Chapter 8

Alkenes and Alkynes II: Addition Reactions

Created by Professor William Tam & Dr. Phillis Chang

Ch. 8 - 1

About The Authors

These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. Phillis Chang. Professor William Tam received his B.Sc. at the University of Hong Kong in 1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards in research and teaching, and according to Essential Science Indicators, he is currently ranked as the Top 1% most cited Chemists worldwide. He has published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem. Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew.

Ch. 8 - 2

1. Addition Reactions of Alkenes

E C C + E Nu C C Nu

Ch. 8 - 3

1A. How To Understand Additions to Alkenes

This is an addition reaction: ENu added across the double bond E

+ E

Nu

C
2 s-bonds Bonds formed

C Nu

p-bond

s-bond

Bonds broken

Ch. 8 - 4

Since p bonds are formed from the overlapping of p orbitals, p electron clouds are above and below the plane of the double bond

p electron clouds

Ch. 8 - 5

Electrophilic electron seeking C=C and CC p bonds are particularly susceptible to electrophilic reagents (electrophiles)

Common electrophile H+, X+ (X = Cl, Br, I), Hg2+, etc.

Ch. 8 - 6

In an electrophilic addition, the p electrons seek an electrophile, breaking the p bond, forming a s bond and leaving a positive charge on the vacant p orbital on the adjacent carbon. Addition of B to form a s bond provides an addition product

Ch. 8 - 7

Nu

E C C + Nu

Nu E C C
Ch. 8 - 8

2. Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism and Markovnikovs Rule

Mechanism
E Nu

A C C

Nu

Nu E C C
Ch. 8 - 9

Mechanism Sometimes do not go through a free carbocation, may go via

E C C

Ch. 8 - 10

Markovnikovs Rule For symmetrical substrates, no problem for regiochemistry

H C H E Nu E H C H C H Nu E H C H Nu C H same H as H Nu E C H C H H same H as H E C H C H H

H C H

Ch. 8 - 11

Markovnikovs Rule But for unsymmetrical substrates, two regioisomers are possible
H C H C H E Nu E CH3 C H C H Nu E CH3 C H Nu C H different H from CH3 H or CH3 C H E C H Nu Nu E C H C H
Ch. 8 - 12

H3C

Markovnikovs Rule In the electrophilic addition of an unsymmetrical electrophile across a double bond of an alkene, the more highly substituted and more stabilized carbocation is formed as the intermediate in preference to the less highly substituted and less stable one

Ch. 8 - 13

Markovnikovs Rule Thus

E Nu E Nu E

E NOT
o o o

Note: carbocation stability 3 > 2 > 1

Ch. 8 - 14

Addition of Hydrogen Halides Addition of HCl, HBr and HI across a C=C bond + H is the electrophile
+ H

Br

slow r.d.s

Br fast

Br

Br NO
Ch. 8 - 15

Ch. 8 - 16

2A. Theoretical Explanation of Markovnikovs Rule

H3C C H C H H H X
step 1 (slow r.d.s.) H CH3 C C H or CH3 H H 2o carbocation (more stable) H C C H H H 1o carbocation (more stable)

One way to state Markovnikovs rule is to say that in the addition of HX to an alkene, the hydrogen atom adds to the carbon atom of the double bond that already has the greater number of hydrogen atoms

Ch. 8 - 17


H Br slow (r.d.s.)

Br

H Br

(1o cation) fast

(minor)

Br Br (major)

(2o cation) fast

Step 1

Step 2

Ch. 8 - 18

Ch. 8 - 19


(1)

Examples
H Cl Cl + H (95 :
H + Br (98 H : 2)
Ch. 8 - 20

H Cl 5)
Br

(2)

Br

2B. Modern Statement of Markovnikovs Rule

In the ionic addition of an unsymmetrical reagent to a double bond, the positive portion of the added reagent attaches itself to a carbon atom of the double bond so as to yield the more stable carbocation as an intermediate
Ch. 8 - 21

Examples
OH Cl

OH Cl (major)

(1)

Cl OH

more stable 3o cation

Cl

OH

Cl OH

less stable 1o cation

(minor)
Ch. 8 - 22

Examples
Cl I
I

I Cl (major)

(2)

Cl

more stable 3o cation

Cl I less stable 1o cation I (minor)

Cl

Ch. 8 - 23

2C. Regioselective Reactions

When a reaction that can potentially yield two or more constitutional isomers actually produces only one (or a predominance of one), the reaction is said to be regioselective
H Cl Cl + (major) H Cl (minor) H

regioisomers Regioselectivity: 95 : 5
Ch. 8 - 24

2D. An Exception to Markovnikovs Rule

H Br H Br (anti-Markovnikov's product)

RO OR heat

Via a radical mechanism (see Chapter 10)

This anti-Markovnikov addition does not take place with HI, HCl, and HF, even when peroxides are present
Ch. 8 - 25

3. Stereochemistry of the Ionic Addition to an Alkene

attack from top
H C Bu C H H
X

X H C CH3

H Bu

CH2

achiral trigonal planar carbocation

X

Bu

H C CH3

attack from bottom

X (R)-2-Halohexane (50%)

Ch. 8 - 26

racemate

Bu (S)-2-Halohexane (50%)

4. Addition of Sulfuric Acid to Alkenes

conc. H2SO4 cold
O HO S O O H

OSO3H H

OSO3H
H

more stable o 3 cation

Addition of HOSO3H across a C=C bond

less stable o 1 cation

Ch. 8 - 27

4A. Alcohols from Alkyl Hydrogen Sulfates

conc. H2SO4 cold OSO3H H H2O heat OH H

The overall result of the addition of sulfuric acid to an alkene followed by hydrolysis is the Markovnikov addition of H and OH

Ch. 8 - 28

5. Addition of Water to Alkenes: Acid-Catalyzed Hydration

Overall process Addition of HOH across a C=C bond + H is the electrophile Follow Markovnikovs rule
H2O dilute H3O+ (e.g. dilute H2SO4, H3PO4) OH H

Ch. 8 - 29

5A. Mechanism
H H O H

H 2O
H

slow (step 1)

fast (step 2) O

more stable 3o cation

H
fast (step 3) H

H
H 2O

H H + OH
Ch. 8 - 30

5B. Rearrangements

Rearrangement can occur with certain carbocations

H2O H2SO4 H
1,2-alkyl shift

NOT OH

OH

H 2O

(major product)

Ch. 8 - 31

6.

Alcohols from Alkenes through OxymercurationDemercuration: Markovnikov Addition Step 1: Oxymercuration

C C Hg(OAc) 2 THF-H2O C HO C HgOAc

Step 2: Demercuration
C HO C HgOAc NaBH4 OH C HO C H
Ch. 8 - 32

6A. Regioselectivity of OxymercurationDemercuration

Oxymercurationdemercuration is also highly regioselective and follows Markovnikovs rule

Hg(OAc) 2 THF-H2O HO HgOAc NaBH4 OH

H HO

Ch. 8 - 33

6B. Rearrangements Seldom Occur in OxymercurationDemercuration

Recall: acid-catalyzed hydration of some alkenes leads to rearrangement products

e.g. H2O H2SO4 OH H

Ch. 8 - 34

H2O H2SO4

1,2-alkyl shift

H H

H 2O

H 2O
OH H
Ch. 8 - 35

Rearrangements of the carbon skeleton seldom occur in oxymercuration demercuration

OH 1. Hg(OAc)2, THF-H2O 2. NaBH4 H

no rearrangement

via

OH

Hg(OAc)

Ch. 8 - 36

6C. Mechanism of Oxymercuration

Does not undergo a free carbocation

Hg OAc OAc

HgOAc AcO +
HgOAc

H 2O
HgOAc

HO

H 2O
H

H
Ch. 8 - 37

Stereochemistry Usually anti-addition

Hg(OAc) 2 H3C

H 2O

H3C

THF-H2O

Hg(OAc)

OH

CH3

Hg(OAc)

Ch. 8 - 38

Although attack by water on the bridged mercurinium ion leads to anti addition of the hydroxyl and mercury groups, the reaction that replaces mercury with hydrogen is not stereocontrolled (it likely involves radicals). This step scrambles the overall stereochemistry The net result of oxymercuration demercuration is a mixture of syn and anti addition of H and OH to the alkene Ch. 8 - 39

Solvomercuration-Demercuration
Hg(O2CCF3)2 THF-ROH OR Hg(O2CCF3) NaBH4 OH OR H
Ch. 8 - 40

7.

Alcohols from Alkenes through HydroborationOxidation: Anti-Markovnikov Syn Hydration

"BH3"

C H

C BH2

Addition of HBH2 across a C=C bond

Ch. 8 - 41

BH3 exists as dimer B2H6 or complex with coordinative solvent

H H B H H H B H (BH3-THF) O H H B H H B H (BH3-DMS)
Ch. 8 - 42

Me S Me

syn addition
1. BH3-THF H3C H 2. H2O2, OH H OH

CH3

Anti-Markovnikov addition of H & OH

Ch. 8 - 43

Compare with oxymercurationdemercuration

Hg(OAc) 2 OH H

H3C

THF-H2O

CH3

Hg(OAc) NaBH4

anti addition
OH

Markovnikov addition of H & OH

CH3

Ch. 8 - 44

8. Hydroboration: Synthesis of Alkylboranes

hydroboration

+H

C H

C B

alkene

boron hydride

alkylborane

Ch. 8 - 45

8A. Mechanism of Hydroboration

H3C H H + B H H H H
H
H3C H H B H H H
H3C H H B H H H H

H p complex

H3C H

H H
four-atom concerted T.S.

H3C H H B

H H

H B syn addition H of H and B

H
Ch. 8 - 46


(1)

Other examples
H BH2-THF H BH2 (99 : 1) + H2B H

(2)

BH2-THF H BH2 (98

+ H2B : 2)
Ch. 8 - 47

8B. Stereochemistry of Hydroboration

Syn addition
H BH3-THF BH2

H3C

CH3

Ch. 8 - 48

9. Oxidation and Hydrolysis of Alkylboranes

H H B B H H BH2

B always ends up on the least hindered carbon

B H (trialkyl borane)

B H

Ch. 8 - 49

Oxidation

H2O2 O

O B O

Ch. 8 - 50

 Via
R
R

R3B

OH

B R

OH

OR

HO

R RO B OR
OR

R R B O OR OH

OH

R O HO B OR OR
RO

OR
Ch. 8 - 51

Hydrolysis
O O B O NaOH H2O

OH

+ Na3BO3
Ch. 8 - 52

Overall synthetic process of hydroboration-oxidation-hydrolysis

1. BH3-THF 2. H2O2 3. NaOH, H2O H OH

Overall: anti-Markovnikov addition of HOH across a C=C bond Opposite regioisomers as oxymercuration-demercuration
Ch. 8 - 53

Example
BH3-THF H3C H
H OH

anti-Markovnikov syn addition

H BH2

CH3

H
H2O2 OH

CH3

This oxidation step occurs with

retention of configuration

Ch. 8 - 54

10. Summary of Alkene Hydration Methods

Summary of Methods for Converting Alkene to Alcohol
Reaction
Acid-catalyzed hydration Oxymercurationdemercuration Hydroborationoxidation

Regiochemistry
Markovnikov addition Markovnikov addition

Stereochemistry
Not controlled

Occurrence of Rearrangements
Frequent

Not controlled

Seldom

Anti-Markovnikov Stereospecific: addition syn addition of H and OH

Seldom

Ch. 8 - 55

Examples
H H2O

via H

1,2-hydride shift

OH

with rearrangement
OH

1. Hg(OAc)2, THF-H2O 2. NaBH4, OH

Markovnikov addition of H2O without rearrangement

H 1. BH3-THF 2. H2O2, OH

anti-MarkovniOH kov, syn addition of H2O

Ch. 8 - 56

11. Protonolysis of Alkylboranes

R B CH3CO2H heat R H + CH3CO2 B

alkylborane

alkane

Protonolysis of an alkylborane takes place with retention of configuration; hydrogen replaces boron where it stands in the alkylborane Overall stereochemistry of hydroboration protonolysis: syn Ch. 8 - 57

e.g.
1. BH3-THF H3C 2. CH3CO2D H H3C H

H D + enantiomer

via H3C H BH2 H

Ch. 8 - 58

12. Electrophilic Addition of Bromine and Chlorine to Alkenes

Addition of XX (X = Cl, Br) across a C=C bond

C C Br2 CCl4 Br C C Br (vicinal dibromide)
Ch. 8 - 59


(1)

Examples
Br2 5 C (anti addition of Br2)
o

Br + Br (racemate)

Br Br

Cl (2) Ph Cl2 Ph 10oC Ph

1 2

Ph

(anti addition of Cl2)

Cl

Ph same as Cl

Ph Cl
Ch. 8 - 60

(rotation of C1-C2 bond)

12A. Mechanism of Halogen Addition

C C + Br Br

BrBr bond becomes polarized when close to alkene

Br Br

Br

+ Br
Br
(vincinal Dibromide)

Br
(bromonium)
Ch. 8 - 61

Stereochemistry Anti addition

Br Br

CCl4

Br Br

H enantiomer + Br (anti)

Br

SN2 reaction

H
Ch. 8 - 62

13. Stereospecific Reactions

A reaction is stereospecific when a particular stereoisomeric form of the starting material reacts by a mechanism that gives a specific stereoisomeric form of the product

Ch. 8 - 63

 Reaction 1
H H3C CH3 H Br2 CCl4 Br H C H3C CH3 C H Br Br H H3C Br H CH3

trans-2-Butene

(2R,3S)-2,3-Dibromobutane
(a meso compound)

Reaction 2
H H3C H CH3 Br2 CCl4 Br H H3C C H C CH3 + H3C Br Br H C C Br H CH3

cis-2-Butene

(2R,3R)

(2S,3S)
Ch. 8 - 64

(a pair of enantiomers)

Addition of bromine to cis-2-Butene

(a) Br C H C CH3 H Br H3C (2R,3R)-2,3-Dibromobutane (chiral)

(a)
H H3C H CH3 Br

Br

(b)
H C

H3C

H C Br

CH3

Br

bromonium ion (achiral)

H (b) H3C C C

Br

H Br CH3 (2S,3S)-2,3-Dibromobutane (chiral)

Ch. 8 - 65

Addition of bromine to trans-2-Butene

(a) Br H C Br H3C (R,S)-2,3-Dibromobutane (meso) CH3 C H

(a)
H H3C CH3 H Br

Br
C Br

(b)
CH3 C H

H3C

Br

bromonium ion (b) (achiral)

H H3C C C

Br CH3

Br H (R,S)-2,3-Dibromobutane (meso)
Ch. 8 - 66

14. Halohydrin Formation

X2 H2O OH C C X

Addition of OH and X (X = Cl, Br) across a C=C bond + X is the electrophile Follow Markovnikovs rule

Ch. 8 - 67

Mechanism
Br Br
H3C
Br

H2O

H3C

H2O

OH

H3C

Br

CH3

Br

Ch. 8 - 68

Other variation If H2O is replaced by ROH, RH will be the nucleophile

e.g. Br2 MeOH OMe Br

Ch. 8 - 69

15. Divalent Carbon Compounds: Carbenes

15A. Structure and Reactions of Methylene
heat or light

CH2

CH2

Diazomethane

Methylene Nitrogen (a carbene)

Ch. 8 - 70

CH2 I

H2C

N II

CH2

N III

CH2

C C

Alkene

Methylene

H H Cyclopropane
Ch. 8 - 71

15B. Reactions of Other Carbenes: Dihalocarbenes :CX2 (e.g. :CCl2) Generation by a-elimination of chloroform

H Cl Cl C Cl

OtBu

+ tBuOH + Cl CCl2

Ch. 8 - 72

Usually a syn (cis) addition across a C=C bond

t

BuOK

H Cl H Cl

CHCl3

(a cyclopropane)

Ch. 8 - 73

Stereospecific reactions
CCl2 Cl Cl

CCl2

Cl

Cl

Ch. 8 - 74

15C. Carbenoids: The Simmons-Smith Cyclopropane Synthesis

CH2I2

Zn(Cu)

(Zinc-copper couple)

C H2 (a carbenoid)

ZnI

Ch. 8 - 75

A stereospecific syn (cis) addition across a C=C bond

CH2I2 Zn(Cu) (trans) (trans)

CH2I2 Zn(Cu) (cis) (cis)

Ch. 8 - 76

16. Oxidation of Alkenes: Syn 1,2-Dihydroxylation

Overall: addition of 2 OH groups across a C=C bond

C C OH OH

Reagents: dilute KMnO4 / OH / H2O / cold or OsO4, pyridine then NaHSO3, H2O
Ch. 8 - 77

16A. Mechanism for Syn Dihydroxylation of Alkenes

dil. KMnO4 OH, H2O cold O C C C OsO4 pyridine O O C O Os O C O Mn C O O OH H2O C C

OH OH + MnO 2

NaHSO3 H2O

OH OH + Os
Ch. 8 - 78

Both reagents give syn dihydroxylation

dil. KMnO 4 OH , H2O, cold

or OsO 4, pyridine then NaHSO3 OH OH (cis-diol)

Ch. 8 - 79

Comparison of the two reagents KMnO4: usually lower yield and possibly side products due to overoxidation
1. KMnO4, 2. H
+

OH O + O OH

(oxidative cleavage of C=C)

OsO4: usually much higher yield but OsO4 is extremely toxic

Ch. 8 - 80

17. Oxidative Cleavage of Alkenes

17A. Cleavage with Hot Basic Potassium Permanganate
b a a or a b a b 2 b KMnO4, OH , H2O O 2 b a O

H3O O b a OH
Ch. 8 - 81


(1)

Other examples
1. KMnO4, OH, H2O, heat 2. H3O

O + O C O

(2)

1. KMnO4, OH, H2O, heat 2. H3O

O O OH
Ch. 8 - 82

17B. Cleavage with Ozone

R R' R" H 1. O3 2. Zn, AcOH or Me2S R O + O R' H R"

Ch. 8 - 83


(1)

Examples
1. O3 2. Zn, AcOH

O
(2) 1. O3 2. Me2S + O
Ch. 8 - 84

O H

Mechanism
C C

C O O

C O

C O

+ O

C O

initial ozonide

O C O O
C O O C O

Zn(OAc) 2 +

ozonide

O + O

C
Ch. 8 - 85

18. Electrophilic Addition of Bromine & Chlorine to Alkynes

R C C H X2 (excess) CH2Cl2 (X = Cl, Br, I) X R C X X C X H

X2

X C H C

H X

X2

X R C X

X C X
Ch. 8 - 86

(anti-addition)

19. Addition of Hydrogen Halides to Alkynes

R C C H H X (excess) X R C X H C H H (X = Cl, Br, I)

Regioselectivity Follow Markovnikovs rule

C C H HBr Br C CH3 C H H HBr

Br H CH3 C C H Br H gem-dibromide
Ch. 8 - 87

H3C

Mechanism
C C H H Br

H CH3 C C H

CH3

Br
Br C CH3 C H H

Br H CH3 C C H Br H

Br

Br C CH3

H C H H

Br

Ch. 8 - 88

Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture
H Br Br H (E) and (Z) (74%)
Ch. 8 - 89

peroxides

20. Oxidative Cleavage of Alkynes

R C C R' 1. O3 2. HOAc
1. KMnO4, OH 2. H3O+

RCO2H

+ R'CO2H

OR
R C C R'

RCO2H + R'CO2H

Ph

Example
C C CH3 1. O3 2. AcOH PhCO2H + CH3CO2H
Ch. 8 - 90

21. How to Plan a Synthesis: Some Approaches & Examples

In planning a synthesis we often have to consider four interrelated aspects: 1. Construction of the carbon skeleton 2. Functional group interconversions 3. Control of regiochemistry 4. Control of stereochemistry
Ch. 8 - 91

21A. Retrosynthetic Analysis

How to synthesize
OH

Retrosynthetic analysis

OH (target molecule) (precursor)

Ch. 8 - 92

 Synthesis

Markovnikov addition of H2O

H+ H2O OH

or

1. Hg(OAc)2, THF-H2O 2. NaBH4, OH

Ch. 8 - 93

How to synthesize Retrosynthetic analysis

OH (target molecule)

OH

(precursor)

Synthesis
1. BH3-THF 2. H2O2, OH OH
Ch. 8 - 94

anti-Markovnikov addition of H2O

21B. Disconnections, Synthons, and Synthetic Equivalents

One approach to retrosynthetic analysis is to consider a retrosynthetic step as a disconnection of one of the bonds In general, we call the fragments of a hypothetical retrosynthetic disconnection Synthons
Ch. 8 - 95

Example
How? Ph H Br Ph Br CH3

Retrosynthetic analysis
(i) Br Ph Br CH3 Ph CH3

(gem-dibromide came from addition of HBr across a CC bond)

Ch. 8 - 96

 Retrosynthetic analysis synthons

(ii) Ph CH3

Ph

CH3

disconnection
H3C I + Ph Na

synthetic equivalent
Ch. 8 - 97

 Synthesis
Ph H NaNH2 liq. NH3 -30oC Ph H3C Na I

(via an SN2 reaction) Br Ph Br CH3 HBr (excess)

Ph

CH3
Ch. 8 - 98

21C. Stereochemical Considerations

Br H3C Br CH3

How? H3C CH3

Ch. 8 - 99

Br

Retrosynthetic analysis The precursor of a vicinal dibromide is usually an alkene Bromination of alkenes are anti addition Br
Br CH3
o

H3C

H3C

CH3 Br (anti addition of Br2)

CH3
Ch. 8 - 100

(rotate 180 ) (anti addition of H2)

H3C CH3

H3C

 Synthesis
H3C CH3 1. Li, liq. NH3 H3C 2. NH4Cl (anti addition of H2) Br2/CCl4 Br H3C Br CH3 same as H3C Br
Ch. 8 - 101

CH3

Br CH3

(anti addition of Br2)

 END OF CHAPTER 8

Ch. 8 - 102