REACTIONS OF ALKENES

6-1

Reduction of Alkenes

6-2

Reduction of Alkenes
Most

alkenes react with H2 in the presence of a transition metal catalyst to give alkanes
+ H2 Cyclohexene Pd 25C, 3 atm Cyclohexane

commonly used catalysts are Pt, Pd, Ru, and Ni the process is called catalytic reduction or, alternatively, catalytic hydrogenation addition occurs with syn stereoselectivity
6-3

Reduction of Alkenes
Mechanism

of catalytic hydrogenation

6-4

Reduction of Alkenes
even though addition syn stereoselectivity, some product may appear to result from trans addition

CH3 CH3 1,2-D imethylcyclohexene

H2 / Pt

CH3
+

CH3 CH3 30% to15% t rans -1,2-D imethylcyclohexane (racemic)

CH3 70% to 85% cis-1,2-D imethylcyclohexan e

6-5

Reduction of Alkenes
reversal of the reaction after the addition of the first hydrogen gives an isomeric alkene, etc.

CH3 CH3 1,2-D imeth ylcyclohexene

H2 / Pt H

CH3 H Pt H CH3

CH3 CH3 1,6-D imeth ylcyclohexene

6-6

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

6-7

H0 of Hydrogenation
N ame Eth yle ne Prop en e 1-Bu te ne cis -2-Bu ten e t rans -2-Bu te ne 2-M eth yl-2-b uten e 2,3-D ime th yl-2-b ute n e S tru ctural Formu la CH2 =CH2 CH3 CH=CH2 H [k J (k cal)/m ol] -137 (-32.8) -126 (-30.1) -127 (-30.3) -120 (-28.6) -115 (-27.6) -113 (-26.9) -111 (-26.6)
6-8

Alkene Stability & Reactivity

H C C H
R C C H H

mono
H

E
di

R C H
R

H C R

Evidence: heats of hydrogenation

H C C R
R C C R

tri
R
R

Reasons: hyperconjugation bond strength

tetra
R

6-9

 The more subtituents that are present, The more opportunities exist for hyperconjugation, and the more stable the alkene.

Hyperconjugation
interaction between the bond orbital of unfilled antibonding C = C and bond orbital of a filled C - H on a neighboring substituent...
6-10

Heats of Hydrogenation - cis & trans reaction profile

E
-120

H3C C H H3C C

CH3

+
H H

H2

-115

C H

C CH3

H2

H H H H H C C C C H H H H H

Reaction Coordinate
6-11

Heats of Hydrogenation - cis & trans Are the entaphy same or different ?
H3C C H
H3C C H C CH3

CH3 C H

H2

H H H H H C C C C H H H H H

H2

H H H H H C C C C H H H H H

6-12

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

6-13

Name of Reactions
React ion

D escrip tive N ame(s )

+

C C

HCl ( HX) H2 O

C C

C C

Br2 ( X2 ) Br2 ( X2 ) H2 O

H Hydrochlorin ation C C Cl (X) (hydrohalogen ation ) H Hydration C C OH (X) Br Bromin ation C C Br (X) (h alogenation) HO C C Br (X) Bromo(halo)hydrin formation

C C

6-14

Name of Reactions
C C
+ Hg(OAc) 2

H2 O

HgOAc Oxymercuration C C HO C C H BH2 C C HO OH C C H H Hydrob oration

C C

BH3

C C

OsO4

D iol formation (oxidation) Hydrogenation (reduction )

C C

H2

6-15

Addition of HX

6-16

Addition of HX

Carried

out with pure reagents or in a polar solvent such as acetic acid

Br H H Br

CH3 CH=CH2 Propene

+ HBr

CH3 CH-CH2 + CH3 CH-CH2 2-Bromoprop ane 1-Bromopropane (not obs erved)

6-17

Addition of HX

Addition

is regioselective

regioselective : one of two or more possible products is formed IN PREFERENCE TO all others that might be formed Markovnikovs rule: H adds to the carbon of the double bond having the greater number of hydrogens

6-18

HBr + 2-Butene
A two-step mechanism Step 1: proton transfer from HBr to the alkene gives a carbocation intermediate

CH3 CH=CHCH3 + H Br

slow , rate determining

H CH3 CH-CHCH3 + Br s ec-Butyl cation (a 2 carbocation intermediate)

6-19

HBr + 2-Butene
Step 2: reaction of the sec-butyl cation (an electrophile) with bromide ion (a nucleophile) completes the reaction

+ CH3 CHCH2 CH3 Br Bromide ion sec-Butyl cation (a nu cleophile) (an electrophile)

fast

Br CH3 CHCH2 CH3 2-Bromobu tane

6-20

HBr + 2-Butene
An

energy diagram for the two-step addition of HBr to 2-butene

the reaction is exergonic

6-21

Carbocations

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

6-22

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

6-23

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

6-24

Carbocation Stability
relative stability
H H C+ H CH3 C+ H Ethyl cation (1) CH3 CH3 C+ H Isopropyl cation (2) CH3 CH3 C+ CH3 t ert-Bu tyl cation (3)

H Methyl cation (meth yl)

Increasin g carbocation s tability

methyl and primary carbocations are so unstable that they are never observed in solution

6-25

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

6-26

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

6-27

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

6-28

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

6-29

Carbocation Rearrangements
in addition of HCl to an alkene

Cl + HCl 3,3-D imethyl1-bu tene + Cl

2-Ch loro-3,3-dimethylbutan e 2-Chloro-2,3-dimethylbu tane (the exp ected p rodu ct; 17%) (the major p rodu ct; 83%)

6-30

Carbocation Rearrangements
in acid-catalyzed hydration of an alkene

+ 3-Methyl-1-buten e

H2 O

H2 SO4

OH 2-Methyl-2-butan ol

6-31

Carbocation Rearrangements
the driving force is rearrangement of a less stable carbocation to a more stable one
CH3 CH3 CCH= CH2 + H H 3-Methyl-1-butene Cl : slow, rate determining CH3 C- CHCH3 + : Cl : CH3

the less stable 2 carbocation rearranges to a more stable 3 one by 1,2-shift of a hydride ion
CH3 CH3 C- CHCH3
+

: :

H A 2 carbocation intermediate

fast

CH3 CH3 C- CHCH3 H A 3 carbocation

+

6-32

Carbocation Rearrangements
reaction of the more stable carbocation (an electrophile) with chloride ion (a nucleophile) completes the reaction
C H 3 C- CH 2 CH 3 + : Cl : + : : CH 3

fast

CH 3 CH 3 C- C H 2 CH 3 : Cl : :

2-Chloro-2-methylbutane

6-33

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 Markovnikovs rule
CH3 CH=CH2 + H2 O Propene H2 SO4 OH H CH3 CH-CH2 2-Propanol

CH3 CH3 C=CH2 + H2 O 2-Methylprop ene

H2 SO4

CH3 CH3 C-CH2 HO H 2-Methyl-2-propanol

6-34

Addition of H2O
Step 1: proton transfer from H3O+ to the alkene
+

CH3 CH= CH 2

H O H H

slow, rate determining

Step 2: reaction of the carbocation (an electrophile) with water (a nucleophile) gives an oxonium ion
+

:
+

CH3 CHCH 3

:O H H

A 2o carbocation intermediate

CH3 CHCH 3

: O- H H

fast

Step 3: proton transfer to water gives the alcohol

CH 3 CHCH 3 H H O: H O+ fast CH 3 CHCH 3 + H O H : OH H
+

CH3 CHCH 3 H H An oxonium ion :

O+

6-35

Addition of Cl2 and Br2

carried out with either the pure reagents or in an inert solvent such as CH2Cl2 Br Br
CH3 CH=CHCH3 2-Buten e
+

Br2

CH2 Cl2

CH3 CH-CHCH3 2,3-D ib romob utane

addition of bromine or chlorine to a cycloalkene gives a trans-dihalocycloalkane

Br
+

Br +

Br2

CH2 Cl2

Cyclohexen e

Br Br trans-1,2-D ibromocyclohexane (a racemic mixture)

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

6-36

Addition of Cl2 and Br2

Step 1: formation of a bridged bromonium ion intermediate
Br Br C C C Br C C Br C C Br C + Br
-

Thes e carbocation s are major contribu ting s tru ctures

The bridged bromoniu m ion retains the geometry

6-37

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
Br C Br
-

Br C Br A nti (cop lan ar) orie ntation of ad ded b romine atoms C C

Br

Br N ew man p roje ction of the p rodu ct Br

Br C C Br
-

Br C C Br A nti (cop lan ar) orie ntation of ad ded b romine atoms

Br N ew man projection of th e p rod uct

6-38

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
Br Br (1S,2S)-1,2-D ibromocyclohexan e Br

+ Br2

Br Br

Br

Br Br (1R,2R)-1,2-D ibromocyclohexane 6-39

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
CH3 CH=CH2 + Cl2 + H2 O Propene HO Cl CH3 CH-CH2 + HCl 1-Chloro-2-p ropanol (a ch loroh yd rin )

6-40

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
Br2 / H2 O 1-Methylcyclop entene OH Br + OH Br + HBr

H H 2-Bromo-1-meth ylcyclopen tanol ( a racemic mixtu re )

to account for the regioselectivity and the anti stereoselectivity, chemists propose the three-step mechanism in the next screen
6-41

Addition of HOCl and HOBr

Step 1: formation of a bridged halonium ion intermediate
: Br : :Br :

: :
H - Br H
-

:Br :

:Br : C C H H R H minor contributin g structure

H R

C C H H R H bridge d bromonium ion

Step 2: attack of H2O on the more substituted carbon opens the three-membered ring
:
:Br : H O: H H R C C H H H H R C :Br : C H H
6-42

Addition of HOCl and HOBr

Step 3: proton transfer to H2O completes the reaction
H R Br C C H H H H O H R C C H H Br
+ H3 O+

+
H

O H

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

6-43

Addition of HOCl and HOBr

bridged bromonium ion from propene

6-44

Oxymercuration/Reduction
Oxymercuration

followed by reduction results in hydration of a carbon-carbon double bond

oxymercuration
+ Hg(OAc) 2 + H2 O OH HgOAc An organ omercury comp ou nd O + CH3 COH A cetic acid

1-Pen tene

Mercu ry(II) acetate

reduction
OH NaBH4 HgOAc H 2-Pen tanol OH O + CH COH + Hg 3 Acetic acid

6-45

Oxymercuration/Reduction
an important feature of oxymercuration/reduction is that it occurs without rearrangement
1 . Hg(OAc) 2 , H2 O 2 . NaBH4 3,3-D imeth yl-1-b utene

OH 3,3-D imeth yl-2-b utanol

oxymercuration occurs with anti stereoselectivity

Hg(OAc) 2 H H H2 O OH H H NaBH4 OH H

HgOAc

Cyclop entene

(Anti ad dition of OH and HgOA c)

H H Cyclopen tanol

6-46

Oxymercuration/Reduction
Step 1: dissociation of mercury(II) acetate

Step 2: formation of a bridged mercurinium ion intermediate; a two-atom three-center bond

6-47

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

6-48

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 CHg 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
6-49

Hydroboration/Oxidation
Hydroboration:

the addition of borane, BH3, to an alkene to form a trialkylborane

H H B H Borane + 3 CH2 = CH2 CH3 CH2 B CH2 CH3 Triethylborane (a trialkylborane) CH2 CH3

Borane

dimerizes to diborane, B2H6

2 BH 3 Borane B2 H6 D iborane

6-50

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
2

: O:

+ B2 H6

+ :O BH3 BH3 TH F

Tetrahydrofuran (THF)

6-51

Hydroboration/Oxidation
Hydroboration

is both

regioselective (boron to the less hindered carbon) and syn stereoselective

+ H CH 3 BH 3 H BR2 H3 C H

1-Methylcyclopentene

(Syn addition of BH 3) (R = 2-methylcyclopentyl)

6-52

Hydroboration/Oxidation
concerted regioselective and syn stereoselective addition of B and H to the carbon-carbon double bond
H B H CH 3 CH 2 CH 2 CH= CH 2 B CH 3 CH 2 CH 2 CH-CH 2

trialkylboranes are rarely isolated oxidation with alkaline hydrogen peroxide gives an alcohol and sodium borate
R3 B + H2 O2 + NaOH A trialkylborane 3 ROH + Na3 BO3 An alcohol

6-53

Hydroboration/Oxidation
Hydrogen

peroxide oxidation of a trialkylborane

step 1: hydroperoxide ion (a nucleophile) donates a pair of electrons to boron (an electrophile)
R + R B O-O-H R A trialk ylb orane Hydrop eroxide ion (an electroph ile) (a nu cleophile) R R B O O H R

step 2: rearrangement of an R group with its pair of bonding electrons to an adjacent oxygen atom
R R B O O H R R R B O R

O-H

6-54

Hydroboration/Oxidation
step 3: reaction of the trialkylborane with aqueous NaOH gives the alcohol and sodium borate
( RO) 3 B + 3 NaOH A trialkylborate 3 ROH + Na3 BO3 Sodiu m b orate

6-55

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

6-56

Another Important Topic

Anti

markonikov Polymerization Oxidation

6-57

Oxidation/Reduction
How do you recognize the reaction whether oxidation/reduction or not

by 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-

6-58

Oxidation/Reduction
three balanced half-reactions
CH3 CH= CH2 + H2 O Propene OH CH3 CHCH3 2-Propanol HO OH CH3 CH= CH2 + 2 H2 O Propene CH3 CH= CH2 + 2 H+ + 2 e Propene CH3 CHCH2 + 2 H+ + 2 e 1,2-Propane diol CH3 CH2 CH3 Propane

6-59

Oxidation with OsO4

OsO4

oxidizes an alkene to a glycol, a compound with OH groups on adjacent carbons

oxidation is syn stereoselective
OsO4 O O Os O O A cyclic osmate OH NaHSO3 H2 O OH cis-1,2-Cyclopentan ediol (a cis glycol)

6-60

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
HOOH Hyd rogen peroxid e CH3 CH3 COOH CH3 t ert -Bu tyl h yd roperoxide (t -BuOOH)

6-61

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
CH3 CH3 C= CHCH2 CH 3 2-Methyl-2-pentene O

1 . O3 CH3 CCH3 2 . ( CH3 ) 2 S Propanone (a ketone)

O + HCCH 2 CH3 Propanal (an aldehyde)

6-62

Oxidation with O3
the initial product is a molozonide which rearranges to an isomeric ozonide
CH 3 CH = CH CH 3 2-Butene O3 O OO C H 3 CH - C H CH 3 A molozonide H H3 C O H O C H 3 CH

C C ( CH 3 ) 2 S CH 3 O O Acetaldehyde An ozonide

6-63

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
6-64

Reaction Stereochemistry
We

saw in Section 6.3D that bromine adds to 2butene to give 2,3-dibromobutane

CH3 CH=CHCH3 2-Buten e
+

Br2

CH2 Cl2

Br Br CH3 CH-CHCH3 2,3-D ib romob utane

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? 6-65

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

6-66

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

6-67

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

6-68

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

6-69

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-2,3dibromobutane

Stereospecific

reaction: a reaction in which the stereochemistry of the product depends on the stereochemistry of the starting material

6-70

Oxidation of 2-Butene
OsO4 oxidation of cis-2-butene gives meso-2,3butanediol
H3 C H H C H H3 C
2 3 2 3

CH3 id entical; a meso compoun d

OsO4 ROOH

HO OH (2S,3R)-2,3-Butanediol HO
2

CH3 cis-2-Butene (achiral)

OH C
3

H H3 C (2R,3S)-2,3-Butanediol

H CH3

6-71

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)
H3 C H C H
2 3 2 3

CH3 H a pair of enantiomers; a racemic mixture

CH3

OsO4 ROOH

HO OH (2S,3S)-2,3-Butaned iol HO
2

H3 C H trans-2-Buten e (achiral)

OH C
3

H H3 C (2R,3R)-2,3-Butaned iol

CH3 H

and oxidation of cis-2-butene gives meso 2,3butanediol (also optically inactive)

6-72

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)
6-73

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
Br2 Br Br redraw as a chair con formation Br Br

(R)-4-t ert -Bu tylcyclohexene

(1S,2S,4R)-1,2-D ibromo-4-t ert -b utylcycloh exane

the presence of the bulky tert-butyl group controls the orientation of the two bromine atoms added to the ring
6-74

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

PPh2 PPh2

BIN AP (S)-(-)-BIN AP []D 2 5 -223 (R)-(+)-BIN A P []D 2 5 +223

6-75

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
(R)-BINAP + RuCl3 (R)-BINAP-Ru

using (R)-BINAP-Ru as a hydrogenation catalyst, (S)naproxen is formed in greater than 98% ee

CH2 COOH H3 CO + H2 (R)-BINAP-Ru press ure CH3 COOH H3 CO (S)-Naproxen (ee > 98%)

6-76

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
(S)-BIN A P-Ru OH H2 OH

(R)-3,7-D imethyl-6-octen-1-ol (R)-BIN A P-Ru OH

(E)-3,7-D imethyl-2,6-octadien -1-ol (Geraniol)

(S)-3,7-D imethyl-6-octen-1-ol

6-77