Lecture Notes: Nucleophilic Conditions and Stereochemistry

Key Concepts

• Nucleophilic Conditions and Acidic Workup
  • Reactions involve nucleophilic attack followed by acidic workup.
  • Nucleophilic attack is essentially an SN2 step, where nucleophiles add opposite to the side of the leaving group.

Example Reactions

Reaction 1: NACN with Epoxide

• Reactants: NaCN (sodium cyanide) - Na⁺ and CN⁻ as nucleophile
• Epoxide Consideration:
  • Two epoxide carbons: focus on the less substituted carbon.
  • The less substituted carbon is identified by its methyl group and an implied hydrogen.
• Stereochemistry:
  • Nucleophile (CN⁻) adds from the plane, opposite the leaving group (epoxide).
  • CN group is drawn pointing down as epoxide was initially up.
  • Result: Methyl group shifts slightly upwards.
• Final Step: Protonation of oxygen.

Reaction 2: NH2⁻ with Epoxide

• Reactants: NH2⁻ as the nucleophile.
• Epoxide Structure:
  • Epoxide is shown with wedges and dashes.
  • Identify less substituted carbon to add nucleophile.
  • Consider stereochemistry with epoxide pointed towards you; the phenyl group down and methyl optionally placed back.
• Stereochemistry:
  • NH2⁻ is added from the opposite side of the epoxide.
  • After opening, chain forms with NH2 back and methyl group as per stereochemistry choice.
  • Final product: Protonated to form BOH.

Reaction 3: Sodium Hydroxide (OH⁻) with Symmetric Epoxide

• Reactants: NaOH, OH⁻ as nucleophile.
• Epoxide Consideration:
  • Symmetric molecule; either side is viable due to equal substitution.
• Stereochemistry:
  • OH⁻ adds opposite to the leaving group.
  • Result: Formation of an anti-diol with OH groups on opposite planes.

Important Notes

• Stereochemistry:
  • Understanding 3D structures and stereochemical outcomes is crucial.
  • Considerations of R/S configurations can confirm molecule identity.
• Reactivity:
  • Nucleophile positioning relative to leaving groups dictates stereochemical outcome.
• Experimentation:
  • Students are encouraged to practice drawing mechanisms and verifying stereochemical outcomes with R/S configurations.