1. Alkene Reactions

2. Addition Reactions Addition is the opposite of elimination
A pi bond is converted to a sigma bond

3. Addition Reactions
A pi bond will often act as a Lewis base (as a nucleophile or as a Brønsted-Lowry base)

4. Addition / Elimination Equilibria
Because an addition is the reverse of an elimination, often the processes are at equilibrium
An equilibrium is a thermodynamic expression
We assess ΔG (the free energy) to determine which side the equilibrium will favor

5. Addition / Elimination Equilibria
To determine which side the equilibrium will favor, we must consider both enthalpy and entropy

6. Addition / Elimination Equilibria
Bonds broken – bonds formed = 166 kcal/mol – 185 kcal/mol = –19 kcal/mol

7. Addition / Elimination Equilibria
Having a –ΔH (or a +ΔSsurr) favors the addition reaction rather than the elimination reaction
To get ΔG (or ΔStot) and make a complete assessment, we must also consider the entropy of the system (ΔSsys)

8. Addition / Elimination Equilibria
Plugging into the formula gives…
To favor addition, a –ΔG (or a +ΔStot) is needed
How can the temperature be adjusted to favor addition?
To favor elimination (the reverse reaction in this example), a +ΔG (or a –ΔStot) is needed
How can the temperature be adjusted to favor elimination?

9. Hydrohalogenation
Regiochemistry becomes important for asymmetrical alkenes
In 1869, Markovnikov showed that in general, H atoms tend to add to the carbon already bearing more H atoms

10. Hydrohalogenation
Markovnikov’s rule could also be stated by saying that in general, halogen atoms tend to add to the carbon that is more substituted with other carbon groups
This is a regioselective reaction, because one constitutional isomer is formed in greater quantity than another
Draw the structure of the minor product

11. Hydrohalogenation
Anti-Markovnikov products are observed when reactions are performed in the presence of peroxides such as H2O2
Why would some reactions follow Markovnikov’s rule, while other reactions give Anti-Markovnikov products?
The answer must be found in the mechanism

12. Hydrohalogenation Mechanism
The mechanism is a two step process
Which step do you think is rate determining?

13. Hydrohalogenation Mechanism

14. Hydrohalogenation Mechanism
Recall that there are two possible products, Markovnikov and anti-Markovnikiv
Which process looks more favorable? WHY?

15. Hydrohalogenation Mechanism
Practice with SkillBuilder 9.1

16. Stereochemical Aspects
In many addition reactions, chirality centers are formed
There are two possible Markovnikov products
Which step in the mechanism determines the stereochemistry of the product?

17. Stereochemical Aspects
Recall the geometry of the carbocation

18. Rearrangements
Rearrangements (hydride or methyl shifts) occur for the carbocation if the shift makes it more stable

19. Rearrangements
A mixture of products limits synthetic utility

20. Hydration
The components of water (-H and –OH) are added across a C=C double bond
The acid catalyst is often shown over the arrow, because it is regenerated rather than being a reactant

21. Hydration Mechanism
Why does the hydrogen add to this carbon of the alkene?

22. Hydration Mechanism

23. Hydration Equilibrium
Similar to Hydrohalogenation, hydration reactions are also at equilibrium

24. Hydration Stereochemistry
Similar to Hydrohalogenation, the stereochemistry of hydration reactions is controlled by the geometry of the carbocation

25. Hydrations Predict the major product(s) for the reaction below
Ethanol (think beer!) is mostly produced from fermentation of sugar using yeast, but industrial synthesis is also used to produce ethanol through a hydration reaction
Predict the major product(s) for the reaction below

26. Oxymercuration-Demercuration
Because rearrangements often produce a mixture of products, the synthetic utility of Markovnikov hydration reactions is somewhat limited
Oxymercuration-demercuration is an alternative process that can yeild Markovnikov products without the possibility of rearrangement

27. Oxymercuration Oxymercuration begins with mercuric acetate
Acetate anion
Alkene pi bond electrons can also attack the mercuric cation
Resonance stabilizes the mercurinium ion and the carbocation.

28. Oxymercuration
The mercurinium ion is also a good electrophile, and it can easily be attacked by a nucleophile, even a weak nucleophile such as water
NaBH4 is generally used to replace the –HgOAc group with a –H group via a free radical mechanism

29. Oxymercuration Intermediates
For laboratory-scale hydration of an alkene, use mercuric acetate in THF followed by sodium borohydride
Produces Markovnikov orientation via mercurinium ion
Works with water and alcohols

30. Hydroboration-Oxidation
To achieve anti-Markovnikov hydration, Hydroboration-Oxidation (2 steps) is often used

31. Hydroboration-Oxidation
Hydroboration-Oxidation reactions achieve syn addition
Anti addition is NOT observed
To answer WHY, we must investigate the mechanism

32. Hydroboration-Oxidation
Let’s examine how this new set of reagents might react
The BH3 molecule is similar to a carbocation but not as reactive, because it does not carry a formal charge

33. Hydroboration-Oxidation
Because of their broken octet, BH3 molecules undergo intermolecular resonance to help fulfill their octets
The hybrid that results from the resonance (diborane) involves a new type of bonding called banana bonds

34. Hydroboration-Oxidation
In the hydroboration reaction, BH3•THF is used. BH3•THF is formed when borane is stabilized with THF (tetrahydrofuran)
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

35. 9.6 Hydroboration-Oxidation
Let’s examine the first step of the Hydroboration mechanism on the next slide
Hydroboration

36. 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

37. 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)

38. 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

39. Hydroboration-Oxidation

40. Hydroboration-Oxidation
Start Here

41. Hydroboration-Oxidation
When ONE chirality center is formed, a racemic mixture results
The squiggle bond above shows two products, a 50/50 mixture of the R and the S enantiomer

42. Hydroboration-Oxidation
When TWO chirality centers are formed, a racemic mixture results

43. Hydroboration-Oxidation
Predict the major product(s) for the reactions below

44. 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)

45. 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

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

47. Catalytic Hydrogenation
Draw product(s) for the reaction below. Pay close attention to stereochemistry

48. Halogenation
Halogenation involves adding two halogen atoms across a C=C double bond
Halogenation is a key step in the production of PVC

49. Halogenation
Halogenation with Cl2 and Br2 is generally effective, but halogenation with I2 is too slow and halogenation with F2 is too violent
Halogenation occurs with anti addition

50. Halogenation Let’s look at the reactivity of Br2. Cl2 is similar
It is nonpolar, but it is polarizable.
Does the Br2 molecule have a good leaving group attached to it?

51. Halogenation We know alkenes can act as nucleophiles
Imagine an alkene attacking Br2. You might imagine the formation of a carbocation
However, this mechanism DOES NOT match the stereospecificity of the reaction.

52. Halogenation

53. Halogenation
Only anti addition is observed

54. Halogenation
Predict the major product(s) for the reactions below

55. Halohydrin Formation
Halohydrins are formed when halogens (Cl2 or Br2) are added to an alkene with WATER as the solvent
The bromonium ion forms from Br2 + alkene, and then it is attacked by water

56. Halohydrin Formation
A proton transfer completes the mechanism producing a neutral halohydrin product
The net reaction is the addition of –X and –OH across a C=C double bond

57. Halohydrin Regioselectivity
The –OH group adds to the more substituted carbon
The key step that determines regioselectivity is the attack of water on the bromonium ion at the more substituted carbon

58. Halohydrin Regioselectivity
When water attacks the bromonium ion, it will attack the side that goes through the lower energy transition state (the carbon that is more stable due to presence of R groups).
Water is a small molecule that can easily access the more sterically hindered site
Transition state

59. Halohydrin Regioselectivity
Predict the major product(s) for the reactions below

60. Anti Dihydroxylation
Dihydroxylation occurs when two –OH groups are added across a C=C double bond
Anti dihydroxylation is achieved through a multi-step process

61. Anti Dihydroxylation First, an epoxide is formed
Replacing the relatively unstable O-O single bond is the thermodynamic driving force for this process

62. Anti Dihydroxylation
Water is a poor nucleophile, so the epoxide is activated with an acid

63. Anti Dihydroxylation
Note the similarities between three key intermediates
Ring strain and a +1 formal charge makes these structures GREAT electrophiles
They also each yield anti products, because the nucleophile must attack from the side opposite the leaving group

64. Syn Dihydroxylation
Like other syn additions, syn dihydroxylation adds across the C=C double bond in ONE step

65. Syn Dihydroxylation MnO41- is similar to OsO4 but more reactive
Syn dihydroxylation can be achieved with KMnO4 but only under mild conditions (cold temperatures)
Diols are often further oxidized by MnO41-, and MnO41- is reactive toward many other functional groups as well
The synthetic utility of MnO41- is limited; therefore, we aren’t going to worry about this reaction

66. Oxidative Cleavage with O3
Common reducing agents include dimethyl sulfide and Zn/H2O.

67. Oxidative Cleavage with O3
Predict the major product(s) for the reaction below
Predict a bicyclic reactant used to form the product below

68. Predicting Addition Products
Analyze the reagents used to determine what groups will be added across the C=C double bond
Determine the regioselectivity (Markovnikov or anti-Markovnikov)
Determine the stereospecificity (syn or anti addition)
Each step can be achieved with minor reagent memorization and a firm grasp of the mechanistic rational
The more familiar you are with the mechanisms, the easier predicting products will be

69. One Step Syntheses
To set up a synthesis, assess the reactants and products to see what changes need to be made
Label each of the processes below

70. One Step Syntheses
To set up a synthesis, assess the reactants and products to see what changes need to be made
Give reagents and conditions for the following

71. Multi-Step Syntheses
Multistep syntheses are more challenging, but the same strategy applies
This is not a simple substitution, addition or elimination, so two processes must be combined

72. Multi-Step Syntheses
For the strategy to work, the regioselectivty must be correct
A smaller base should be used to produce the more stable Zaitsev product

73. Multi-Step Syntheses
For the strategy to work, the regioselectivty must be correct
Will the regioselectivity for the HBr reaction give the desired product?

74. Multistep Rxns
The synthesis of most alcohols may require multiple steps (i.e., to get product X from reactant A, a product (B, C …X) must be created).
To solve these problems, work backwards from the final product.
Oxidize 2° alcohol to form ketone.
Use acid-catalyzed hydration (addition) to form alcohol.
The completed series of rxns.

75. Additional Practice Problems
Predict the major product for the addition reaction below. Be aware of possible rearrangements and stereochemical concerns.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

76. Additional Practice Problems
What reagents are necessary to achieve the following synthesis?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e