Do Minh, Anosike Stella I, Beng Timothy K
Department of Chemistry, Central Washington University Ellensburg WA 98926 USA
RSC Adv. 2023 Aug 29;13(37):25691-25698. doi: 10.1039/d3ra04690g.
An intrinsic goal when designing synthetic methodology is to identify approaches whereby readily accessible precursors are converted into an array of products, which efficiently tap into new 3D-chemical space. In these studies, readily available bicyclic lactam-bromolactones have been interrogated in several fragment growth protocols by utilizing the halogen and lactone motifs as versatile linchpins for strategic construction of C-C, C-N, C-O, and C-S bonds. Diastereospecific C(sp)-C(sp) Kumada coupling of sterically imposing [5,5]-bicyclic lactam-bromolactones with several aryl Grignard reagents, under palladium catalysis, furnishes diarylmethane-tethered lactam-lactones in synthetically attractive yields, stereoinvertive fashion, and with a tolerance for many functional groups. When [5,6]-bicyclic lactam-bromolactones, which are prone to β-hydride elimination are employed, efficient arylation is observed only under Co(acac)-catalyzed conditions. Importantly, these [5,6]-bicyclic lactam-bromolactones undergo retentive arylation, independent of the transition metal catalyst. A base-mediated cascade deconstructive amidation of the [5,6]-bicyclic lactam-bromolactones with primary aliphatic amines proceeds efficiently to afford epoxide-tethered lactam carboxamides, which bear four contiguous stereocenters. Furthermore, an unusual route to homoallylic thioesters has been uncovered through deconstructive contra-thermodynamic thioesterification of the lactam-fused bromolactone precursors.
设计合成方法的一个内在目标是确定一些方法，通过这些方法可将易于获得的前体转化为一系列产物，从而有效地开拓新的三维化学空间。在这些研究中，通过将卤素和内酯基序用作构建C-C、C-N、C-O和C-S键的通用关键结构单元，在几种片段增长方案中对易于获得的双环内酰胺-溴代内酯进行了研究。在钯催化下，空间位阻较大的[5,5]-双环内酰胺-溴代内酯与几种芳基格氏试剂进行非对映选择性C(sp)-C(sp) Kumada偶联反应，以具有合成吸引力的产率、立体反转的方式得到二芳基甲烷连接的内酰胺-内酯，并且对许多官能团具有耐受性。当使用易于发生β-氢消除的[5,6]-双环内酰胺-溴代内酯时，仅在Co(acac)催化的条件下观察到有效的芳基化反应。重要的是，这些[5,6]-双环内酰胺-溴代内酯发生构型保持的芳基化反应，与过渡金属催化剂无关。[5,6]-双环内酰胺-溴代内酯与伯脂肪胺在碱介导下进行级联解构酰胺化反应，有效地得到环氧连接的内酰胺羧酰胺，其带有四个相邻的立体中心。此外，通过对内酰胺稠合的溴代内酯前体进行解构反热力学硫酯化反应，发现了一条通往高烯丙基硫酯的不同寻常的路线。
