Development and Scale-Up of a New Sulfone-Based Bismacycle as a Universal Precursor for Bi(V)-Mediated Electrophilic Arylation
Development and Scale-Up of a New Sulfone-Based Bismacycle as a Universal Precursor for Bi(V)-Mediated Electrophilic Arylation
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DOI：
10.1021/acs.oprd.3c00509
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发表时间：
2024-02-07
影响因子：
3.4
通讯作者：
Ball，Liam T.
中科院分区：
文献类型：
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作者：
Fox，Andrew;Ball，Liam T.
铋（V）介导的亲电芳基化反应的范围和实际效用已大大提高了最近开发的用户友好的协议的基础上模块化bismaclitazone试剂。在这里，我们报告了一个新的工作台稳定的bismaclavin溴的可扩展的合成，并证明它可以被用作亲电芳基化的“通用前体”。相对于已建立的相关bismacycles的合成，新的协议受益于改进的步骤和容器的经济性，减少生产时间，并完全消除低温和不需要的溶剂（Et2O和CH2Cl2）。通过使用实验设计开发的耐用、无色谱纯化程序对合成进行补充。我们表明，这一过程是高度可重复的，在100 mmol的规模，两个独立的实验得到61和62%的产率分离的材料。我们预计，这种有效的方法合成一种新的bismaclavin前体将加快（a）更广泛地吸收现有的铋介导的芳基化方法的合成社区和（B）正在进行的努力，以开发新的铋介导的转化。
The scope and practical utility of bismuth(V)-mediated electrophilic arylation have been greatly improved by the recent development of user-friendly protocols based on modular bismacycle reagents. Here, we report the scalable synthesis of a new bench-stable bismacycle bromide and demonstrate that it can be used as a “universal precursor” in electrophilic arylation. Relative to established syntheses of related bismacycles, the new protocol benefits from improved step- and vessel-economy, reduced production time, and the complete elimination of cryogenic temperatures and undesirable solvents (Et2O and CH2Cl2). The synthesis is complemented by a robust, chromatography-free purification procedure that was developed by using design of experiments. We show that this process is highly reproducible at the 100 mmol scale, with two independent experiments giving 61 and 62% yields of isolated material. We anticipate that this efficient method for the synthesis of a new bismacycle precursor will expedite both (a) wider uptake of existing bismuth-mediated arylation methods by the synthetic community and (b) ongoing efforts to develop new bismuth-mediated transformations.