Highly diastereoselective and enantioselective carbon-carbon bond formations in conjugate additions of lithiated N-Boc allylamines to nitroalkenes: enantioselective synthesis of 3,4- and 3,4,5-substituted piperidines including (-)-paroxetine.
Highly diastereoselective and enantioselective carbon-carbon bond formations in conjugate additions of lithiated N-Boc allylamines to nitroalkenes: enantioselective synthesis of 3,4- and 3,4,5-substituted piperidines including (-)-paroxetine.
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锂化 N-Boc 烯丙胺与硝基烯烃的共轭加成过程中形成高度非对映选择性和对映选择性碳-碳键：对映选择性合成 3,4- 和 3,4,5- 取代哌啶，包括 (-)-帕罗西汀。
DOI：
10.1021/ja005748w
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发表时间：
2001
影响因子：
15
通讯作者：
Beak,P
中科院分区：
文献类型：
--
作者：
Johnson,TA;Curtis,MD;Beak,P
碳-碳键形成反应在一个步骤中产生两个具有高非对映体和对映体选择性的立体中心，可以为有价值的结构开辟新的战略方法。哌啶环是许多具有生物活性的生物碱、天然产物和药物的中心结构。1已开发用于合成对映体富集的取代哌啶的一般策略利用氨基酸、手性催化剂和助剂2，并且集中于2-和6-位的不对称碳取代。在哌啶环的3-、4-和5-位提供取代的方法是相当有限的。2，4我们现在报告（−）-鹰爪豆碱介导的锂化和N-Boc-N-（对甲氧基苯基）烯丙胺与α，β-不饱和硝基化合物的共轭加成的发展。该加成反应具有很高的对映体和非对映体选择性，是高效合成3-、4-和5-位取代的高对映体富集哌啶的关键步骤。逆合成分析如下所示。
Carbon− carbon bond-forming reactions that create two stereogenic centers with high diastereo-and enantioselectivity in a single step can open new strategic approaches to valued structures. The piperidine ring is the central structure of many biologically active alkaloid natural products and pharmaceuticals. 1 General strategies which have been developed for the synthesis of enantioenriched, substituted piperidines utilize amino acids, chiral catalysts, and auxiliaries 2 and focus on asymmetric carbon substitution at the 2-and 6-positions. 2, 3 Methods providing substitution at the 3-, 4-, and 5-positions of the piperidine ring are quite limited. 2, 4 We now report the development of (−)-sparteine-mediated lithiation and conjugate addition of N-Boc-N-(p-methoxyphenyl) allylamines to α, β-unsaturated nitro compounds. This addition occurs with high enantio-and diastereoselectivity and serves as the key step in the efficient synthesis of highly enantioenriched piperidines with substitution at the 3-, 4-, and 5-positions. The retrosynthetic analysis is shown below.