Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light

Area of Science:

• Organic Chemistry
• Photochemistry
• Biochemistry

Background:

• Dihydronicotinamides, such as NADH, are crucial biological reductants.
• Generating alkyl radicals often requires auxiliary photocatalysts.
• Reductive decarboxylation of esters is a known chemical transformation.

Purpose of the Study:

• To develop a photocatalyst-free method for generating alkyl radicals using photoexcited dihydronicotinamides.
• To demonstrate the application of this method in aliphatic photocoupling reactions.
• To explore the utility of this reaction in DNA functionalization.

Main Methods:

• Utilizing photoexcited dihydronicotinamides (e.g., NADH) to induce reductive decarboxylation of redox-active esters.
• Performing aliphatic photocoupling between carboxylate derivatives and electron-poor olefins under visible light.
• Investigating the reaction's tolerance to water, air, and other carboxylic acids.
• Applying the methodology for the functionalization of DNA.

Main Results:

• Photoexcited dihydronicotinamides efficiently generate alkyl radicals without external photocatalysts.
• The developed photocoupling reaction exhibits high rates, even under dilute conditions.
• The reaction demonstrates significant tolerance to water and air.
• The method is orthogonal to other carboxylic acids and successfully functionalizes DNA.

Conclusions:

• Visible light-mediated reductive decarboxylation using NADH and analogues offers a sustainable route to alkyl radicals.
• This approach enables efficient and orthogonal aliphatic photocoupling with broad substrate scope.
• The methodology presents a valuable tool for DNA functionalization and other synthetic applications.