Zhang Sheng, Cha Lide, Li Lijun, Hu Yanbin, Li Yanan, Zha Zhenggen, Wang Zhiyong
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry & Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, PR China.
J Org Chem. 2016 Apr 15;81(8):3177-87. doi: 10.1021/acs.joc.6b00087. Epub 2016 Apr 7.
A primary amine-catalyzed asymmetric formal aza-Diels-Alder reaction of trifluoromethyl hemiaminals with enones was developed via a chiral gem-diamine intermediate. This novel protocol allowed facile access to structurally diverse trifluoromethyl-substituted piperidine scaffolds with high stereoselectivity. The utility of this method was further demonstrated through a concise approach to biologically active 4-hydroxypiperidine. More importantly, a stepwise mechanism involving an asymmetric induction process was proposed to rationalize the positive correlation between the chirality of the gem-diamine intermediate and the formal aza-Diels-Alder product.
通过手性偕二胺中间体，开发了一种伯胺催化的三氟甲基半胺与烯酮的不对称形式氮杂狄尔斯-阿尔德反应。这种新方法能够以高立体选择性轻松获得结构多样的三氟甲基取代哌啶骨架。通过一种简洁的方法合成具有生物活性的4-羟基哌啶，进一步证明了该方法的实用性。更重要的是，提出了一种涉及不对称诱导过程的分步机理，以合理化偕二胺中间体的手性与形式氮杂狄尔斯-阿尔德产物之间的正相关关系。
