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Readily accessible sp3-rich cyclic hydrazine frameworks exploiting nitrogen fluxionality
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Dean, Conor, Rajkumar, Sundaram, Roesner, Stefan, Carson, Nessa, Clarkson, Guy J., Wills, Martin, Jones, Matthew L. and Shipman, Michael (2020) Readily accessible sp3-rich cyclic hydrazine frameworks exploiting nitrogen fluxionality. Chemical Science, 11 (6). pp. 1636-1642. doi:10.1039/C9SC04849A ISSN 2041-6520.
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WRAP-readily-accessible-rich-cyclic-hydrazine-frameworks-nitrogen-Shipman-2020.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial. Download (1427Kb) | Preview |
Official URL: http://dx.doi.org/10.1039/C9SC04849A
Abstract
Increased molecular complexity correlates with improved chances of success in the drug development process. Here, a strategy for the creation of sp3-rich, non-planar heterocyclic scaffolds suitable for drug discovery is described that obviates the need to generate multiple stereogenic centers with independent control. Asymmetric transfer hydrogenation using a tethered Ru-catalyst is used to efficiently produce a range of enantiopure cyclic hydrazine building blocks (up to 99% ee). Iterative CāN functionalization at the two nitrogen atoms of these compounds produces novel hydrazine and hydrazide based chemical libraries. Wide chemical diversification is possible through variation in the hydrazine structure, use of different functionalization chemistries and coupling partners, and controlled engagement of each nitrogen of the hydrazine in turn. Principal Moment of Inertia (PMI) analysis of this small hydrazine library reveals excellent shape diversity and three-dimensionality. NMR and crystallographic studies confirm these frameworks prefer to orient their substituents in three-dimensional space under the control of a single stereogenic center through exploitation of the fluxional behavior of the two nitrogen atoms.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QC Physics Q Science > QD Chemistry |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Hydrazines, Molecular crystals, Nuclear magnetic resonance | |||||||||||||||
Journal or Publication Title: | Chemical Science | |||||||||||||||
Publisher: | Royal Society of Chemistry | |||||||||||||||
ISSN: | 2041-6520 | |||||||||||||||
Official Date: | 2020 | |||||||||||||||
Dates: |
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Volume: | 11 | |||||||||||||||
Number: | 6 | |||||||||||||||
Page Range: | pp. 1636-1642 | |||||||||||||||
DOI: | 10.1039/C9SC04849A | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Copyright Holders: | Ā© The Royal Society of Chemistry 2020 | |||||||||||||||
Date of first compliant deposit: | 2 January 2020 | |||||||||||||||
Date of first compliant Open Access: | 2 January 2020 | |||||||||||||||
RIOXX Funder/Project Grant: |
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