Highly enantioselective phase-transfer-catalyzed alkylation of protected α-amino acid amides toward practical asymmetric synthesis of vicinal diamines, α-amino ketones, and α-amino alcohols
Highly enantioselective phase-transfer-catalyzed alkylation of protected α-amino acid amides toward practical asymmetric synthesis of vicinal diamines, α-amino ketones, and α-amino alcohols
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DOI：
10.1021/ja0459328
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发表时间：
2005-04-13
影响因子：
15
通讯作者：
Maruoka, K
中科院分区：
文献类型：
--
作者：
Ooi, T;Takeuchi, M;Maruoka, K
通过成功利用设计的 4 型手性季铵盐作为催化剂，在相转移条件下实现了受保护的甘氨酸二苯甲基 (Dpm) 酰胺 1 和 Weinreb 酰胺 10 的高度对映选择性烷基化。特别是，衍生自1b和4c的手性烯醇铵具有显着的反应活性，使得与反应性较低的简单仲烷基卤化物的反应具有高效率和对映选择性。这种手性烯醇铵的另一个独特特征是它能够识别 β 支链伯烷基卤化物的手性，这在烷基化过程中提供了令人印象深刻的动力学分辨率和双立体分化水平，从而可以控制两个 α 和 γ 立体中心。结合随后在环戊基甲基醚 (CPME) 中使用 LiAlH4 进行的还原，该系统可以轻松获得结构多样的光学活性邻位二胺。此外，光学活性α-氨基酸Weinreb酰胺11可以通过格氏试剂的简单处理有效地转化为相应的氨基酮。此外，还实现了光学活性α-氨基酮还原和烷基化为顺式和反式α-氨基醇，并且几乎完全相对和绝对立体化学控制。有了(S,S)-和(R,R)-4，本方法使包括Weinreb酰胺在内的α-氨基酰胺的两种对映异构体易于获得，具有巨大的结构变化，并且还建立了具有所需立体化学的邻位二胺、α-氨基酮和α-氨基醇的通用且实用的路线。
Highly enantioselective alkylation of protected glycine diphenylmethyl (Dpm) amide 1 and Weinreb amide 10 has been realized under phase-transfer conditions by the successful utilization of designer chiral quaternary ammonium salts of type 4 as catalyst. Particularly, remarkable reactivity of the chiral ammonium enolate derived from 1b and 4c allowed the reaction with less reactive simple secondary alkyl halides with high efficiency and enantioselectivity. An additional unique feature of this chiral ammonium enolate is its ability to recognize the chirality of beta-branched primary alkyl halides, which provides impressive levels of kinetic resolution and double stereodifferentiation during the alkylation, allowing for two alpha- and gamma-stereocenters to be controlled. Combined with the subsequent reduction using LiAlH4 in cyclopentyl methyl ether (CPME), this system offers a facile access to structurally diverse optically active vicinal diamines. Furthermore, the optically active a-amino acid Weinreb amide 11 can be efficiently converted to the corresponding amino ketone by a simple treatment with Grignard reagents. In addition, reduction and alkylation of the optically active alpha-amino ketone into both syn and anti alpha-amino alcohols with almost complete relative and absolute stereochemical control have been achieved. With (S,S)- and (R,R)-4 in hand, the present approach renders both enantionners of alpha-amino amides including Weinreb amides readily available with enormous structural variation and also establishes a general and practical route to vicinal diamines, a-amino ketones, and a-amino alcohols with the desired stereochemistry.