Catalytic Asymmetric Synthesis of Unprotected β²-Amino Acids

We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β²-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β²-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β²-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.