Reactions and Synthesis Chapter 7 Alkenes: Reactions and Synthesis

Introduction Alkenes react with many electrophiles to give useful products by addition (often through special reagents) alcohols (add H-OH) alkanes (add H-H) halohydrins (add HO-X) dihalides (add X-X) halides (add H-X) diols (add HO-OH) cyclopropane (add :CH2)

I. Synthesis of Alkenes Dehydrohalogenation of Alkyl Halides Dehydration of Alcohols

Preparation of Alkenes: A Preview of Elimination Reactions Alkenes are commonly made by elimination reactions dehydrohalogenation dehydration

A. Dehydrohalogenation of Alkyl Halides Dehydrohalogenation is elimination (loss) of HX from an alkyl halide uses strong base (KOH)

B. Dehydration of Alcohols Dehydration is elimination of water (H-OH) from an alcohol requires strong acids (sulfuric acid, 50 ºC)

Practice Problem: One problem with elimination reactions is that Practice Problem: One problem with elimination reactions is that mixtures of products are often formed. For example, treatment of 2-bromo-2- methylbutane with KOH in ethanol yields a mixture of two alkene products. What are their likely structures?

Practice Problem: How many alkene products, including E,Z Practice Problem: How many alkene products, including E,Z isomers, might be obtained by dehydration of 3-methyl-3-hexanol (3-methyl-3- hydroxyhexane) with aqueous sulfuric acid?

II. Addition Reactions of Alkenes Addition of Halogens Halohydrin Formation Addition of Water: Oxymercuration Addition of Water: Hydroboration

II. Addition Reactions of Alkenes Addition of Carbenes Reduction of Alkenes: Hydrogenation Oxidation of Alkenes: Hydroxylation and Cleavage

II. Addition Reactions of Alkenes Biological Alkene Addition Reactions Addition of Radicals

A. Addition of Halogens Bromine and chlorine add to alkenes to give 1,2-dihalides, an industrially important process F2 is too reactive and I2 does not add Cl2 reacts as Cl+ Cl- and Br2 reacts similarly

Addition of Halogens is Anti Addition of halogens occurs with anti stereochemistry. The two ends of the double bonds are attacked from different sides Only the trans isomer is produced

Possible Mechanism of Halogen Addition ? Addition of Br2 to cyclopentene is exclusively trans + Formation of a carbocation does not explain the anti stereochemistry

Mechanism of Halogen Addition In 1937, Kimball and Roberts proposed the reaction intermediate to be a bromonium ion, R2Br+, and not a carbocation. This is a one-step process

Br+ adds to an alkene producing a cyclic ion Bromonium ion: Bromine shares charge with carbon Br “shields” one side and gives trans addition

Bromonium Ion Mechanism Electrophilic addition of bromine to give a cation is followed by cyclization to give a bromonium ion This bromoniun ion is a reactive electrophile and bromide ion is a good nucleophile +

The Reality of Bromonium Ions Bromonium ions were postulated more than 60 years ago to explain the stereochemical course of the addition (to give the trans-dibromide from a cyclic alkene) Olah - showed that bromonium ions are stable in liquid SO2 with SbF5 and can be studied directly

Addition of Halogens: Summary Bromine and chlorine add to alkenes to give 1,2-dihalides via three-membered ring bromonium ion or chloronium ion intermediates anti stereochemistry

Practice Problem: What product would you expect to obtain from Practice Problem: What product would you expect to obtain from addition of Cl2 to 1,2-dimethylcyclohexene? Show the stereochemistry of the product.

Practice Problem: Addition of HCl to 1,2-dimethylcyclohexene Practice Problem: Addition of HCl to 1,2-dimethylcyclohexene yields a mixture of two products. Show the stereochemistry of each, and explain why a mixture is formed.

B. Halohydrin Formation HO-X adds to an alkene to give a 1,2-halo alcohol, called a halohydrin The actual reagent is the dihalogen (Br2 or Cl2) in the presence of water in an organic solvent H2O acts as the nucleophile

Mechanism of Bromohydrin formation

An Alternative to Bromine Bromine is a difficult reagent to use for this reaction N-Bromosuccinimide (NBS) produces bromine in organic solvents and is a safer source

Mechanism of Bromohydrin Formation Br2 forms a bromonium ion, then water adds Orientation toward stable C+ species Aromatic rings do not react

Halohydrin Formation: Summary HO-X adds to an alkene to give a 1,2-halo alcohol, called a halohydrin Bromonium ion or chloronium ion intermediates Anti stereochemistry Markovnikov regiochemistry (X ~ H)

Practice Problem: What product would you expect from the Practice Problem: What product would you expect from the reaction of cyclopentene with NBS and water? Show the stereochemistry.

Practice Problem: When an unsymmetrical alkene such as Practice Problem: When an unsymmetrical alkene such as propene is treated with N-bromosuccinimide in aqueous dimethyl sulfoxide, the major product has the bromine atom bonded to the less highly substituted carbon atom. Is this Markovnikov or non-Markovnikov orientation? Explain.

C. Addition of Water: Oxymercuration Hydration of an alkene is the addition of H-OH to an alkene to give an alcohol Acid catalysts are used at high temperature in industrial processes: ethylene is converted to ethanol

Mechanism of Acid-catalyzed Hydration Protonation of the alkene gives a carbocation intermediate

Mechanism of Acid-catalyzed Hydration: Example

Oxymercuration For laboratory-scale hydration of an alkene Use mercuric acetate in aqueous THF followed by sodium borohydride Markovnikov orientation via mercurinium ion

Mechanism of Oxymercuration

Mechanism of Oxymercuration: Example

Oxymercuration-Reduction: Summary HO-H adds to an alkene to give an alcohol Markovnikov regiochemistry (OH attaches to the more highly substituted carbon) Mecurinium ion intermediates

Practice Problem: What products would you expect from Practice Problem: What products would you expect from oxymercuration of the following alkenes?

Practice Problem: What alkenes might the following alcohols Practice Problem: What alkenes might the following alcohols have been prepared from?

D. Addition of Water: Hydroboration In 1959, Herbert Brown (HB) invented hydroboration (HB) Borane adds to an alkene to give an organoborane

Borane (BH3) is a Lewis acid Borane (BH3) is electron deficient Boron has six electrons in its outer shell BH3 coordinates to oxygen electron pairs in ethers (THF)

Hydroboration-Oxidation Forms an Alcohol from an Alkene Addition of H-BH2 (from BH3-THF complex) to three alkenes gives a trialkylborane Oxidation with alkaline hydrogen peroxide in water produces the alcohol derived from the alkene

Orientation in Hydration via Hydroboration H and OH add with syn stereochemistry, to the same face of the alkene (opposite of anti addition) Regiochemistry is opposite to Markovnikov orientation OH is added to carbon with most H’s

Mechanism of Hydroboration Borane is a Lewis acid Alkene is a Lewis base Transition state involves anionic development on B Four-center, cyclic transition state The components of BH3 are across C=C

Mechanism of Hydroboration

Hydroboration: Orientation in Addition Step Addition in least crowded orientation, syn Addition also is via most stable carbocation

Hydroboration: Electronic Effects Give Non-Markovnikov More stable carbocation resembles a 3o carbocation

Hydroboration: Steric Effects Give Non-Markovnikov More stable carbocation is also consistent with steric preferences

Oxidation: Oxygen Insertion Step H2O2, OH- inserts OH in place of B Retains syn orientation

Hydroboration-oxidation: Summary Borane adds to an alkene to give an organoborane which is then oxidized by alkaline H2O2 to give an alcohol Syn stereochemistry Non-Markovnikov regiochemistry

Practice Problem: Show the structures of the products you Practice Problem: Show the structures of the products you would obtain by hydroboration/oxidation of the following alkenes:

Practice Problem: What alkenes might be used to prepare the Practice Problem: What alkenes might be used to prepare the following alcohols by hydroboration/oxidation?

Practice Problem: The following cycloalkene gives a mixture of Practice Problem: The following cycloalkene gives a mixture of two alcohols on hydroboration followed by oxidation. Draw the structures of both, explain the result.

E. Addition of Carbenes A carbene (R2C:) adds to an alkene to give a cyclopropane A carbene is electrically neutral with six electrons in the outer shell The carbene functional group is “half of an alkene” A carbene is electron-deficient and acts as an electrophile

Formation of Dichlorocarbene Base removes proton from chloroform Stabilized carbanion remains Unimolecular Elimination of Cl- gives electron deficient species, dichlorocarbene

Formation of Dichlorocarbene

Structure of Dichlorocarbene Dichlorocarbene is sp2 hybridized. It has a vacant p orbital

Reaction of Dichlorocarbene Addition of dichlorocarbene is stereospecific Only a single stereoisomer is formed

Simmons-Smith Reaction Equivalent of addition of CH2: Reaction of diiodomethane with zinc-copper alloy produces a carbenoid species Carbenoid forms cyclopropane by cycloaddition

Addition of Carbenes: Summary A carbene (R2C:) adds to an alkene to give a cyclopropane Stereospecific No intermediate

Practice Problem: What products would you expect from the Practice Problem: What products would you expect from the following reactions?

F. Reduction of Alkenes: Hydrogenation H-H adds to an alkene to give an alkane Reduction in general is addition of H2 or its equivalent It requires metal catalyst, Pt or Pd as powders, on carbon and H2 Hydrogen is first adsorbed on catalyst Reaction is heterogeneous (process is not in solution)

Catalytic Hydrogenation is syn Reaction is heterogeneous (process is not in solution) Reaction is syn Hydrogens add to the double bond from the same face

Mechanism of Catalytic Hydrogenation Heterogeneous – reaction between phases Addition of H-H is syn

Hydrogen Addition - Selectivity Selective for C=C. No reaction with C=O, CN Polyunsaturated liquid oils become solids If one side is blocked, hydrogen adds to other

Polyunsaturated liquid oils become solids upon catalytic hydrogenation

Hydrogenation: Summary H-H adds to an alkene to give an alkane Syn stereochemistry

Practice Problem: What product would you obtain from catalytic Practice Problem: What product would you obtain from catalytic hydrogenation of the following alkenes?

G. Oxidation of Alkenes Alkene Hydroxylation Oxidative Cleavage of Alkenes

1. Alkene Hydroxylation HO-OH adds to an alkene to give a 1,2-dialcohol or diol (also called a glycol) It is catalyzed by osmium tetroxide OsO4 Stereochemistry of addition is syn

Osmium Tetroxide Catalyzed Formation of Diols Hydroxylation of alkenes converts alkenes to cis-1,2-diol is catalyzed by osmium tetroxide OsO4, then sodium bisulfite NaHSO3 occurs via cyclic osmate di-ester intermediate

Alkene Hydroxylation: Summary HO-OH adds to an alkene to give a 1,2-dialcohol or diol (also called a glycol) Syn stereochemistry Osmate intermediate

2. Oxidative Cleavage of Alkenes Ozonolysis Permanganate Oxidation Oxidative Cleavage of 1,2-diols

a. Ozonolysis Ozone, O3, adds to alkenes to form molozonide which is then reduced by zinc, Zn, to give ketones and/or aldehydes

Examples of Ozonolysis of Alkenes Used in determination of structure of an unknown alkene

Structure Elucidation With Ozone Cleavage products reveal an alkene’s structure

b. Permanganate Oxidation Oxidizing reagents other than ozone also cleave alkenes Potassium permanganate (KMnO4) can produce carboxylic acids and carbon dioxide if H’s are present on C=C

c. Oxidative Cleavage of 1,2-diols Reaction of a 1,2-diol with periodic (per-iodic) acid, HIO4 , cleaves the diol into two carbonyl compounds Sequence of diol formation with OsO4 followed by diol cleavage is a good alternative to ozonolysis

Mechanism of Periodic Acid Oxidation It occurs via cyclic periodate intermediate

Oxidative Cleavage: Summary

Practice Problem: What alkene would you start with to prepare Practice Problem: What alkene would you start with to prepare each of the following compounds?

Practice Problem: What products would you expect from Practice Problem: What products would you expect from reaction of 1-methylcyclohexene with the following reagents? Aqueous acidic KMnO4 O3, followed by Zn, CH3CO2H

Practice Problem: Propose structures for alkenes that yield the Practice Problem: Propose structures for alkenes that yield the following products on reaction with ozone followed by treatment with Zn: (CH3)2C=O + H2C=O 2 equiv CH3CH2CH=O

H. Biological Alkene Addition Reactions Living organisms convert organic molecules using enzymes as catalysts Many reactions are similar to organic chemistry conversions, except they occur in neutral water They are usually more specific for reactant and stereochemistry

Example of Biological Hydration Fumarase catalyzes fumaric acid to malic acid It is specific for trans isomer Addition of H-OH is anti

I. Addition of Radicals to Alkenes: Polymers A polymer is a very large molecule consisting of repeating units of simpler molecules, formed by polymerization

Alkenes react with radical catalysts to undergo radical polymerization For example: Ethylene is polymerized to polyethylene

Free Radical Polymerization of Alkenes Alkenes combine many times to give polymer Reactivity is induced by formation of free radicals

Free Radical Polymerization: Initiation A few radicals are generated by the reaction of a molecule that readily forms radicals from a nonradical molecule A bond is broken homolytically

Free Radical Polymerization: Propagation Radical from intiation step adds to another alkene to generate alkene-derived radical This radical adds to another alkene, and so on many times

Free Radical Polymerization: Termination Chain propagation ends when two radical chains combine Not controlled specifically but affected by reactivity and concentration

Other Polymers Other alkenes give other common polymers

Unsymmetrical Monomers If alkene is unsymmetrical, reaction is via more highly substituted radical

Practice Problem: Show the monomer units you would use to Practice Problem: Show the monomer units you would use to prepare the following polymers:

Chain Branching During Polymerization During radical propagation chain can develop forks leading to branching One mechanism of branching is short chain branching in which an internal hydrogen is abstracted

Long Chain Branching In long chain-branching, a hydrogen from another chain is abstracted

Cationic Polymerization Vinyl monomers react with Brønsted or Lewis acid to produce a reactive carbocation that adds to alkenes and propagates via lengthening carbocations

Practice Problem: One of the chain-termination steps that Practice Problem: One of the chain-termination steps that sometimes occurs to interrupt polymerization is the following reaction between radicals: Propose a mechanism for this reaction, using fishbook arrows to indicate electron flow

Practice Problem: tert-Butyl vinyl ether is polymerized Practice Problem: tert-Butyl vinyl ether is polymerized commercially for use in adhesives by cationic process. Draw a segment of poly(tert-butyl vinyl ether), and show the mechanism of the chain-carrying step:

Chapter 7 The End