School of Chemical and Physical Sciences, Victoria University of Wellington , P.O. Box 600, Wellington, New Zealand.
J Org Chem. 2013 Oct 4;78(19):9791-802. doi: 10.1021/jo401512h. Epub 2013 Sep 19.
A protecting-group-free synthetic strategy for the synthesis of piperidines has been explored. Key in the synthesis is an I2-mediated carbamate annulation, which allows for the cyclization of hydroxy-substituted alkenylamines into piperidines, pyrrolidines, and furans. In this work, four chiral scaffolds were compared and contrasted, and it was observed that with both d-galactose and 2-deoxy-d-galactose as starting materials, the transformations into the piperidines 1-deoxygalactonorjirimycin (DGJ) and 4-epi-fagomine, respectively, could be achieved in few steps and good overall yields. When d-glucose was used as a starting material, only the furan product was formed, whereas the use of 2-deoxy-d-glucose resulted in reduced chemo- and stereoselectivity and the formation of four products. A mechanistic explanation for the formation of each annulation product could be provided, which has improved our understanding of the scope and limitations of the carbamate annulation for piperidine synthesis.
我们探索了一种无保护基团的哌啶合成策略。该合成的关键在于 I2 介导的氨基甲酸酯环化反应，它可以使羟基取代的烯基胺环化成哌啶、吡咯烷和呋喃。在这项工作中，我们比较了四种手性骨架，观察到以 d-半乳糖和 2-脱氧-d-半乳糖为起始原料时，分别可以经过几步反应以较好的总收率得到哌啶 1-脱氧半乳糖诺力霉素（DGJ）和 4-差向-野尻霉素。而以 d-葡萄糖为起始原料时，只能得到呋喃产物，而使用 2-脱氧-d-葡萄糖则导致化学和立体选择性降低，并生成四个产物。我们可以对每个环化产物的形成提供一个机制解释，这提高了我们对氨基甲酸酯环化反应用于哌啶合成的范围和限制的理解。
