Spieß Philipp, Brześkiewicz Jakub, Meyrelles Ricardo, Just David, Maulide Nuno
Institute of Organic Chemistry, University of Vienna, Währingerstraße 38, 1090, Vienna, Austria.
Angew Chem Int Ed Engl. 2024 May 6;63(19):e202318304. doi: 10.1002/anie.202318304. Epub 2024 Mar 19.
The nature of protecting group chemistry necessitates a deprotection step to restore the initially blocked functionality prior to further transformation. As this aspect of protecting group manipulation inevitably adds to the step count of any synthetic sequence, the development of methods enabling simultaneous deprotection and functionalization ("deprotective functionalization"-distinct from "deprotection followed by functionalization") is appealing, as it has the potential to improve efficiency and streamline synthetic routes. Herein, we report a deprotective functionalization of the newly introduced Nms-amides guided by density functional theory (DFT) analysis, which exploits the inherent Nms reactivity. Mechanistic studies further substantiate and help rationalize the exquisite reactivity of Nms-amides, as other commonly used protecting groups are shown not to exhibit the same reactivity patterns. The practicality of this approach was ultimately demonstrated in selected case studies.
保护基团化学的性质决定了在进一步转化之前需要进行脱保护步骤以恢复最初被保护的官能团。由于保护基团操作的这一方面不可避免地增加了任何合成序列的步骤数，因此开发能够同时进行脱保护和官能化的方法（“脱保护官能化”——不同于“先脱保护后官能化”）很有吸引力，因为它有可能提高效率并简化合成路线。在此，我们报告了一种在密度泛函理论（DFT）分析指导下对新引入的Nms-酰胺进行的脱保护官能化反应，该反应利用了Nms的固有反应性。机理研究进一步证实并有助于解释Nms-酰胺的独特反应性，因为其他常用的保护基团并未表现出相同的反应模式。这种方法的实用性最终在选定的案例研究中得到了证明。
