Design of Photoredox-Catalyzed Giese-Type Reaction for the Synthesis of Chiral Quaternary α-Aryl Amino Acid Derivatives via Clayden Rearrangement

Chiral quaternary alpha-aryl amino acids are biologically valued but synthetically challenging building blocks. Herein, we report a strategy for the synthesis of molecular architectures by unifying a photoredox catalytic asymmetric Giese-type reaction and Clayden rearrangement. A new class of chiral Karady-Beckwith dehydroalanines is designed and serves as a versatile handle for the photoredox-mediated highly stereoselective Giese-type reaction with feedstock carboxylic acids and tertiary amines. Subsequent Clayden rearrangement delivers chiral quaternary alpha-aryl amino acid derivatives with high stereoselectivity. The versatile approach offers a reliable source for the assembly of highly demanding chiral building blocks.

Automated summary

This study reports a new method for the synthesis of chiral quaternary alpha-aryl amino acid derivatives. The method involves a photoredox catalytic asymmetric Giese-type reaction and Clayden rearrangement, offering a reliable source for the assembly of highly demanding chiral building blocks.