N,O-アセタールと炭素求核剤とのマンニッヒ型反応によるβ-アミノ酸合成

抄録

We have found that a catalytic amount (5 mol%) of Hf(OTf)₄ doped 1 equiv of Me₃SiCl catalyzes Mannich-type reaction of typical carbon nucleophiles, such as ketene silyl acetals and enol silyl ethers with a novel type of N,O-acetals having both an amino group and an ester group, leading to the preparation of non-natural beta-amino acid derivatives in good to excellent yields. In particular, the reaction with an N,O-acetal having an N,N-bis(trimethylsilyl) group directly gave an aspartic acid derivative having an N-underivatized amino group with an usual aqueous workup. In addition, it was successful to synthesize the beta-lactam derivative starting from the prepared beta-amino acid derivative in the presence of a base as a Grignard reagent through intramolecular cyclization.