Chapter 6 - Organic Chemistry by fjwuxn


    William H. Brown
    Christopher S. Foote
    Brent L. Iverson
of Alkenes
    Chapter 6

Characteristic Reactions
 React ion                                     D escrip tive N ame(s )
   C C       +    HCl                C C       Hydrochlorin ation
                 ( HX)                  Cl (X) (hydrohalogen ation )
   C C       +   H2 O                C C       Hydration
                                 (X) Br
   C C       +   Br2                 C C       Bromin ation
                 ( X2 )                 Br (X) (h alogenation)
                          H2 O
   C C       +   Br2               C C         Bromo(halo)hydrin
                 ( X2 )              Br (X)    formation

Characteristic Reactions

                       H2 O      HgOAc
   C C   + Hg(OAc) 2           C C     Oxymercuration

   C C   +   BH3               C C      Hydrob oration
                               H BH2

   C C   +   OsO4              C C      D iol formation
                              HO OH     (oxidation)

   C C   +   H2                C C      Hydrogenation
                               H H      (reduction )

Reaction Mechanisms
A reaction mechanism describes how a reaction
 • which bonds are broken and which new ones are
 • 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

Gibbs Free Energy
 Gibbs free energy change, DG0: a thermodynamic
 function relating enthalpy, entropy, and
                 DG0 = DH0 –TDS0
  • 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

Gibbs Free Energy
 • a change in Gibbs free energy is directly related to
   chemical equilibrium
                 DG 0 = -RT ln Keq
 • summary of the relationships between DG0, DH0, DS0,
   and the position of chemical equilibrium
                      DS0 < 0                     DS0 > 0
               DG 0 > 0; th e               At h igh er temperatures
               position of equilib riu m    w hen TDS0 > DH0 an d
    DH 0 > 0
               favors reactants             DG 0 < 0, th e position of
                                            equ ilibrium favors
               At low er temp eratu res
                                            DG 0 < 0; th e
    DH 0 < 0   w hen TDS0 < DH0 an d
                                            position of equilib riu m
               DG 0 < 0, th e position of
                                            favors products
               equ ilibrium favors
Energy Diagrams
         change, DH0: the difference in total
 Enthalpy
 bond energy between reactants and products
  • a measure of bond making (exothermic) and bond
    breaking (endothermic)
     of reaction, DH0: the difference in enthalpy
 Heat
 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

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               Reaction
  positions of atoms during             coordinate
  a reaction

Activation Energy
 Transition   state:
  • an unstable species of maximum energy formed
    during the course of a reaction
  • a maximum on an energy diagram
 ActivationEnergy, DG‡: the difference in Gibbs
 free energy between reactants and a transition
  • if DG‡ is large, few collisions occur with sufficient
    energy to reach the transition state; reaction is slow
  • if DG‡ is small, many collisions occur with sufficient
    energy to reach the transition state; reaction is fast

Energy Diagram
 • a one-step reaction with no intermediate

Energy Diagram
A   two-step reaction with one intermediate

Developing a Reaction Mechanism
   How it is done
    • design experiments to reveal details of a particular chemical
    • propose a set or sets of steps that might account for the overall
    • 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

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

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

Addition of HX
 Carriedout with pure reagents or in a polar
 solvent such as acetic acid
                               Br H             H   Br
  CH3 CH=CH2    + HBr       CH3 CH-CH2 + CH3 CH-CH2
     Propene              2-Bromoprop ane 1-Bromopropane
                                           (not obs erved)
 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
  • 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
HBr + 2-Butene
 A two-step mechanism
  Step 1: proton transfer from HBr to the alkene gives a carbocation
                                slow , rate
                           determining
   CH3 CH=CHCH3 + H Br                         CH3 CH-CHCH3 + Br
                                              s ec-Butyl cation
                                             (a 2° carbocation
   Step 2: reaction of the sec-butyl cation (an electrophile) with
     bromide ion (a nucleophile) completes the reaction
                    + CH3 CHCH2 CH3        fast
              Br                                   CH3 CHCH2 CH3
       Bromide ion     sec-Butyl cation           2-Bromobu tane
      (a nu cleophile) (an electrophile)

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

   Carbocation: a species in which a carbon atom has only
    six electrons in its valence shell and bears positive
   Carbocations are
     • classified as 1°, 2°, or 3° depending on the number of
       carbons bonded to the carbon bearing the positive
     • electrophiles; that is, they are electron-loving
     • Lewis acids

 • 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

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°
 • methyl and 1° carbocations are so unstable that they
   are never observed in solution

Carbocation Stability
 • relative stability
              H             H             CH3              CH3
         H   C+     CH3 C+        CH3 C+          CH3 C+
              H              H            H                  CH3
        Methyl        Ethyl       Isopropyl        t ert-Bu tyl
         cation       cation        cation            cation
        (meth yl)      (1°)          (2°)               (3°)
                    Increasin g carbocation s tability

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

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
 • we account for this electron-releasing ability of alkyl
   groups by (1) the inductive effect, and (2)

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

 • 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

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 Markovnikov’s rule
                                       OH H
                          H2 SO4
      CH3 CH=CH2 + H2 O            CH3 CH-CH2
        Propene                    2-Propanol
          CH3                            CH3
                          H2 SO4
       CH3 C=CH2 + H2 O             CH3 C-CH2
                                      HO H
    2-Methylprop ene           2-Methyl-2-propanol

Addition of H2O
 • Step 1: proton transfer from H3O+ to the alkene
                                       slow, rate
                                 +    determining           +

   CH3 CH= CH 2     +   H O H                           CH3 CHCH 3   +       :O H
                             H                      A 2o carbocation         H
 • Step 2: reaction of the carbocation (an electrophile)
   with water (a nucleophile) gives an oxonium ion
        CH3 CHCH 3      +    : O- H            CH3 CHCH 3
                             H                     O+

                                              An oxonium ion
 • Step 3: proton transfer to water gives the alcohol
                                      fast                               +

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

           O:                                                  H


       H                                                                         6-27
Carbocation Rearrangements
 Inelectrophilic 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

Carbocation Rearrangements
   • in addition of HCl to an alkene
            + HCl                               +          Cl

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

   • in acid-catalyzed hydration of an alkene
                                       H2 SO4
                           +   H2 O
         3-Methyl-1-buten e                     2-Methyl-2-butan ol

Carbocation Rearrangements
 • the driving force is rearrangement of a less stable
   carbocation to a more stable one
       CH3                        slow, rate           CH3
                                 determining                            -

   CH3 CCH= CH2 + H      Cl :                      CH3 C- CHCH3 + : Cl :


       H                                                H
  3-Methyl-1-butene                                A 2° carbocation

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

Carbocation Rearrangements
 • reaction of the more stable carbocation (an
   electrophile) with chloride ion (a nucleophile)
   completes the reaction
       CH 3                                  CH 3
                             -   fast

   CH 3 C- CH 2 CH 3 + : Cl :           CH 3 C- CH 2 CH 3

                                            : Cl :


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         +    Br2                   CH3 CH-CHCH3
                                         CH2 Cl2
         2-Buten e                                  2,3-D ib romob utane
 • addition of bromine or chlorine to a cycloalkene gives
   a trans-dihalocycloalkane
                                                   Br           Br
                 +   Br2                                +
                               CH2 Cl2
                                                    Br           Br
       Cyclohexen e
                                         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
Addition of Cl2 and Br2
 • Step 1: formation of a bridged bromonium ion
                     Br                 Br                 Br
  C    C         C        C         C        C         C        C   + Br

                Thes e carbocation s are major    The bridged bromoniu m
                  contribu ting s tru ctures     ion retains the geometry

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              Br
          C        C                              C       C
 Br   -                                                                       Br
                                  A nti (cop lan ar) orie ntation   N ew man p roje ction
                                   of ad ded b romine atoms            of the p rodu ct
              Br                        Br

          C        C                         C        C
                            -                                                  Br
                       Br       A nti (cop lan ar) orie ntation     N ew man projection
                                 of ad ded b romine atoms              of th e p rod uct
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
                                      (1S,2S)-1,2-D ibromo-
                                 Br        cyclohexan e
        + Br2

                                      (1R,2R)-1,2-D ibromo-
                                           cyclohexane      6-35
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
                                       HO Cl
      CH3 CH=CH2 + Cl2 + H2 O        CH3 CH-CH2       + HCl
       Propene                  1-Chloro-2-p ropanol
                                   (a ch loroh yd rin )

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            OH              OH
                                                +               + HBr
                                           Br              Br
                                         H               H
  1-Methylcyclop entene
                                  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

Addition of HOCl and HOBr
 Step 1: formation of a bridged halonium ion intermediate
          : Br :
     :Br :

                                        :Br :                   :Br :

 H                 H - Br
     C       C                  C     C                     C     C
 R                 H        H             H              H             H
                            R           H                R           H
                        bridge d bromonium              minor contributin g
                                  ion                       structure
 Step 2: attack of H2O on the more substituted carbon
 opens the three-membered ring

                            :Br :                H           :Br :
                       C        C                       C   C
                   H                    H

         H O:      R                H               +               H
                                                    O           H
             H                                  H       H

Addition of HOCl and HOBr
  • Step 3: proton transfer to H2O completes the reaction
          H                Br        H                Br
         R                          R
                   C   C                      C   C            + H3 O+
             +                  H                          H
             O                          O
         H   • •
                   H       H        H   • •           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
Addition of HOCl and HOBr
 • bridged bromonium ion from propene

 Oxymercuration   followed by reduction results in
  hydration of a carbon-carbon double bond
  • oxymercuration                                  OH              O
              + Hg(OAc) 2 + H2 O                              + CH3 COH
 1-Pen tene    Mercu ry(II)              An organ omercury         A cetic
                acetate                     comp ou nd              acid

  • reduction
                OH                          OH
                              NaBH4                 + CH COH + Hg
                  HgOAc                        H
                                      2-Pen tanol    Acetic acid
    • 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                    3,3-D imeth yl-2-b utanol

    • oxymercuration occurs with anti stereoselectivity
                 Hg(OAc) 2                              NaBH4
                                     OH        H                     OH         H
                    H2 O
H           H
                                     H         HgOAc                H         H
Cyclop entene                      (Anti ad dition of             Cyclopen tanol
                                   OH and HgOA c)

 • Step 1: dissociation of mercury(II) acetate

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

 • Step 3: regioselective attack of H2O (a nucleophile) on
   the bridged intermediate opens the three-membered

 • Step 4: reduction of the C-HgOAc bond

 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

 Hydroboration: the addition of borane, BH3, to an
 alkene to form a trialkylborane
             H                                  CH2 CH3
       H B       + 3 CH2 = CH2      CH3 CH2 B
           H                                     CH2 CH3
       Borane                         Triethylborane
                                     (a trialkylborane)

 Borane   dimerizes to diborane, B2H6
                 2 BH 3            B2 H6
                 Borane          Diborane

 • borane forms a stable complex with ethers such as
 • the reagent is used most often as a commercially
   available solution of BH3 in THF

                 : O:                     + -
            2           + B2 H6   2      :O BH3
         Tetrahydrofuran              BH3 • TH F

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

                          +   BH 3         H      H3 C
     H             CH 3
                                           BR2       H
    1-Methylcyclopentene               (Syn addition of BH3)
                                     (R = 2-methylcyclopentyl)

 • concerted regioselective and syn stereoselective
   addition of B and H to the carbon-carbon double bond
                     
                    H B
                                             H   B
      CH 3 CH 2 CH 2 CH= CH 2   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       3 ROH + Na3 BO3
      A trialkyl-                An alcohol

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

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

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

 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
  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-

 • three balanced half-reactions
  CH3 CH= CH2 + H2 O           CH3 CHCH3
    Propene                    2-Propanol

                                    HO OH
  CH3 CH= CH2 + 2 H2 O           CH3 CHCH2 + 2 H+ + 2 e -
    Propene                    1,2-Propane diol

  CH3 CH= CH2 + 2 H+ + 2 e -           CH3 CH2 CH3
    Propene                               Propane

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

                           O O                       OH
           OsO4                     NaHSO3
                                      H2 O
                           O O                          OH
                  A cyclic osmate       cis-1,2-Cyclopentan ediol
                                               (a cis glycol)

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

Oxidation with O3
 Treatmentof an alkene with ozone followed by a
 weak reducing agent cleaves the C=C and forms
 two carbonyl groups in its place
      CH3                                  O            O
  CH3 C= CHCH2 CH 3     1 . O3          CH3 CCH3     + HCCH 2 CH3
                        2 . ( CH3 ) 2 S
   2-Methyl-2-pentene                   Propanone       Propanal
                                        (a ketone)    (an aldehyde)

Oxidation with O3
 • the initial product is a molozonide which rearranges to
   an isomeric ozonide
                             O OO
 CH 3 CH= CH CH 3        CH 3 CH- CHCH3
      2-Butene           A molozonide

                           H    O   H                     O
                             C   C       ( CH3 ) 2 S
                         H3 C       CH 3             CH 3 CH
                              O O
                            An ozonide              Acetaldehyde

Reduction of Alkenes
 Most alkenes react with H2 in the presence of a
 transition metal catalyst to give alkanes
                 + H2
                         25°C, 3 atm
         Cyclohexene               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

Reduction of Alkenes
 Mechanism   of catalytic hydrogenation

Reduction of Alkenes
 • even though addition syn stereoselectivity, some
   product may appear to result from trans addition
             CH3                          CH3                     CH3
                      H2 / Pt
             CH3                           CH3                      CH3
                                   70% to 85%               30% to15%
    1,2-D imethyl-              cis-1,2-D imethyl-    t rans -1,2-D imethyl-
     cyclohexene                   cyclohexan e            cyclohexane

 • reversal of the reaction after the addition of the first
   hydrogen gives an isomeric alkene, etc.
                CH3                                                     CH3
                         H2 / Pt            H
                CH3                                                     CH3
       1,2-D imeth yl-
                                   H    H CH3                 1,6-D imeth yl-
       cyclohexene                                            cyclohexene
DH0 of Hydrogenation
 Reduction   of an alkene to an alkane is
    • there is net conversion of one pi bond to one sigma
 DH0   depends on the degree of substitution
    • the greater the substitution, the lower the value of DH°
    DH0 for a trans alkene is lower than that of an
    isomeric cis alkene
    • a trans alkene is more stable than a cis alkene

DH0 of Hydrogenation
                               S tru ctural          DH°
   N ame                       Formu la       [k J (k cal)/m ol]
 Eth yle ne                    CH2 =CH2          -137 (-32.8)
 Prop en e                     CH3 CH=CH2       -126 (-30.1)
 1-Bu te ne                                     -127 (-30.3)

 cis -2-Bu ten e                                -120 (-28.6)

 t rans -2-Bu te ne                             -115 (-27.6)

 2-M eth yl-2-b uten e                          -113 (-26.9)

 2,3-D ime th yl-2-b ute n e                    -111 (-26.6)

Reaction Stereochemistry
 Inseveral 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
Reaction Stereochemistry
 Wesaw in Section 6.3D that bromine adds to 2-
 butene to give 2,3-dibromobutane
                                                 Br Br
       CH3 CH=CHCH3   +   Br2               CH3 CH-CHCH3
                                CH2 Cl2
          2-Buten e                       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?                    6-64
Bromination of cis-2-Butene
 • reaction of cis-2-butene with bromine forms bridged
   bromonium ions which are meso and identical

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

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

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

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

Oxidation of 2-Butene
 • OsO4 oxidation of cis-2-butene gives meso-2,3-
                                         H                   H
                                  H3 C
                                                 2   3           CH3
                                         C               C
                                     HO          OH
   H       2   3   H      OsO4                                         id entical;
                                 (2S,3R)-2,3-Butanediol                a meso
          C    C
 H3 C               CH3   ROOH                                         compoun d
                                   HO                    OH
                                             2       3
         (achiral)                       C           C
                                    H                        CH3
                                    H3 C

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)
                                       H               CH3
                                H3 C
                                           2       3     H
                                           C       C
                                  HO           OH
   H    2    3   CH3   OsO4                                   a pair of
                              (2S,3S)-2,3-Butaned iol         enantiomers;
        C    C
 H3 C                  ROOH                                   a racemic
                                 HO                    OH     mixture
    trans-2-Buten e
                                       2       3
       (achiral)                       C       C
                                 H                     H
                                 H3 C
                               (2R,3R)-2,3-Butaned iol
  • and oxidation of cis-2-butene gives meso 2,3-
    butanediol (also optically inactive)
Reaction Stereochemistry
 Wehave 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)
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
                                                  redraw as
                                                   a chair
                        Br2                                                  Br
                                           Br   con formation

                                      Br                                          Br
 (R)-4-t ert -Bu tyl-
   cyclohexene                (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

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



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

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                                               CH3

                COOH          (R)-BINAP-Ru                          COOH
                       + H2
                                 press ure
H3 CO                                        H3 CO
                                                       (ee > 98%)
 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
                                H2                 (R)-3,7-D imethyl-6-octen-1-ol
(E)-3,7-D imethyl-2,6-octadien -1-ol   (R)-BIN A P-Ru
            (Geraniol)                                                       OH
                                                   (S)-3,7-D imethyl-6-octen-1-ol

of Alkenes
  End Chapter 6


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