Enantioselective Synthesis of Polycyclic γ-Lactams with Multiple Chiral Carbon Centers via Ni(0)-Catalyzed Asymmetric Carbonylative Cycloadditions without Stirring
Enantioselective Synthesis of Polycyclic γ-Lactams with Multiple Chiral Carbon Centers via Ni(0)-Catalyzed Asymmetric Carbonylative Cycloadditions without Stirring
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DOI：
10.1021/jacs.9b12493
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发表时间：
2020-01-22
影响因子：
15
通讯作者：
Ogoshi, Sensuke
中科院分区：
文献类型：
--
作者：
Ashida, Keita;Hoshimoto, Yoichi;Ogoshi, Sensuke
具有多个连续立体碳中心的伽马-内酰胺衍生物广泛存在于生理活性化合物中。因此，以立体控制的方式开发直接和可靠的合成路线来获得这样的手性结构基元应该是重要的。在这里，我们报道了一种以对映选择性和原子经济的方式构建包含两个以上连续立体中心的多环伽马-内酰胺衍生物的策略。此外，我们还首次实现了Strigolactam衍生物GR-24的对映选择性合成，GR-24是一种潜在的种子萌发刺激剂和植物生长调节剂的外消旋变体。这一过程的关键是镍(0)/手性亚磷酰胺催化的烯亚胺和一氧化碳之间的不对称[2+2+1]羰基化环加成反应，该环加成反应具有对映选择性，可得到高达90%的ee(重结晶后达99%ee)。机理研究的结果，包括手性杂镍环的分离，支持在镍(0)上的氧化环化过程中决定了伽马-内酰胺的两个邻接碳原子的对映体选择性。
gamma-Lactam derivatives with multiple contiguous stereogenic carbon centers are ubiquitous in physiologically active compounds. The development of straightforward and reliable synthetic routes to such chiral structural motifs in a stereocontrolled manner should thus be of importance. Herein, we report a strategy to construct polycyclic gamma-lactam derivatives that contain more than two contiguous stereogenic centers in an enantioselective as well as atom-economic manner. Moreover, we have achieved the first enantioselective synthesis of strigolactam derivative GR-24, a racemic variant of which is a potential seed germination stimulator and plantgrowth regulator. A key of the procedure presented here is a nickel(0)/chiral phosphoramidite-catalyzed asymmetric [2+2+1] carbonylative cycloaddition between readily accessible ene-imines and carbon monoxide, which proceeded enantioselectively to furnish up to 90% ee (>99% ee after recrystallization). The results of mechanistic studies, including the isolation of a chiral heteronickelacycle, support that the enantioselectivity on the two contiguous carbon atoms of the gamma-lactams is determined during the oxidative cyclization on nickel(0).