Development and Scale-Up of a New Sulfone-Based Bismacycle as a Universal Precursor for Bi(V)-Mediated Electrophilic Arylation

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.

近期，基于模块化铋环试剂的易于操作协议的发展显著提升了铋(V)-介导的亲电芳基化反应的范畴和实际应用价值。本研究报告了一种可扩展合成的新型台式稳定的铋环溴化物，并证实其可作为亲电芳基化的“通用前体”使用。与现有铋环合成方法相比，该新方法得益于步骤和容器经济的提升、生产时间的缩短，以及低温和不良溶剂（乙二醚和二氯甲烷）的完全消除。该合成过程辅以通过实验设计开发出的稳健、无需色谱纯化的纯化程序。我们展示了该过程在100毫摩尔规模上高度可重复，两个独立的实验分别给出了61%和62%的分离物质产率。我们预期，这种高效合成新型铋环前体的方法将加速（a）合成界对现有铋介导芳基化方法的更广泛采用，以及（b）开发新型铋介导转化的持续努力。