α-亚甲基内酰胺的对映选择性1,3-偶极环加成反应构建螺环化合物

Nishiura Yuji, Gonzalez Kevin J, Cusumano Alexander Q, Stoltz Brian M

The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.

Org Lett. 2023 Sep 8;25(35):6469-6473. doi: 10.1021/acs.orglett.3c01978. Epub 2023 Aug 29.

Spirocyclic scaffolds are important motifs due to their potential to bestow favorable effects on pharmaceutical compounds. However, there is a need for efficient methods for their enantioselective construction. We report a method for the asymmetric 1,3-dipolar cycloaddition of diazoacetates or nitrile oxides with α-methylene lactams to prepare chiral spirocyclic heterocycles. The methodology is high yielding (up to 91% yield) and enantioselective (up to 89% ee) for a wide range of -substituents and 6- and 7-membered ring lactam substrates.

螺环骨架是重要的结构基元，因为它们有可能赋予药物化合物良好的效果。然而，需要有高效的方法来进行它们的对映选择性构建。我们报道了一种用重氮乙酸酯或氧化腈与α-亚甲基内酰胺进行不对称1,3-偶极环加成反应来制备手性螺环杂环的方法。该方法对于多种取代基以及6元和7元环内酰胺底物具有高产率（高达91%的产率）和对映选择性（高达89%的对映体过量）。