In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the phenyl ring. Today, after more than a decade, the difficulty in their large-scale preparation is still a problem, that often outweighs the corresponding derivatives to becoming clinical candidates. Here, we report a practical general reaction that gives bicyclo[1.1.1]pentanes on mg- to kg-quantities using just light. No additional additives or catalysts are needed. Using this strategy, we have prepared >300 functionalized bicyclo[1.1.1]pentanes on a (multi)gram scale. So far, this is the most general and practical approach to bicyclo[1.1.1]pentanes. Many of these molecules, which were previously commercialized, are already being used in drug discovery by pharmaceutical companies Gilead Sciences, Hoffman-La Roche, Idorsia, Merck, Janssen Pharm., etc. This work should ease the transition of bicyclo[1.1.1]pentane-containing bioactive compounds to clinical candidates, and subsequently to drugs.

中文翻译：

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最大的双环[1.1.1]戊烷库，用于光药物发现

2012年，双环[1.1.1]戊烷被证明是苯环的生物等排体。十多年后的今天，大规模制备的难度仍然是一个问题，这往往比相应的衍生物成为临床候选者更重要。在这里，我们报告了一种实用的一般反应，仅使用光即可产生毫克至公斤量的双环[1.1.1]戊烷。不需要额外的添加剂或催化剂。使用这种策略，我们在（多）克规模上制备了 >300 种官能化双环[1.1.1]戊烷。到目前为止，这是最通用和实用的双环[1.1.1]戊烷方法。其中许多分子此前已商业化，现已被吉利德科学公司、霍夫曼罗氏公司、Idorsia、默克公司、杨森制药公司等制药公司用于药物发现。