Abstract

A simple and effective one-pot cascade procedure to provide 2,4-disubstituted thiazoles and symmetrical dimeric thiazoles directly from commercially available acid chlorides and β-azido disulfides in moderate to high yields is described. This cascade transformation consists of disulfide cleavage, thiocarbonylation, phosphine-promoted intramolecular Staudinger/aza-Wittig reaction and dehydrogenation to form the corresponding thiazoles. The application of our methodology is demonstrated by the concise two-step synthesis of anticancer agent SMART and its O-linked dimer in 64% and 46% overall yields, respectively. This directed cascade reaction could be easily handled and scaled up under mild conditions, enabling the construction of focused thiazole derivatives for further pharmacological evaluation.

A simple and effective one-pot cascade procedure to provide 2,4-disubstituted thiazoles and symmetrical dimeric thiazoles directly from commercially available acid chlorides and β-azido disulfides in moderate to high yields is described. This cascade transformation consists of disulfide cleavage, thiocarbonylation, phosphine-promoted intramolecular Staudinger/aza-Wittig reaction and dehydrogenation to form the corresponding thiazoles. The application of our methodology is demonstrated by the concise two-step synthesis of anticancer agent SMART and its O-linked dimer in 64% and 46% overall yields, respectively. This directed cascade reaction could be easily handled and scaled up under mild conditions, enabling the construction of focused thiazole derivatives for further pharmacological evaluation.

中文翻译：

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直接由酰基氯和β-叠氮基二硫化物直接高效合成一锅2,4-二取代的噻唑和二聚噻唑

摘要

描述了一种简单且有效的一锅级联方法，该方法可直接从市售酰氯和β-叠氮基二硫化物以中等至高收率提供2,4-二取代的噻唑和对称的二聚噻唑。该级联转化由二硫键裂解，硫代羰基化，膦促进的分子内斯托丁格/氮杂-维蒂希反应和脱氢反应形成相应的噻唑组成。我们的方法的应用通过抗癌剂SMART及其O联二聚体的简洁的两步合成法得以证明，其总收率分别为64％和46％。这种直接的级联反应可以在温和的条件下轻松处理和扩大规模，从而能够构建聚焦的噻唑衍生物，以进行进一步的药理评估。

描述了一种简单且有效的一锅级联方法，该方法可直接从市售酰氯和β-叠氮基二硫化物以中等至高收率提供2,4-二取代的噻唑和对称的二聚噻唑。该级联转化由二硫键裂解，硫代羰基化，膦促进的分子内斯托丁格/氮杂-维蒂希反应和脱氢反应形成相应的噻唑组成。我们的方法的应用通过抗癌剂SMART及其O联二聚体的简洁的两步合成法得以证明，其总收率分别为64％和46％。这种直接的级联反应可以在温和的条件下轻松处理和扩大规模，从而能够构建聚焦的噻唑衍生物，以进行进一步的药理评估。