Zn-catalyzed enantio- and diastereoselective formal [4 + 2] cycloaddition involving two electron-deficient partners: asymmetric synthesis of piperidines from 1-azadienes and nitro-alkenes.
Zn-catalyzed enantio- and diastereoselective formal [4 + 2] cycloaddition involving two electron-deficient partners: asymmetric synthesis of piperidines from 1-azadienes and nitro-alkenes.
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DOI：
10.1021/jacs.5b00033
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发表时间：
2015-04-08
影响因子：
15
通讯作者：
Rovis T
中科院分区：
文献类型：
--
作者：
Chu JC;Dalton DM;Rovis T
我们报道了通过1-氮杂二烯和硝基烯烃的[4+2]环加成催化不对称合成哌啶。该反应使用地球上丰富的锌作为催化剂，具有高度的非对映和区域选择性。新型 BOPA 配体 (F-BOPA) 在此过程中赋予高反应活性和对映选择性。发现与双(恶唑啉)相邻的芳烃上存在邻位取代特别有影响，因为限制了1-氮杂二烯与路易斯酸的不期望的配位，从而允许反应在较低温度下进行。使用一系列配体进行的一系列二次动力学同位素效应研究表明了转化的逐步机制，包括亚胺与硝基烯烃的初始迈克尔型加成，然后是环化事件。逐步机制消除了协同机制固有的电子需求，解释了两个缺电子伙伴之间成功的环加成。
We report a catalytic asymmetric synthesis of piperidines through [4+2] cycloaddition of 1-azadienes and nitroalkenes. The reaction uses earth abundant Zn as catalyst, and is highly diastereo- and regio-selective. A novel BOPA ligand (F-BOPA) confers high reactivity and enantioselectivity in the process. The presence of ortho substitution on the arenes adjacent to the bis(oxazolines) was found to be particularly impactful, due to limiting the undesired coordination of 1-azadiene to the Lewis acid, and thus allowing the reaction to be carried out at lower temperature. A series of secondary kinetic isotope effect studies using a range of ligands implicates a stepwise mechanism for the transformation, involving an initial Michael-type addition of the imine to the nitroalkene followed by a cyclization event. The step-wise mechanism obviates the electronic requirement inherent to a concerted mechanism, explaining the successful cycloaddition between two electron-deficient partners.