8. Alkenes: Reactions and Synthesis 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

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

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) require strong acids (sulfuric acid, 50 ºC)

Preview of Elimination Reactions Dehydrohalogenation: Loss of HX With D and strong base (KOH)

Preview of Elimination Reactions Dehydration: Loss of HOH With strong acid cat (H2SO4)

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

Biological Halogenation Occurs in marine organisms. “Br1+” or “Cl1+” like compounds made by oxidizing Br1- or Cl1- with H2O2 p. 218

Which product will result from the following reaction? Learning Check: Which product will result from the following reaction? 1. 2. 5. 4. 3. 1 2 3 4 5

Which product will result from the following reaction? Solution: Which product will result from the following reaction? 1. 2. 5. 4. 3. 1 2 3 4 5

8.3 Addition of Hypohalous Acids to Alkenes: Halohydrin Formation 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

Learning Check: Which of the compounds will result from the reaction of NBS/H2O/DMSO with 1-methylcyclopentene? 2. 1. 5. 3. 4. 1 2 3 4 5

Solution: Which of the compounds will result from the reaction of NBS/H2O/DMSO with 1-methylcyclopentene? 2. 1. 5. 3. 4. 1 2 3 4 5

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

Figure 7.2: MECHANISM: Mechanism of the acid-catalyzed hydration of an alkene to yield an alcohol. Protonation of the alkene gives a carbocation intermediate that reacts with water. Fig. 7-2, p. 221

Biological Addition of Water p. 222

Oxymercuration p. 222

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

8.5 Addition of Water to Alkenes: Hydroboration Herbert Brown (HB) invented hydroboration (HB) Borane (BH3) is electron deficient is a Lewis acid Borane adds to an alkene to give an organoborane

BH3-THF Complex THF = Tetrahydrofuran; a common ether solvent p. 223

Hydroboration-Oxidation: Alkene  Alcohol 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 consistent with steric preferences

Example: p. 225

Learning Check p. 225

Solution: Options are: So: p. 226

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

Examples: p. 232

Examples: p. 232

Learning Check: What product would you obtain from catalytic hydrogenation of the following alkenes? p. 232

Biological Example: Fig. 7-8, p. 233 Figure 7.8: Catalytic hydrogenation of polyunsaturated fats leads to saturated products, along with a small amount of isomerized trans fats. Fig. 7-8, p. 233

Learning Check: Which compound is the best starting material for hydrogenation to decalin shown below? 1. 2. 3. 5. 4. 1 2 3 4 5

Solution: Which compound is the best starting material for hydrogenation to decalin shown below? 1. 2. 3. 5. 4. 1 2 3 4 5

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

Ways to Make Epoxides p. 234

Use Epoxides to make Diols

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

8.8 Oxidaton of Alkenes: Cleavage to Carbonyl Compounds Ozone, O3, adds to alkenes to form molozonide Reduce molozonide to obtain ketones and/or aldehydes

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

Compound X reacts with O3 (followed by Zn/AcOH) to give I and II. Learning Check: Compound X reacts with O3 (followed by Zn/AcOH) to give I and II. Which of the following could be X? 1. 2. 5. 3. 4. 1 2 3 4 5

Compound X reacts with O3 (followed by Zn/AcOH) to give I and II. Solution: Compound X reacts with O3 (followed by Zn/AcOH) to give I and II. Which of the following could be X? 1. 2. 5. 3. 4. 1 2 3 4 5

Permangante 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

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

What is the major product of the following reaction? Learning Check: What is the major product of the following reaction? 2. 1. 5. 3. 4. 1 2 3 4 5

What is the major product of the following reaction? Solution: What is the major product of the following reaction? 2. 1. 5. 3. 4. 1 2 3 4 5

Learning Check: Which of the following will react with periodic acid (HIO4) to give an aldehyde? 1. 2. 5. 3. 4. 1 2 3 4 5

Solution: Which of the following will react with periodic acid (HIO4) to give an aldehyde? 1. 2. 5. 3. 4. 1 2 3 4 5

8.9 Addition of Carbenes to Alkenes The carbene functional group is “half of an alkene” Carbenes are electrically 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

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

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

Polymers

Free Radical Polymerization: Initiation Alkenes react with radical catalysts to undergo radical polymerization Ethylene is polymerized to poyethylene, for example 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

Other Polymers Table 7-1, p. 242

Which monomer would give the polymer shown below? Learning Check: Which monomer would give the polymer shown below? 2. 1. 5. 4. 3. 1 2 3 4 5

Which monomer would give the polymer shown below? Solution: Which monomer would give the polymer shown below? 2. 1. 5. 4. 3. 1 2 3 4 5

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 than 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

Natural Rubber Natural rubber is obtained from the bark of the rubber tree, Hevea brasiliensis, grown on enormous plantations in Southeast Asia. p. 245

8.12 Stereochemistry of Reactions: Addition of H2O to Alkenes Many reactions can produce new chirality centers from compounds without them What is the stereochemistry of the chiral product? What relative amounts of stereoisomers form? Example addition of H2O to 1-butene

Achiral Intermediate Gives Racemic Product Addition via carbocation Top and bottom are equally accessible

8.13 Stereochemistry of Reactions: Addition of H2O to a Chiral Alkene What is the sterochemical result of the addition of H2O to a chiral alkene R-4- methyl-1-hexene Product has 2 chiral centers

Figure 9.16: Stereochemistry of the addition of H2O to the chiral alkene, (R)-4-methyl-1-hexene. A mixture of diastereomeric 2R,4R and 2S,4R products is formed in unequal amounts because reaction of the chiral carbocation intermediate is not equally likely from top and bottom. The product mixture is optically active. Fig. 9-16, p. 313

Summary

Learning Check: Which sequence of reagents is necessary to carry out the following synthesis? Br2/hv; NaOH; RCO3H; H3O+ Cl2/heat; KOH; OsO4; NaHSO3/H2O H2/Pd; NBS/H2O/DMSO; H3O+ KOH; OsO4; NaHSO3/H2O NaOH; Br2/H2O; KOH; H3O+

Solution: Which sequence of reagents is necessary to carry out the following synthesis? Br2/hv; NaOH; RCO3H; H3O+ Cl2/heat; KOH; OsO4; NaHSO3/H2O H2/Pd; NBS/H2O/DMSO; H3O+ KOH; OsO4; NaHSO3/H2O NaOH; Br2/H2O; KOH; H3O+

Learning Check: Which alkene would produce two identical ketones when reacted with KMnO4/H+? 2. 1. 3. 4. 5. 1 2 3 4 5

Solution: Which alkene would produce two identical ketones when reacted with KMnO4/H+? 2. 1. 3. 4. 5. 1 2 3 4 5

Learning Check: What kind of intermediate is involved in the biosynthesis of prostaglandins from arachidonic acid? carbocations carbanions carbon-base radicals bromonium ions carbenes

Solution: What kind of intermediate is involved in the biosynthesis of prostaglandins from arachidonic acid? carbocations carbanions carbon-base radicals bromonium ions carbenes

What is the best reagent to carry out the following reaction? Learning Check: What is the best reagent to carry out the following reaction? CH2Cl2/Zn(Cu) CH2l2/Zn(Cu); Cl2 CH2Cl2/KOH CHCl3/KOH Cl2/H2O, CH3I/KOH

What is the best reagent to carry out the following reaction? Solution: What is the best reagent to carry out the following reaction? CH2Cl2/Zn(Cu) CH2l2/Zn(Cu); Cl2 CH2Cl2/KOH CHCl3/KOH Cl2/H2O, CH3I/KOH

Learning Check: Which of the following reactions would not yield at least one alcohol functional group? hydroboration of an internal alkene, followed by H2O2/NaOH reaction of a mono-substituted alkene with NBS/H2O/DMSO osmium tetroxide oxidation of a tetrasubstituted cyclic alkene, followed by NaHSO3 oxymercuration/demercuration of terminal alkene oxidative cleavage of a tetrasubstituted alkene using KMnO4/H+

Solution: Which of the following reactions would not yield at least one alcohol functional group? hydroboration of an internal alkene, followed by H2O2/NaOH reaction of a mono-substituted alkene with NBS/H2O/DMSO osmium tetroxide oxidation of a tetrasubstituted cyclic alkene, followed by NaHSO3 oxymercuration/demercuration of terminal alkene oxidative cleavage of a tetrasubstituted alkene using KMnO4/H+

Learning Check: Which of the following compounds would yield trialkylborane shown below when treated with BH3/THF? 2-methylbut-1-ene 2-methylbut-2-ene 3-methylbut-1-ene 2-methylpropene (E)-2-pentene

Solution: Which of the following compounds would yield trialkylborane shown below when treated with BH3/THF? 2-methylbut-1-ene 2-methylbut-2-ene 3-methylbut-1-ene 2-methylpropene (E)-2-pentene

Learning Check: What is the product of reaction of 1-methylcyclohexene with Hg(OAc)2/H2O/THF followed by NaBD4? (D = 2H) 1. 2. 3. 4. 5. 1 2 3 4 5

Solution: What is the product of reaction of 1-methylcyclohexene with Hg(OAc)2/H2O/THF followed by NaBD4? (D = 2H) 1. 2. 3. 4. 5. 1 2 3 4 5

Learning Check: Which reaction sequence on an alkene will accomplish the same end result as treating the alkene with O3 followed by Zn/AcOH? RCO3H followed by KMnO4/H3O+ BH3/THF followed by OsO4 followed by NaHSO3/H2O OsO4/NMO followed by HIO4 Hg(OAc)2/H2O/THF followed by NaBH4 followed by KOH Br2/H2O followed by KOH, followed by H3O+

Solution: Which reaction sequence on an alkene will accomplish the same end result as treating the alkene with O3 followed by Zn/AcOH? RCO3H followed by KMnO4/H3O+ BH3/THF followed by OsO4 followed by NaHSO3/H2O OsO4/NMO followed by HIO4 Hg(OAc)2/H2O/THF followed by NaBH4 followed by KOH Br2/H2O followed by KOH, followed by H3O+