Retrosynthesis Introduction Notes

Retrosynthesis Concepts

  • Retrosynthesis (RS): Working backward to determine how to synthesize a target molecule.
  • Retrosynthetic Arrow: Represents the backward process of retrosynthesis.
  • Target Molecule (TM): The desired molecule to be synthesized.
  • Disconnection Line: Indicates the breaking of a bond in retrosynthesis.
  • Synthons: Idealized fragments resulting from disconnection, often charged.
  • Synthetic Equivalents: Real, usable reagents that correspond to synthons.
  • “Redraw” Symbol: Used to indicate a simple transformation (not covered in detail).
  • Forward Synthesis (FS): The actual, step-by-step synthesis from available starting materials.

Core Procedures

  • Disconnections: Breaking bonds to simplify the target molecule.
  • Functional Group Interconversions (FGIs): Transforming one functional group into another.
  • Functional Group Additions (FGAs): Adding functional groups to the molecule.

Disconnections

  • Formal dissection of the target molecule into fragments.
  • Usually made at functional groups.
  • Lead to synthons (imaginary molecules).

Deciding Between Disconnections

  • Assess Synthetic Equivalents: Determine if suitable synthetic equivalents exist for both synthons.
  • Discard Options: Eliminate options lacking viable synthetic equivalents.
  • Consider Polarity: Ensure the synthons have appropriate nucleophilic (-) or electrophilic (+) character.

Forward Synthesis

  • Plan Forward Syntheses: Use organic chemistry knowledge to propose a forward synthesis for each disconnection.
  • Evaluate Feasibility: Check for potential problems like selectivity issues or functional group instability.

General Principles

  • Work systematically and methodically.
  • Identify nucleophiles and electrophiles.
  • Ensure the total atom count remains constant during disconnections.
  • Multiple rounds of disconnections are often needed.