Chapter 8 Alkenes: Reactions and Synthesis

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

Why this chapter? To begin a systematic description of major functional groups Begin to focus on general principles and patterns of reactivity that tie organic chemistry

8.1 Preparation of Alkenes: A Preview of Elimination Reactions Alkenes are commonly made by elimination of HX from alkyl halide (dehydrohalogenation) Uses heat and KOH elimination of H-OH from an alcohol (dehydration) requires strong acids (sulfuric acid, 50 ºC)

Reactions for Making Unsaturateds - Video 1) Reactions for Making Unsaturateds – dehydration and dehydrohalogenation http://www.youtube.com/watch?feature=player_detailpage&v=OkZcMgvscLQ

8.2 Addition of Halogens to Alkenes Bromine and chlorine add to alkenes to give 1,2-dihaldes, an industrially important process F2 is too reactive and I2 does not add Cl2 reacts as Cl+ Cl- Br2 is similar

Addition of Br2 to Cyclopentene Addition is exclusively trans

Mechanism of Bromine Addition Br+ adds to an alkene producing a cyclic ion Bromonium ion, bromine shares charge with carbon 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

Halogenation of an Alkene - Video http://www.youtube.com/watch?v=RxbNTDhP-Qg&feature=player_embedded

8.3 Halohydrins from Alkenes: Addition of HOX This is formally the addition of HO-X to an alkene to give a 1,2-halo alcohol, called a halohydrin The actual reagent is the dihalogen (Br2 or Cl2) in water in an organic solvent)

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

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

Halohydrin Formation - Video http://www.youtube.com/watch?v=FaOOx6IZxV8

8.4 Hydration of Alkenes: Addition of H2O by Oxymercuration Hydration of an alkene is the addition of H-OH to give an alcohol Acid catalysts are used in high temperature industrial processes: ethylene is converted to ethanol

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

Hydration of Alkenes - Video 1) Acidic hydration of alkenes http://www.youtube.com/watch?v=G9zJL8PGwa0&feature=player_embedded 2) Oxymercuration of alkenes for hydration: video 1 http://www.youtube.com/watch?feature=player_detailpage&v=EjGIwqnxqmo 3) Oxymercuration of alkenes for hydration: video 2 http://www.youtube.com/watch?feature=player_detailpage&v=wp7z0XVjUd0

8.5 Hydration of Alkenes: Addition of H2O by Hydroboration Borane (BH3) is electron deficient Borane adds to an alkene to give an organoborane

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

Mechanism of Hydroboration Borane is a Lewis acid Alkene is Lewis base Transition state involves anionic development on B The components of BH3 are added across C=C More stable carbocation is also consistent with steric preferences

Hydroboration-Oxidation - Video http://www.youtube.com/watch?v=ak--LSQe7pk&feature=player_embedded

8.6 Reduction of Alkenes: Hydrogenation Addition of H-H across C=C Reduction in general is addition of H2 or its equivalent Requires Pt or Pd as powders on carbon and H2 Hydrogen is first adsorbed on catalyst Reaction is heterogeneous (process is not in solution)

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

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

8.7 Oxidation of Alkenes: Epoxidation and Hydroxylation Epoxidation results in a cyclic ether with an oxygen atom Stereochemistry of addition is syn

Organic Mechanism - Epoxidation with mCPBA - Video http://www.youtube.com/watch?feature=player_detailpage&v=WwTCf-bv1SQ 2) Preparation of Epoxides – halohydrin treated with sodium hydride (strong base) http://www.youtube.com/watch?feature=player_detailpage&v=Rt93fEfxHjQ

Acid catalyzed epoxide opening to produce diol - Video 1) Opening of epoxides with acid and water to give trans diols http://www.youtube.com/watch?feature=player_detailpage&v=XX9JQd4MhBM

Osmium Tetroxide Catalyzed Formation of Diols Hydroxylation - converts to syn-diol Osmium tetroxide, then sodium bisulfite Via cyclic osmate di-ester

Osmium Tetroxide Catalyzed Formation of Diols - Video Syn Dihydroxylation http://www.youtube.com/watch?feature=player_detailpage&v=76KtDSfWnkw

8.8 Oxidation of Alkenes: Cleavage to Carbonyl Compounds Ozone, O3, adds to alkenes to form molozonide Molozonideis converted to ozonide that may be reduced to obtain ketones and/or aldehydes

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

Example of Ozonolysis of Alkenes - Videos 1) ozonolysis - oxidative cleavage http://www.youtube.com/watch?feature=player_detailpage&v=Q_KsGV9VD54

Permangate Oxidation of Alkenes 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

Permanganate Oxidation of Alkenes - Video 1) Oxidative Cleavage Alkenes and Aromatic Side Chains with Potassium Permanganate http://www.youtube.com/watch?feature=player_detailpage&v=IuMiG13RZzE

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

Cleavage of 1,2-diols - Video 1) Periodate Cleavage – END AT 9:36 http://www.youtube.com/watch?feature=player_detailpage&v=xrLxWvCmzXo

8.9 Addition of Carbenes to Alkenes: Cyclopropane Synthesis The carbene functional group is “half of an alkene” Carbenes are electronically neutral with six electrons in the outer shell They add symmetrically across double bonds to form cyclopropanes

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

Reaction of Dichlorocarbene Addition of dichlorocarbene is stereospecific cis

Reaction of Dichlorocarbene - Video 1) Addition of Carbenes to Alkenes - START VIDEO AT 24:50 MINS; END AT 36:55 http://www.youtube.com/watch?feature=player_detailpage&v=vuxCkDOJS6o

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

Simmons-Smith Reaction - Video 1) Cyclopropane Simmons-Smith reaction - START VIDEO AT 5:55 MINS_END AT 17:55 http://www.youtube.com/watch?feature=player_detailpage&v=nKk0JVrQkAY

8.10 Radical Additions to Alkenes: Chain-Growth 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 Ethylene is polymerized to polyethylene, for example

Free Radical Polymerization: Initiation 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

Polymerization: Propagation Radical from initiation adds to alkene to generate alkene derived radical This radical adds to another alkene, and so on many times

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

Addition Polymerization - Video 1) Radical Addition to Alkenes: Chain-Growth Polymer http://www.youtube.com/watch?feature=player_detailpage&v=o3Hq4gXuKB0

8.11 Biological Additions of Radicals to Alkenes Severe limitations to the usefulness of radical addition reactions in the lab In contrast to electrophilic additions, reactive intermediate is not quenched so it reacts again and again uncontrollably

Biological Reactions Biological reactions different from in the laboratory One substrate molecule at a time is present in the active site of an enzyme Biological reactions are more controlled, more specific than other reactions

Pathway of Biosynthesis of Prostaglandins

8.12 and 8.13 Addition of water to achiral and chrial alkanes As a general rule, the formation of a new chirality center by reaction of achiral reactants always leads to racemic mextures of enantiomeric products. As a general rule, the formation of a new chirality center by the reaction of a chiral reactant leads to unequal amounts of diasteromeric products. This is because the carbocation has no plane of symmetry and is chiral, it does not react equally well from the top and bottom faces. One of the two faces is likely, for steric reasons, to be a bit more accessible than the other face, thus leading to a mixture of R and S products in some ratio other than 50:50.

8.12 and 8.13 Addition of water to achiral and chrial alkanes - Video Addition of Water (Acid-Catalyzed) Mechanism http://www.youtube.com/watch?list=PLA31DCAA0F31D83FA&v=sEiQm7IzUg8&feature=player_detailpage

Let’s Work a Problem Which Reaction would one predict to be faster, addition of HBr to cyclohexene or to 1-methylcyclohexene?

Answer First, draw out both reactants with HBr. What we should realize at this point is that the formation of the intermediate that is more stabilized via carbocation formation is the one that will form product faster. At this point, we should see that the intermediate formed via the 3˚ intermediate from 1-methylcyclohexene (as opposed to the 2˚ carbocation intermediate in the case of cyclohexene) will proceed faster.