Nature-Inspired Radical Pyridoxal-Mediated C-C Bond Formation.

Area of Science:

• Organic Chemistry
• Biochemistry
• Catalysis

Background:

• Pyridoxal-5'-phosphate (PLP) is a versatile cofactor enabling numerous chemical transformations.
• Current PLP chemistry primarily relies on two-electron processes, limiting its application in synthesizing tetrasubstituted carbon centers.
• Accessing radical pathways is crucial for expanding PLP-catalyzed reactions.

Purpose of the Study:

• To demonstrate the generation and utilization of a radical PLP-based intermediate.
• To explore C-C bond-forming reactions using this radical intermediate.
• To broaden the scope of PLP chemistry through single-electron oxidation pathways.

Main Methods:

• Generation of a quinonoid intermediate.
• Single-electron oxidation of the quinonoid intermediate using a suitable oxidant.
• Application of the resulting semiquinone radical in C-C bond-forming reactions.

Main Results:

• Successfully accessed a radical PLP-based intermediate.
• Demonstrated C-C bond formation using the semiquinone radical.
• Synthesized α-tertiary amino acids and esters via the radical pathway.
• Showcased substrate scope including diverse amine classes and small molecule coupling partners.

Conclusions:

• The study establishes a novel radical reaction pathway for PLP chemistry.
• This approach overcomes limitations of traditional two-electron processes for C-C bond formation.
• The versatile semiquinone radical intermediate holds potential for developing new synthetic methodologies.