Robby Vroemans

Synlett
DOI: 10.1055/a-2442-1796

Spirocyclobutanes have gained significant attention in medicinal chemistry discovery programs due to their broad spectrum of biological activities and clinical applications. Utilizing ring strain in small molecules to drive organic transformations is one of the most powerful tools in chemical synthesis. Our research group has focused on developing new synthetic strategies enabled by ring strain to construct complex molecules selectively and efficiently. This account summarizes our recent efforts toward the synthesis of a library of functionalized spirocyclobutanes by harnessing the ring strain of bicyclo[1.1.0]butanes. Three spicrocyclization cascades have been developed to incorporate a diverse range of radical precursors into spirocycobutanes.1 Introduction2 Synthesis of Spirocyclobutyl Lactones and -Lactams using Bifunctional Reagents3 Dual Photoredox/Nickel Catalysis for the Synthesis of Spirocyclobutyl Lactams4 Synthesis of Spirocyclobutyl Oxindoles under Photoredox Catalysis5 DFT Studies6 Conclusion
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Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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Iron catalysis: A sustainable and chemo-selective strategy for the synthesis of functionalized branched alcohols is reported using Fe-catalysis. A commercially available catalytic system does not need any special ligand and liberated water and hydrogen as side products. Sequential transformations to substituted pyrroles, chromenes and synthesis of donepezil drug were obtained (>57 entries). Preliminary mechanistic investigations were performed to understand the catalytic pathways.

Abstract

Herein, we have reported a sustainable and chemo-selective strategy for the synthesis of functionalized branched alcohols. A commercially available catalytic system does not need any special ligand and liberated water and hydrogen as side products. A series of alkyl primary alcohols (C4–C10), including methanol, were tolerated in good to high yield. Sequential transformations to substituted pyrroles, chromenes and synthesis of donepezil drug were obtained (>57 entries). Preliminary mechanistic investigations were performed to understand the catalytic pathways.

Institute and/or researcher Twitter usernames:Sain Singh @drsainsinghIIT Roorkee @iitroorkee

Abstract

Three novel cyclometalated ruthenium complexes ([Ru.L⁽⁹⁾ ] [Ru.L⁽¹⁰⁾ ] and [Ru.L⁽¹¹⁾ ]) featuring azo functionalities were synthesized and characterized using a variety of spectroscopic techniques, namely FT-IR, electronic absorption spectroscopy, and ESI-MS. Representative solid-state structures of the acquired complexes were determined through X-ray crystallography. These complexes were evidenced to be efficient catalysts for the synthesis of various α-alkylated compounds utilizing simple acetophenone derivatives with easily affordable and economically viable alcohols, which were isolated and characterized via ¹H and ¹³C NMR spectroscopy. The optimum reaction conditions were found by employing toluene as solvent and potassium tert-butoxide as a base at 115 °C temperature utilizing 0.8 mol % of catalyst [Ru.L⁽¹⁰⁾ ]. The yield of the desired compounds was found to be in the range of 83–97 %. Additionally, mass spectrometry provided insights into the in-situ generated ruthenium hydride and ruthenium alkoxy intermediates, shedding light on the catalytic mechanism.

Abstract

Biomass has been identified as the ultimate sustainable resource for all carbon-based consumer products of the chemical industries in the future. Its catalytic conversion leads to the formation of various platform chemicals that could partially or even fully replace the fossil-based building blocks that have been currently used in synthetic chemical processes. Among these compounds, levulinic acid (LA) has been recognized as a member of the “Top Value Added Chemicals from Biomass” and has attracted significant attention since the seminal paper reported by Werpy and Petersen in 2004. This review summarizes the properties, recent advances, and developments in the chemistry of levulinic acid. The production of LA from both plant and animal-based carbohydrate feedstocks via 5-hydroxymethylfurfural or furfuryl alcohol is discussed from a mechanistic perspective, highlighting intrinsic molecular-level limitations to LA formation. The efficiencies of recently developed catalytic systems are also summarized and compared. Furthermore, the conversion of LA into high-value-added downstream chemicals, including its role in the synthesis of complex molecular structures, is overviewed. This section discussed the reactions of LA in the points of view of its various transformations on carbonyl-, carboxy-, methyl-, and methylene functional groups. The reactions of these functionalities with C−, N−, O−, and S-nucleophiles, alcohols, amines, organometallic reagents, oxygen etc. were thematically summarized. Our review also outlooks to highlight the challenges and opportunities associated with the extensive research area of organic chemistry of levulinic acid.

Reaction scheme for promoter synthesis.

Abstract

One-pot epoxy formulations, containing uncured resin, curing agent, and promoter, require the promoter to be insoluble in the resin at room temperature to prevent premature polymerization. Here, we introduce three novel reaction promoters synthesized by reacting amino propyl imidazole (API) and various diisocyanates such as HMDI, IPDI, or MDI. We evaluate the impact of these promoters on the physical properties, storage stability, and curing kinetics of the resulting epoxy formulations. The results of the kinetic study showed that the compositions containing each synthesized promoter acted as reaction promoters, as evidenced by the lower activation energy in the differential scanning calorimetry (DSC) experiment. The results of the mechanical properties showed that HMDI-API promoter improved both tensile and flexural strength, while exhibiting high storage stability. The findings provide valuable insights for selecting suitable promoters for specific applications in one-pot epoxy systems.

Synlett
DOI: 10.1055/a-2427-7689

Here, we have reported a visible-light-mediated organic photoredox-catalyzed difunctionalization of vinyl arenes via radical–radical coupling. A stabilized benzylic radical at the α-position is generated via the regioselective addition of phosphonyl radical at the β-position of the styrene. Subsequently, benzyl or allyl radical, generated via the deaminative pathway from the Katritzky salt, combines with the α-radical of the styrene to furnish the functionalised C–P and C–C bonds in a single reaction.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Synlett
DOI: 10.1055/s-0043-1775406

Retrosynthesis refers to the process of deconstructing a target molecule step by step until simpler and commercially available synthetic precursors are identified to develop a valid synthetic pathway. As a powerful problem-solving tool, it has gradually been expanded to other fields of chemistry. The application of a ‘retrosynthesis mindset’ can be relevant beyond chemistry, such as in education, research management, and science advice. In this Letter, we discuss the concept of the retrosynthesis mindset and its implications within and beyond chemistry in the hope of highlighting a broader potential and encouraging the adoption of such a mindset to enhance problem solving and strategic planning across disciplines.1 Introduction2 Retrosynthesis Education3 Retrosynthesis Within and Beyond the Lab4 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Synlett
DOI: 10.1055/a-2384-6655

Herein, we report a straightforward approach for synthesizing C3-alkylated indoles selectively via an iron-catalyzed alkylation of indoles using alcohols as the alkylating agents. A well-defined, air-stable, and easy-to-prepare Fe(II) catalyst of a redox-active tridentate arylazo scaffold was used as a catalyst. Various C3-alkylated indoles were prepared selectively in moderate to good isolated yields by coupling indoles with different substituted alcohols. The methodology is compatible with the gram-scale synthesis. Control experiments were performed to unveil the mechanism, which revealed that the alkylation reaction proceeds via borrowing-hydrogen pathway where the coordinated azo-aromatic ligand actively participates during catalysis, acting as an electron and hydrogen reservoir.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Synthesis
DOI: 10.1055/a-2402-6757

A novel bifunctional photocatalyst combining an aza-BODIPY and a chiral oxazoline has been developed. This photocatalyst enables the asymmetric hydroxylation of β‑ketoesters under an oxygen atmosphere and irradiation with 18-W red LEDs. This procedure offers a convenient and potentially general approach to obtain enantioenriched α-hydroxy-β-dicarbonyl products. The results reported in this manuscript demonstrate the promise of this new organic photocatalyst design and will help expand the application of BODIPY-based chiral photocatalysts.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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