Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, College of Chemistry, Northeast Normal University, Changchun 130024, China.
J Org Chem. 2020 Oct 2;85(19):12408-12417. doi: 10.1021/acs.joc.0c01643. Epub 2020 Sep 16.
In view of the importance of both fluorinated synthons and homoenolate equivalents, synthetic application of difluorocyclopropanols is desired but remains challenging due to their thermodynamic instability. Herein, we use siloxydifluorocyclopropanes as difluorocyclopropanol precursors to carry out new Cu-catalyzed ring-opening defluorinative alkylation. With α-bromo carboxylic esters as coupling partners, the reaction affords γ-fluoro-δ-ketoesters a Cu/Cu catalytic cycle. Interestingly, by the use of α-bromoamides, the ring-opening defluorinative alkylation is followed by an additional intramolecular C-N oxidative coupling to deliver a lactam intermediate, which further undergoes defluorination, hydrolysis, ring opening, and dehydration cascade a Cu/Cu/Cu catalytic pathway, leading to γ,δ-diketonitriles as the final products.
鉴于氟代合成子和偕同烯醇化物等价物的重要性，人们希望将二氟环丙醇应用于合成，但由于其热力学不稳定性，这仍然具有挑战性。在此，我们使用硅氧二氟环丙烷作为二氟环丙醇前体，进行新的 Cu 催化开环脱氟烷基化反应。以α-溴代羧酸酯作为偶联试剂，该反应提供γ-氟-δ-酮酸酯，涉及 Cu/Cu 催化循环。有趣的是，通过使用α-溴代酰胺，开环脱氟烷基化反应后会进一步进行分子内 C-N 氧化偶联，得到内酰胺中间体，其进一步经历脱氟、水解、开环和脱水级联反应，涉及 Cu/Cu/Cu 催化途径，生成γ,δ-二酮腈作为最终产物。
