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Open AccessArticle

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

Chair of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland
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Author to whom correspondence should be addressed.
This paper is dedicated to Professor Grzegorz Mlostoń on the occasion of his 70-th birthday.
Academic Editors: Zbigniew Czarnocki and Joanna Szawkało
Molecules 2020, 25(3), 727; https://doi.org/10.3390/molecules25030727
Received: 11 January 2020 / Revised: 1 February 2020 / Accepted: 6 February 2020 / Published: 7 February 2020
(This article belongs to the Special Issue Stereochemistry in Action)
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)2 under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN3 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 vic-diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in SN2 reaction (25–58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral vic-diamines of defined stereochemistries. View Full-Text
Keywords: chiral β-amino alcohols; Mitsunobu reaction; 2-(2-pyridyl)aziridines; slow inversion at aziridine nitrogen; stereodivergent synthesis of chiral 1,2-diamines chiral β-amino alcohols; Mitsunobu reaction; 2-(2-pyridyl)aziridines; slow inversion at aziridine nitrogen; stereodivergent synthesis of chiral 1,2-diamines
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MDPI and ACS Style

Wosińska-Hrydczuk, M.; Boratyński, P.J.; Skarżewski, J. Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties. Molecules 2020, 25, 727. https://doi.org/10.3390/molecules25030727

AMA Style

Wosińska-Hrydczuk M, Boratyński PJ, Skarżewski J. Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties. Molecules. 2020; 25(3):727. https://doi.org/10.3390/molecules25030727

Chicago/Turabian Style

Wosińska-Hrydczuk, Marzena; Boratyński, Przemysław J.; Skarżewski, Jacek. 2020. "Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties" Molecules 25, no. 3: 727. https://doi.org/10.3390/molecules25030727

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