6-6-22
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
6-6-33
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
6-6-44
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
6-6-55
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 = H0 –TS0
6-6-66
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
6-6-77
Energy DiagramsEnergy Diagrams Enthalpy change, Enthalpy change, : : 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, :: 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
6-6-88
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
En
erg
y
6-6-99
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
6-6-1212
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
6-6-1313
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
6-6-1414
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
6-6-1515
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++
6-6-1616
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++
sec-Butyl cation(a 2° carbocationintermediate)
slow, ratedetermining
Br CH3CHCH2CH3 CH3CHCH2CH3
Br
sec-Butyl cation(an electrophile)
+
Bromide ion(a nucleophile)
fast
2-Bromobutane
6-6-1717
HBr + 2-ButeneHBr + 2-Butene
An energy diagram for the two-step addition of HBr to 2-butene• the reaction is exergonic
6-6-1818
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
6-6-1919
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
6-6-2020
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
6-6-2121
Carbocation StabilityCarbocation Stability
• 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
6-6-2222
Carbocation StabilityCarbocation 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
6-6-2323
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
6-6-2424
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
6-6-2525
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
+
6-6-2626
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:
:
:
:
6-6-2727
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
6-6-2828
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
+
6-6-2929
Carbocation RearrangementsCarbocation Rearrangements
• 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
6-6-3030
Carbocation RearrangementsCarbocation Rearrangements
• 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: ::
6-6-3131
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+
6-6-3232
Addition of ClAddition of Cl22 and Br and Br22
• 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
+
6-6-3333
Addition of ClAddition of Cl22 and Br and Br22
• 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
6-6-3434
Addition of ClAddition of Cl22 and Br and Br22
• 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
6-6-3535
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
+++
6-6-3636
Addition of HOCl and HOBrAddition 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
• 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
6-6-3737
Addition of HOCl and HOBrAddition of HOCl and HOBr
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:
:
:
:
:
:
:: ::
:
6-6-3838
Addition of HOCl and HOBrAddition of HOCl and HOBr
• 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
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
++ +
6-6-4141
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
6-6-4242
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
6-6-4343
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
6-6-4444
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
6-6-4545
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
6-6-4646
Hydroboration/OxidationHydroboration/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
22
Tetrahydrofuran (THF)
-++O O BH3B2H6
BH3•THF
:::
6-6-4747
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)
6-6-4848
Hydroboration/OxidationHydroboration/Oxidation
• 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
H B
CH3CH2CH2CH=CH2 CH3CH2CH2CH-CH2
H B
R3B H2O2 NaOH 3ROH Na3BO3
A trialkyl-borane
+An alcohol
++
6-6-4949
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)
6-6-5050
Hydroboration/OxidationHydroboration/Oxidation
• step 3: reaction of the trialkylborane with aqueous NaOH gives the alcohol and sodium borate
(RO)3B 3NaOH 3ROH + Na3BO3
A trialkylborate Sodium borate+
6-6-5151
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-
6-6-5252
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
6-6-5353
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
6-6-5454
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)
6-6-5555
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
6-6-5656
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
6-6-5757
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
• 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
6-6-6060
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
6-6-6161
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)
6-6-6262
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
6-6-6363
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+
6-6-6464
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
6-6-6565
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
6-6-6666
Bromination of Bromination of transtrans-2-Butene-2-Butene
• reaction with bromine forms bridged bromonium ion intermediates which are enantiomers
6-6-6767
Bromination of Bromination of transtrans-2-Butene-2-Butene
• attack of bromide ion in either carbon of either enantiomer gives meso-2,3-dibromobutane
6-6-6868
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
6-6-6969
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
6-6-7070
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
6-6-7171
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)
6-6-7272
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
6-6-7373
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[]D
25 -223(R)-(+)-BINAP
[]D25 +223
6-6-7474
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+
6-6-7575
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