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Chapter 8

Alkenes and Alkynes II:


Addition Reactions

Created by
Professor William Tam & Dr. Phillis
Chang
Copyright 2014 by John Wiley & Sons, Inc. All rights reserved.

Table of Contents
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.

Addition Reactions of Alkenes


Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism
& Markovnikovs Rule
Stereochemistry of the Ionic Addition to an Alkene
Addition of Water to Alkenes: Acid-Catalyzed Hydration
Alcohols from Alkenes through OxymercurationDemercuration:
Markovnikov Addition
Alcohols from Alkenes through HydroborationOxidation: AntiMarkovnikov Syn Hydration
Hydroboration: Synthesis of Alkylboranes
Oxidation and Hydrolysis of Alkylboranes
Summary of Alkene Hydration Methods
Protonolysis of Alkylboranes
Electrophilic Addition of Bromine & Chlorine to Alkenes
Stereospecific Reactions
Halohydrin Formation
Divalent Carbon Compounds: Carbenes
Oxidation of Alkenes: Syn 1,2-Dihydroxylation
Oxidative Cleavage of Alkenes
Electrophilic Addition of Bromine & Chlorine to Alkynes
Addition of Hydrogen Halides to Alkynes
Oxidative Cleavage of Alkynes
How to Plan a Synthesis: Some Approaches & Examples
2014 by John Wiley & Sons, Inc. All rights reserved.

1A. How To Understand Additions

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

+E

Nu

C
Nu

-bond

-bond

Bonds broken

2 -bonds
Bonds formed

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Since bonds are formed from the overlapping of p


orbitals, electron clouds are above and below the
plane of the double bond

electron
clouds

Electrophilic
electron seeking
C=C and CC bonds are particularly
susceptible to electrophilic reagents
(electrophiles)
Common electrophiles
H+, X+ (X = Cl, Br, I), Hg2+, etc.

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Nu

Nu E
C

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2. Electrophilic Addition:
Markovnikovs Rule

Mechanism

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Markovnikovs Rule
For symmetrical substrates, no
problem for regiochemistry

H
C

Nu

E
H

same
H as H

E
C

Nu

Nu

same
H as H

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Nu E
C

Markovnikovs Rule
But for unsymmetrical
substrates, two regioisomers
are possible E
E

H3C

C
H

Nu

CH3

or

CH3

H
Nu

Nu

CH3

Nu

2014 by John Wiley & Sons, Inc. All rights reserved.

different
H from CH3

Nu E
C

Markovnikovs Rule
In the electrophilic addition of an electrophile
across an unsymmetrical 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

Note: carbocation stability 3 > 2 > 1


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2A. Theoretical Explanation of


Markovnikovs Rule
H3C

H
C

C
H


H X
step 1
(slow
r.d.s.)

H
CH3

H
H or CH3

H H
2o carbocation

H H
1o carbocation

(more stable)

(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
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Br

(1o cation) fast

(minor)

Br

Br

slow
(r.d.s.)

Br

(2o cation) fast

Step 1
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Step 2

Br
(major)

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(1)

Examples
H

Cl

Cl

H
+
H

(95

(2)

5)

Br

Br
+

Br
(98
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Cl

H
:

2)

Examples
OH

OH

Cl

(1)


Cl OH

more stable
3o cation

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Cl
(major)

Examples
Cl
I
more stable
3o cation

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I
Cl
(major)

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
Cl
H
H

Cl

+
(major)

Cl
(minor)

regioisomers
Regioselectivity:

95

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2D. The ANTI-Markovnikovs Rule

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
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Stereochemistry of the Ionic


Addition to an Alkene
attack from top
H

H
C

Bu

C
H

H
Bu

CH2 H

H C CH3
Bu
(S)-2-Halohexane
(50%)

achiral
trigonal planar
carbocation

Bu C
X

attack from

racemate

CH3

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

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Addition of Water to Alkenes:

Acid-Catalyzed Hydration

H
H

H2O

slow

fast
(step 2)

(step 1)

more stable

3o cation

Follows Markovnikovs
rule
OH

H2O
+

dilute H3O
(e.g. dilute H
2SO4, H3PO4)

fast
(step 3)

H2O

H
O

H
H

+
OH

4B. Rearrangements

Rearrangement can occur with certain


carbocations
H2O

H2SO4

1,2-alkyl shift

NOT
OH

H2O

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OxymercurationDemercuration:
Markovnikov Addition
Step 1: Oxymercuration
C

Hg(OAc)2
THF-H2O

Follows Markovnikovs
rule
Step 2: Demercuration

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C
HO

C
HgOAc

2. Oxymercuration
Demercuration
H2O

H2SO4

1,2-alkyl shift
H

H
H

H2O

H2O
OH

e.g.

H2O
H2SO4

OH
H

Rearrangements of the carbon


skeleton seldom occur in
oxymercurationdemercuration
OH
1. Hg(OAc)2, THF-H2O
2. NaBH4

no rearrangement
via

OH

Hg(OAc)
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5C. Mechanism of
Does
not undergo a free carbocation
Oxymercuration

H2O attacks the carbon of the bridged Hg


ion that is better able to bear the partial
+ve charge

HgOAc

AcO +

H2O

HgOAc
HO
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H2O

Stereochemistry
Usually anti-addition

OH

CH3

Hg(OAc)

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H2O

Solvomercuration-Demercuration

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3. HydroborationOxidation:
Anti-Markovnikov Syn Hydration
C

"BH3"

BH2

Addition of HBH2 across a C=C


H H
bond
H B B H
H

H
H

H
O

H
(BH3-THF)

Me
S
Me

(BH3-DMS)

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syn addition

Anti-Markovnikov addition
of H & OH
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Compare with oxymercurationdemercuration


OH

CH3

Hg(OAc)

Hg(OAc)2
H3C

THF-H2O

anti addition
Markovnikov addition
of H & OH
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NaBH4

OH

CH3

anti-Markovnikov
syn addition

Example

BH3-THF
H3C

This oxidation step occurs


with retention of
configuration
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BH2

CH3

Markovnikov

Anti-Markovnikov

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Summary of Alkene Hydration


Methods
Summary of Methods for Converting Alkene to
Alcohol
Reaction

Regiochemistr
y

Occurrence of
Stereochemistr Rearrangemen
y
ts

Acid-catalyzed
hydration

Markovnikov
addition

Not controlled

Frequent

Oxymercuratio
ndemercuration

Markovnikov
addition

Not controlled

Seldom

Stereospecific:
syn addition of
H and OH

Seldom

Hydroboration- Antioxidation
Markovnikov
addition

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3. Electrophilic Addition of
Bromine & Chlorine to Alkenes

Addition of XX (X = Cl, Br) across


a C=C bond
C

Br2
CCl4

Br
C

C
Br

(vicinal
dibromide)
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Examples

(1)

Br

Br2

Br
+

5 C

Br

(anti addition of Br2)

Br

(racemate)
Cl

(2) Ph

Cl2
Ph

10oC

Ph

(anti addition of Cl2)

Ph

Cl

Ph

Ph

Cl

Cl

same as
(rotation of C1-C2 bond)
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11A. Mechanism of Halogen


Addition
C

Br

Br

BrBr bond
becomes polarized
when close to
alkene

Br
Br

Br

+ Br
Br

Br

(vicinal
dibromid
(bromoniu
e) 2014 by John Wiley & Sons, Inc. Allm)
rights reserved.

Stereochemistry
Anti addition
Br

Br

Br

CCl4
Br
H

Br

Br

enantiomer +
(anti)
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SN2 reaction

Addition of bromine to cis-2Br


Butene
(a)
C

(a)
H
H3C

H
CH3

Br

Br

H3C

Br (b)

H
C

H
C

CH3

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

CH3

Br
bromonium
ion
(b)
(achiral)

H
H3C

Br
C

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

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Addition of bromine to trans-2CH3


Br
Butene
(a)
H
(a)

H
H3C

CH3
H

Br

Br

H3C

Br (b)

CH3
C H

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

Br
bromonium
ion
(b)
(achiral)

H
H3C

Br
C

CH3

Br
H
(R,S)-2,3-Dibromobutane
(meso)

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4. Halohydrin Formation
X2
C

H2O

OH
C

C
X

Addition of OH and X (X = Cl, Br)


across a C=C bond
X+ is the electrophile

Follows

Markovnikovs rule

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Mechanism
Br

H3C

H2O

Br

H2O

H3C

Br

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OH

CH3

Br

Other variation
If H2O is replaced by ROH, ROH
will be the nucleophile
e.g.
Br2
MeOH

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OMe
Br

Divalent Carbon Compounds:


Carbenes

4A. Structure and Reactions of


Methylene

CH2

Diazomethane

heat

CH2

or light

Methylene Nitrogen
(a carbene)

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. Reactions of Other Carbenes:


Dihalocarbenes
:CX2 (e.g. :CCl2)
Generation by -elimination of
chloroform

H
Cl

C
Cl

OtBu
Cl

CCl2 + tBuOH + Cl

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Usually a syn (cis) addition across


a C=C bond
H

BuOK

Cl

CHCl3

H
Stereospecific reactions

Cl

(a cyclopropane)

CCl2

CCl2
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Cl

Cl

Cl

Cl

5. The Simmons-Smith
CH2I 2

Zn(Cu)

(Zinc-copper
couple)

ZnI

C
H2
(a carbenoid)

A stereospecific syn (cis) addition

6. 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 / HO /


H2O / cold or OsO4, pyridine then
NaHSO3, H2O
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15A. Mechanism for Syn


Dihydroxylation of Alkenes

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Both reagents give syn


dihydroxylation

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Comparison of the two reagents


KMnO4: usually lower yield and
possibly side products due to
over-oxidation
1. KMnO4,
+

2. H

OH

+ O

(oxidative cleavage of C=C)

OH

OsO4: usually much higher yield


but OsO4 is extremely toxic
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Oxidative Cleavage of Alkenes


7. Cleavage with Hot Basic
Potassium Permanganate

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Other examples

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7A. Cleavage with Ozone


R

R"

R'

1. O3
2. Zn, AcOH
or Me2S

R"
O + O

R'

H
O

(1)

1. O3
2. Zn, AcOH
O

(2)

1. O3
2. Me2S
+
O

Mechanism

O
O

C
O

initial ozonide

O
C
O

C
O

C
O

ozonide

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C
O

Addition of Hydrogen Halides


to Alkynes
R

H3C

X (excess)

(X = Cl, Br, I)

Regioselectivity
Follows Markovnikovs rule
C

HBr

Br

H
C

CH3

C
H

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HBr

Br H
CH3

Br H
gem-dibromide

Mechanism

CH3

Br

H
CH3

Br

C
H

Br

H
C

CH3
Br H
CH3

Br H

Br

Br
C
CH3

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C
H

Br

C
H

Anti-Markovnikov addition of
hydrogen bromide to alkynes
occurs when peroxides are
present in the reaction mixture
H

Br

peroxides

Br
H
(E) and (Z)
(74%)

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0. 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
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20A. Retrosynthetic Analysis

How to synthesize

?
OH

Retrosynthetic analysis

OH
(target molecule)
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(precursor)

Synthesis

Markovnikov addition
of H2O

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How to synthesize

OH

Retrosynthetic analysis
OH
(target molecule)

(precursor)

Synthesis

anti-Markovnikov addition of
H 2O
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B. 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
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Example
How?
Ph

Br

Br
CH3

Ph

Retrosynthetic analysis
(i)

Br
Ph

Br
CH3

Ph

(gem-dibromide came from


addition of HBr across a CC
bond)
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CH3

Retrosynthetic analysis
synthons
(ii)

Ph

CH3

Ph

+ CH3

disconnection
H3C

+ Ph

Na

synthetic equivalent
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