Palladium Nanoparticle-Catalyzed Stereoselective Domino Synthesis of 3‑Allylidene-2(3H)‑oxindoles and 3‑Allylidene-2(3H)‑benzofuranones

A single-step, stereoselective protocol for the synthesis of unsymmetrically substituted (E)-3-allylideneoxindole and (E)-3-allylidenebenzofuran from readily accessible starting materials using palladium binaphthyl nanoparticles (Pd-BNPs) has been developed. Pd-BNP showing a wide range of functional group tolerance and an immense array of substrate scope have been explored with the successful synthesis of the drug molecule “tubulin polymerization inhibitor” free from trace metal impurities. The model reaction is extended to a gram-scale synthesis, and one of the products is utilized for derivatization. The Pd-BNP has been recycled up to 5 catalytic cycles without any loss in reaction yields and particle size of nanoparticles.

本研究开发了一种单步立体选择性合成方案，可从易得起始原料出发，以联萘钯纳米颗粒（Pd-BNPs）为催化剂，合成不对称取代(E)-3-亚烯丙基氧化吲哚与(E)-3-亚烯丙基苯并呋喃。该Pd-BNP催化剂展现出优异的官能团耐受性与宽泛的底物适用范围，已成功用于合成不含痕量金属杂质的“微管蛋白聚合抑制剂”药物分子。该模型反应可拓展至克级规模合成，其中一种产物可用于衍生化反应。Pd-BNP可循环使用至多5个催化循环，反应收率与纳米颗粒粒径均无明显损失。