chapter 7. alkenes react with many electrophiles to give useful products by addition (often through...

Chapter 7

• Alkenes react with many electrophiles to give useful products by addition (often through special reagents)

– alcoholsalcohols (add HH--OHOH)

– alkanesalkanes (add HH-HH)

– halohydrinshalohydrins (add HOHO-XX)

– dihalidesdihalides (add XX-XX)

– halideshalides (add HH-XX)

– diolsdiols (add HOHO-OHOH)

– cyclopropanecyclopropane (add :CH:CH22)

IntroductionIntroduction

I. Synthesis of AlkenesI. Synthesis of Alkenes I. Synthesis of AlkenesI. Synthesis of Alkenes

A.A. Dehydrohalogenation of Alkyl Dehydrohalogenation of Alkyl HalidesHalides

B.B. Dehydration of AlcoholsDehydration of Alcohols

A.A. Dehydrohalogenation of Alkyl Dehydrohalogenation of Alkyl HalidesHalides

B.B. Dehydration of AlcoholsDehydration of Alcohols

• Alkenes are commonly made by elimination reactionselimination reactions– dehydrohalogenationdehydrohalogenation– dehydrationdehydration

Preparation of Alkenes: Preparation of Alkenes: A Preview of Elimination A Preview of Elimination ReactionsReactions

A.A. Dehydrohalogenation of Alkyl HalidesDehydrohalogenation of Alkyl Halides

A.A. Dehydrohalogenation of Alkyl HalidesDehydrohalogenation of Alkyl Halides

DehydrohalogenationDehydrohalogenation is elimination (loss) of HX from an alkyl halide

– uses strong base (KOH)strong base (KOH)

B.B. Dehydration of AlcoholsDehydration of Alcohols

B.B. Dehydration of AlcoholsDehydration of Alcohols

DehydrationDehydration is elimination of water (H-OH) from an alcohol

– requires strong acidsstrong acids (sulfuric acid, 50 ºC)

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

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

II. Addition Reactions of AlkenesII. Addition Reactions of Alkenes II. Addition Reactions of AlkenesII. Addition Reactions of Alkenes

A.A. Addition of HalogensAddition of Halogens

B.B. Halohydrin FormationHalohydrin Formation

C.C. Addition of Water: OxymercurationAddition of Water: Oxymercuration

D.D. Addition of Water: HydroborationAddition of Water: Hydroboration

A.A. Addition of HalogensAddition of Halogens

B.B. Halohydrin FormationHalohydrin Formation

C.C. Addition of Water: OxymercurationAddition of Water: Oxymercuration

D.D. Addition of Water: HydroborationAddition of Water: Hydroboration

II. Addition Reactions of AlkenesII. Addition Reactions of Alkenes II. Addition Reactions of AlkenesII. Addition Reactions of Alkenes

E.E. Addition of CarbenesAddition of Carbenes

F.F. Reduction of Alkenes: HydrogenationReduction of Alkenes: Hydrogenation

G.G. Oxidation of Alkenes: Hydroxylation Oxidation of Alkenes: Hydroxylation and Cleavageand Cleavage

E.E. Addition of CarbenesAddition of Carbenes

F.F. Reduction of Alkenes: HydrogenationReduction of Alkenes: Hydrogenation

G.G. Oxidation of Alkenes: Hydroxylation Oxidation of Alkenes: Hydroxylation and Cleavageand Cleavage

II. Addition Reactions of AlkenesII. Addition Reactions of Alkenes II. Addition Reactions of AlkenesII. Addition Reactions of Alkenes

H.H. Biological Alkene Addition ReactionsBiological Alkene Addition Reactions

I.I. Addition of RadicalsAddition of Radicals

H.H. Biological Alkene Addition ReactionsBiological Alkene Addition Reactions

I.I. Addition of RadicalsAddition of Radicals

A.A. Addition of HalogensAddition of Halogens

A.A. Addition of HalogensAddition of Halogens

• BromineBromine and chlorinechlorine add to alkenes to give 1,2-dihalides1,2-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 occurs with anti stereochemistry. anti stereochemistry.

– The two ends of the double bonds are attacked from different sides

– Only the trans isomer is produced

Addition of Halogens is Anti Addition of Halogens is Anti

• Addition of Br2 to cyclopentene is exclusively trans

Possible Mechanism of Halogen Addition ?Possible Mechanism of Halogen Addition ?

+

– Formation of a carbocation does not explain the anti stereochemistry

• In 1937, Kimball and Roberts proposed the reaction intermediate to be a bromonium ionbromonium ion, R2Br+, and not a carbocation.

– This is a one-step process

Mechanism of Halogen AdditionMechanism of Halogen Addition

• Br+ adds to an alkene producing a cyclic ion• Bromonium ionBromonium ion: Bromine shares charge with carbon

– Br “shields” one side and gives trans addition

Bromonium Ion MechanismBromonium Ion Mechanism

• Electrophilic addition of bromine to give a cation is followed by cyclization to give a bromonium ionbromonium ion

• This bromoniun ion is a reactive electrophile and bromide ion is a good nucleophile

+

The Reality of Bromonium IonsThe 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 - Olah - showed that bromonium ions are stable in liquid SO2 with SbF5 and can be studied directly

Addition of Halogens: Addition of Halogens: SummarySummary

Addition of Halogens: Addition of Halogens: SummarySummary

• BromineBromine and chlorinechlorine add to alkenes to give 1,2-dihalides1,2-dihalides

– via three-membered ring bromonium ionbromonium ion or chloronium ionchloronium ion intermediates– anti anti stereochemistry

Practice ProblemPractice Problem: What product would you expect to obtain from : What product would you expect to obtain from addition of Cl addition of Cl22 to 1,2-dimethylcyclohexene? to 1,2-dimethylcyclohexene?

Show the stereochemistry of the product. Show the stereochemistry of the product.

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

B.B. Halohydrin FormationHalohydrin Formation

B.B. Halohydrin FormationHalohydrin Formation

• HO-XHO-X adds to an alkene to give a 1,2-halo alcohol, called a halohydrinhalohydrin

– The actual reagent is the dihalogen (Br2 or Cl2) in the presence of water in an organic solvent

– H2O acts as the nucleophile

Mechanism ofMechanism of Bromohydrin formationBromohydrin formation

An Alternative to BromineAn Alternative to Bromine

• Bromine is a difficult reagent to use for this reaction

• N-BromosuccinimideN-Bromosuccinimide (NBSNBS) produces bromine in organic solvents and is a safer source

Mechanism of Bromohydrin FormationMechanism of Bromohydrin Formation

• Br2 forms a bromonium ion, then water adds

– Orientation toward stable C+ species

– Aromatic rings do not react

Halohydrin Formation: Halohydrin Formation: SummarySummary

Halohydrin Formation: Halohydrin Formation: SummarySummary

• HO-XHO-X adds to an alkene to give a 1,2-halo alcohol, called a halohydrinhalohydrin

– BromoniumBromonium ion or chloroniumchloronium ion intermediates – AntiAnti stereochemistry– MarkovnikovMarkovnikov regiochemistry (XX ~ H)

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

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

Explain. Explain.

C.C. Addition of Water: OxymercurationAddition of Water: Oxymercuration

C.C. Addition of Water: OxymercurationAddition of Water: Oxymercuration

• Hydration of an alkene is the addition of H-OHH-OH to an alkene to give an alcoholalcohol

– Acid catalystsAcid catalysts are used at high temperature in industrial processes: ethylene is converted to ethanol

Mechanism of Acid-Mechanism of Acid-catalyzed Hydrationcatalyzed Hydration

• Protonation of the alkene gives a carbocation intermediate

Mechanism of Acid-catalyzed Hydration: Mechanism of Acid-catalyzed Hydration: ExampleExample

OxymercurationOxymercuration

• For laboratory-scale hydration of an alkene– Use mercuric acetate in aqueous THF followed by

sodium borohydride

• MarkovnikovMarkovnikov orientation– via mercurinium ion

Mechanism of Mechanism of OxymercurationOxymercuration

Mechanism of Oxymercuration: Mechanism of Oxymercuration: ExampleExample

Oxymercuration-Reduction: Oxymercuration-Reduction: SummarySummary

Oxymercuration-Reduction: Oxymercuration-Reduction: SummarySummary

• HO-HHO-H adds to an alkene to give an alcoholalcohol

– MarkovnikovMarkovnikov regiochemistry (OH attaches to the more highly substituted carbon)

– Mecurinium Mecurinium ion intermediates

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

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

D.D. Addition of Water: HydroborationAddition of Water: Hydroboration

D.D. Addition of Water: HydroborationAddition of Water: Hydroboration

• In 1959, Herbert Brown (HB) invented hydroboration (HB)

• Borane Borane adds to an alkene to give an organoboraneorganoborane

Borane (BHBorane (BH33) is a Lewis acid) 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 Hydroboration-Oxidation Forms an Alcohol from an AlkeneAlkene

• Addition of H-BHAddition of H-BH22 (from BH3-THF complex) to three alkenes gives a trialkylboranetrialkylborane

• Oxidation Oxidation with alkaline hydrogen peroxide alkaline hydrogen peroxide in water produces the alcoholalcohol derived from the alkene

Orientation in Hydration via HydroborationOrientation in Hydration via Hydroboration

• H and OH add with syn stereochemistrysyn stereochemistry, to the same face of the alkene (opposite of anti addition)

• Regiochemistry is opposite to Markovnikovopposite to Markovnikov orientation– OH is added to carbon with most H’s

Mechanism of HydroborationMechanism 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 Mechanism of Hydroboration

Hydroboration: Orientation in Addition StepHydroboration: Orientation in Addition Step

• Addition in least crowded orientation, syn• Addition also is via most stable carbocation

Hydroboration: Electronic Effects Give Non-MarkovnikovHydroboration: Electronic Effects Give Non-Markovnikov

• More stable carbocation resembles a 3o carbocation

• More stable carbocation is also consistent with steric preferences

Hydroboration: Steric Effects Give Non-MarkovnikovHydroboration: Steric Effects Give Non-Markovnikov

Oxidation: Oxygen Insertion StepOxidation: Oxygen Insertion Step

• H2O2, OH- inserts OH in place of B

• Retains syn orientation

Hydroboration-oxidation: Hydroboration-oxidation: SummarySummary

Hydroboration-oxidation: Hydroboration-oxidation: SummarySummary

Borane Borane adds to an alkene to give an organoborane organoborane which is then oxidized by alkaline Halkaline H22OO22 to give an alcoholalcohol

– Syn Syn stereochemistry– Non-MarkovnikovNon-Markovnikov regiochemistry

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

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

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

E.E. Addition of CarbenesAddition of Carbenes

E.E. Addition of CarbenesAddition of Carbenes

• A carbene (RA carbene (R22C:) C:) adds to an alkene to give a

cyclopropanecyclopropane

– 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 DichlorocarbeneFormation of Dichlorocarbene

• Base removes proton from chloroform

• Stabilized carbanion remains

• Unimolecular Elimination of Cl- gives electron deficient species, dichlorocarbene

Formation of DichlorocarbeneFormation of Dichlorocarbene

Structure of DichlorocarbeneStructure of Dichlorocarbene

• Dichlorocarbene is sp2 hybridized.– It has a vacant p orbital

Reaction of DichlorocarbeneReaction of Dichlorocarbene

• Addition of dichlorocarbene is stereospecific stereospecific – Only a single stereoisomer is formed

Simmons-Smith ReactionSimmons-Smith Reaction

• Equivalent of addition of CH2:

• Reaction of diiodomethane with zinc-copper alloy produces a carbenoid carbenoid species

• Carbenoid forms cyclopropane by cycloadditioncycloaddition

Addition of Carbenes: Addition of Carbenes: SummarySummary

Addition of Carbenes: Addition of Carbenes: SummarySummary

• A carbene (RA carbene (R22C:) C:) adds to an alkene to give a cyclopropanecyclopropane

– Stereospecific– No intermediate

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

F.F. Reduction of Alkenes: HydrogenationReduction of Alkenes: Hydrogenation

F.F. Reduction of Alkenes: HydrogenationReduction of Alkenes: Hydrogenation

• H-HH-H adds to an alkene to give an alkanealkane

– 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)

– Reaction is heterogeneousheterogeneous (process is not in solution)

– Reaction is syn • Hydrogens add to the double bond from the same face

Catalytic Hydrogenation is synCatalytic Hydrogenation is syn

Mechanism of Catalytic HydrogenationMechanism of Catalytic Hydrogenation

• Heterogeneous – reaction between phases• Addition of H-H is synsyn

Hydrogen Addition - SelectivityHydrogen Addition - Selectivity

• Selective for C=C. No reaction with C=O, CN

• Polyunsaturated liquid oils become solids• If one side is blocked, hydrogen adds to other

• Polyunsaturated liquid oils become solids upon catalytic hydrogenation

Hydrogenation: Hydrogenation: SummarySummary

Hydrogenation: Hydrogenation: SummarySummary

• H-HH-H adds to an alkene to give an alkane alkane

– Syn Syn stereochemistry

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

GG.. Oxidation of AlkenesOxidation of Alkenes

GG.. Oxidation of AlkenesOxidation of Alkenes

1.1. Alkene HydroxylationAlkene Hydroxylation

2.2. Oxidative Cleavage of AlkenesOxidative Cleavage of Alkenes

1.1. Alkene HydroxylationAlkene Hydroxylation

2.2. Oxidative Cleavage of AlkenesOxidative Cleavage of Alkenes

11.. Alkene HydroxylationAlkene Hydroxylation

11.. Alkene HydroxylationAlkene Hydroxylation

• HO-OHHO-OH adds to an alkene to give a 1,2-dialcohol or dioldiol (also called a glycolglycol)

– It is catalyzed by osmium tetroxide OsO4

– Stereochemistry of addition is synsyn

Hydroxylation of alkenes– converts alkenes to cis-1,2-diolcis-1,2-diol

– is catalyzed by osmium tetroxide OsO4, then sodium bisulfite NaHSO3

– occurs via cyclic osmateosmate di-ester intermediate

Osmium Tetroxide Catalyzed Formation of DiolsOsmium Tetroxide Catalyzed Formation of Diols

Alkene Hydroxylation: Alkene Hydroxylation: SummarySummary

Alkene Hydroxylation: Alkene Hydroxylation: SummarySummary

• HO-OHHO-OH adds to an alkene to give a 1,2-dialcohol or dioldiol (also called a glycolglycol)

– Syn Syn stereochemistry– Osmate Osmate intermediate

22.. Oxidative Cleavage of AlkenesOxidative Cleavage of Alkenes

22.. Oxidative Cleavage of AlkenesOxidative Cleavage of Alkenes

a.a. OzonolysisOzonolysis

b.b. Permanganate OxidationPermanganate Oxidation

c.c. Oxidative Cleavage of 1,2-diolsOxidative Cleavage of 1,2-diols

a.a. OzonolysisOzonolysis

b.b. Permanganate OxidationPermanganate Oxidation

c.c. Oxidative Cleavage of 1,2-diolsOxidative Cleavage of 1,2-diols

OzoneOzone, O3, adds to alkenes to form molozonide molozonide which is then reduced by zinczinc, Zn, to give ketones ketones and/or aldehydesaldehydes

a.a. OzonolysisOzonolysis

Used in determination of structure of an unknown alkene

Examples of Ozonolysis of AlkenesExamples of Ozonolysis of Alkenes

Cleavage products reveal an alkene’s structure

Structure Elucidation With OzoneStructure Elucidation With Ozone

b.b. Permanganate OxidationPermanganate Oxidation

• Oxidizing reagents other than ozone also cleave alkenes

• Potassium permanganatePotassium permanganate (KMnO4) can produce carboxylic acidscarboxylic acids and carbon dioxide if H’s are present on C=C

c.c. Oxidative Cleavage of 1,2-diolsOxidative 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

It occurs via cyclic periodatecyclic periodate intermediate

Mechanism of Periodic Acid OxidationMechanism of Periodic Acid Oxidation

Oxidative Cleavage: Oxidative Cleavage: SummarySummary

Oxidative Cleavage: Oxidative Cleavage: SummarySummary

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

Practice ProblemPractice Problem: What products would you expect from : What products would you expect from reaction of 1-methylcyclohexene with the reaction of 1-methylcyclohexene with the following reagents? following reagents?

a) Aqueous acidic KMnO4

b) O3, followed by Zn, CH3CO2H

Practice ProblemPractice Problem: Propose structures for alkenes that yield the : Propose structures for alkenes that yield the following products on reaction with ozone following products on reaction with ozone followed by treatment with Zn: followed by treatment with Zn:

a) (CH3)2C=O + H2C=O

b) 2 equiv CH3CH2CH=O

H.H. Biological Alkene Addition ReactionsBiological Alkene Addition Reactions

H.H. Biological Alkene Addition ReactionsBiological Alkene Addition Reactions

• Living organisms convert organic molecules using enzymesenzymes as catalysts

– Many reactions are similar to organic chemistry conversions, except they occur in neutral waterneutral water

– They are usually more specificspecific for reactant and stereochemistry

Fumarase catalyzes fumaric acid to malic acid

– It is specific for transtrans isomer

– Addition of H-OH is antianti

Example of Biological HydrationExample of Biological Hydration

II.. Addition of Radicals to Alkenes: Addition of Radicals to Alkenes: PolymersPolymers

II.. Addition of Radicals to Alkenes: Addition of Radicals to Alkenes: PolymersPolymers

• A polymerpolymer is a very large molecule consisting of repeating units of simpler molecules, formed by polymerizationpolymerization

Alkenes react with radical catalysts to undergo radical polymerization

• For example: Ethylene is polymerized to polyethylene

Alkenes combine many times to give polymer

– Reactivity is induced by formation of free radicals

Free Radical Polymerization of AlkenesFree Radical Polymerization of Alkenes

Free Radical Polymerization: Free Radical Polymerization: InitiationInitiation

InitiationInitiation: – A few radicals are generated by the reaction of a

molecule that readily forms radicals from a nonradical molecule

– A bond is broken homolytically homolytically

Free Radical Polymerization: Free Radical Polymerization: PropagationPropagation

PropagationPropagation: – 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: Free Radical Polymerization: TerminationTermination

TerminationTermination: – Chain propagation ends when two radical chains

combine– Not controlled specifically but affected by reactivity and

concentration

Other PolymersOther Polymers

• Other alkenes give other common polymers

Unsymmetrical MonomersUnsymmetrical Monomers

• If alkene is unsymmetrical, reaction is via more highly substituted radical

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

Chain Branching During PolymerizationChain Branching During Polymerization

• During radical propagation chain can develop forks leading to branching

• One mechanism of branching is short chain branchingshort chain branching in which an internal hydrogen is abstracted

Long Chain BranchingLong Chain Branching

• In long chain-branchinglong chain-branching, a hydrogen from another chain is abstracted

Cationic PolymerizationCationic Polymerization

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

Practice ProblemPractice Problem: One of the chain-termination steps that : One of the chain-termination steps that sometimes occurs to interrupt polymerization sometimes occurs to interrupt polymerization is the following reaction between radicals: is the following reaction between radicals:

Propose a mechanism for this reaction, using Propose a mechanism for this reaction, using fishbook arrows to indicate electron flow fishbook arrows to indicate electron flow

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

Chapter 7