition of H2 (Hydrogenation)
• Will Now Add Additional Reagents to Our Arsenal
 HX (I, Br, Cl)
 Br2
 H2SO4
 Cl2
 H2 O
 I2
Why Do Additions to Alkenes Work?
• Conversion of p Bond to 2 s Bonds Typically Energy Favored
• Two s Bonds Higher Energy than One p + One s
• Overall Process is thus Typically Exothermic
• p Electrons are Exposed (ABOVE and BELOW sp2 Plane)
• p Bonds Good at Capturing Electrophiles (H+, Lewis Acids, X2)
• Metal Ions With Vacant Orbitals Also Good Electrophiles
• Let’s Look at the Addition Reaction of a Hydrogen Halide
Addition Reactions: HX to Alkenes
H
C
C
Br
H
Br
H
• General Order of HX Reactivity:
HI > HBr > HCl > HF
• Usually Dissolved in Solvent (CH3CO2H, CH2Cl2)
• Can be Bubbled Through Solution as a Gas
• Addition of HCl not Generally Useful (Works w/ Silica Gel)
Br
Addition Reactions: HBr to Alkenes
H
C
C
Br
H
Br
H
Br
• p Bond (Nucleophile) Protonate  Carbocation Intermediate
• Carbocation Captured by Br¯ (Nucleophile)  HBr Added
• HBr (or other HX) Addition in Two Overall Steps
• H+ and Carbocation are the Respective Electrophiles
• This is a SYMMETRIC Alkene  ASYMMETRIC ALKENES?
Markovnikov’s Rule: HBr to Alkenes
Br
HBr
Br
o
CH2Cl2, 0 C
MAJOR
MINOR (TRACE)
• 2-Bromopropane is Major Product
• Only Very Small Amount of 1-Bromopropane Observed
• True With Other Alkenes
Br
HBr
Br
o
CH2Cl2, 0 C
MAJOR
MINOR (TRACE)
Markovnikov’s Rule: Why?
Br
HBr
Br
o
CH2Cl2, 0 C
MAJOR
MINOR (TRACE)
• Product Distribution Explained When Looking at Intermediates
• Recall Discussion of Carbocation Stability (2° > 1°)
• Major Product Formed From More Stable C+ Intermediate
H
H
Less Stable
Carbocation
H
Br
More Stable
Carbocation
Markovnikov’s Rule: C+ Stability
H
H
Less Stable
Carbocation
H
Br
More Stable
Carbocation
• We Know 2° Carbocations More Stable Than 1°
• Major Product Formed From More Stable C+ Intermediate
• Means TS in 2° Carbocation Pathway Lower in Energy
• Lower Energy of Activation
• Activation Energies in 1° Carbocation Pathways Much Larger
Markovnikov’s Rule: Summary
MARKOVNIKOV’S RULE:
In the ionic additions of an unsymmetrical
reagent to a double bond, the positive portion
of the adding reagent attaches itself to a
carbon atom of the double bond so as to yield
the MORE STABLE CARBOCATION as an
INTERMEDIATE
Cl
Cl
I
Cl

Recall Bond Polarization: I
I
I

Cl
This Addition “Preference” is Called REGIOSELECTIVITY
Stereochemistry in Ionic Additions
Br
Br
Top Capture
H
H
H
Br
CH3
Bottom Capture
Br
CH3
+
CH3
H
Br
• Just as We Saw in SN1: C+ Has TWO FACES
• Top and Bottom Attack Give Two Stereochemical Products
• R and S Enantiomers Formed as a Racemic Mixture (50:50)
H2SO4 Addition to Alkenes
O
O
H
O
S
O
C
C
H
O
O
H
S
O
O
H
H
C
OSO3H
C
• Must Add COLD Sulfuric Acid; Form Alkyl Hydrogen Sulfates
• Regioselective Reaction: Obeys Markovnikov’s Rule
• Note Mechanistic Similarities w/ HX Addition to Alkenes
Alcohols From Alkyl Hydrogen Sulfates
H
H
OSO3H
OH
H2O

• HYDROLYSIS Reaction of Alkyl Hydrogen Sulfate
• Simply Heat the Sulfate in Water
• Net Reaction is Markovnikov Addition of H2O to Alkene
• Used in One Industrial Ethanol Making Process
Addition of H2O to Alkenes: Hydration
C
C
+
HOH
H3O
H
OH
• HYDRATION Reaction of an Alkene
• Acid Catalyzed Addition of H2O Across Double Bond
• Net Reaction is Markovnikov Addition of H2O to Alkene
• We’ve Seen a Similar Reaction: Acid Catalyzed Dehydration
• Carbocation Rearrangements Possible w/ Dehydration Reactions
What is the MECHANISM for this reaction? Know this!
Oxymercuration-Demercuration
OXYMERCURATION:
C
C
+
H2O
+
Hg(OAc)2
THF
OH HgOAc
DEMERCURATION:
NaOH, NaBH4
OH HgOAc
OH H
• Net Reaction: Markovnikov Addition of H2O to Alkene
• Both Reactions Quite Rapid; Alcohol Yields Usually > 90%
• NaBH4: Sodium Borohydride  “H¯” Delivering Agent
Oxymercuration-Demercuration (2)
H
H
H
Hg(OAc)2
C
Pr
C
H
H
Pr
H
NaOH, NaBH4
H
Pr
H
THF/H2O
H
OH H
OH HgOAc
Me
Hg(OAc)2
Me
OH
HgOAc
OH
H
NaOH, NaBH4
THF/H2O
H
• Added Benefit of Oxymercuration/Demercuration:
 C+ REARRANGEMENTS Seldomly Observed
 Consider Example Seen on Next Slide
H
Oxymercuration-Demercuration (3)
1. Hg(OAc)2,
THF/H2O
2. NaOH, NaBH4
HgOAc
OH
HgOAc
Hg Stabilization
• Would Expect 2° Carbocation to Rearrange to 3°
• Added C+ Stabilization from Hg Atom Prevents Rearrangment
• Useful Hydration Process for Avoiding Skeletal Migrations
Hydroboration—Oxidation Reactions
BH3 : THF
Hydroboration
(CH3CH2CH2)3B
H2O2, NaOH
OH
Oxidation
• Hydroboration: Addition of H and B to Alkene
• Neutral Boron has 3 Coordination Sites
 Get Trialkyl Boranes as an Intermediate (Tripropylborane)
• Oxidation: H2O2, NaOH Oxidize to Trialkylborate Ester
• Oxidation Followed by a Hydrolysis, Cleaves Borate Ester
• ANTI-MARKOVNIKOV Product (Good for 1° Alcohols!)
Hydroboration—Oxidation Reactions (2)
 We Mentioned anti-Markovnikov Regiochemistry
 Reaction also Proceeds with SYN Stereochemistry
Me
Me
1. BH3 : THF
2. H2O2, NaOH
H
H
H
OH
H and OH Delivered anti-Markovnikov to the
SAME FACE of the p Bond
Sections 8.8 and 8.9 Deal w/ Mechanistic Aspects. This is
Interesting, but is NOT Testable Material (You May Omit)
Addition of Cl2 and Br2 to Alkenes
H3CHC
CHCH3
H3CH2CHC
CH2
Cl2
-9 oC
Cl2
H3CHC
Cl
CHCH3
Cl
H3CH2CHC
-9 oC
Cl
CH2
Cl
Br
Br2
-5 oC
H
H
+ Enantiomer
Br
• Obtain Vicinal Dihalides as Reaction Products
• Want to use a Non-Nucleophilic Solvent (Due to Intermediate)
 Important to Run Reactions in Dark (Avoid Radicals)
General Mechanism of Dihalide Addition
Br
Br
Br
-BrC
Br
C
Br
Br
• Intermediate is a BROMONIUM ION (in Br2 Case)
• Nucleophilic Solvents Can Capture (Open) Bromonium Ion
 Bromonium Ion Opening is SN2  Anti Addition of Br2
Stereochemistry of Dihalide Additions
• Can Open Symmetric Bromonium Ions at Either Carbon
• Always (for now) Anti (Trans) Addition of X2
• Reaction Products Are Enantiomers
• Racemic Mixtures (50:50) in Symmetric Bromonium Ions
• Will Get Excess of One Enantiomer in Asymmetric Cases
• Stereospecific Reactions: One Stereoiomeric Form of the
Starting Material Reacts in Such a Way to Form a
Specific Stereoisomeric Form of the Product
Halohydrin Formation
Br
Br
Br
-H+
-BrC
C
Br
HO
H2O
• Intermediate is Still a BROMONIUM ION (in Br2 Case)
• Nucleophilic Solvents Can Capture (Open) Bromonium Ion
 H2O Opens the Bromonium Ion; Another H2O Deprotonates
 Product is Halohydrin  Net X-OH Addition to Alkene
 Still Can Get Stereoisomeric Products (Open Either End)
Divalent Carbon Compounds: Carbenes
CH2
N
N
Diazomethane
Heat or Light
CH2 +
Methylene
(A Carbene)
N
N
• Common Way of Generating Carbenes (Divalent Carbon)
• Diazomethane: 3 Resonance Structures (Draw Others??)
• Carbenes are Highly Reactive Species; Short-Lived
• Excellent Utility is in the Synthesis of Cyclopropanes
• Let’s Look at Some Reactions Making Use of Carbenes
Divalent Carbon Compounds: Carbenes
C
C
+
CH2
C
C
C
H2
KOC(CH3)3
CHCl3
Cl
Cl
CH2I2, Zn(Cu)
• Halogen Substituted Carbenes from Haloforms (CHCl3, etc.)
• Last Reaction is Called the “Simmons-Smith” Reaction
Oxidation: Syn Dihydroxylation
OH
1. OsO4, pyridine
OH
2. Na2SO3/H2O
Propene
1,2-propanediol
(propylene glycol)
• C=C is Oxidized by OsO4
• Addition of Hydroxyl Groups Proceeds w/ SYN Stereochemistry
• Can Also use KMNO4 (More Powerful, May Cleave Diol)
• If Using KMNO4, Want COLD Reaction Temperatures
• OsO4 is Expensive; Can Use Catalytically if NMO is Added
Oxidation: Syn Dihydroxylation (2)
OsO4, 25 oC
Pyridine
O
O
Os
O
O
Osmate Ester
• Syn Addition Due to 5-Centered Transition State
• Transition State Same for KMNO4 Oxidations
• Cleavage of Osmate Ester Does Not Change C-O Stereochem
Oxidative Cleavage of Alkenes
O
KMnO4, NaOH
H2O, 
1. KMnO4, NaOH

2
O
O
+
O
C
O
2. H3O+
• Diol Believed to be Intermediate in Cleavage Reaction
• Unsubstituted Alkene Carbons Oxidized to Carbon Dioxide
• Monosubstituted Alkene Carbons Oxidized to Carboxylates
• Disubstituted Alkene Carbons Oxidized to Ketones
How You May See Oxidative Cleavage
An Unknown Alkene (C8H16) Gives Two
Products When Treated w/ Hot KMnO4:
C8H16
1. KMnO4, H2O
NaOH, 
2. H3O+
OH
+
O
O
The Products are a Carboxylic Acid and a Ketone, So Our Alkene Must Be
Trisubstituted. We Don't Know if it is CIS or TRANS, but we Can Put the
Rest of the Structure Together:
or
Ozonolysis of Alkenes
Me
O
Me
Me
1. O3, CH2Cl2, -78 oC
O +
2. Zn/HOAc
Et
Et
Me
H
O
Me
1. O3, CH2Cl2, -78 oC
H
Me
2. Zn/HOAc
O
• Milder Conditions than Treating w/ KMnO4
• “Workup” w/ Zn/HOAc  Oxidative Cleavage (Ald and Ket)
• Go Through Exceptionally Unstable Intermediate (Ozonide)
Dihalide Addition To Alkynes
Me
Me
Me
Me
Me
Br
Br
Br2
CCl4
Br2
CCl4
Br
Me
Me
Br
Me
Br
Br
Me
Cl
Cl
Cl
Cl2
CCl4
Cl2
CCl4
Cl
Me
Me
Me
Cl
Cl
• Addition Reactions, Just as in Alkenes (adds Once or Twice)
• Anti Additions, First Product Usually a Trans Dihaloalkene
• Can Get Relatively Good Trans Dihaloalkene Yields (1 eq X2)
Addition of HX to Alkynes
Me
Me
Me
H
Br
HBr
HBr
H
Me
Br
Me
Me
H
Br
geminal dihaloalkane
• Addition Reactions, Just as in Alkenes (adds Once or Twice)
• Final Product Typically Geminal Dihaloalkene
• Both Additions Follow Markovnikov’s Rule (explains gem.)
• Alumina Accelerates Reaction Rate (as seen w/ Alkenes)
Oxidative Cleavage of Alkynes
O
Me
i
Pr
Et
Ph
O
1. O3, CH2Cl2,
2. Zn/HOAc
+
Me
OH
Et
O
1. O3, CH2Cl2,
O
+
2. Zn/HOAc
i
Pr
OH
Ph
O
Me
Et
OH
O
1. KMnO4, NaOH
2. HOAc
OH
+
Me
OH
Et
OH
• Can Use Either Ozonolysis or KMnO4 as with Alkenes
• Products of the Oxidative Cleavage are Carboxylic Acids
Anti-Markovnikov HBr Addition
HBr
peroxides
Br
Me
Me
H
Br
HBr
peroxides
H
H
• Addition of Peroxides (ROOR)  ANTI-MARKOVNIKOV
• Goes Through a Radical Mechanism (Chapter 10)
• Right Now Focus on Regiochemistry (Know the Reaction)