Synthetic and theoretical investigation on the one-pot halogenation of β-amino alcohols and nucleophilic ring opening of aziridinium ions.
Synthetic and theoretical investigation on the one-pot halogenation of β-amino alcohols and nucleophilic ring opening of aziridinium ions.
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DOI：
10.1039/c5ob01692d
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发表时间：
2016-01-21
影响因子：
3.2
通讯作者：
Chong HS
中科院分区：
文献类型：
--
作者：
Chen Y;Sun X;Wu N;Li J;Jin S;Zhong Y;Liu Z;Rogachev A;Chong HS
氮杂吡啶鎓离子是合成对映体富集的结构单元的有用的反应中间体。然而，N，N-二烷基氮丙啶鎓离子在光学活性分子的合成中与其他三元环同源物、氮丙啶和环氧化物相比相对利用不足。光学活性氮丙啶鎓离子和仲β-卤代胺作为氮丙啶鎓离子的前体分子的表征几乎没有报道，并且通常是不清楚的。本文首次报道了具有光学活性的氮丙啶鎓离子和β-卤代仲胺的合成、实验和理论表征。以N，N-取代丙氨醇为原料，通过卤代物在氮丙啶离子的受阻碳上形成和开环，有效地合成了光学活性的N，N-取代β-卤代仲胺。通过核磁共振和计算分析表征了光学活性β-卤代胺和氮丙啶离子。通过X射线晶体学分析证实了光学活性β-氯胺的结构。氮丙啶离子衍生自N，N-二苄基丙氨醇，试图为X-射线晶体结构测定，但保持稳定，只有几个小时，这是足够长的NMR和光学活性的分析。采用密度泛函理论和高精度的DLPNO-CCSD（T）方法对卤代氮丙啶离子的立体定向开环反应进行了计算研究。利用氮丙啶离子的高区域选择性和立体选择性开环反应，将β-氨基醇高效一锅转化为对映体富集的β-氨基醇、β-氨基腈和邻二胺衍生物。
Aziridinium ions are useful reactive intermediates for synthesis of enantiomerically enriched building blocks. However, N,N-dialkyl aziridinium ions are relatively underutilized in synthesis of optically active molecules as compared to other three-membered ring cogeners, aziridines and epoxides. Characterization of both optically active aziridinium ions and secondary β-halo amines as precursor molecules of aziridinium ions has been scarcely reported and is often unclear. In this paper, we report for the first time preparation and experimental and theoretical characterization of optically active aziridinium ions and secondary β-halo amines. Optically active secondary N,N-substituted β-halo amines were efficiently synthesized from N,N-substituted alaniol via formation and ring opening at the more hindered carbon of aziridinium ions by halides. Optically active β-halo amines and aziridinium ions were characterized by NMR and computational analysis. The structure of an optically active β-chloro amine was confirmed via X-ray crystallographic analysis. The aziridinium ions derived from N,N-dibenzyl alaniol were attempted for X-ray crystallographic structural determination but remained stable only for several hours which was long enough for analyses of NMR and optical activity. The stereospecific ring opening of aziridinium ions by halides were computationally studied using DFT and highly-accurate DLPNO-CCSD(T) methods. Highly regioselective and stereoselective ring opening of aziridinium ions was applied to efficient one-pot conversion of β-alaniols to enantiomerically enriched β-amino alcohols, β-amino nitriles, and vicinal diamine derivatives.