A three-step procedure for asymmetric catalytic reductive amidation of ketones
A three-step procedure for asymmetric catalytic reductive amidation of ketones
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DOI：
10.1021/jo9809332
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发表时间：
1998-09-04
影响因子：
3.6
通讯作者：
Johnson, NB
中科院分区：
文献类型：
--
作者：
Burk, MJ;Casy, G;Johnson, NB
光学活性胺作为拆分剂、手性助剂以及作为许多重要生物活性化合物的组分的价值已得到充分证明。因此，开发生产对映体纯胺的实用方法具有重要意义。我们最近描述了阳离子 Me-DuPHOS-Rh 和 Me-BPE-Rh 催化剂对 N-Ac-R-亚芳基酰胺高度对映选择性氢化成相应 N-Ac-R-芳基烷基胺的有效性。 1 尽管这种氢化过程表面上有用，但由于缺乏有效的烯酰胺底物合成方法2、3，基本上使得该方法无效，特别是对于对映体纯胺的工业制造而言。除了在不对称氢化反应中证明烯酰胺的用途外，1, 4 它们还应用于有机合成的许多其他领域。 5 为了切实可行地获得 2 型前手性烯酰胺，我们现在开发了一种从简单酮出发的有效两步路线。我们公开的初步结果表明，使用 Me-DuPHOS-Rh 和/或 Me-BPE-Rh 催化剂体系可以容易地制备一系列新的烯酰胺，并以高对映选择性进行氢化。从概念上讲，组合的三步程序提供了一种酮的不对称催化还原酰胺化（1 f 3）的新方法。
The value of optically active amines as resolving agents, as chiral auxiliaries, and as components of many important biologically active compounds is well documented. Accordingly, the development of practical methods for the production of enantiomerically pure amines is of cardinal interest. We recently have described the effectiveness of cationic Me-DuPHOS-Rh and Me-BPE-Rh catalysts for highly enantioselective hydrogenation of N-Ac-R-arylenamides to the corresponding N-Ac-R-arylalkylamines. 1 Despite the ostensible utility of this hydrogenation procedure, the dearth of efficient methods for synthesis of the enamide substrates2, 3 essentially has rendered this process unavailing, particularly for industrial manufacture of enantiomerically pure amines. In addition to the demonstrated use of enamides in asymmetric hydrogenation reactions, 1, 4 they have found application in numerous other areas of organic synthesis. 5 In an effort to provide practical access to prochiral enamides of type 2, we now have developed an efficacious two-step route from simple ketones. We disclose preliminary results that indicate that a range of new enamides may be prepared readily and hydrogenated with high enantioselectivities using the Me-DuPHOS-Rh and/or Me-BPE-Rh catalyst systems. Conceptually, the combined three-step procedure offers a novel method for asymmetric catalytic reductive amidation of ketones (1 f 3).