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Created byProfessor William Tam & Dr. Phillis
Chang Ch. 8 - 1
Chapter 8
Alkenes and Alkynes II:Addition Reactions
Ch. 8 - 2
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 - 3
C C E Nu
E
C C
Nu
+
1. Addition Reactions of Alkenes
Ch. 8 - 4
1A.How To Understand Additions
to Alkenes This is an addition reaction: E–Nu added across the double bond
C C E Nu
E
C C
Nu
+
Bonds broken Bonds formed
p-bond s-bond 2 s-bonds
Ch. 8 - 5
Since p bonds are formed from the overlapping of p orbitals, p electron clouds are above and below the plane of the double bond
C Cp electron clouds
Ch. 8 - 6
Electrophilic●electron seeking●C=C and C≡C p bonds are
particularly susceptible to electrophilic reagents (electrophiles)
Common electrophile●H+, X+ (X = Cl, Br, I), Hg2+, etc.
Ch. 8 - 7
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 - 8
C CE Nu
C C
E
+ Nu
Nu
C C
E
Ch. 8 - 9
C C
A
CC
E
CC
NuNuE Nu
2. Electrophilic Addition ofHydrogen Halides to Alkenes: Mechanism and Markovnikov’sRule
Mechanism
Ch. 8 - 10
C C
E
Mechanism●Sometimes do not go through a
“free carbocation”, may go via
Ch. 8 - 11
C C
H
H
H
HE Nu
E
CC H
H
H
H
E
C CH
H
H
H
E
C CH
H
H
H
Nu E
CC H
H
H
H
Nu
Nu
same as
same as
Markovnikov’s Rule ●For symmetrical substrates, no
problem for regiochemistry
Ch. 8 - 12
E NuC C
H
H3C
H
H E
CC H
H
CH3
H
E
C CCH3
H
H
H
E
C CCH3
H
H
H
Nu E
CC H
H
CH3
H
Nu
Nu Nu
or
different from
Markovnikov’s Rule ●But for unsymmetrical
substrates, two regioisomers are possible
Ch. 8 - 13
Markovnikov’s 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 - 14
E NuE Nu E
Markovnikov’s Rule ●Thus
E
NOT
Note: carbocation stability 3o > 2o > 1o
Ch. 8 - 15
BrBr
fast
Addition of Hydrogen Halides●Addition of HCl, HBr and HI
across a C=C bond●H+ is the electrophile
slow
r.d.s
H Br+
Br
NO
Ch. 8 - 16
Ch. 8 - 17
2A.Theoretical Explanation ofMarkovnikov’s Rule
H XC C
H
H3C
H
H
H
CC H
H
CH3
H
H
C CCH3
H
H
H
or
2o carbocation
(more stable)
1o carbocation
(more stable)
step 1(slowr.d.s.)
One way to state Markovnikov’s 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 - 18
H Br
H H
Br
Br
fast(1o cation)(minor)
slow(r.d.s.)
Br
fast
H
Br
H
(2o cation)
(major)
☓
Step 1 Step 2
Ch. 8 - 19
Ch. 8 - 20
Examples
+(1)H Cl
Cl
H
H
Cl
(95 : 5)
+(2)H Br
(98 : 2)
H
Br
Br
H
Ch. 8 - 21
2B.Modern Statement of Markovnikov’s 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 - 22
Examples
(1)Cl OH
Cl
OH
Cl
OH
(major)more stable
3o cation
Cl Cl
OH
OH
(minor)less stable
1o cation
Ch. 8 - 23
Examples
(2)I Cl
Cl
(major)more stable
3o cation
I I
Cl
(minor)less stable
1o cation
ClCl
II
Ch. 8 - 24
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
H
H
Cl
95 : 5
(major) (minor)
Regioselectivity:
regioisomers
Ch. 8 - 25
2D. An Exception to Markovnikov’s 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
H Br Br(anti-Markovnikov'sproduct)RO OR
heat H
Ch. 8 - 26
C C
H
H
Bu
HH X
3. Stereochemistry of the IonicAddition to an Alkene
C CH2 HH
Bu
X
X
achiraltrigonal planar
carbocation
C CH3H
X
Bu(S)-2-Halohexane
(50%)
C CH3
H
X
Bu
(R)-2-Halohexane(50%)
attack from top
attack from bottom
race
mate
Ch. 8 - 27
4. Addition of Sulfuric Acid to Alkenes
conc. H2SO4
cold
OSO3H
H
HOS
O
HO
O
H
OSO3H
Addition of H–OSO3H across a C=C bond
Hmore stable3o cation
less stable1o cation
Ch. 8 - 28
4A.Alcohols from Alkyl HydrogenSulfates
The overall result of the addition of sulfuric acid to an alkene followed by hydrolysis is the Markovnikov addition of H– and –OH
conc. H2SO4
cold
OSO3H
H
OH
H
H2O
heat
Ch. 8 - 29
5. Addition of Water to Alkenes:Acid-Catalyzed Hydration
Overall process●Addition of H–OH across a C=C
bond●H+ is the electrophile●Follow Markovnikov’s rule
OH HH2O
dilute H3O+
(e.g. dilute H2SO4, H3PO4)
Ch. 8 - 30
H O
H
H
more stable
3o cation
slow
(step 1)
H
H2O
fast
(step 2)
H
OH H
H2Ofast(step 3)
H
OH
+H O
H
H
5A.Mechanism
Ch. 8 - 31
5B.Rearrangements Rearrangement can occur with certain
carbocations
H2O
H2SO4H
1,2-alkyl shift
H2OOH
(major product)
OH
NOT
Ch. 8 - 32
6. Alcohols from Alkenes throughOxymercuration–Demercuration:Markovnikov Addition
Step 1: Oxymercuration
C C
HO HgOAc
C CHg(OAc)2
THF-H2O
Step 2: Demercuration
C C
HO HgOAc
NaBH4
OHC C
HO H
Ch. 8 - 33
6A.Regioselectivity of Oxymercura-tion–Demercuration Oxymercuration–demercuration is
also highly regioselective and follows Markovnikov’s rule
HO
HgOAcHg(OAc)2
THF-H2O
NaBH4
OH
HO
H
Ch. 8 - 34
6B.Rearrangements Seldom Occur inOxymercuration–Demercuration Recall: acid-catalyzed hydration of
some alkenes leads to rearrangement products
H2O
H2SO4
OH
H
e.g.
Ch. 8 - 35
O
H
H H
H
1,2-alkyl shift
HH2O
OH
H
H2O
H2O
H2SO4
Ch. 8 - 36
Rearrangements of the carbon skeleton seldom occur in oxymercuration–demercuration
H
OH
1. Hg(OAc)2, THF-H2O
2. NaBH4
Hg(OAc)
OHvia
no rearrangement
Ch. 8 - 37
HgOAc
+AcO
HO
HgOAc
O
HgOAc
HH
6C. Mechanism of Oxymercuration Does not undergo a “free
carbocation”
OAc
Hg
OAc
H2O
H2O
Ch. 8 - 38
H3C H
H3CHg(OAc)
Hg(OAc)2
THF-H2O
Stereochemistry●Usually anti-addition
H2O
OH
CH3
H
Hg(OAc)
Ch. 8 - 39
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 - 40
Solvomercuration-Demercuration
OR
Hg(O2CCF3)
NaBH4
OH
OR
H
Hg(O2CCF3)2
THF-ROH
Ch. 8 - 41
7. Alcohols from Alkenes throughHydroboration–Oxidation:Anti-Markovnikov Syn Hydration
Addition of H–BH2 across a C=C bond
C C C C
H BH2
"BH3"
Ch. 8 - 42
BH3 exists as dimer B2H6 or complex with coordinative solvent
B B
H
H
H H
H
H
OB
H
H
H
Me
S
Me
B
H
H
H
(BH3-THF) (BH3-DMS)
Ch. 8 - 43
H3C H
1. BH3-THF
2. H2O2, OH
H
CH3
OH
H
syn addition
Anti-Markovnikov additionof “H” & “OH”
Ch. 8 - 44
H3C H
Hg(OAc)2
THF-H2O
OH
CH3
H
Hg(OAc)
NaBH4
OH
CH3
H
H
anti addition
Markovnikov additionof “H” & “OH”
Compare with oxymercuration-demercuration
Ch. 8 - 45
8. Hydroboration: Synthesis ofAlkylboranes
C Chydroboration
C C
BH
H B+
alkene boronhydride
alkylborane
Ch. 8 - 46
8A.Mechanism of Hydroboration
H
H3C
H
H
+
H BH
H
H
H3C
H
H
H BH
H
complex
H
H3C
H
H
H BH
H
HH3C
HH
H B
HH
four-atomconcerted T.S.
HH3C
HH
H B
H
H
syn additionof H and B
Ch. 8 - 47
Other examples
(1)H BH2-THF
H BH2 H2B H
+
(99 : 1)
(2)H BH2-THF
H BH2 H2B H
+
(98 : 2)
Ch. 8 - 48
8B.Stereochemistry of Hydroboration
Syn addition
H3C HBH3-THF
H
CH3
BH2
H
Ch. 8 - 49
9. Oxidation and Hydrolysis ofAlkylboranes
H B
(trialkyl borane)
H B
H
H
H BH2
BH
B
H
B always endsup on the leasthindered carbon
Ch. 8 - 50
Oxidation
BH2O2
O
BO O
Ch. 8 - 51
●Via
R3B O OH
R
B
R
R O OHR
BOR
R
O OH
ROB
OR
ROHO
R
B
OR
O OR
HORO
BOR
OR
R
B
O
R OR
OH
Ch. 8 - 52
Hydrolysis
NaOHH2O
O
BO O
OH + Na3BO33
Ch. 8 - 53
Overall synthetic process of hydroboration-oxidation-hydrolysis
OHH
1. BH3-THF
2. H2O23. NaOH, H2O
●Overall: anti-Markovnikov addition of H–OH across a C=C bond
●Opposite regioisomers as oxymercuration-demercuration
Ch. 8 - 54
Example
H3C H
BH3-THFH
CH3
BH2
H
H2O2
OHH
CH3
OH
H
anti-Markovnikovsyn addition
This oxidation step occurs with retention of configuration
Ch. 8 - 55
10.Summary of Alkene HydrationMethods
Summary of Methods for Converting Alkene to Alcohol
ReactionRegiochemistr
yStereochemistr
y
Occurrence of Rearrangemen
ts
Acid-catalyzed hydration
Markovnikov addition
Not controlled Frequent
Oxymercuration-demercuration
Markovnikov addition
Not controlled Seldom
Hydroboration-oxidation
Anti-Markovnikov addition
Stereospecific: syn addition ofH – and –OH
Seldom
Ch. 8 - 56
Examples
H
H2OH
OH
1. Hg(OAc)2, THF-H2O
2. NaBH4, OHH
OH
1. BH3-THF
2. H2O2, OHOH
H
with rearrangement
Markovnikov addition of H2O without rearrangement
anti-Markovni-kov, syn addition of H2O
H
Hvia1,2-hydride
shift
Ch. 8 - 57
11.Protonolysis of Alkylboranes
R B R H CH3CO2 B+heat
CH3CO2H
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 - 58
e.g.
H3C H H D
HH3C1. BH3-THF
2. CH3CO2D
+ enantiomer
H BH2
HH3C
via
Ch. 8 - 59
12. Electrophilic Addition of Bromine and Chlorine to Alkenes
Addition of X–X (X = Cl, Br) across a C=C bond
Br2C C
Br
C C
BrCCl4
(vicinaldibromide)
Ch. 8 - 60
Examples
(anti addition of Br2)
Br
Br
Br
Br
+Br2
5oC
(racemate)
(1)
(anti addition of Cl2)
Cl2
10oC(2) Ph
PhPh
Ph
Cl
Cl
Cl
PhPh
Cl
same as
(rotation of C1-C2 bond)
1
2
Ch. 8 - 61
Br
+ Br
C C
Br
Br
12A. Mechanism of Halogen Addition
C C + Br Br
Br
Br
Br–Br bond becomes polarized when close to alkene
(vincinalDibromid
e)(bromoniu
m)
Ch. 8 - 62
Br
Br
H H CCl4
Br Br
Stereochemistry●Anti addition
H
Br
Br
H
SN2 reaction
(anti)
enantiomer +
Ch. 8 - 63
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 - 64
●Reaction 1
Br2
H3C
H
H
CH3 Br
CHH3C
C
CH3
Br
H
CCl4
trans-2-Butene
H3C
BrBr
CH3
H H
(2R,3S)-2,3-Dibromobutane(a meso compound)
●Reaction 2Br2
H3C
H
CH3
H Br
CHH3C
C
H
Br
CH3
CCl4
cis-2-Butene (2R,3R)
Br
C HCH3
C
H
Br
H3C
(2S,3S)
+
(a pair of enantiomers)
Ch. 8 - 65
C CH3CH
CH3
H
Br
bromoniumion
(achiral)
Addition of bromine to cis-2-Butene
C CH3C
H
CH3
H
Br
Br
Br
CHH3C
C
H
Br
CH3
(2R,3R)-2,3-Dibromobutane(chiral)
(a)
Br
C HCH3
C
H
Br
H3C
(2S,3S)-2,3-Dibromobutane(chiral)
(b)
Br(a) (b)
Ch. 8 - 66
C CH3CH
HCH3
Br
bromoniumion
(achiral)
Addition of bromine to trans-2-Butene
C CH3C
H
H
CH3
Br
Br
Br
CHH3C
C
CH3
Br
H
(R,S)-2,3-Dibromobutane(meso)
(a)
Br
C CH3H
C
H
Br
H3C
(R,S)-2,3-Dibromobutane(meso)
(b)
Br(a) (b)
Ch. 8 - 67
14. Halohydrin Formation
Addition of –OH and –X (X = Cl, Br) across a C=C bond
X+ is the electrophile Follow Markovnikov’s rule
X2C C
OH
C C
XH2O
Ch. 8 - 68
H3C HH2O
Br Br
BrH3C H
H3CBr
H2O
OH
CH3
H
Br
Mechanism
Ch. 8 - 69
OMe
Br
Br2
MeOH
e.g.
Other variation●If H2O is replaced by ROH, RÖH
will be the nucleophile
Ch. 8 - 70
15.Divalent Carbon Compounds:Carbenes
15A. Structure and Reactions of Methylene
CH2 N N CH2 + N Nheat
or light
Diazomethane Methylene(a carbene)
Nitrogen
Ch. 8 - 71
CH2 N N
I
N NH2C CH2 N N
II III
C C CH2+ CC
CH H
Alkene Methylene Cyclopropane
Ch. 8 - 72
15B. Reactions of Other Carbenes: Dihalocarbenes
CCl2
H
CCl
ClCl
OtBuCl+ tBuOH +
:CX2 (e.g. :CCl2) Generation by a-elimination of
chloroform
Ch. 8 - 73
H
H
Cl
Cl
(a cyclopropane)
tBuOK
CHCl3
Usually a syn (cis) addition across a C=C bond
Ch. 8 - 74
ClCl
ClCl
CCl2
CCl2
Stereospecific reactions
Ch. 8 - 75
15C. Carbenoids: The Simmons-Smith Cyclopropane Synthesis
CH2I2 Zn(Cu)+
(Zinc-coppercouple)
(a carbenoid)
ICH2
ZnI
Ch. 8 - 76
A stereospecific syn (cis) addition across a C=C bond
CH2I2
Zn(Cu)(trans) (trans)
CH2I2
Zn(Cu)
(cis) (cis)
Ch. 8 - 77
16.Oxidation of Alkenes:Syn 1,2-Dihydroxylation
Overall: addition of 2 OH groups across a C=C bond
Reagents: dilute KMnO4 / OH⊖ / H2O / cold or OsO4, pyridine then NaHSO3, H2O
C C
OH OH
Ch. 8 - 78
16A. Mechanism for Syn Dihydroxylation of Alkenes
C C
dil. KMnO4
OH , H2O
cold
C C
O O
MnOO
OH
H2OC C
OH OH
+ MnO2
C C
O O
OsO O
NaHSO3
H2OC C
OH OH
+ Os
OsO4pyridine
Ch. 8 - 79
Both reagents give syn dihydroxylation
H H
H H
OH OH
or OsO4, pyridinethen NaHSO3
(cis-diol)
dil. KMnO4OH , H2O, cold
Ch. 8 - 80
Comparison of the two reagents●KMnO4: usually lower yield and
possibly side products due to over-oxidation
O
OH
OH
O+1. KMnO4,
2. H+
●OsO4: usually much higher yield but OsO4 is extremely toxic
(oxidative cleavage of C=C)
Ch. 8 - 81
17.Oxidative Cleavage of Alkenes
17A. Cleavage with Hot Basic Potassium Permanganate
KMnO4, OH , H2O
O
O
a2
or
O
OH2
H3O
b
a
b
a
b
ab a
b
ab
Ch. 8 - 82
Other examples
1. KMnO4, OH , H2O, heat
2. H3O O
O C O
+
(1)
O
O
OH
1. KMnO4, OH , H2O, heat
2. H3O(2)
Ch. 8 - 83
17B. Cleavage with Ozone
R'
R
H
R"
O
R'
R
O
H
R"1. O3+
2. Zn, AcOH or Me2S
Ch. 8 - 84
Examples
(1)1. O3
2. Zn, AcOH
O
O
+
(2)O
H
O
1. O3
2. Me2S
Ch. 8 - 85
Mechanism
C C
OO
O
CO
C
OO
C C
OO
O
initial ozonide
C
O
C
OO
+
O O
CO
C
ozonide +C O CO
+Zn(OAc)2
Ch. 8 - 86
18.Electrophilic Addition of Bromine & Chlorine to Alkynes
C CR H
X
C C
X
R
X
H
XCH2Cl2
(X = Cl, Br, I)
X2 (excess)
C CR H
X
C C
X
R
X
H
X
C C
H
X
X
H X2X2
(anti-addition)
Ch. 8 - 87
19.Addition of Hydrogen Halidesto Alkynes
C CR H
X
C C
H
R
X
H
H(X = Cl, Br, I)
X (excess)H
Regioselectivity●Follow Markovnikov’s rule
C C
Br
CH3
Br
H
H
Hgem-dibromide
C CH3C HHBr
C C
CH3
Br
H
H HBr
Ch. 8 - 88
Mechanism
C CCH3 HH Br
C C
H
H
CH3Br
C C
CH3
Br
H
H
C C
H
H
HCH3
BrBrC
H
H
H
C
Br
CH3
Br
H Br
Ch. 8 - 89
Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture
H Br
peroxidesBr
H
(E) and (Z)
(74%)
Ch. 8 - 90
20.Oxidative Cleavage of Alkynes
C CR R' + R'CO2H1. O3
2. HOAcRCO2H
C CR R' + R'CO2H1. KMnO4, OH
2. H3O+
RCO2H
Example1. O3
2. AcOHC CPh CH3 PhCO2H + CH3CO2H
OR
Ch. 8 - 91
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
skeleton2. Functional group
interconversions3. Control of regiochemistry4. Control of stereochemistry
Ch. 8 - 92
How to synthesize ?
OH
(target molecule) (precursor)
OH
●Retrosynthetic analysis
21A. Retrosynthetic Analysis
Ch. 8 - 93
●Synthesis
OH
H+
H2O
1. Hg(OAc)2, THF-H2O
2. NaBH4, OH
or
Markovnikov additionof H2O
Ch. 8 - 94
How to synthesize ?
(target molecule) (precursor)
OH
OH
●Retrosynthetic analysis
●Synthesis
OH
1. BH3-THF
2. H2O2, OH
anti-Markovnikov addition of H2O
Ch. 8 - 95
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
21B. Disconnections, Synthons, and Synthetic Equivalents
Ch. 8 - 96
Example
HPhPh
CH3
Br BrHow?
●Retrosynthetic analysis
CH3PhPh
CH3
Br Br(i)
(gem-dibromide came from addition of HBr across a C≡C bond)
Ch. 8 - 97
●Retrosynthetic analysis
CH3Ph(ii)
disconnection
Ph + CH3
Ph Na+H3C I
synthons
synthetic equivalent
Ch. 8 - 98
●Synthesis
Ph Na
H3C I
Ph HNaNH2
liq. NH3
-30oC
(via an SN2 reaction)
Ph CH3HBr
(excess)PhCH3
Br Br
Ch. 8 - 99
21C. Stereochemical Considerations
CH3H3C
How?
H3C
BrBr
CH3
Ch. 8 - 100
Retrosynthetic analysis●The precursor of a vicinal
dibromide is usually an alkene●Bromination of alkenes are anti
addition
H3C
BrBr
CH3
(rotate 180o)
H3CCH3
Br
Br
H3CCH3CH3H3C
(anti addition of Br2)
(anti addition of H2)
Ch. 8 - 101
●Synthesis
H3C CH32. NH4Cl
1. Li, liq. NH3
H3CCH3
Br2/CCl4
H3CCH3
Br
BrH3C
Br
CH3
Br same
as
(anti addition of Br2)
(anti addition of H2)
Ch. 8 - 102
END OF CHAPTER 8