Rh(I)-Catalyzed Intramolecular Decarbonylation of Thioesters

Area of Science:

• Organic Chemistry
• Organometallic Chemistry
• Catalysis

Background:

• Thioethers are crucial components in pharmaceuticals and materials science.
• Existing methods for thioether synthesis often require harsh conditions or lack functional group tolerance.
• Decarbonylative reactions offer atom-economical pathways but are challenging to develop for C-S bond formation.

Purpose of the Study:

• To develop a novel rhodium-catalyzed decarbonylative thioetherification of thioesters.
• To establish a mild and efficient method for synthesizing diverse thioethers.
• To demonstrate the utility of this method in late-stage functionalization and cross-coupling reactions.

Main Methods:

• Utilizing a rhodium catalyst, specifically [Rh(cod)Cl]2 (2 mol %), for the decarbonylative coupling of thioesters.
• Exploring the reaction scope with various thioesters and aryl halides (chlorides and bromides).
• Investigating the tolerance of the catalytic system to different functional groups.

Main Results:

• Achieved the first rhodium-catalyzed decarbonylative thioetherification of thioesters.
• Demonstrated excellent functional group tolerance, including challenging aryl chlorides and bromides.
• Successfully performed gram-scale synthesis and late-stage derivatization of pharmaceutical compounds.
• Reported orthogonal site-selective cross-couplings via C-S/C-Br cleavage.

Conclusions:

• The developed protocol provides an efficient and versatile route to thioethers.
• This method overcomes limitations of previous decarbonylative strategies and metal catalysts.
• The reaction's applicability in complex molecule synthesis highlights its potential impact in medicinal chemistry and materials science.