Example: brevetoxin synthesis

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Example brevetoxin synthesis
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Elimination reactions

• A problem that often occurs in substitution
  reactions is elimination

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E1-elimination
n k substrate

• The mechanism is similar to that of the SN1
  reaction the first step is formation of the
  carbocation via heterolytic cleavage

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Substitution vs elimination

• Elimination and substitution reactions are
  competing processes in this case, the tertiary
  carbocation gives
• in the presence of a strong base (EtO) primarily
  elimination
• if there is only a nucleophile present mainly
  substitution

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The Saytzeff elimination

• Saytzeff elimination in the elimination process,
  formation of the most substituted double bond is
  favored

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Explanation

• In the transition state for elimination, the
  increased stability of the most substituted
  double bond is already felt so that there is a
  lower energy barrier for elimination of Ha

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Problems

• 6.20 Predict the products of the E1/SN1
  reactions of the following molecules in water

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The E2 elimination
n k substrate base

• As in the SN2 reaction, the rate is dependent on
  the concentration of both reaction partners

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E2 vs SN2

• There exists an analogous similarity between the
  E2 and SN2 reaction strong nucleophiles favor
  substitution, while strong bases favor elimination

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Steric bulk favors elimination

• We already saw that SN2 substitution on a
  tertiary carbon is not possible, therefore E2
  elimination will prevail (beside E1 elimination)

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Other examples

• Note that at a primary carbon atom, only SN2 and
  no SN1 substitution is possible

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Stereochemistry of the E2 rxn

• Possible orientations of the proton that
  eliminates and the leaving group

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E2 and the anti-conformation

• The E2 elimination takes place in a single
  process in the anti-conformation proton
  abstraction, double bond formation and cleavage
  of the CL bond occur simultaneously

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Resemblance to SN2

• The mechanism is more or less analogous to the
  SN2 substitution
• The process is also called anti-elimination or
  antiperiplanar elimination

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How to visualize this aspect ?

• What are the products of E2 elimination of both
  diastereomers ?

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The answer..
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Regiochemistry

• Generally, formation of the most substituted
  double bond is favored
• Note the occurrence of E- and Z-isomers

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Saytzeff vs Hofmann elimination
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Influence of the base
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Effect of the leaving group

• Especially quarternary ammonium leaving groups
  favor the Hofmann product

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The E1cB elimination

• The E1cB reaction resembles the SN2 reaction,
  with the difference that there is an anion formed
  prior to the loss of the leaving group

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The three eliminations

• E1cB the proton is removed first, an anion is
  formed
• E1 the leaving group departs first, a cation is
  formed
• E2 all processes occur at the same time

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Example of an E1cB reaction

• This reaction is possible if there is a group
  present that can stabilize the negative charge

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Stability of anions

• The more substituted the carbanion, the less
  stable it is this is a result of the inductively
  electron donating alkyl groups

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The synthetic outlook
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Formation of CC-bonds

• Formation of CC-bonds is a synthetically
  important reaction

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Summary
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Summary (2)
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Problems

• Make problems 6.30, 6.31, 6.32, 6.38, 6.53,
  6.54, 6.56, 6.59