Organic Chemistry

1
Reactions of Alkenes
Chapter 6
2
6.1 Characteristic Reactions, Table 6-1

• The reaction typical of alkenes is addition

3
Characteristic Reactions, Table 6-1
4
6.2 Reaction 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

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Gibbs Free Energy

• Gibbs free energy change, DG0 (standard state) a
  thermodynamic function relating enthalpy,
  entropy, and temperature
• 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 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

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Gibbs Free Energy

• a change in Gibbs free energy is directly related
  to chemical equilibrium
• summary of the relationships between DG0, DH0,
  DS0, and the position of chemical equilibrium

7
Energy Diagrams

• Enthalpy change, DH0 the difference in total
  bond energy between reactants and products
• a measure of bond making (exothermic) and bond
  breaking (endothermic)
• Heat of reaction, DH0 the difference in enthalpy
  between reactants and products
• 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 reaction a reaction in which the
  enthalpy of the products is higher than that of
  the reactants a reaction in which heat is
  absorbed

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A. Energy Diagrams

• Energy diagram a graph showing the changes in
  energy that occur during a chemical reaction
• Reaction coordinate a measure in the change in
  positions of atoms during a reaction

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Activation Energy

• Transition state
• an unstable species of maximum energy formed
  during the course of a reaction
• a maximum on an energy diagram
• Activation Energy, ?G 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

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Energy Diagram, Fig. 6-1

• A one-step reaction with no intermediate

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Energy Diagram, Fig. 6-2

• A two-step reaction with one intermediate

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B. Developing 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

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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
• they help us understand what events occur in the
  pathway from reactants to products

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6.3 Electrophilic Additions

• An alkene reacts using electrons from the pi bond
  as a nucleophile, the other reactant is an
  electrophile.
• 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

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A. Addition of HX

• Carried out with pure reagents or in a polar
  solvent such as acetic acid
• Addition is regioselective
• 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
• Markovnikovs 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 Hs.

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HBr 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

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HBr 2-Butene, Fig. 6-4

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

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Carbocations

• 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

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Carbocations, Fig. 6-3

• 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

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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

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Carbocation Stability

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

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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

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The Inductive Effect, Fig. 6-5

• 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

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Hyperconjugation, Fig. 6-6

• 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

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B. 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

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Addition of H2O

• Step 1 proton transfer from H3O to the alkene
• Step 2 reaction of the carbocation (an
  electrophile) with water (a nucleophile) gives an
  oxonium ion
• Step 3 proton transfer to water gives the alcohol

H
O

H
O
H

H
H
intermediate


fast



O
H

H
H
An oxonium ion
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C. 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

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Carbocation Rearrangements

• in addition of HCl to an alkene
• in acid-catalyzed hydration of an alkene

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Carbocation 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

fast


H
H
A 3 carbocation
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Carbocation Rearrangements

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

-

fast








2-Chloro-2-methylbutane
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D. Addition of Cl2 and Br2

• 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 stereoselectivity
  halogen atoms add to opposite faces of the double
  bond
• this selectivity discussed in detail in Section
  6.7

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Addition of Cl2 and Br2

• Step 1 formation of a bridged bromonium ion
  intermediate

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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

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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

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E. 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

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

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Addition of HOCl and HOBr

• Step 1 forms a bridged halonium ion
  intermediate
• Step 2 attack of H2O on the more substituted
  carbon opens the three-membered ring

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Addition of HOCl and HOBr

• Step 3 proton transfer to H2O completes the
  reaction
• As the e-plot 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

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Addition of HOCl and HOBr

• bridged bromonium ion from propene

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F. Oxymercuration/Reduction

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

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Oxymercuration/Reduction

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

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Oxymercuration/Reduction

• Step 1 dissociation of mercury(II) acetate
• Step 2 formation of a bridged mercurinium ion
  intermediate a two-atom three-center bond

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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

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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 3-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

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6.4 Hydroboration/Oxidation

• Hydroboration the addition of borane, BH3, to an
  alkene to form a trialkylborane
• Borane dimerizes to diborane, B2H6

H
H
B
B

H
Borane
Borane
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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

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Hydroboration/Oxidation

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

H

H
H
1-Methylcyclopentene
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Hydroboration/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

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Hydroboration/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

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Hydroboration/Oxidation

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

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6.5 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
• Recognize 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-

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Oxidation/Reduction

• three balanced half-reactions

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Oxidation to glycols

• Alkene is converted to a cis-1,2-diol
• Two reagents
• Osmium tetroxide (expensive!), followed by
  hydrogen peroxide or
• Cold (25o), dilute aqueous potassium
  permanganate, followed by hydrolysis with base

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A. Oxidation with OsO4

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

O
O
O
O
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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

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B. Oxidation with dilute KMnO4

• KMnO4 (dilute) oxidizes an alkene to a glycol,
  as did OsO4, here the cyclic ester is hydrolyzed
  with base.
• oxidation is syn stereoselective

O
O
O
O
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Cleavage of both bonds of an alkene

• Both the pi and sigma bonds of the alkene are
  broken (cleavage of the double bond)
• Two reagent systems
• Ozone followed by reduction or
• Hot, concentrated potassium permanganate in base,
  followed by acidification

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C. Oxidation with O3

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

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Oxidation with O3

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

O
O
O
2-Butene
A molozonide
H
H
O
O
C
C
O
O
Acetaldehyde
An ozonide
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D. Oxidation with conc. KMnO4

• Treatment of an alkene with permanganate cleaves
  the CC and and continues to oxidize the two
  alkene carbon atoms if they contain hydrogen atoms

O
O
2-Methyl-2-pentene
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Determining cleavage products

• Predicting products from cleavage of an alkene,
  CC, depends upon the number of Hs on each C of
  the double bond
• hydrogens Products
• on carbon From O3 From conc KMnO4
• None ketone ketone
• One aldehyde carboxylic acid
• Two formaldehyde CO2 HOH

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6.6 Reduction 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 reduction or,
  alternatively, catalytic hydrogenation
• addition occurs with syn stereoselectivity

Pd
25C, 3 atm
Cyclohexene
Cyclohexane
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A. Reduction of Alkenes

• Mechanism of catalytic hydrogenation

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Reduction 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.

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B. ?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

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?H0 of Hydrogenation, Table 6-2
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6.7 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

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A. Reaction 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?

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Bromination of cis-2-Butene

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

70
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

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Bromination of trans-2-Butene

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

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Bromination of trans-2-Butene

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

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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-2,3-dibromobutane
• Stereospecific reaction a reaction in which the
  stereochemistry of the product depends on the
  stereochemistry of the starting material

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Oxidation of 2-Butene

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

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

76
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)

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

78
C. 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

79
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
• using (R)-BINAP-Ru as a hydrogenation catalyst,
  (S)-naproxen is formed in greater than 98 ee

80
Reaction Stereochemistry

• BINAP-Ru complexes are somewhat specific for the
  types of CC they reduce
• to be reduced, the double bond must have some
  kind of a neighboring group that serves a
  directing group

81
Reactions of Alkenes
End Chapter 6