Highly Enantioselective Synthesis of Propargyl Amides through Rh-Catalyzed Asymmetric Hydroalkynylation of Enamides: Scope, Mechanism, and Origin of Selectivity
Highly Enantioselective Synthesis of Propargyl Amides through Rh-Catalyzed Asymmetric Hydroalkynylation of Enamides: Scope, Mechanism, and Origin of Selectivity
复制标题
通过 Rh 催化的烯酰胺不对称氢化炔基化高度对映选择性合成炔丙酰胺：范围、机制和选择性起源
DOI：
10.1021/jacs.7b12054
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发表时间：
2018-01-10
影响因子：
15
通讯作者：
Li, Bi-Jie
中科院分区：
文献类型：
--
作者：
Bai, Xiao-Yan;Zhang, Wen-Wen;Li, Bi-Jie
手性炔丙基酰胺在有机合成中是特别有用的结构单元。炔丙基酰胺的对映选择性合成是非常理想的。常规方法涉及使用化学计量量的金属试剂或手性助剂。相比之下，与末端炔的直接炔基化是有吸引力的，因为它避免了使用化学计量的有机金属试剂。醛、胺和炔的不对称偶联（A（3）-偶联）为合成N-烷基和N-芳基取代的炔丙基胺提供了一种有效的方法，但这种策略不适合直接对映选择性合成炔丙基酰胺。我们已经开发了一种新的策略，并在这里报告铑催化的烯酰胺的不对称氢炔基化反应。炔基化在烯酰胺的α位区域选择性地发生以产生手性炔丙基酰胺。观察到高产率和对映体选择性。先前制备手性炔丙基胺的炔基化方法涉及亲核加成到缺电子亚胺。相比之下，我们目前的方法通过富电子烯烃的区域选择性加氢炔基化进行。动力学研究表明，迁移插入的烯酰胺的氢化铑是营业额限制。计算研究揭示了区域和对映体选择性的起源。这一新策略提供了一种从末端炔直接合成手性炔丙基酰胺的有效方法。
Chiral propargyl amides are particularly useful structural units in organic synthesis. The enantioselective synthesis of propargyl amide is highly desirable. Conventional approach involves the use of a stoichiometric amount of metal reagent or chiral auxiliary. In comparison, direct alkynylation with terminal alkyne is attractive because it avoids the use of stoichiometric organometallic reagent. The asymmetric coupling of aldehyde, amine, and alkyne (A(3)-coupling) provides an efficient method for the synthesis of N-alkyl and N-aryl-substituted propargyl amines, but this strategy is not amenable for the direct enantioselective synthesis of propargyl amide. We have developed a new strategy and report here a Rh-catalyzed asymmetric hydroalkynylation of enamides. Alkynylations occur regioselectively at the alpha position of an enamide to produce chiral propargyl amides. High yield and enantioselectivity were observed. Previous alkynylation methods to prepare chiral propargyl amine involve the nucleophilic addition to an electron-deficient imine. In contrast, our current approach proceeds through regioselective hydroalkynylation of an electron-rich alkene. Kinetic studies indicated that migratory insertion of the enamide to the rhodium hydride is turnover limiting. Computational studies revealed the origin of regio- and enantioselectivities. This novel strategy provides an efficient method to access chiral propargyl amides directly from terminal alkynes.