Catalytic enantioselective nucleophilic desymmetrization of phosphonate esters

Molecules that contain a stereogenic phosphorus atom are crucial to medicine, agrochemistry and catalysis. While methods are available for the selective construction of various chiral organophosphorus compounds, catalytic enantioselective approaches for their synthesis are far less common. Given the vastness of possible substituent combinations around a phosphorus atom, protocols for their preparation should also be divergent, providing facile access not only to one but to many classes of phosphorus compounds. Here we introduce a catalytic and enantioselective strategy for the preparation of an enantioenriched phosphorus(V) centre that can be diversified enantiospecifically to a wide range of biologically relevant phosphorus(V) compounds. The process, which involves an enantioselective nucleophilic substitution catalysed by a superbasic bifunctional iminophosphorane catalyst, can accommodate a wide range of carbon substituents at phosphorus. The resulting stable, yet versatile, synthetic intermediates can be combined with a multitude of medicinally relevant O-, N- and S-based nucleophiles

Designing tandem catalytic reductive functionalisation strategies of carbonyl derivatives

Chapter 1 introduces tertiary amide-based reductive functionalisation strategies as attractive access points towards medicinally relevant α-branched tertiary amine building blocks. Within the scope of this synthetic transformation, Vaska’s complex is highlighted as a chemoselective transition metal catalyst that has come to the forefront for facilitating tertiary amide and lactam hydrosilylation in a mild and efficient manner in both small molecular systems and complex natural product synthesis. Chapter 2 provides a brief description of the Density Functional Theory-based computational methods that were used in Chapters 3 and 5 to complement the corresponding experimental findings. Chapter 3 describes the development of a dual catalytic umpolung reductive functionalisation strategy that enabled the generation of nucleophilic α-amino radical intermediates from robust tertiary amide starting points under a mild set of hydrosilylative/photocatalytic conditions. The work showcases how a tandem, dual catalytic approach can be utilised to enable reductive coupling of amides with electrophiles, previously inaccessible using Vaska’s complex-based hydrosilylative chemistry. Chapter 4 demonstrates how a derivative of Vaska’s complex can facilitate the hydrosilylation of α,β-unsaturated ketones. This finding provided a new synthetic opportunity for the iridium (I)-catalysed reductive functionalisation strategy to be used with carbonyl functionalities beyond the established tertiary amide motif. Inspired by the dual catalytic methodology developed in Chapter 3, the hydrosilylation step was combined with a secondary, chiral catalytic cycle to access enantioenriched products from feedstock enones, which have been thus far unprecedented for Vaska’s catalyst-based methodologies. Chapter 5 features a computational study that was undertaken to elucidate the mechanism and origins of stereoselectivity for a novel, organocatalytic, nucleophilic desymmetrisation of prochiral phosphonate ester reaction developed in the Dixon group. The systematic approach that was used to construct a computational model of the experimental conditions is presented. An analysis of the key, non-covalent interactions that governed both stereoselectivity and reactivity of the system is also provided

Regional Databases within Invasive Plant Species Distribution Monitoring

ABSTRACT In the hierarchical system of invasive species inventory the regional level is the basic one. The article is devoted to the use of regional databases at the organization of biological invasions monitoring. The accumulation of information in the database about the land cover at the regional level leads to the accumulation of data about the distribution of invasive species. The use of spatial modeling methods allow to create predictive maps of invasive species potential habitat in the region

Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes

The construction of diverse sp3-rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of 2,7-diazabicyclo[3.2.1]octanes (bridged 1,3-diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4-substituted quinoline substrates, with subsequent Hantzsch ester-promoted reduction to a dihydropyridine intermediate which undergoes in situ two-electron ring closure to form the bridged diazepane architecture. A wide scope of N-arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all-carbon quaternary centers. Computational and experimental mechanistic studies provide insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.<br /

Reverse Polarity Reductive Functionalization of Tertiary Amides via a Dual Iridium Catalyzed Hydrosilylation & SET Strategy

A new strategy for the mild generation of synthetically valuable α-amino radicals from robust tertiary amide building blocks has been developed. By combining Vaska’s complex-catalyzed tertiary amide reductive activation and photochemical single electron reduction into a streamlined tandem process, metastable hemiaminal intermediates were successfully transformed into nucleophilic α-amino free radical species. This umpolung approach to such reactive intermediates was exemplified through coupling with an electrophilic dehydroalanine acceptor, resulting in the synthesis of an array of α-functionalized tertiary amine derivatives, previously inaccessible from the amide starting materials. The utility of the strategy was expanded to include secondary amide substrates, intramolecular variants and late stage functionalization of an active pharmaceutical ingredient. DFT analyses were used to establish the reaction mechanism and elements of the chemical system that were responsible for the reaction’s efficiency

Effective transformation of household savings in the context of a systemic economic crisis

The modern world is characterized by a high degree of digitalization, so citizens have access to an increasing variety of savings options. In just a few clicks, people can purchase shares of the largest companies, invest in real estate rental funds, open deposits in almost any bank, and purchase digital assets. However, financial literacy has not yet reached the level needed to use all financial instruments consciously. Since confidence in the banking and financial system is low, people save in cash, which slows economic growth. The study of various forms of savings and their reliability and availability can increase cashflow from individuals, triggering growth, especially in the current crisis conditions of 2020–2022, with unprecedented sanctions. The purpose of the study is to develop recommendations for the development of modern forms of effective savings for the population under the conditions of a systemic economic crisis. The study uses publicly available data on personal savings rates and relevant scholarly literature and uses the methods of analysis and synthesis, comparison, deduction, and statistical generalizations. In the course of the study, key savings trends and urgent income issues were identified, allowing for the formulation of several recommendations to improve the efficiency of modern savings methods

Modular Synthesis of β‑Amino Boronate Peptidomimetics

Herein, we describe the synthesis of novel β-amino boronate peptidomimetics from amphoteric α-borylaldehydes in the Ugi multicomponent reaction. A mild deprotection method provided the free and stable boronic acid forms of the target molecules, which display notable stability toward protodeborylation. Despite the presence of Lewis acidic boron, there is no evidence for hydrolysis of the adjacent amide via a 5- or 6-membered ring intermediate. This methodology should facilitate the development of libraries of new boron-containing antibiotics and antifungal agents

Catalytic Enantioselective Nucleophilic Desymmetrisation of Phosphonate Esters

Compounds containing one or more stereogenic phosphorous atoms in the P(V) oxidation state are important to chemistry, biology and medicine. These include marketed antiviral drugs such as Tenofovir alafenamide and Remdesivir, an effective treatment for Ebola which has also recently been approved for use against SARS-CoV-2 in the US. Existing approaches for the stereoselective synthesis of P-stereogenic centers, while elegant, remain mostly diastereoselective, with catalytic enantioselective approaches being limited in application. Accordingly, conceptually novel, broad-scope, catalytic strategies for the efficient stereoselective synthesis of diverse stereogenic P(V) containing compounds remain essential. To this end, we describe a novel enantioselective two-stage strategy, exploiting a catalytic and highly enantioselective desymmetrisation of phosphonate esters. Pivoting on the first stereocontrolled, sequential nucleophilic substitution of enantiotopic leaving groups from readily accessible pro-chiral P(V) precursors, a bifunctional iminophosphorane (BIMP) superbase catalyst was found to be essential in delivering reactive desymmetrised intermediates capable of downstream enantiospecific substitution. This uniquely modular, catalytic platform allows broad-scope, stereoselective access to a diverse library of chiral P(V) compounds including those with O, N and S-linkages

A Two-Mediator System Based on a Nanocomposite of Redox-Active Polymer Poly(thionine) and SWCNT as an Effective Electron Carrier for Eukaryotic Microorganisms in Biosensor Analyzers

Electropolymerized thionine was used as a redox-active polymer to create a two-mediated microbial biosensor for determining biochemical oxygen demand (BOD). The electrochemical characteristics of the conducting system were studied by cyclic voltammetry and electrochemical impedance spectroscopy. It has been shown that the most promising in terms of the rate of interaction with the yeast B. adeninivorans is the system based on poly(thionine), single-walled carbon nanotubes (SWCNT), and neutral red (kint = 0.071 dm3/(g·s)). The biosensor based on this system is characterized by high sensitivity (the lower limit of determined BOD concentrations is 0.4 mgO2/dm3). Sample analysis by means of the developed analytical system showed that the results of the standard dilution method and those using the biosensor differed insignificantly. Thus, for the first time, the fundamental possibility of effectively using nanocomposite materials based on SWCNT and the redox-active polymer poly(thionine) as one of the components of two-mediator systems for electron transfer from yeast microorganisms to the electrode has been shown. It opens up prospects for creating stable and highly sensitive electrochemical systems based on eukaryotes