Selective deprotection of thioacetates (-SAc) in the presence of methyl esters (-COOMe) can be challenging due to the potential hydrolysis of esters under many deprotection conditions. However, several selective methods exist:
1. Raney Nickel Desulfurization
- Reagent: Raney Nickel in ethanol or methanol
- Mechanism: Raney Nickel cleaves the C–S bond, converting thioacetates into free thiols (-SH).
- Selectivity: Methyl esters remain intact as they are not affected under these conditions.
- Example: Used frequently in peptide chemistry for thiol deprotection.
2. Sodium Methoxide (NaOMe) in Methanol (Mild Conditions)
- Reagent: Catalytic or mild NaOMe in MeOH at low temperature (0–5°C)
- Mechanism: Thioacetates undergo transesterification faster than methyl esters.
- Selectivity: Controlled conditions allow selective removal of thioacetates while minimizing ester cleavage.
- Example: Common in sugar and peptide chemistry.
3. Thiolysis with Mercaptoethanol or Dithiothreitol (DTT)
- Reagents:
- Mercaptoethanol (HOCH₂CH₂SH)
- DTT (Dithiothreitol)
- Mechanism: Thiols exchange with the acetate group selectively.
- Selectivity: Methyl esters remain unaffected.
- Example: Used in biochemical applications for selective deprotection.
4. Ammonium Hydroxide in Methanol
- Reagent: NH₄OH in MeOH
- Mechanism: Ammonolysis of thioacetates is significantly faster than ester hydrolysis under controlled conditions.
- Selectivity: Works best when esters are sterically hindered.
5. Zinc and Acetic Acid (Zn/AcOH Reduction)
- Reagent: Zn dust in AcOH (or HCl/THF)
- Mechanism: Selective reduction of thioacetates without affecting esters.
- Selectivity: Methyl esters are stable under these conditions.
Conclusion:
- Best choice: Raney Nickel, NaOMe (mild), or thiolysis with mercaptoethanol are the most selective methods.
- Avoid: Strong bases (e.g., NaOH, KOH) or acids (e.g., HCl, TFA) which can hydrolyze methyl esters.
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