Reformatsky reaction template

Zinc inserts into ethyl bromoacetate to give an organozinc reagent; it adds to acetone, and acid work-up gives ethyl 3-hydroxy-3-methylbutanoate.

Mechanism step by step

An α-bromo ester, zinc and a ketone give a β-hydroxy ester

1. Organozinc reagent – Zinc inserts into the C–Br bond (a zinc enolate in solution)
2. Addition – The C–Zn bond attacks the ketone carbon; O binds zinc
3. Work-up – Dilute acid protonates the zinc alkoxide

Key points

• Organozinc reagents are less reactive than Grignard reagents, so they do not attack the ester group.
• Aldehydes and ketones both work; dehydration of the product gives an α,β-unsaturated ester.
• The zinc enolate is a dimer in the solid; the addition goes through a six-membered chair transition state.
• Activated zinc (washed, or Zn–Cu) makes the insertion start more easily.

Drawn with 83 atoms, 6 arrows, 9 shapes – every one editable in MolDraw.

Sources

• Kürti & Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier 2005 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020 Textbook