B₂Pin₂-enabled reductive thioesterification of aryl triflates with thiocarbonates

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Catalysis

Background:

• Aryl thioesters are important functional groups in pharmaceuticals and materials science.
• Current synthetic methods often rely on stoichiometric metal reductants like zinc, which can be inefficient and environmentally burdensome.
• Developing catalytic and scalable methods for aryl thioester synthesis is crucial for industrial applications.

Purpose of the Study:

• To develop a novel B2Pin2-mediated reductive coupling for aryl thioester synthesis.
• To demonstrate the superiority of this method over existing zinc-based protocols, particularly for challenging substrates.
• To explore the potential of this methodology for the synthesis of pharmaceutical intermediates and establish a foundation for broader C(sp2)-C(sp2) couplings.

Main Methods:

• Reductive coupling of aryl triflates with thiocarbonates mediated by bis(pinacolato)diboron (B2Pin2).
• Utilizing earth-abundant metals as catalysts or mediators.
• Optimization of reaction conditions for mild and efficient thioesterification.

Main Results:

• Successful synthesis of aryl thioesters via B2Pin2-mediated reductive coupling.
• Demonstrated improved efficiency for pyridyl and sterically hindered aryl triflates compared to Zn-based methods.
• Validated the utility of the method for thioesterification of pharmaceutical compounds like apixaban, ezetimibe, and ethinyl estradiol derivatives under mild conditions.

Conclusions:

• The B2Pin2-mediated reductive coupling offers a robust and versatile method for aryl thioester synthesis.
• This methodology presents a scalable and sustainable alternative to traditional reductants, utilizing earth-abundant resources.
• The findings pave the way for broader applications of B2Pin2 in reductive C(sp2)-C(sp2) couplings.