New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures
New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures
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DOI：
10.1021/jacs.7b07319
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发表时间：
2017-09-20
影响因子：
15
通讯作者：
Njardarson, Jon T.
中科院分区：
文献类型：
--
作者：
Chogii, Isaac;Das, Pradipta;Njardarson, Jon T.
我们报告有用的新的锂辅助的不对称阴离子加速氨基Cope重排级联。策略性氮原子手性助剂通过（1）使得能够原位组装手性3-氨基-1，5-二烯前体，（2）经由烯醇化锂螯合物促进重排，和（3）经由所得手性烯酰胺中间体或亚胺产物赋予其对连续的分子间或分子内C-C或C-X键形成事件的影响而起到三个关键作用。用密度泛函理论对氨基Cope重排反应的机理进行了探讨。一个逐步的解离-重组机制被发现是有利的。手性助剂的立体化学通过影响二烯醇锂和亚磺酰亚胺片段在重组步骤中的取向来决定科普产物的立体化学。这些强大的不对称阴离子加速氨基Cope使级联打开大门，快速和可预测的组装复杂的手性无环和环状含氮基序在一锅。
We report useful new lithium-assisted asymmetric anion-accelerated amino-Cope rearrangement cascades. A strategic nitrogen atom chiral auxiliary serves three critical roles, by (1) enabling in situ assembly of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement via a lithium enolate chelate, and (3) imparting its influence on consecutive inter- or intramolecular C-C or C-X bond-forming events via resulting chiral enamide intermediates or imine products. The mechanism of the amino-Cope rearrangement was explored with density functional theory. A stepwise dissociation-recombination mechanism was found to be favored. The stereochemistry of the chiral auxiliary determines the stereochemistry of the Cope product by influencing the orientation of the lithium dienolate and sulfinylimine fragments in the recombination step. These robust asymmetric anion-accelerated amino-Cope enabled cascades open the door for rapid and predictable assembly of complex chiral acyclic and cyclic nitrogen-containing motifs in one pot.