Divergent and Scalable Synthesis of α‑Hydroxy/Keto-β-amino Acid Analogues by the Catalytic Enantioselective Addition of Glyoxylate Cyanohydrin to Imines

The
catalytic enantioselective addition of glyoxylate cyanohydrin
to imines to afford α-keto-β-amino acid equivalents is
reported. Sterically tuned aminobenzothiadiazine catalysts provided
high yields and stereoselectivities (up to 100% yield, 99% ee, >99:1
dr) for both aromatic and aliphatic imines, and the stereodivergent
synthesis of both diastereomers was achieved. The optimal catalytic
system was scalable, even with a low catalyst loading. The resulting
adducts were converted into various chiral building blocks, including
β-amino acid analogues, which are important motifs in medicinal
chemistry, while maintaining a high enantiomeric excess.