Related Experiment Video
Updated: Jul 17, 2026
04:38
Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Operationally simple and efficient workup procedure for TBAF-mediated desilylation: application to halichondrin
Yosuke Kaburagi1, Yoshito Kishi
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Organic Letters
|February 9, 2007
Summary
A new workup method simplifies tetrabutylammonium fluoride (TBAF)-mediated t-butyldimethylsilyl (TBS) deprotection. This efficient process avoids aqueous extraction, making it ideal for multiple TBS deprotections in complex syntheses.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Process Chemistry
Background:
- Tetrabutylammonium fluoride (TBAF) is commonly used for silyl ether deprotection.
- Traditional workup procedures for TBAF-mediated reactions involve tedious aqueous extraction.
- Removal of TBAF and its byproducts can be challenging, complicating multi-step syntheses.
Purpose of the Study:
- To develop a simplified and efficient workup method for TBAF-mediated t-butyldimethylsilyl (TBS) deprotection.
- To eliminate the need for aqueous extraction in TBS deprotection protocols.
- To enhance the applicability of TBS deprotection in complex synthetic sequences.
Main Methods:
- Addition of a sulfonic acid resin and calcium carbonate to the reaction mixture.
- Filtration to remove the resin and calcium carbonate.
- Evaporation of the solvent to isolate the deprotected product.
Main Results:
- Successfully developed an operationally simple and efficient workup for TBAF-mediated TBS deprotection.
- Eliminated the requirement for aqueous-phase extraction, significantly reducing workup time and complexity.
- Demonstrated the method's effectiveness in the synthesis of halichondrin, specifically the transformation of 1a to 3a.
Conclusions:
- The developed workup method offers a streamlined approach to TBS deprotection.
- This protocol is highly amenable to multiple deprotection steps, beneficial for complex molecule synthesis.
- The method provides a practical and efficient alternative to traditional workup procedures in organic synthesis.
Related Concept Videos
01:26Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
Radical substitution reactions can be used to remove functional groups from molecules. The hydrogenolysis of alkyl halides is one such reaction, where the weak Sn–H bond in tributyltin hydride reacts with alkyl halides to form alkanes. Here, the reagent Bu3SnH yields tributyltin halide as a byproduct.
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
01:01Acid Halides to Carboxylic Acids: Hydrolysis
Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
02:26Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.