Molybdän- und Wolfram-Katalysatoren mit tripodalen Liganden für die Alkin-Metathese & Isolierung eines homoleptischen Mo(V) Alkoxid-Komplexes

Eine neue Generation an Molybdän-Alkylidin-Katalysatoren für die Alkinmetathese wurde entwickelt. Zuvor waren wohldefinierte Molybdän-Alkylidin-Katalysatoren mit einem tripodalen Ligandensystem nicht zugänglich, weshalb diese Arbeit einen wichtigen Meilenstein auf dem Gebiet der Alkinmetathese markiert. Ein neu entwickelter tripodaler Silanolatligand und eine verbesserte Komplexierungsmethode ermöglichen nun den Zugang zu diesen Katalysatoren im Gramm-Maßstab. Das modulare Liganden-Design bot die Möglichkeit verschiedene Katalysator Variationen herzustellen, um die wichtigen Parameter für die Katalyse zu untersuchen. Eine systematische 95Mo-NMR Studie lieferte wertvolle Einblicke in die elektronische Struktur dieser Komplexe und erwies sich als sehr nützliche Methode für die Optimierung des Liganden- und Katalysatordesigns. Die chemische Verschiebungstensoranalyse des Alkylidin-Kohlenstoffatoms wies eine erhöhte Elektrophilie nach, die durch die tripodale Ligandensphäre vermittelt wird. Das Benchmarking der katalytischen Aktivität mit einer Reihe verschiedener Katalysatoren zeigte, dass der Komplex mit Methyl-substituierten tripodalen Silanolatliganden der aktivste Katalysator ist. Die Isolation eines Molybdän-Metallacyclobutadien-Komplexes mit Triphenylsilanolat-Liganden und eine umfangreiche Studie zur Bildung von Molybdän-Metallatetrahedranen mit tripodaler Ligandensphäre bewies, dass beide Intermediate reversibel zugänglich sind und miteinander im Gleichgewicht stehen. Darüber hinaus erzeugt die tripodale Ligandensphäre zwei verschiedene Molybdän-Metallacyclobutadienformen, die eine Pseudorotation für das Durchlaufen des katalytischen Zyklus benötigen. Die neu entwickelten Katalysatoren weisten eine unübertroffene Toleranz gegenüber funktionellen Gruppen auf, tolerierten protische Gruppen wie ungeschützte Alkohole, und zeigten sogar eine gewisse Stabilität gegenüber Wasser. Zusätzlich wurde das ausgezeichnete Anwendungsprofil an verschiedenen, herausfordernden Ringschluss-Alkinmetathese Reaktionen für die Naturstoffsynthese erfolgreich unter Beweis gestellt. Daher haben wir für die neu entwickelten Molybdän-Alkylidin-Katalysatoren die Bezeichnung „canopy catalysts“ eingeführt. Im zweiten Teil dieser Arbeit haben wir eine Vielzahl an tripodalen Wolfram-Alkylidin-Komplexen hergestellt und dabei einen neuen Katalysator für die Alkinmetathese entwickelt, der den klassischen Schrock-Katalysator bei Weitem übertrifft. Eine detaillierte spektroskopische, kristallographische und theoretische Untersuchung dieser Wolfram-Alkylidin-Komplexe lieferte Einblicke in deren geometrische sowie elektronische Struktur. In diesem Kontext zeigte die 183W-NMR Spektroskopie eindrücklich, dass der tripodale Silanolatligand den Wolfram-Komplex besonders Lewis-sauer macht. Dadurch wird das Wolfram-Metallacyclobutadien-Intermediat soweit stabilisiert, dass die katalytische Aktivität zum Erliegen kommt. Alle hergestellten Wolfram Komplexe mit tripodalen Silanolatliganden oder auch literatur-bekannte Wolfram-Katalysatoren ergaben enttäuschende Ergebnisse bei einfachen Metathese-Testreaktionen. Die schwächeren Donoreigenschaften der Silanolatliganden führten am Wolframalkylidin nur zu geringer katalytischer Aktivität. Dies hat uns dazu verleitet, einen tripodalen Alkoxid-Liganden zu entwickeln, der durch Komplexierung den entsprechenden Wolfram Komplex in sehr guten Ausbeuten und im Gramm-Maßstab zugänglich macht. Dieser Wolfram Komplex übertrifft alle anderen getesteten Katalysatoren hinsichtlich Aktivität und Selektivität. Im dritten Kapitel berichten wir über die Isolierung des ersten, monomeren, homoleptischen, fünffach koordinierten Alkoxid-Mo(V)-Komplexes. Hochvalente Molybdänkomplexe mit Alkoxid-Liganden sind dafür prädestiniert Molybdän-Oxo-Komplexe zu bilden und/oder zu dimerisieren. Der isolierte [Mo(OtBu)5] Komplex ist das erste Beispiel einer völlig neuen Klasse an hochvalenten Molybdänkomplexen. Ebenso ist es uns gelungen einen Molybdän-Nitrido-Komplex mit tert-Butoxid-Liganden zu isolieren. Vorhergehende Arbeiten zeigten, dass tert-Butoxid-Liganden niedervalente Mo(III)-Komplexe nicht ausreichend vor der konkurrierenden Dimerisierung schützen können, wodurch deren Reaktivität im Unbekannten blieb. Interessanterweise wird der Molybdän-Nitrido-Komplex durch die Aktivierung eines Acetonitril-Moleküls am Mo(III)-Alkoxid-Komplex gebildet

Classifying and understanding the reactivities of Mo based alkyne metathesis catalysts from 95Mo NMR chemical shift descriptors

The most active alkyne metathesis catalysts rely on well-defined Mo alkylidynes, X3MoCR (X = OR), in particular the recently developed canopy catalyst family bearing silanolate ligand sets. Recent efforts to understand catalyst reactivity patterns have shown that NMR chemical shifts are powerful descriptors, though previous studies have mostly focused on ligand-based NMR descriptors. Here, we show in the con-text of alkyne metathesis that 95Mo chemical shift tensors encode detailed information on the electronic structure of potent catalysts. Analysis by first principles calculations of 95Mo chemical shift tensors ex-tracted from solid-state 95Mo NMR spectra show a direct link of chemical shift values with the energies of the HOMO and LUMO, two molecular orbitals involved in the key [2+2]-cycloaddition step, thus linking 95Mo chemical shifts to reactivity. In particular, the 95Mo chemical shifts are driven by ligand electronega-tivity (σ-donation) and electron delocalization through Mo-O π-interactions, thus explaining the unique reactivity of the silanolate canopy catalysts. These results further motivate exploration of transition-metal NMR signatures and their relations to electronic structure and reactivity

Canopy Catalysts for Alkyne Metathesis: Investigations into a Bimolecular Decomposition Pathway and the Stability of the Podand Cap

Molybdenum alkylidyne complexes with a trisilanolate podand ligand framework (“canopy catalysts”) are the arguably most selective catalysts for alkyne metathesis known to date. Among them, complex 1 a endowed with a fence of lateral methyl substituents on the silicon linkers is the most reactive, although fairly high loadings are required in certain applications. It is now shown that this catalyst decomposes readily via a bimolecular pathway that engages the Mo≡CR entities in a stoichiometric triple-bond metathesis event to furnish RC≡CR and the corresponding dinuclear complex, 8, with a Mo≡Mo core. In addition to the regular analytical techniques, $^{95}$Mo NMR was used to confirm this unusual outcome. This rapid degradation mechanism is largely avoided by increasing the size of the peripheral substituents on silicon, without unduly compromising the activity of the resulting complexes. When chemically challenged, however, canopy catalysts can open the apparently somewhat strained tripodal ligand cages; this reorganization leads to the formation of cyclo-tetrameric arrays composed of four metal alkylidyne units linked together via one silanol arm of the ligand backbone. The analogous tungsten alkylidyne complex 6, endowed with a tripodal tris-alkoxide (rather than siloxide) ligand framework, is even more susceptible to such a controlled and reversible cyclo-oligomerization. The structures of the resulting giant macrocyclic ensembles were established by single-crystal X-ray diffraction

"Canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework

A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne metathesis, which is distinguished by a tripodal trisilanolate ligand architecture, is presented. Complexes of type 1 combine the virtues of previous generations of silanolate-based catalysts with a significantly improved functional group tolerance. They are easy to prepare on scale; the modularity of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the application profile of the catalysts to be optimized. This opportunity is manifested in the development of catalyst 1f, which is as reactive as the best ancestors but exhibits an unrivaled scope. The new catalysts work well in the presence of unprotected alcohols and various other protic groups. The chelate effect entails even a certain stability toward water, which marks a big leap forward in metal alkylidyne chemistry in general. At the same time, they tolerate many donor sites, including basic nitrogen and numerous heterocycles. This aspect is substantiated by applications to polyfunctional (natural) products. A combined spectroscopic, crystallographic, and computational study provides insights into structure and electronic character of complexes of type 1. Particularly informative are a density functional theory (DFT)-based chemical shift tensor analysis of the alkylidyne carbon atom and 95Mo NMR spectroscopy; this analytical tool had been rarely used in organometallic chemistry before but turns out to be a sensitive probe that deserves more attention. The data show that the podand ligands render a Mo-alkylidyne a priori more electrophilic than analogous monodentate triarylsilanols; proper ligand tuning, however, allows the Lewis acidity as well as the steric demand about the central atom to be adjusted to the point that excellent performance of the catalyst is ensured.ISSN:0002-7863ISSN:1520-512

Automated Processing of Chromatograms: A comprehensive Python Package with GUI for Intelligent Peak Identification and Deconvolution in Chemical Reaction Analysis

Reaction screening and high-throughput experimentation (HTE) coupled with liquid chromatography (HPLC, UHPLC) are becoming more important than ever in synthetic chemistry. With growing number of experiments, it is increasingly difficult to ensure correct peak identification and integration, especially due to unknown side components which often overlap with the peaks of interest. We developed a comprehensive Python package with web-based graphical user interface (GUI) for automated processing of chromatograms, including baseline correction, intelligent peak picking, peak purity checks, deconvolution of overlapping peaks, and compound tracking. The algorithm accuracy was benchmarked using three datasets and compared to the previous MOCCA implementation and published results. The processing is fully automated with the possibility to include calibration and internal standards. The software supports chromatograms with photo-diode array detector (DAD) data from most commercial HPLC systems, and the Python package and GUI implementation are open-source to allow addition of new features and further development

183

Triarylsilanolates are privileged ancillary ligands for molybdenum alkylidyne catalysts for alkyne metathesis but lead to disappointing results and poor stability in the tungsten series. 1H,183W heteronuclear multiple bond correlation spectroscopy, exploiting a favorable 5J‐coupling between the 183W center and the peripheral protons on the alkylidyne cap, revealed that these ligands upregulate the Lewis acidity to an extent that the tungstenacyclobutadiene formed in the initial [2+2] cycloaddition step is over‐stabilized and the catalytic turnover brought to a halt. Guided by the 183W NMR shifts as a proxy for the Lewis acidity of the central atom and by an accompanying chemical shift tensor analysis of the alkylidyne unit, the ligand design was revisited and a more strongly π‐donating all‐alkoxide ligand prepared. The new expanded chelate complex has a tempered Lewis acidity and outperforms the classical Schrock catalyst, carrying monodentate tert‐butoxy ligands, in terms of rate and functional‐group compatibility

CIME4R: Exploring iterative, AI-guided chemical reaction optimization campaigns in their parameter space

Datsets and creation scripts used for the case studies of the paper "CIME4R: Exploring iterative, AI-guided chemical reaction optimization campaigns in their parameter space

CIME4R: Exploring iterative, AI-guided chemical reaction optimization campaigns in their parameter space

Chemical reaction optimization (RO) is an iterative process that results in large and high-dimensional datasets. Current tools only allow for limited analysis and understanding of parameter spaces, making it hard for scientists to review or follow changes throughout the process. With the recent emergence of using artificial intelligence (AI) models to aid RO, another level of complexity was added. It is critical to assess the quality of a model’s prediction and understand its decision to aid human-AI collaboration and trust calibration. To that regard, we propose CIME4R—an open-source interactive web application for analyzing RO data and AI predictions. CIME4R supports users in (i) comprehending a reaction parameter space, (ii) investigating how the RO process developed over iterations, (iii) identifying critical factors of a reaction, and (iv) understanding model predictions. This aids users in making informed decisions during the RO process and helps them review an RO process in retrospect, especially in the realm of AI-guided RO. CIME4R aids decision-making through the interaction between humans and AI by combining the strengths of expert experience and high computational precision. We developed and tested CIME4R together with domain experts and verified its usefulness with three case studies. With CIME4R the experts were able to produce valuable insights from past RO campaigns and make informed decisions on which experiments to perform next. We believe that CIME4R is the beginning of an open-source community project that improves the workflow of scientists working in the reaction optimization domain