1. Reactions of Alkenes
Chapter 6

2. Characteristic Reactions

3. Characteristic Reactions

4. Reaction Mechanisms
A reaction mechanism describes how a reaction occurs
which bonds are broken and which new ones are formed
the order and relative rates of the various bond-breaking and bond-forming steps
if in solution, the role of the solvent
if there is a catalyst, the role of a catalyst
the position of all atoms and energy of the entire system during the reaction

5. Gibbs Free Energy
Gibbs free energy change, DG0: a thermodynamic function relating enthalpy, entropy, and temperature
exergonic reaction: a reaction in which the Gibbs free energy of the products is lower than that of the reactants; the position of equilibrium for an exergonic reaction favors products
endergonic reaction: a reaction in which the Gibbs free energy of the products is higher than that of the reactants; the position of equilibrium for an endergonic reaction favors starting materials

6. Gibbs Free Energy
a change in Gibbs free energy is directly related to chemical equilibrium
summary of the relationships between DG0, DH0, DS0, and the position of chemical equilibrium

7. Energy Diagrams
Enthalpy change, DH0: the difference in total bond energy between reactants and products
a measure of bond making (exothermic) and bond breaking (endothermic)
Heat of reaction, DH0: the difference in enthalpy between reactants and products
exothermic reaction: a reaction in which the enthalpy of the products is lower than that of the reactants; a reaction in which heat is released
endothermic reaction: a reaction in which the enthalpy of the products is higher than that of the reactants; a reaction in which heat is absorbed

8. Energy Diagrams
Energy diagram: a graph showing the changes in energy that occur during a chemical reaction
Reaction coordinate: a measure in the change in positions of atoms during a reaction

9. Activation Energy Transition state:
an unstable species of maximum energy formed during the course of a reaction
a maximum on an energy diagram
Activation Energy, G‡: the difference in Gibbs free energy between reactants and a transition state
if G‡ is large, few collisions occur with sufficient energy to reach the transition state; reaction is slow
if G‡ is small, many collisions occur with sufficient energy to reach the transition state; reaction is fast

10. Energy Diagram
a one-step reaction with no intermediate

11. Energy Diagram
A two-step reaction with one intermediate

12. Developing a Reaction Mechanism
How it is done
design experiments to reveal details of a particular chemical reaction
propose a set or sets of steps that might account for the overall transformation
a mechanism becomes established when it is shown to be consistent with every test that can be devised
this does mean that the mechanism is correct, only that it is the best explanation we are able to devise

13. Why Mechanisms?
they are the framework within which to organize descriptive chemistry
they provide an intellectual satisfaction derived from constructing models that accurately reflect the behavior of chemical systems
they are tools with which to search for new information and new understanding

14. Electrophilic Additions
hydrohalogenation using HCl, HBr, HI
hydration using H2O in the presence of H2SO4
halogenation using Cl2, Br2
halohydrination using HOCl, HOBr
oxymercuration using Hg(OAc)2, H2O followed by reduction

15. Addition of HX
Carried out with pure reagents or in a polar solvent such as acetic acid
Addition is regioselective
regioselective reaction: an addition or substitution reaction in which one of two or more possible products is formed in preference to all others that might be formed
Markovnikov’s rule: in the addition of HX, H2O, or ROH to an alkene, H adds to the carbon of the double bond having the greater number of hydrogens

16. HBr + 2-Butene A two-step mechanism
Step 1: proton transfer from HBr to the alkene gives a carbocation intermediate
Step 2: reaction of the sec-butyl cation (an electrophile) with bromide ion (a nucleophile) completes the reaction

17. HBr + 2-Butene
An energy diagram for the two-step addition of HBr to 2-butene
the reaction is exergonic

18. Carbocations
Carbocation: a species in which a carbon atom has only six electrons in its valence shell and bears positive charge
Carbocations are
classified as 1°, 2°, or 3° depending on the number of carbons bonded to the carbon bearing the positive charge
electrophiles; that is, they are electron-loving
Lewis acids

19. Carbocations
bond angles about a positively charged carbon are approximately 120°
carbon uses sp2 hybrid orbitals to form sigma bonds to the three attached groups
the unhybridized 2p orbital lies perpendicular to the sigma bond framework and contains no electrons

20. Carbocation Stability
a 3° carbocation is more stable than a 2° carbocation, and requires a lower activation energy for its formation
a 2° carbocation is, in turn, more stable than a 1° carbocation,
methyl and 1° carbocations are so unstable that they are never observed in solution

21. Carbocation Stability
relative stability
methyl and primary carbocations are so unstable that they are never observed in solution

22. Carbocation Stability
we can account for the relative stability of carbocations if we assume that alkyl groups bonded to the positively charged carbon are electron releasing and thereby delocalize the positive charge of the cation
we account for this electron-releasing ability of alkyl groups by (1) the inductive effect, and (2) hyperconjugation

23. The Inductive Effect
the positively charged carbon polarizes electrons of adjacent sigma bonds toward it
the positive charge on the cation is thus localized over nearby atoms
the larger the volume over which the positive charge is delocalized, the greater the stability of the cation

24. Hyperconjugation
involves partial overlap of the -bonding orbital of an adjacent C-H or C-C bond with the vacant 2p orbital of the cationic carbon
the result is delocalization of the positive charge

25. Addition of H2O addition of water is called hydration
acid-catalyzed hydration of an alkene is regioselective; hydrogen adds preferentially to the less substituted carbon of the double bond
HOH adds in accordance with Markovnikov’s rule

26. Addition of H2O Step 1: proton transfer from H3O+ to the alkene
Step 2: reaction of the carbocation (an electrophile) with water (a nucleophile) gives an oxonium ion
Step 3: proton transfer to water gives the alcohol
slow, rate
determining + : + : C H 3 = 2 H O H C H 3 + : O H +
A 2 o
carbocation H H
intermediate + :
fast C H 3 + : O - H C H 3 O + H : H H
An oxonium ion

27. Carbocation Rearrangements
In electrophilic addition to alkenes, there is the possibility for rearrangement
Rearrangement: a change in connectivity of the atoms in a product compared with the connectivity of the same atoms in the starting material

28. Carbocation Rearrangements
in addition of HCl to an alkene
in acid-catalyzed hydration of an alkene

29. Carbocation Rearrangements
the driving force is rearrangement of a less stable carbocation to a more stable one
the less stable 2° carbocation rearranges to a more stable 3° one by 1,2-shift of a hydride ion C H 3 C H 3
fast C H 3 - C H 3 - + + H H
A 3° carbocation

30. Carbocation Rearrangements
reaction of the more stable carbocation (an electrophile) with chloride ion (a nucleophile) completes the reaction C H 3 C H 3 : -
fast C H 3 - 2 + : C l : C H 3 - 2 + : : C l : :
2-Chloro-2-methylbutane

31. Addition of Cl2 and Br2
carried out with either the pure reagents or in an inert solvent such as CH2Cl2
addition of bromine or chlorine to a cycloalkene gives a trans-dihalocycloalkane
addition occurs with anti stereoselectivity; halogen atoms add from the opposite face of the double bond
we will discuss this selectivity in detail in Section 6.7

32. Addition of Cl2 and Br2
Step 1: formation of a bridged bromonium ion intermediate

33. Addition of Cl2 and Br2
Step 2: attack of halide ion (a nucleophile) from the opposite side of the bromonium ion (an electrophile) opens the three-membered ring to give the product

34. Addition of Cl2 and Br2
for a cyclohexene, anti coplanar addition corresponds to trans diaxial addition
the initial trans diaxial conformation is in equilibrium with the more stable trans diequatorial conformation
because the bromonium ion can form on either face of the alkene with equal probability, both trans enantiomers are formed as a racemic mixture

35. Addition of HOCl and HOBr
Treatment of an alkene with Br2 or Cl2 in water forms a halohydrin
Halohydrin: a compound containing -OH and -X on adjacent carbons

36. Addition of HOCl and HOBr
reaction is both regiospecific (OH adds to the more substituted carbon) and anti stereoselective
both selectivities are illustrated by the addition of HOBr to 1-methylcyclopentene
to account for the regioselectivity and the anti stereoselectivity, chemists propose the three-step mechanism in the next screen

37. Addition of HOCl and HOBr
Step 1: formation of a bridged halonium ion intermediate
Step 2: attack of H2O on the more substituted carbon opens the three-membered ring

38. Addition of HOCl and HOBr
Step 3: proton transfer to H2O completes the reaction
As the elpot map on the next screen shows
the C-X bond to the more substituted carbon is longer than the one to the less substituted carbon
because of this difference in bond lengths, the transition state for ring opening can be reached more easily by attack of the nucleophile at the more substituted carbon

39. Addition of HOCl and HOBr
bridged bromonium ion from propene

40. Oxymercuration/Reduction
Oxymercuration followed by reduction results in hydration of a carbon-carbon double bond
oxymercuration
reduction

41. Oxymercuration/Reduction
an important feature of oxymercuration/reduction is that it occurs without rearrangement
oxymercuration occurs with anti stereoselectivity

42. Oxymercuration/Reduction
Step 1: dissociation of mercury(II) acetate
Step 2: formation of a bridged mercurinium ion intermediate; a two-atom three-center bond

43. Oxymercuration/Reduction
Step 3: regioselective attack of H2O (a nucleophile) on the bridged intermediate opens the three-membered ring
Step 4: reduction of the C-HgOAc bond

44. Oxymercuration/Reduction
Anti stereoselective
we account for the stereoselectivity by formation of the bridged bromonium ion and anti attack of the nucleophile which opens the three-membered ring
Regioselective
of the two carbons of the mercurinium ion intermediate, the more substituted carbon has the greater degree of partial positive character
alternatively, computer modeling indicates that the C-Hg bond to the more substituted carbon of the bridged intermediate is longer than the one to the less substituted carbon
therefore, the ring-opening transition state is reached more easily by attack at the more substituted carbon

45. Hydroboration/Oxidation
Hydroboration: the addition of borane, BH3, to an alkene to form a trialkylborane
Borane dimerizes to diborane, B2H6 H C H 2 3 H B + 3 C H 2 = C H 3 2 B H C H 2 3
Borane
Triethylborane
(a trialkylborane) 2 B H 3 B 2 H 6
Borane D
iborane

46. Hydroboration/Oxidation
borane forms a stable complex with ethers such as THF
the reagent is used most often as a commercially available solution of BH3 in THF

47. Hydroboration/Oxidation
Hydroboration is both
regioselective (boron to the less hindered carbon)
and syn stereoselective + B H 3 H H 3 C H C H 3 B R 2 H
1-Methylcyclopentene
(Syn addition of BH 3 )
(R = 2-methylcyclopentyl)

48. Hydroboration/Oxidation
concerted regioselective and syn stereoselective addition of B and H to the carbon-carbon double bond
trialkylboranes are rarely isolated
oxidation with alkaline hydrogen peroxide gives an alcohol and sodium borate

49. Hydroboration/Oxidation
Hydrogen peroxide oxidation of a trialkylborane
step 1: hydroperoxide ion (a nucleophile) donates a pair of electrons to boron (an electrophile)
step 2: rearrangement of an R group with its pair of bonding electrons to an adjacent oxygen atom

50. Hydroboration/Oxidation
step 3: reaction of the trialkylborane with aqueous NaOH gives the alcohol and sodium borate

51. Oxidation/Reduction Oxidation: the loss of electrons
alternatively, the loss of H, the gain of O, or both
Reduction: the gain of electrons
alternatively, the gain of H, the loss of O, or both
Recognize using a balanced half-reaction
1. write a half-reaction showing one reactant and its product(s)
2. complete a material balance; use H2O and H+ in acid solution, use H2O and OH- in basic solution
3. complete a charge balance using electrons, e-

52. Oxidation/Reduction
three balanced half-reactions

53. Oxidation with OsO4
OsO4 oxidizes an alkene to a glycol, a compound with OH groups on adjacent carbons
oxidation is syn stereoselective

54. Oxidation with OsO4 OsO4 is both expensive and highly toxic
it is used in catalytic amounts with another oxidizing agent to reoxidize its reduced forms and, thus, recycle OsO4

55. Oxidation with O3
Treatment of an alkene with ozone followed by a weak reducing agent cleaves the C=C and forms two carbonyl groups in its place C H 3 O O 1 . O 3 C H 3 = 2 C H 3 + 2 2 . ( C H 3 ) S
2-Methyl-2-pentene
Propanone
(a ketone)
Propanal
(an aldehyde)

56. Oxidation with O3
the initial product is a molozonide which rearranges to an isomeric ozonide O O O O 3 C H 3 = C H 3 -
2-Butene
A molozonide H O H O C C ( C H 3 ) 2 S H 3 C C H 3 C H 3 O O
An ozonide
Acetaldehyde

57. Reduction of Alkenes
Most alkenes react with H2 in the presence of a transition metal catalyst to give alkanes
commonly used catalysts are Pt, Pd, Ru, and Ni
the process is called catalytic reduction or, alternatively, catalytic hydrogenation
addition occurs with syn stereoselectivity Pd
+ H 2
25°C, 3 atm
Cyclohexene
Cyclohexane

58. Reduction of Alkenes
Mechanism of catalytic hydrogenation

59. Reduction of Alkenes
even though addition syn stereoselectivity, some product may appear to result from trans addition
reversal of the reaction after the addition of the first hydrogen gives an isomeric alkene, etc.

60. H0 of Hydrogenation Reduction of an alkene to an alkane is exothermic
there is net conversion of one pi bond to one sigma bond
H0 depends on the degree of substitution
the greater the substitution, the lower the value of H°
H0 for a trans alkene is lower than that of an isomeric cis alkene
a trans alkene is more stable than a cis alkene

61. H0 of Hydrogenation

62. Reaction Stereochemistry
In several of the reactions presented in this chapter, chiral centers are created
Where one or more chiral centers are created, is the product
one enantiomer and, if so, which one?
a pair of enantiomers as a racemic mixture?
a meso compound?
a mixture of stereoisomers?
As we will see, the stereochemistry of the product for some reactions depends on the stereochemistry of the starting material; that is, some reactions are stereospecific

63. Reaction Stereochemistry
We saw in Section 6.3D that bromine adds to 2-butene to give 2,3-dibromobutane
two stereoisomers are possible for 2-butene; a pair of cis,trans isomers
three stereoisomers are possible for the product; a pair of enantiomers and a meso compound
if we start with the cis isomer, what is the stereochemistry of the product?
if we start with the trans isomer, what is the stereochemistry of the product?

64. Bromination of cis-2-Butene
reaction of cis-2-butene with bromine forms bridged bromonium ions which are meso and identical

65. Bromination of cis-2-Butene
attack of bromide ion at carbons 2 and 3 occurs with equal probability to give enantiomeric products as a racemic mixture

66. Bromination of trans-2-Butene
reaction with bromine forms bridged bromonium ion intermediates which are enantiomers

67. Bromination of trans-2-Butene
attack of bromide ion in either carbon of either enantiomer gives meso-2,3-dibromobutane

68. Bromination of 2-Butene
Given these results, we say that addition of Br2 or Cl2 to an alkene is stereospecific
bromination of cis-2-butene gives the enantiomers of 2,3-dibromobutane as a racemic mixture
bromination of trans-2-butene gives meso-2,3-dibromobutane
Stereospecific reaction: a reaction in which the stereochemistry of the product depends on the stereochemistry of the starting material

69. Oxidation of 2-Butene
OsO4 oxidation of cis-2-butene gives meso-2,3-butanediol

70. Oxidation of 2-Butene OsO4 oxidation of an alkene is stereospecific
oxidation of trans-2-butene gives the enantiomers of 2,3-butanediol as a racemic mixture (optically inactive)
and oxidation of cis-2-butene gives meso 2,3-butanediol (also optically inactive)

71. Reaction Stereochemistry
We have seen two examples in which reaction of achiral starting materials gives chiral products
in each case, the product is formed as a racemic mixture (which is optically inactive) or as a meso compound (which is also optically inactive)
These examples illustrate a very important point about the creation of chiral molecules
optically active (enantiomerically pure) products can never be produced from achiral starting materials and achiral reagents under achiral conditions
although the molecules of product may be chiral, the product is always optically inactive (either meso or a pair of enantiomers)

72. Reaction Stereochemistry
Next let us consider the reaction of a chiral starting material in an achiral environment
the bromination of (R)-4-tert-butylcyclohexene
only a single diastereomer is formed
the presence of the bulky tert-butyl group controls the orientation of the two bromine atoms added to the ring

73. Reaction Stereochemistry
Finally, consider the reaction of an achiral starting material in an chiral environment
BINAP can be resolved into its R and S enantiomers

74. Reaction Stereochemistry
treating (R)-BINAP with ruthenium(III) chloride forms a complex in which ruthenium is bound in the chiral environment of the larger BINAP molecule
this complex is soluble in CH2Cl2 and can be used as a homogeneous hydrogenation catalyst
using (R)-BINAP-Ru as a hydrogenation catalyst, (S)-naproxen is formed in greater than 98% ee

75. Reaction Stereochemistry
BINAP-Ru complexes are somewhat specific for the types of C=C they reduce
to be reduced, the double bond must have some kind of a neighboring group that serves a directing group