Organic

6-6-11

Organic Organic ChemistryChemistry

William H. BrownWilliam H. Brown

Christopher S. FooteChristopher S. Foote

Brent L. IversonBrent L. Iverson

William H. BrownWilliam H. Brown

Christopher S. FooteChristopher S. Foote

Brent L. IversonBrent L. Iverson

6-6-22

Reactions Reactions of Alkenesof Alkenes

Chapter 6Chapter 6

6-6-33

Characteristic ReactionsCharacteristic Reactions

CC

C C

C C

Br2

(HX)HCl

H2O

(X2)

C C Br2(X2)

H2O

(X)

C CH

OH

C CBr

Br (X)

C CHO

Br (X)

C CH

Cl (X)

Descriptive Name(s )Reaction

+

+

+

Bromination(halogenation)

Hydrochlorination(hydrohalogenation)

Hydration

+ Bromo(halo)hydrinformation

6-6-44

Characteristic ReactionsCharacteristic Reactions

CC

C C

CC

BH3

OsO4

H2

C C Hg(OAc)2H2O

C CBH2H

C CHO OH

C CHH

C CHO

HgOAc

+

+

+

Hydroboration

Diol formation(oxidation)

Hydrogenation(reduction)

+ Oxymercuration

6-6-55

Reaction MechanismsReaction Mechanisms A reaction mechanism describes how a reaction

occurs• which bonds are broken and which new ones are

formed• the order and relative rates of the various bond-

breaking and bond-forming steps• if in solution, the role of the solvent• if there is a catalyst, the role of a catalyst• the position of all atoms and energy of the entire

system during the reaction

6-6-66

Gibbs Free EnergyGibbs Free Energy Gibbs free energy change, Gibbs free energy change, GG00:: a thermodynamic

function relating enthalpy, entropy, and temperature

• exergonic reaction:exergonic reaction: a reaction in which the Gibbs free energy of the products is lower than that of the reactants; the position of equilibrium for an exergonic reaction favors products

• endergonic reaction:endergonic reaction: a reaction in which the Gibbs free energy of the products is higher than that of the reactants; the position of equilibrium for an endergonic reaction favors starting materials

G0 = ΔH0 –TΔS0

6-6-77

Gibbs Free EnergyGibbs Free Energy

• a change in Gibbs free energy is directly related to chemical equilibrium

• summary of the relationships between G0, H0, S0, and the position of chemical equilibrium

G0 = -RT ln Keq

At higher temperatureswhen TS0 > H0 and G0 < 0, the position of equilibrium favorsproducts

G0 > 0; theposition of equilibriumfavors reactants

G0 < 0; theposition of equilibriumfavors products

At lower temperatures whenTS0 < H0 andG0 < 0, the position of equilibrium favorsproducts

H0 > 0

H0 < 0

S0 < 0 S0 > 0

6-6-88

Energy DiagramsEnergy Diagrams Enthalpy change, Enthalpy change, 00: : the difference in total

bond energy between reactants and products• a measure of bond making (exothermic) and bond

breaking (endothermic)

Heat of reaction, Heat of reaction, 00:: the difference in enthalpy between reactants and products• exothermic reaction:exothermic reaction: a reaction in which the enthalpy

of the products is lower than that of the reactants; a reaction in which heat is released

• endothermic reactionendothermic reaction: a reaction in which the enthalpy of the products is higher than that of the reactants; a reaction in which heat is absorbed

6-6-99

Energy DiagramsEnergy Diagrams Energy diagram:Energy diagram: a graph

showing the changes in energy that occur during a chemical reaction

Reaction coordinate:Reaction coordinate: a measure in the change in positions of atoms during a reaction

Reactioncoordinate

Energy

6-6-1010

Activation EnergyActivation Energy Transition state:Transition state: • an unstable species of maximum energy formed

during the course of a reaction• a maximum on an energy diagram

Activation Energy, Activation Energy, GG‡‡:: the difference in Gibbs free energy between reactants and a transition state• if G‡ is large, few collisions occur with sufficient

energy to reach the transition state; reaction is slow• if G‡ is small, many collisions occur with sufficient

energy to reach the transition state; reaction is fast

6-6-1111

Energy DiagramEnergy Diagram

• a one-step reaction with no intermediate

6-6-1212

Energy DiagramEnergy Diagram A two-step reaction with one intermediate

6-6-1313

Developing a Reaction MechanismDeveloping a Reaction Mechanism How it is done

• design experiments to reveal details of a particular chemical reaction

• propose a set or sets of steps that might account for the overall transformation

• a mechanism becomes established when it is shown to be consistent with every test that can be devised

• this does mean that the mechanism is correct, only that it is the best explanation we are able to devise

6-6-1414

Why Mechanisms?Why Mechanisms?

• they are the framework within which to organize descriptive chemistry

• they provide an intellectual satisfaction derived from constructing models that accurately reflect the behavior of chemical systems

• they are tools with which to search for new information and new understanding

6-6-1515

Electrophilic AdditionsElectrophilic 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

6-6-1616

Addition of HXAddition of HX Carried out with pure reagents or in a polar

solvent such as acetic acid

Addition is regioselective • regioselective reaction:regioselective reaction: an addition or substitution

reaction in which one of two or more possible products is formed in preference to all others that might be formed

• Markovnikov’s rule:Markovnikov’s rule: in the addition of HX, H2O, or ROH to an alkene, H adds to the carbon of the double bond having the greater number of hydrogens

CH3CH=CH2 HBr CH3CH-CH2

Br H

CH3CH-CH2

H Br

1-Bromopropane (not observed)

2-BromopropanePropene++

6-6-1717

HBr + 2-ButeneHBr + 2-Butene A two-step mechanism

Step 1: proton transfer from HBr to the alkene gives a carbocation intermediate

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

CH3CH=CHCH3 H Br CH3CH-CHCH3

HBr++

δ−δ+

sec-Butyl cation(a 2° carbocationintermediate)

slow, ratedetermining

Br CH3CHCH2CH3 CH3CHCH2CH3

Br

sec-Butyl cation(an electrophile)

+

Bromide ion(a nucleophile)

fast

2-Bromobutane

6-6-1818

HBr + 2-ButeneHBr + 2-Butene

An energy diagram for the two-step addition of HBr to 2-butene• the reaction is exergonic

6-6-1919

CarbocationsCarbocations Carbocation:Carbocation: 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

6-6-2020

CarbocationsCarbocations

• 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

6-6-2121

Carbocation StabilityCarbocation 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

6-6-2222


• relative stability

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

Methyl cation

(methyl)

Ethyl cation(1°)

Isopropyl cation

(2°)

tert-Butyl cation(3°)

Increasing carbocation stability

+ + + +C

H

H

CH3 CCH3

CH3

H

C

CH3

CH3

CH3CH

H

H

6-6-2323


• 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

6-6-2424

The Inductive EffectThe 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

6-6-2525

HyperconjugationHyperconjugation

• 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

6-6-2626

Addition of HAddition of H22OO

• 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 Markovnikov’s rule

CH3CH=CH2 H2OH2SO4 CH3CH-CH2

HOH

Propene 2-Propanol+

CH3C=CH2

CH3

H2OH2SO4

HO

CH3

HCH3C-CH2

2-Methyl-2-propanol2-Methylpropene

+

6-6-2727

Addition of HAddition of H22OO

• Step 1: proton transfer from H3O+ to the alkene

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

• Step 3: proton transfer to water gives the alcohol

++

+

intermediateA 2o carbocation

+HO

H

HOH

H

CH3CH=CH2 CH3CHCH3

slow, ratedetermining ::

:

:

:+

+

+

An oxonium ion

H OHH

CH3CHCH3 O-H CH3CHCH3fast

:

::

++

+OH HO

H

HH

H O HCH3CHCH3 CH3CHCH3fast

OH:

:

::

6-6-2828

Carbocation RearrangementsCarbocation Rearrangements In electrophilic addition to alkenes, there is the

possibility for rearrangement Rearrangement:Rearrangement: a change in connectivity of the

atoms in a product compared with the connectivity of the same atoms in the starting material

6-6-2929

Carbocation RearrangementsCarbocation Rearrangements

• in addition of HCl to an alkene

• in acid-catalyzed hydration of an alkene

HCl+ +

2-Chloro-3,3-dimethylbutane(the expected product; 17%)

2-Chloro-2,3-dimethylbutane(the major product; 83%)

3,3-Dimethyl-1-butene

ClCl

H2SO4H2O

OH

3-Methyl-1-butene 2-Methyl-2-butanol

+

6-6-3030


• the driving force is rearrangement of a less stable carbocation to a more stable one

• the less stable 2° carbocation rearranges to a more stable 3° one by 1,2-shift of a hydride ion

+

A 2° carbocation intermediate

3-Methyl-1-butene

++

CH3

HClH

CH3

CH3CCH=CH2 CH3C-CHCH3

slow, ratedetermining

H:::

-Cl:: ::

++

A 3° carbocation

CH3

H

CH3

H

CH3C-CHCH3 CH3C-CHCH3fast

6-6-3131


• reaction of the more stable carbocation (an electrophile) with chloride ion (a nucleophile) completes the reaction

-Cl

:: ::

2-Chloro-2-methylbutane

++

CH3 CH3

CH3C-CH2CH3 CH3C-CH2CH3fast

Cl: ::

6-6-3232

Addition of ClAddition of Cl22 and Br and Br22

• carried out with either the pure reagents or in an inert solvent such as CH2Cl2

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

• addition occurs with anti stereoselectivityanti stereoselectivity; halogen atoms add from the opposite face of the double bond

• we will discuss this selectivity in detail in Section 6.7

Br2 CH2Cl2

Br

Br

Br

Br+

trans-1,2-Dibromocyclohexane(a racemic mixture)

Cyclohexene

+

CH3CH=CHCH3 Br2 CH2Cl2CH3CH-CHCH3

Br Br

2,3-Dibromobutane2-Butene+

6-6-3333


• Step 1: formation of a bridged bromonium ion intermediate

C C

Br

Br

C C

BrC C

Br

C C

BrBr -

The bridged bromoniumion retains the geometry

These carbocations are major contributing structures

+

6-6-3434


• 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

Anti (coplanar) orientationof added bromine atoms

C C

Br

Br

Br

BrNewman projection

of the product

C C

Br

Br -

Anti (coplanar) orientationof added bromine atoms

C C

Br

Br -

CC

Br

BrBr

Br

Newman projectionof the product

6-6-3535


• 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

Br2

Br

Br

Br

Br

BrBr

BrBr

+

(1R,2R)-1,2-Dibromo-cyclohexane

(1S,2S)-1,2-Dibromo-cyclohexane

6-6-3636

Addition of HOCl and HOBrAddition of HOCl and HOBr

Treatment of an alkene with Br2 or Cl2 in water forms a halohydrin

Halohydrin:Halohydrin: a compound containing -OH and -X on adjacent carbons

CH3CH=CH2 Cl2 H2O CH3CH-CH2

ClHOHCl

1-Chloro-2-propanol (a chlorohydrin)

Propene

+++

6-6-3737


• 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

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

2-Bromo-1-methylcyclopentanol( a racemic mixture )

Br2/H2O OH

1-Methylcyclopentene

+ HBr+

HBr

OH

HBr

6-6-3838


Step 1: formation of a bridged halonium ion intermediate

Step 2: attack of H2O on the more substituted carbon opens the three-membered ring

C C

Br

OH

H

HR

OH

H H H

+C C

Br

R HH H

::

:

::

:::

C C

Br

R HH H

C C

Br

R HH H

C CR H

H H -Br -

bridged bromoniumion

minor contributingstructure

Br

Br:

:

:

:

:

::: ::

:

6-6-3939


• Step 3: proton transfer to H2O completes the reaction

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

H3O++C C

Br

O HH

HR

• •H H

+

O H

H

C C

Br

O HH

HR

• •H

6-6-4040


• bridged bromonium ion from propene

6-6-4141

Oxymercuration/ReductionOxymercuration/Reduction Oxymercuration followed by reduction results in

hydration of a carbon-carbon double bond• oxymercuration

• reductionOH

HgOAc

NaBH4

OH

H

CH3COHO

Hg

2-Pentanol

+

Acetic acid

+

Hg(OAc)2 H2O

OH

HgOAc

CH3COHO

Aceticacid

An organomercury compound

Mercury(II) acetate

1-Pentene

++ +

6-6-4242

Oxymercuration/ReductionOxymercuration/Reduction

• an important feature of oxymercuration/reduction is that it occurs without rearrangement

• oxymercuration occurs with anti stereoselectivity

3,3-Dimethyl-2-butanol3,3-Dimethyl-1-butene

1. Hg(OAc)2, H2O2. NaBH4

OH

H H

Hg(OAc)2

H2O

H HgOAc

OH HNaBH4 OH H

HH

(Anti addition ofOH and HgOAc)

CyclopentanolCyclopentene

6-6-4343

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

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

6-6-4444

Oxymercuration/ReductionOxymercuration/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

6-6-4545

Oxymercuration/ReductionOxymercuration/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 C-Hg 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

6-6-4646

Hydroboration/OxidationHydroboration/Oxidation

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

Borane dimerizes to diborane, B2H6

Borane

H BH

H

3CH2=CH2 CH3CH2 BCH2CH3

CH2CH3

Triethylborane(a trialkylborane)

+

Borane Diborane

2BH3 B2H6

6-6-4747


• 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

22

Tetrahydrofuran (THF)

-++O O BH3B2H6

BH3•THF

:::

6-6-4848

Hydroboration/OxidationHydroboration/Oxidation Hydroboration is both • regioselective (boron to the less hindered carbon) • and syn stereoselective

CH3H

BH3

BR2

H H3C

H

+

1-Methylcyclopentene (Syn addition of BH3)(R = 2-methylcyclopentyl)

6-6-4949


• concerted regioselective and syn stereoselective addition of B and H to the carbon-carbon double bond

• trialkylboranes are rarely isolated• oxidation with alkaline hydrogen peroxide gives an

alcohol and sodium borate

δ− δ+H B

CH3CH2CH2CH=CH2 CH3CH2CH2CH-CH2

H B

R3B H2O2 NaOH 3ROH Na3BO3

A trialkyl-borane

+An alcohol

++

6-6-5050

Hydroboration/OxidationHydroboration/Oxidation Hydrogen peroxide oxidation of a trialkylborane• step 1: hydroperoxide ion (a nucleophile) donates a

pair of electrons to boron (an electrophile)

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

B

R

R

R O O H B

R

R O

R

O-H-

+

B

R

RR B

R

RR O-O-H B

R

RR O O HB

R

RR O O H+

A trialkylborane(an electrophile)

Hydroperoxide ion(a nucleophile)

6-6-5151


• step 3: reaction of the trialkylborane with aqueous NaOH gives the alcohol and sodium borate

(RO)3B 3NaOH 3ROH + Na3BO3

A trialkylborate Sodium borate+

6-6-5252

Oxidation/ReductionOxidation/Reduction Oxidation:Oxidation: the loss of electrons• alternatively, the loss of H, the gain of O, or both

Reduction:Reduction: the gain of electrons• alternatively, the gain of H, the loss of O, or both

Recognize using a balanced half-reaction1. 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-

6-6-5353

Oxidation/ReductionOxidation/Reduction

• three balanced half-reactions

CH3CH=CH2 CH3CHCH3+ H2O

Propene 2-Propanol

OH

CH3CH=CH2 CH3CHCH2+ 2H2O + 2H+ + 2e-

Propene 1,2-Propanediol

HO OH

CH3CH2CH3+ 2H+ + 2e-

Propene

CH3CH=CH2

Propane

6-6-5454

Oxidation with OsOOxidation with OsO44

OsO4 oxidizes an alkene to a glycolglycol, a compound with OH groups on adjacent carbons• oxidation is syn stereoselective

OsO4

OOs

O O

O

NaHSO3

H2O

cis-1,2-Cyclopentanediol (a cis glycol)

A cyclic osmate

OH

OH

6-6-5555

Oxidation with OsOOxidation with OsO44

• 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 CH3COOHCH3

CH3

Hydrogenperoxide

tert-Butyl hydroperoxide (t-BuOOH)

6-6-5656

Oxidation with OOxidation with O33

Treatment of an alkene with ozone followed by a weak reducing agent cleaves the C=C and forms two carbonyl groups in its place

Propanal(an aldehyde)

Propanone(a ketone)

2-Methyl-2-pentene

CH3 O OCH3C=CHCH2CH3

1. O32. (CH3)2S

CH3CCH3 + HCCH2CH3

6-6-5757

Oxidation with OOxidation with O33

• the initial product is a molozonide which rearranges to an isomeric ozonide

Acetaldehyde

2-Butene

O

CH3CH=CHCH3O3

(CH3 )2S CH3CH

CH3CH-CHCH3

O OO

O OC

OC

H

CH3

H

H3C

A molozonide

An ozonide

6-6-5858

Reduction of AlkenesReduction of Alkenes

Most alkenes react with H2 in the presence of a transition metal catalyst to give alkanes

• commonly used catalysts are Pt, Pd, Ru, and Ni• the process is called catalytic reductioncatalytic reduction or,

alternatively, catalytic hydrogenationcatalytic hydrogenation• addition occurs with syn stereoselectivity

+ H2Pd

Cyclohexene Cyclohexane25°C, 3 atm

6-6-5959

Reduction of AlkenesReduction of Alkenes Mechanism of catalytic hydrogenation

6-6-6060

Reduction of AlkenesReduction of Alkenes

• even though addition syn stereoselectivity, some product may appear to result from trans addition

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

H2/ Pt

CH3

CH3

CH3

CH3

H H

HPt

CH3

1,2-Dimethyl- cyclohexene

1,6-Dimethyl- cyclohexene

CH3

CH3

CH3

CH3

CH3

CH3

CH3

30% to15%70% to 85%cis-1,2-Dimethyl-

cyclohexane1,2-Dimethyl-cyclohexene

+

trans-1,2-Dimethyl-cyclohexane(racemic)

H2/Pt

6-6-6161

HH00 of Hydrogenation 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

6-6-6262

HH00 of Hydrogenation of Hydrogenation

CH2=CH2

CH3CH=CH2

NameStructural Formula

H°[kJ (kcal)/mol]

Ethylene

Propene

1-Butene

cis-2-Butene

trans-2-Butene

2-Methyl-2-butene

2,3-Dimethyl-2-butene

-137 (-32.8)

-126 (-30.1)

-127 (-30.3)

-120 (-28.6)

-115 (-27.6)

-113 (-26.9)

-111 (-26.6)

6-6-6363

Reaction StereochemistryReaction 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 stereospecificstereospecific

6-6-6464

Reaction StereochemistryReaction Stereochemistry We saw in Section 6.3D that bromine adds to 2-

butene to give 2,3-dibromobutane

• 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?

CH3CH=CHCH3 Br2 CH2Cl2CH3CH-CHCH3

Br Br

2,3-Dibromobutane2-Butene+

6-6-6565

Bromination of Bromination of ciscis-2-Butene-2-Butene

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

6-6-6666

Bromination of Bromination of ciscis-2-Butene-2-Butene

• attack of bromide ion at carbons 2 and 3 occurs with equal probability to give enantiomeric products as a racemic mixture

6-6-6767

Bromination of Bromination of transtrans-2-Butene-2-Butene

• reaction with bromine forms bridged bromonium ion intermediates which are enantiomers

6-6-6868

Bromination of Bromination of transtrans-2-Butene-2-Butene

• attack of bromide ion in either carbon of either enantiomer gives meso-2,3-dibromobutane

6-6-6969

Bromination of 2-ButeneBromination 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-2,3-

dibromobutane

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

6-6-7070

Oxidation of 2-ButeneOxidation of 2-Butene

• OsO4 oxidation of cis-2-butene gives meso-2,3-butanediol

C CH

H3C

H

CH3

OsO4

ROOH

C

HO

C

OH

HCH3

H3CH

HO

CHH3C

C

OH

CH3

H

cis-2-Butene (achiral)

identical;a meso compound

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

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

2

2

2

3

3

3

6-6-7171

Oxidation of 2-ButeneOxidation 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)

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

CH

CH3C

H3C

H OsO4

ROOH

C CCH3

H

OH

H3CH

HO

C

HH3C

CH

CH3

OHHO

(2R,3R)-2,3-Butanediol

(2S,3S)-2,3-Butanediola pair ofenantiomers;a racemicmixturetrans-2-Butene

(achiral)

32

2

2

3

3

6-6-7272

Reaction StereochemistryReaction 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)

6-6-7373

Reaction StereochemistryReaction 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

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

Br2

Br

Br

(1S,2S,4R)-1,2-Dibromo-4-tert-butylcyclohexane(R)-4-tert-Butyl-

cyclohexene

Br

Br

redraw asa chair

conformation

6-6-7474

Reaction StereochemistryReaction 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

BINAP

(S)-(-)-BINAP[α]D

25 -223(R)-(+)-BINAP[α]D

25 +223

6-6-7575

Reaction StereochemistryReaction 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

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

H3CO

COOH

CH2

H2

(R)-BINAP-Ru

H3CO

COOH+ pressure

(S)-Naproxen(ee > 98%)

CH3

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

6-6-7676

Reaction StereochemistryReaction 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)-BINAP-Ru

OHH2

(R)-BINAP-Ru

OH

OH(E)-3,7-Dimethyl-2,6-octadien-1-ol

(Geraniol)

(R)-3,7-Dimethyl-6-octen-1-ol

(S)-3,7-Dimethyl-6-octen-1-ol

6-6-7777

Reactions Reactions of Alkenesof Alkenes

End Chapter 6End Chapter 6

Organic

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