Universal Metal-Free Deborylation-Deuteration via Redox-Decoupled Tandem Flow Electrosynthesis

Area of Science:

• Organic Chemistry
• Electrochemistry
• Synthetic Methodology

Background:

• Flow electrochemical synthesis offers potential for producing valuable compounds like deuterated molecules.
• Limitations include inefficient half-reactions and flow cell design constraints, hindering broader application.
• Developing efficient and versatile deuteration methods remains a key challenge in organic synthesis.

Purpose of the Study:

• To develop a novel, efficient, and broadly applicable method for metal-free deuteration of organoboron compounds using flow electrochemistry.
• To overcome limitations of conventional flow cells by employing a redox-decoupled strategy.
• To demonstrate the synthesis of deuterated drug molecules and assess the platform's scalability and durability.

Main Methods:

• A redox-decoupled strategy was implemented in a single-cell tandem flow reactor.
• Sequential electrochemical steps were used to separate deborylation and deuteration processes.
• Deuteration was achieved using deuterium oxide (D2O) as the deuterium source.

Main Results:

• The method enabled universal, metal-free deuteration of over 100 diverse organoboron derivatives (boronic acids, esters, borates).
• High yields, excellent deuterium incorporation, and tolerance to labile functional groups were achieved.
• The system demonstrated industrial-grade durability (>1200 h continuous operation) and enabled scalable synthesis of deuterated drug d-mexiletine.

Conclusions:

• The developed strategy significantly expands the scope and efficiency of flow electrochemistry for deuteration.
• This approach provides a green, economic, and efficient pathway for synthesizing deuterated compounds.
• The platform facilitates the unprotected and scalable synthesis of complex deuterated molecules, including pharmaceuticals.