Universität zu Köln

Wang, Xiaochen ORCID: 0009-0008-7146-8854 (2026). Hydrogen Bonding Cyclodiphosphazanes: Enantioselective Catalysis. PhD thesis, Universität zu Köln.

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Abstract

The present work focuses on the design, synthesis, characterization and application of new chiral cyclophosph(V)azanes as hydrogen bond catalysts. Their applications include the catalytic asymmetric Michael additions of different nucleophiles to nitroolefin. In addition, L-proline derivatives are explored as a potential chiral scaffold for the catalysts. In the first part of this work, chiral diaminocyclohexan as a classical chiral scaffold for hydrogen bond catalysts was synthesized according to the literature. Subsequently, a series of six novel chiral cyclophosph(V)azanes as hydrogen bond catalysts, featuring varying amino groups and chalcogen atoms on the phosphorus atom, were designed and synthesized, with yields from 8 to 46%. The new catalysts were identified through different analysis, including 31P-NMR spectrum and X-ray crystal structure. In the second part of this work, the newly synthesized chiral cyclophosph(V)azane catalysts were employed in catalytic asymmetric Michael additions of different nucleophiles to β-nitrostyrene. After screening the catalysts and condition like solvent and temperature, catalyses of 2-hydroxy-1,4-naphthoquinone gave the bests results, with yields up to 99% and ee-s up to 90%. Among other catalytic additions which only screened the catalysts, catalyses of 4-hydroxycoumarin resulted in yields up to 64% and ee-s up to 17%, addition of Kojic acid chloride gave the yields up to 70% and ee-s up to 80%, and adduct from Meldrum’s acid achieved the yields up to 76% and ee-s up to 55%. In the context of reactions involving a single novel catalyst, diethylmalonate and indole exhibited no conversion, acetylacetone yielded a 10% yield, and N-Boc-oxindole attained an 84% yield, while its ee-s could not be determined. In the final part of the work, the synthesis of L-proline derivatives was attempted as a chiral scaffold for hydrogen bond catalysts. The 9-step synthetic route with trityl group as the protecting group was conducted, reproducing the literature method. The 2 desired products were successfully obtained prior to the final step, and for the Mitsunobu reaction on trityl prolinol, as the key step, the configuration of C5 was ascertained through X-ray crystal analysis, aligning with the argument from literature. Subsequently, a novel synthetic route involving the Mitsunobu reaction on methyl prolinol was implemented. The Mitsunobu reaction on methyl prolinol resulted in a ring expansion product, demonstrating the formation of an aziridinium ion intermediate by methyl prolinol. In addition, a nucleophilic attack at C1 position by azide was observed, rather than C5 as seen in trityl prolinol.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Wang, Xiaochen wxccpu@gmail.com https://orcid.org/0009-0008-7146-8854 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-799773
Date:	2026
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry
Subjects:	Chemistry and allied sciences
Uncontrolled Keywords:	Keywords Language Hydrogen Bonding UNSPECIFIED Cyclodiphosphazanes UNSPECIFIED Enantioselective Catalysis UNSPECIFIED
Date of oral exam:	18 March 2025
Referee:	Name Academic Title Goldfuss, Bernd Prof. Dr. Griesbeck, Axel Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79977