State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, 361005, Xiamen, China.
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 300071, Tianjin, China.
Nat Commun. 2019 Jul 19;10(1):3234. doi: 10.1038/s41467-019-11245-2.
Rearrangement reactions have attracted considerable interest over the past decades due to their high bond-forming efficiency and atom economy in the construction of complex organic architectures. In contrast to the well-established [3,3]-rearrangement, [1,3] O-to-C rearrangement has been far less vigorously investigated, and stereospecific [1,3]-rearrangement is extremely rare. Here, we report a metal-free intramolecular hydroalkoxylation/[1,3]-rearrangement, leading to the practical and atom-economical assembly of various valuable medium-sized lactams with wide substrate scope and excellent diastereoselectivity. Moreover, such an asymmetric cascade cyclization has also been realized by chiral Brønsted acid-catalyzed kinetic resolution. In addition, biological tests reveal that some of these medium-sized lactams displayed their bioactivity as antitumor agents against melanoma cells, esophageal cancer cells and breast cancer cells. A mechanistic rationale for the reaction is further supported by control experiments and theoretical calculations.
在过去的几十年中，由于在构建复杂有机结构时具有高效的成键效率和原子经济性，重排反应引起了相当大的关注。与成熟的[3,3]-重排相比，[1,3]O 到 C 的重排研究得很少，而立体特异性[1,3]-重排则极为罕见。在这里，我们报告了一种无金属的分子内氢烷氧基化/[1,3]-重排反应，可实现各种有价值的中到大环内酰胺的实用且原子经济性的组装，具有广泛的底物范围和优异的非对映选择性。此外，通过手性 Brønsted 酸催化的动力学拆分也实现了这种不对称级联环化。此外，生物测试表明，这些中环内酰胺中的一些具有作为抗肿瘤剂针对黑色素瘤细胞、食管癌细胞和乳腺癌细胞的生物活性。通过对照实验和理论计算进一步支持了反应的机理。
