title: Design and Synthesis of Stereogenic-at-Iron Complexes with Multidentate Ligands and Application in Asymmetric Catalysis
title: Design und Synthese von Stereogenic-at-Iron Komplexen mit mehrzähnigen Liganden und Anwendung in asymmetrischer Katalyse
titleType: AlternativeTitle
Creators: name: Steinlandt, Philipp Stefan
Publisher: name: Philipps-Universität Marburg
Year: 2023
Subjects: Nachhaltigkeit
Chemistry &amp; allied sciences
Chemie
2H-azirines
enantioselektive Katalyse
Katalysatordesign
metallzentrierte Chiralität
Stickstoff-Liganden
mehrzähnige Liganden
2H-Azirine
multidentate ligands
Aminosäure-Derivate
metal-centered stereogenicity
stereogenic-at-iron
Eisen
diastereomere Komplexe
Eisen-Katalyse
chiral iron complexes
asymmetrische Katalyse

description: Asymmetric catalysis is an indispensable tool of great importance for the economic and sustainable synthesis of non-racemic chiral molecules. In addition to organic compounds and biomolecules, chiral transition metal complexes represent a pivotal pillar for generating enantiomerically pure products. The design and development of metal complexes for the transfer of stereochemical information form the very foundation of creating a sophisticated chiral environment to achieve sufficient enantioselectivities. Often, the applied catalysts comprise a stereogenic metal center that gives rise to a distinct chiral topology. Therefore, considerations regarding the metal-centered chirality are crucial in the composition of novel catalysts. In recent years, the Meggers group demonstrated the potential of emphasizing the absolute configuration at the metal with numerous iridium(III), rhodium(III), ruthenium(II), and iron(II) complexes and their applicability in asymmetric transition metal catalysis. Chapter 3.1. A synthetic access to furnish pentadentate, achiral ligands that give rise to iron(II) complexes comprising metal-centered stereogenicity upon coordination (chiral-at-metal) is described. A ligand scaffold containing a mesityl substituted dipicolylamine moiety connected to a quinoline ring by an amido tether is shown to provide a paramagnetic complex without the required feasibility of extensive NMR spectroscopic analysis. By substitution of the 8-amido quinoline motif with a 2,2’-bipyridyl group, the corresponding racemic iron(II) complex exhibits diamagnetic properties, hence facilitating NMR measurements. A subsequent chiral auxiliary mediated separation of the enantiomeric mixture of complexes with chiral oxazolines, sulfoxides, and carboxylic acids is demonstrated to give insufficient results. Chapter 3.2 and 3.3. The modular synthesis of pentadentate, chiral ligands comprising a central dipicolylamine motif generating metal-centered chirality upon complexation (stereogenic-at-metal) is depicted. Incorporation of a methyl group into the ligand framework results in a diastereomeric mixture of iron complexes after reaction with Fe(II)-perchlorate. The necessity of a laborious separation is prevented by exploiting the different thermodynamic stabilities of the diastereomers. The ligand centered chirality can act as a chiral lever enabling a subsequent isomerization to furnish the diastereomerically pure iron(II) complex. The rate of this interconversion is significantly influenced by the steric demand of the chiral lever and is demonstrated to improve with the incorporation of a bulkier isopropyl motif. A following structural elucidation via NMR spectroscopic measurements and X-ray crystallographic analysis confirms the overall topology and coordination mode. The modular synthetic approach of the ligand synthesis provides the convenient possibility of derivatization which is shown by incorporation of a mesitylene and a benzimidazole group. The efficiency of the obtained catalysts is then demonstrated for a ring contraction of isoxazoles under open flask conditions to afford chiral 2H-azirines with high enantioselectivities (up to 93% ee) and an exceptional activity affording turnover numbers (TON) of up to 10,000. Chapter 3.4. The design and synthesis of novel non-C2-symmetric, tetradentate chiral ligands to obtain octahedral complexes with heterotopic reaction sites is demonstrated. The central stereogenic motif of this ligand scaffold is represented by a proline-derived chiral diamine backbone that enables a convenient synthetic access to the final ligands. Moreover, this backbone provides a high selectivity towards a cis-alpha topology of the corresponding Fe(II)-complexes while evincing a lambda-configuration at the metal center. Pyridyl, benzimidazolyl, and benzothiazolyl groups are incorporated as terminal coordinating groups and all nine possible combinations of the dichloro complexes are synthesized. The influence of the catalyst symmetry in regard to the steric and electronic environment is evaluated with the asymmetric ring contraction of isoxazoles to furnish enantiomerically enriched 2H-azirines. A catalyst comprising a terminal pyridine and a benzothiazole group provides the best results and is applied in a substrate scope of 19 different isoxazoles. The corresponding 2H-azirines are obtained with high enantioselectivites (up to 92% ee) and excellent yields (up to &gt;99%) under open flask conditions. A subsequent survey of the versatility of the chiral products showcases their usefulness as synthetic intermediates without loss of enantioselectivity in the synthesis of several alpha-amino acid derivatives. Additionally, an unprecedented transformation of 2H-azirines to directly access a racemic beta-amino acid derivative is shown.