Catalytic Asymmetric Synthesis of Unprotected β2-Amino Acids

J Am Chem Soc. 2021 Mar 10;143(9):3312-3317. doi: 10.1021/jacs.1c00249. Epub 2021 Mar 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't