Up-Scale Pseudotelescopic Photoinduced Arndt-Eistert α-Amino Acid Homologation in a Flow Reactor Cascade

We present an efficient, pseudotelescopic synthesis of β-amino acids via the Arndt-Eistert homologation of α-amino acids using a flow reactor cascade. Our system utilizes flow generation of diazomethane, diazoketone preparation, and subsequent photoflow Wolff rearrangement without intermediate isolation. This innovative method enhances safety, improves scalability, and allows access to substrates previously unavailable in thermal/catalytic Wolff rearrangement. Notably, the reaction conditions are mild, which lead to high yields and excellent purity, thereby expanding the synthetic utility of the Wolff rearrangement. This work unveils a versatile and scalable approach to β-amino acid synthesis, opening new synthetic and medicinal chemistry avenues.