Institute of Microbial Chemistry, Tokyo.
Chem Pharm Bull (Tokyo). 2021;69(12):1160-1169. doi: 10.1248/cpb.c21-00750.
Isoxazolidin-5-ones have been regarded as β-amino acid surrogates owing to their labile N-O bond. While many efforts have been devoted to the catalytic enantioselective synthesis of the core of this heterocycle, its further transformation has been less explored, especially in the context of catalysis. This review summarizes the author's research on the development of catalytic reactions using isoxazolidin-5-ones as substrates. Asymmetric catalysis has proven effective for C-C bond formation at the carbonyl α-carbon. Catalytic asymmetric allylation and direct Mannich-type reactions have been developed. Further, the resulting products have been readily converted into the corresponding quaternary β-amino acids. Moreover, isoxazolidin-5-ones have been identified as alkyl nitrene precursors in the presence of a suitable metal catalyst. The generated metallonitrene undergoes either the electrophilic amination of the aromatic ring or aliphatic C-H insertion, affording a series of cyclic β-amino acids. A remarkable difference in chemoselectivity between rhodium and copper alkyl nitrenes has also been demonstrated, highlighting the unique nature of the underexplored reactive intermediates. The various linear and cyclic β-amino acids obtained through the study are likely to find great utility in a broad range of chemical sciences.
异恶唑啉-5-酮因其不稳定的 N-O 键而被视为β-氨基酸类似物。尽管人们已经投入了大量精力来催化对映选择性合成该杂环的核心，但对其进一步转化的研究却较少，尤其是在催化方面。本文总结了作者在以异恶唑啉-5-酮为底物的催化反应开发方面的研究。不对称催化在羰基α-碳上形成 C-C 键方面非常有效。已经开发了催化不对称烯丙基化和直接曼尼希型反应。此外，所得产物很容易转化为相应的季铵β-氨基酸。此外，在合适的金属催化剂存在下，异恶唑啉-5-酮被鉴定为烷基氮烯前体。生成的金属氮烯经历芳环的亲电氨基化或脂肪族 C-H 插入，得到一系列环状β-氨基酸。还证明了铑和铜烷基氮烯之间的化学选择性有显著差异，突出了反应性中间体这一未充分研究领域的独特性质。通过该研究获得的各种线性和环状β-氨基酸很可能在广泛的化学科学中得到广泛应用。
