Synthese des Grundgerüsts der Sungeidine
Zusammenfassung der Projektergebnisse
2 Summary of research activities 2.1 Sungeidines The synthesis of sungeidine natural products relied on late-stage Buchwald–Hartwig type C–C coupling of an eastern with a western fragment as well as an optional arylation to access the core of the sungeidine natural product family (10). For that purpose, the synthesis of a decorated anthracenyl halide 11 as well as a secondary amine such as 12 or amide were planned (Scheme 3). Scheme 3: Late stage coupling and arylation to access the core of sungeidines 10. Strategies investigated and reported herein did not enable convenient access to the core of sungeidine natural products 1, but will aid in the future explorations of these novel natural products. For the synthesis of the western anthracenyl motif 11, the strategies described herein focused on the early installation of anthracenyl core 13 (Figure 1), which was thought to be a viable advanced intermediate. Different reactive sites of the molecule were investigated in detail, but none gave access to the desired sulfur containing building block 11. Peri strain was identified as a key reason that prevented selective functionalization of 13 along with conjugation of the ester functionality with the anthracenyl’s π-system. For the synthesis of eastern fragment 12, an additional intramolecular approach was investigated, which presumably failed due to inherent steric congestion of key intermediate 14. 1 Figure 1: Key fragments and advanced intermediates for the construction of the core of sungeidine natural products 10. 2.2 Oxopyrrolium cycloadditions The Diels–Alder reaction of in situ generated oxopyrrolium ions 2 with electron-rich dienes like silyl enol ethers was a promising approach for the construction of the eastern fragment (i.e., 12), but failed due to instability of the substrates tested under the examined conditions. Although silyl enol ethers were unsuccessful substrates, dienes such as 15 were successful cycloaddition partners for the construction of annulation products 16 (Scheme 4). Moreover, the process was rendered enantioselective using a combination of CuII and chiral BOX ligands (ee’s up to 29%), but some optimization still remains to be done. Annulation product 16 was primarily formed and could be epimerized to give epi-16 in a Lewis acidmediated process. Scheme 4: Diels–Alder reaction of oxopyrrolium ions 18 with dienes.
