Aiming at the development of alternative and low-impact synthetic pathways, we herein report the exploitation and the simultaneous employment of different tools to improve the overall sustainability of the Suzuki–Miyaura (SM) cross-coupling process with a circular economy approach. For the first time, in this study, we have combined the use of our biowaste-derived heterogeneous catalyst Pd/PiNe with the biomass-derived reaction medium γ-valerolactone (GVL) proving that an optimised protocol can be obtained for the SM process with a significant substrate scope. The microwave irradiation technology highly enhanced the energy efficiency, allowing the synthesis of different biphenyls and reducing the reaction time. In addition, the good efficiency and selectivity of the SM reaction led to further optimisation of the work-up procedure, minimising the waste generation and the E-factor values associated with the process (3.2–9.4). The optimised conditions tolerated the free carboxylic acid group well, realizing the step-economical preparation of the non-steroidal anti-inflammatory analgesic Fenbufen in quantitative yield. Finally, the scale-up of the MW-assisted process was performed in synergy with the optimisation of the continuous flow protocol and the waste minimised synthesis of Fenbufen was achieved.

中文翻译：

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使用源自生物废物的 Pd/PiNe 多相催化剂，在 GVL 中微波辅助间歇式和连续流 Suzuki-Miyaura 反应

为了开发替代性和低影响的合成途径，我们在此报告了不同工具的开发和同时使用，以通过循环经济方法提高铃木-宫浦（SM）交叉耦合过程的整体可持续性。在这项研究中，我们首次将生物废物衍生的多相催化剂 Pd/PiNe 与生物质衍生的反应介质 γ-戊内酯 (GVL) 结合使用，证明可以为 SM 工艺获得优化的方案一个重要的底物范围。微波辐射技术大大提高了能量效率，可以合成不同的联苯并减少反应时间。此外，SM 反应的良好效率和选择性导致了后处理程序的进一步优化，最大限度地减少了废物的产生和与该过程相关的E因子值 (3.2–9.4)。优化的条件对游离羧酸基团具有良好的耐受性，实现了非甾体抗炎镇痛药芬布芬的一步经济、定量制备。最后，与连续流动方案的优化协同进行了MW辅助工艺的放大，并实现了芬布芬的废物最小化合成。