Saito Hayate, Shimokawa Jun, Yorimitsu Hideki
Department of Chemistry, Graduate School of Science, Kyoto University Sakyo-ku Kyoto 606-8502 Japan
Chem Sci. 2021 Jun 8;12(27):9546-9555. doi: 10.1039/d1sc02083h. eCollection 2021 Jul 14.
Organic synthesis is performed based on precise choices of functional groups and reactions employed. In a multistep synthesis, an ideal functional group should be compatible with various reaction conditions and unaltered until it is subjected to a selective conversion. The current study was set out to search for a silicon functionality that meets these criteria. Here we have established a new silicon-based synthetic methodology centred on a bulky 7-membered dialkoxysilyl group (2,4,4,7,7-pentamethyl-1,3,2-dioxasilepan-2-yl) that uniquely has both stability and on-demand reactivity. The exceptional stability of this functional group was corroborated by both experimental and computational studies which demonstrated that key factors for its stability were a 7-membered structure and steric hindrance. In turn, the dioxasilepanyl group was found to become reactive and to be easily transformed in the presence of appropriate activators. Combined with the development of easy and robust methods to introduce the dioxasilepanyl group onto aryl rings, these findings have allowed a shorter and more efficient synthesis of a bioactive molecule, thus demonstrating the potential utility of the easily accessible dioxasilepanyl group in organic synthesis.
有机合成是基于对官能团和所采用反应的精确选择来进行的。在多步合成中，理想的官能团应与各种反应条件兼容，并且在进行选择性转化之前保持不变。当前的研究旨在寻找一种符合这些标准的硅官能团。在此，我们建立了一种新的基于硅的合成方法，该方法以一个庞大的七元二烷氧基硅基（2,4,4,7,7 - 五甲基 - 1,3,2 - 二氧杂硅庚烷 - 2 - 基）为中心，该基团独特地兼具稳定性和按需反应性。实验和计算研究均证实了该官能团的卓越稳定性，表明其稳定性的关键因素是七元结构和空间位阻。反过来，发现二氧杂硅庚烷基团在存在适当活化剂的情况下会变得具有反应性并且易于转化。结合将二氧杂硅庚烷基团引入芳环的简便且可靠方法的开发，这些发现使得生物活性分子的合成更短且更高效，从而证明了易于获得的二氧杂硅庚烷基团在有机合成中的潜在用途。
