Rh-Catalyzed Solvent-Controlled Carboamidation for Divergent Synthesis of α-and β-Amino Acids

Divergent synthesis aims to build different molecules from the same starting materials using small changes in reaction conditions. It is a valuable yet challenging goal in synthesis. Here, we share how simply switching between two solvents — HFIP and THF — can steer a rhodium-catalyzed reaction toward making either α‑ or β‑amino acids from the same starting materials. This method works with many functional groups, avoids protecting‑group steps, and has been used to quickly prepare bioactive compounds such as N‑Ac sitagliptin. DFT calculations show that the two reaction paths have different energy barriers, which explains why the solvent choice controls the product structure.