Stereoconvergent Photo-Biocatalytic Cascade to Optically Enriched Amines from Racemic Carboxylic Acids.

Area of Science:

• Organic Synthesis
• Photocatalysis
• Biocatalysis
• Green Chemistry

Background:

• Enantiomerically pure amines are crucial building blocks in pharmaceuticals.
• Traditional synthesis methods often involve harsh conditions, toxic reagents, or multiple steps.
• Integrating photoredox and biocatalysis offers a promising avenue for sustainable chiral amine synthesis.

Purpose of the Study:

• To develop a synergistic one-pot/two-step cascade synthesis of enantiomerically pure amines.
• To utilize photoredox catalysis and biocatalysis starting from readily available racemic carboxylic acids.
• To achieve high efficiency, stereoselectivity, and sustainability in amine synthesis.

Main Methods:

• Decarboxylative oxidation of racemic carboxylic acids using visible light (blue LED) and a metal-free photocatalyst (sodium anthraquinone-2-sulfonate, SAS).
• Stereoselective reductive amination of *in situ*-generated ketones using transaminases.
• Aqueous reaction medium with minimal organic co-solvents (acetonitrile or DMSO).

Main Results:

• Quantitative conversion (>99%) in the photocatalytic oxidation step.
• High enantiomeric excesses (93%–99.9%) and conversions (>99%) for the two-step synthesis of various chiral amines.
• Successful transformation of NSAIDs (ibuprofen, flurbiprofen, naproxen) into dehomologated chiral amines.
• Scalable synthesis of (R)-1-(naphthalen-1-yl)-ethan-1-amine with 92% yield and >99% ee.
• One-step synthesis of the drug cinacalcet from the synthesized amine with >99% ee and 76% isolated yield.

Conclusions:

• The developed photobiocatalytic cascade strategy provides an efficient and sustainable route to enantiomerically pure amines.
• The method avoids transition metal catalysts and hazardous reagents like hydrogen gas.
• This approach demonstrates potential for synthesizing complex pharmaceutical intermediates and drugs.