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How to deprotect Trimethylsilylacetylene?

May 7,2026

Trimethylsilylacetylene is a widely used terminal alkyne protecting agent in organic synthesis, commonly used in Sonogashira coupling reactions, heterocyclic synthesis, and the preparation of pharmaceutical intermediates to protect the active terminal alkyne group and avoid side reactions during synthesis. Its trimethylsilylacetyl (TMS) protecting group can be efficiently removed under mild conditions. The most common method is treatment with tetrabutylammonium fluoride (TBAF) in a neutral or weakly alkaline environment. This method achieves rapid and clean deprotection without damaging other sensitive functional groups. In addition, mild inorganic bases, such as potassium carbonate, sodium hydroxide alcoholic solutions, or weakly acidic conditions, can also achieve TMS deprotection. This method is suitable for substrates intolerant to fluoride reagents, and the entire process can be carried out at room temperature with simple post-processing and high reaction yields.

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