SHARPLESS ASYMMETRIC EPOXIDATION

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SHARPLESS ASYMMETRIC EPOXIDATION
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Chapter 6ALKYL HALIDES NUCLEOPHILIC
SUBSTITUTION AND ELIMINATION
Chapter 6 Alkyl Halides Nucleophilic
Substitution and Elimination
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SOME COMMON PESTICIDES
DDT
Lindane
Kepone
Aldrin
Chlordane
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BOILING POINT TRENDS
Size of hydrocarbon part
Type of halogen
of halogen atoms
For comparison CH3 CH3 bp 89 oC
Chapter 6 Alkyl Halides Nucleophilic
Substitution and Elimination
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RELATIVE SIZE
CH3CH2F
CH3CH2Cl
CH3CH2Br
CH3CH2I
Chapter 6 Alkyl Halides Nucleophilic
Substitution and Elimination
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COMPARISON OF SN1 AND SN2 REACTIONS

• Effect of Nucleophile
• SN2 Strong nucleophiles
• SN1 Irrelevant since nucleophile does not
  participate in rate-determining step
• Effect of Substrate
• SN2 CH3 gt 1o gt 2o (3o is sterically too
  hindered)
• SN1 3o gt 2o (1o or CH3 do not easily form
  cations)
• Effect of Solvent
• SN2 Promoted by polar aprotic solvents or
  non-polar solvents
• SN1 Promoted by polar protic solvents

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COMPARISON OF SN1 AND SN2 REACTIONS

• Leaving Group Effect
• Both SN2 and SN1 require good leaving groups
  higher electronegativity and polarizability weak
  bases
• Kinetics
• SN2 A bimolecular reaction Rate kRXNuc
• SN1 A monomolecular reaction Rate kRX
• Stereochemistry
• SN2 Inversion of configuration
• SN1 Complete or partial racemization
• Rearrangements
• SN2 Rearrangements not possible (because it is
  a concerted process)
• SN1 Rearrangements are common (because the
  intermediate cation often rearranges to a more
  stable cation)

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COMPARISON OF E1 AND E2 REACTIONS

• Effect of the Base
• E2 Strong bases are required
• E1 Irrelevant since base does not participate
  in rate-determining step
• Effect of Substrate
• E2 3o gt 2o gt 1o (CH3 does not undergo E2)
• E1 3o gt 2o (1o do not easily form carbocations
  and usually do not undergo E1 CH3 does not
  undergo E1)
• Effect of Solvent
• E2 Solvent polarity is not very important
• E1 Promoted by polar protic solvents
• Leaving Group Effect
• Both E2 and E1 require good leaving groups
  higher electronegativity and polarizability weak
  bases

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COMPARISON OF E1 AND E2 REACTIONS

• Kinetics
• E2 A bimolecular reaction Rate kRXB-
• E1 A monomolecular reaction Rate kRX
• Stereochemistry
• E2 Requires a coplanar arrangement of C H and
  C Leaving Group bonds. Anti-coplanar is
  preferred but the reaction can also occur
  through a syn-coplanar if the anti-coplanar is
  not achievable
• E1 Occurs via a flat carbocation. No
  particular geometry required.
• Orientation of Elimination
• Both E1 and E2 The predominant product (if more
  than one is possible) is the alkene with most
  substituted double bond (the Saytzeff product).
  This is known as the Saytzeff rule.
• Rearrangements
• E2 Rearrangements not possible (because it is
  a concerted process)
• E1 Rearrangements are common (because the
  intermediate carbocation often rearranges to a
  more stable carbocation)

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SUBSTITUTION VERSUS ELIMINATION

• Strong nucleophile and a methyl substrate SN2
  reaction.
• Strong nucleophile (base) and primary substrate
  (1o) An SN2 reaction is most likely. Some E2
  product might be obtained as well.
• Strong nucleophile (base) and secondary substrate
  (2o) Both SN2 and E2 reactions will occur and a
  mixture of substitution and elimination products
  is likely. Difficult to predict whether SN2 or
  E2 will predominate.
• Strong nucleophile (base) and tertiary substrate
  (3o) An E2 reaction. SN2 does not occur since
  substrate is too sterically hindered.

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SUBSTITUTION VERSUS ELIMINATION

• Weak nucleophile (base) and methyl substrate No
  reaction.
• Weak nucleophile (base) and primary substrate
  (1o) No reaction. EXCEPTION If the primary
  substrate can undergo a concerted process of
  ionization rearrangement to give a more stable
  carbocation (as is the case with neopentyl
  substrates) then the outcome is a mixture of SN1
  and E1.
• Weak nucleophile (base) and secondary substrate
  (2o) Both SN1 and E1 will occur and a mixture
  of substitution and elimination products is
  likely.
• Weak nucleophile (base) and tertiary substrate
  (3o) Both SN1 and E1.

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SUBSTITUTION VERSUS ELIMINATION
ONE GENERAL CONCLUSION With strong nucleophiles
(bases) the reactions occur via bimolecular
mechanism SN2 or E2. With weak nucleophiles
(bases) the reactions occur via monomolecular
mechanism SN1 or E1.
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SUBSTITUTION VERSUS ELIMINATION

• Temperature of the reaction Increase of
  temperature favors elimination. Reason
  Elimination starts with two species (base and
  substrate) but produces three (the conjugate acid
  of the starting base an alkene molecule and the
  leaving group). This increased number of
  molecules (or ions) causes an increase of
  entropy i.e. a positive entropy change (DS).
  This in its turn increases the favorable
  contribution of the TDS-term in the overall Gibbs
  free energy change (because DG DH TDS)
  making the Gibbs free energy change more negative.

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SUBSTITUTION VERSUS ELIMINATION

• Steric bulk of the nucleophile (base) In
  concerted reactions (SN2 or E2) the nucleophile
  (base) participates in the rate-determining step.
  It has to approach closely the molecule and
  attack the electrophilic carbon center (then it
  is a nucleophile) or the proton at an adjacent
  carbon (then it is a base). Approaching closely
  the carbon center is more sensitive to changes of
  size. That is why the share (percentage) of
  elimination increases with an increasing size of
  the nucleophile (base).