The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering and The Caltech Center for Catalysis and Chemical Synthesis, California Institute of Technology, Pasadena, California 91125, USA.
Nat Chem. 2011 Dec 18;4(2):130-3. doi: 10.1038/nchem.1222.
The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.
手性氮杂环(N-杂环)的对映选择性合成是一项重要的化学研究工作,涉及多个学科,包括天然产物的全合成和药物化学。在本文中,我们描述了易于获得的内酰胺的高对映选择性钯催化脱羧烯丙基烷基化反应,形成 3,3-二取代吡咯烷酮、哌啶酮、己内酰胺和结构相关的内酰胺。鉴于季氮杂环在生物活性生物碱和药物中的普遍性,我们设想我们的方法将为这些结构的从头不对称合成提供一种合成途径。作为这些研究的切入点,我们展示了所描述的催化如何提供对映纯的季氮杂环,这些季氮杂环可以捕获以前用于合成 Aspidosperma 生物碱 quebrachamine 和 rhazinilam 的合成中间体,但以前只能通过手性辅助剂方法或外消旋混合物获得。