Chair of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland.
Molecules. 2020 Feb 7;25(3):727. doi: 10.3390/molecules25030727.
In this report, we describe the synthetic elaboration of the easily available enantiomerically pure β-amino alcohols. Attempted direct substitution of the hydroxyl group by azido-functionality in the Mitsunobu reaction with hydrazoic acid was inefficient or led to a diastereomeric mixture. These outcomes resulted from the participation of aziridines. Intentionally performed internal Mitsunobu reaction of β-amino alcohols gave eight chiral aziridines in 45-82% yield. The structural and configuration identity of products was confirmed by NMR data compared to the DFT calculated GIAO values. For 1,2,3-trisubstituted aziridines slow configurational inversion at the endocyclic nitrogen atom was observed by NMR at room temperature. Moreover, when aziridine was titrated with Zn(OAc) under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN to form the corresponding azido amines as single regio- and diastereomers in 90-97% yield. Different results were obtained for 1,2-disubstituted and 1,2,3-trisubstituted aziridines. For the later aziridines ring closure and ring opening occurred at different carbon stereocenters, thus yielding products with two inverted configurations, compared to the starting amino alcohol. The 1,2-disubstituted aziridines produced azido amines of the same configuration as the starting β-amino alcohols. To obtain a complete series of diastereomeric -diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in S2 reaction (25-58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral -diamines of defined stereochemistries.
在本报告中，我们描述了容易获得的对映纯β-氨基醇的合成阐述。在与叠氮酸的 Mitsunobu 反应中，尝试直接取代羟基的叠氮官能团效率低下，或者导致非对映混合物。这些结果是由于氮丙啶的参与。β-氨基醇的有意进行的内部 Mitsunobu 反应以 45-82%的收率得到了八个手性氮丙啶。通过 NMR 数据与 DFT 计算的 GIAO 值相比，产物的结构和构型同一性得到了证实。对于 1,2,3-三取代氮丙啶，在室温下通过 NMR 观察到环内氮原子的缓慢构型反转。此外，当氮丙啶在 NMR 控制下用 Zn(OAc)滴定时，只有两个 N-差向异构体之一直接参与络合。氮丙啶与 HN 开环形成相应的叠氮胺，以 90-97%的收率作为单一区域和非对映异构体。对于 1,2-取代和 1,2,3-三取代氮丙啶，得到了不同的结果。对于后者的氮丙啶，环合和开环发生在不同的碳立体中心，因此与起始的氨基醇相比，生成具有两个反转构型的产物。1,2-取代的氮丙啶生成与起始的β-氨基醇具有相同构型的叠氮胺。为了获得完整的一系列非对映异构-diamines，我们将氨基醇转化为环状磺酰胺酯，它们在 S2 反应中与叠氮化钠反应（总收率为 25-58%）。无论哪种方式获得的叠氮化物都经历了 Staudinger 还原，得到了一系列具有确定立体化学的六个新的手性-diamines。
