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Directed Metalation and Highly Selective Synthesis with Alkyl Lithium Reagents

Directed Metalation and Highly Selective Synthesis with Alkyl Lithium Reagents

Alkyl lithium (e.g. n-BuLi, s-BuLi) combines strong nucleophilicity and basicity, key for advanced organic synthesis. Its directed ortho-metalation (DoM) enables highly regioselective functionalization of aromatic rings.

Key Properties

  • Strong basicity: deprotonation and carbanion formation;
  • Directed metalation: ortho-selectivity via directing groups;
  • Low-temperature activity: with ammonia or dry-ice baths for selectivity.

Applications

In pharmaceutical intermediates, alkyl lithium is used for aryl lithiation, halogen-lithium exchange and polymerization initiation, improving purity and yield.

Safety and Storage

Alkyl lithium is pyrophoric with water and air; store and use under inert atmosphere and low temperature with dedicated fire safety.

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