Task In Organic Chemistry Research Articles

An Approach for Highly Enantioselective Synthesis of meta-Disubstituted [n]Paracyclophanes.

Atroposelective synthesis of meta-disubstituted [n]paracyclophanes is a difficult task in organic chemistry. We describe a facile approach for the synthesis of meta-disubstituted [n]paracyclophanes using Pd-catalyzed enantioselective C-H olefination and sequential reductive cleavage. A wide range of [n]paracyclophanes was obtained with excellent enantioselectivity. Thermodynamic analysis revealed that the rotational barrier of meta-disubstituted [n]paracyclophanes was lower than that of para-disubstituted [n]paracyclophanes. The synthesized planar-chiral [14]paracyclophane showed a bright fluorescence emission and impressive circularly polarized luminescence activity.

Catalytic C(sp3)-H Trifluoroethylation of Amino Acids and Carboxylic Acids.

Integrating of the trifluoroethyl (-CH2CF3) group into the organic compounds by activating the distal C(sp3)-H bond is a challenging but crucial task in organic chemistry. This transformation imparts unique physicochemical properties to the compounds, such as enhanced lipophilicity, metabolic stability, and altered electronic characteristics. In this study, we unveil a new palladium-catalyzed method to directly introduce the trifluoroethyl group into amino acid and carboxylic acid derivatives. Remarkably, this method effectively activates the β-C(sp3)-H bond across various substrates at room temperature. Utilizing mesityl(2,2,2-trifluoroethyl)iodonium triflate as a trifluoroethyl source, our approach selectively targets the distal β-C(sp3)-H bonds of amino and carboxylic acids, ensuring high chemoselectivity and enabling the straightforward synthesis of a diverse array of important γ-trifluoromethyl amino acid and carboxylic acid derivatives. Furthermore, the practical applicability of this methodology is demonstrated through its scalability for gram-scale synthesis.

Generalized kekulenes and clarenes as novel families of cycloarenes: structures, stability, and spectroscopic properties.

Cycloarenes constitute a captivating class of polycyclic aromatic hydrocarbons with unique structures and properties, but their synthesis represents a challenging task in organic chemistry. Kekulenes and edge-extended kekulenes as classic types of cycloarenes play an important role in the comprehension of π electron distribution, but their sparse molecular diversity considerably limits their further development and application. In this work, we propose two novel classes of cycloarenes, the generalized kekulenes and the clarenes. Using density functional theory, we carry out a comprehensive study of all possible isomers of the generalized kekulenes and clarenes with different sizes. By applying a simple Hückel model, we show that π delocalization plays a crucial role in determining the relative stability of isomers. We also discover that π-π stacking is commonly present in certain larger clarenes and provides a considerable additional stabilization effect, making the corresponding isomers the lowest-energy ones. Among all considered typical looped polyarenes, generalized kekulenes and/or clarenes are revealed to be the energetically most stable forms, suggesting that these novel cycloarenes proposed here would be viable targets for future synthetic work. The simulated 1H NMR spectra and UV-vis absorption spectra provide valuable information about the electronic and optoelectronic properties for the most stable generalized kekulene and clarene species and may support their identification in future synthesis and experimental characterization.

The Digital Task Navigator as a Scaffold for Supporting Higher Education Students while Solving Tasks in Organic Chemistry

The Digital Task Navigator as a Scaffold for Supporting Higher Education Students while Solving Tasks in Organic Chemistry

Versatile Biocatalytic C(sp3 )-H Oxyfunctionalization for the Site- Selective and Stereodivergent Synthesis of α- and β-Hydroxy Acids.

C(sp3 )-H oxyfunctionalization, the insertion of an O-atom into C(sp3 )-H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3 )-H oxyfunctionalization has the potential to overcome limitations inherent to small-molecule-mediated approaches by delivering catalyst-controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3 )-H bonds, providing concise synthetic routes towards four types of 92 α- and β-hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.

Versatile Biocatalytic C(sp3)−H Oxyfunctionalization for the Site‐ Selective and Stereodivergent Synthesis of α‐ and β‐Hydroxy Acids

AbstractC(sp3)−H oxyfunctionalization, the insertion of an O‐atom into C(sp3)−H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3)−H oxyfunctionalization has the potential to overcome limitations inherent to small‐molecule‐mediated approaches by delivering catalyst‐controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α‐ketoglutarate‐dependent iron dioxygenases that catalyze the site‐ and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3)−H bonds, providing concise synthetic routes towards four types of 92 α‐ and β‐hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.

RetroRanker: leveraging reaction changes to improve retrosynthesis prediction through re-ranking

Retrosynthesis is an important task in organic chemistry. Recently, numerous data-driven approaches have achieved promising results in this task. However, in practice, these data-driven methods might lead to sub-optimal outcomes by making predictions based on the training data distribution, a phenomenon we refer as frequency bias. For example, in template-based approaches, low-ranked predictions are typically generated by less common templates with low confidence scores which might be too low to be comparable, and it is observed that recorded reactants can be among these low-ranked predictions. In this work, we introduce RetroRanker, a ranking model built upon graph neural networks, designed to mitigate the frequency bias in predictions of existing retrosynthesis models through re-ranking. RetroRanker incorporates potential reaction changes of each set of predicted reactants in obtaining the given product to lower the rank of chemically unreasonable predictions. The predicted re-ranked results on publicly available retrosynthesis benchmarks demonstrate that we can achieve improvement on most state-of-the-art models with RetroRanker. Our preliminary studies also indicate that RetroRanker can enhance the performance of multi-step retrosynthesis.

Atroposelective remote meta-C−H arylation of 2-arylanilines

Enantioselective remote C−H activation is a challenging task in organic chemistry, and atroposelective synthesis of remotely substituted axially chiral molecules via direct C−H activation remains elusive. In this issue of Chem, Yu, Wang, and co-workers report an atroposelective meta-C−H arylation of 2-arylanilines via an enantioselective palladation relay strategy. Enantioselective remote C−H activation is a challenging task in organic chemistry, and atroposelective synthesis of remotely substituted axially chiral molecules via direct C−H activation remains elusive. In this issue of Chem, Yu, Wang, and co-workers report an atroposelective meta-C−H arylation of 2-arylanilines via an enantioselective palladation relay strategy. Atroposelective remote meta-C–H activationLi et al.ChemMay 1, 2023In BriefThe stereoselective and expedient preparation of axially chiral compounds, abundant in chiral catalysts, pharmaceuticals, and natural products, is a critical objective in synthesis. More specifically, accessing remotely substituted axially chiral motifs remains a significant challenge. We disclose an atroposelective Pd-catalyzed remote C–H activation arylation of 2-arylanilines via an enantioselective palladation relay strategy. This protocol enables direct access to valuable new axially chiral chemical space. Full-Text PDF

Single-step retrosynthesis prediction by leveraging commonly preserved substructures

Retrosynthesis analysis is an important task in organic chemistry with numerous industrial applications. Previously, machine learning approaches employing natural language processing techniques achieved promising results in this task by first representing reactant molecules as strings and subsequently predicting reactant molecules using text generation or machine translation models. Chemists cannot readily derive useful insights from traditional approaches that rely largely on atom-level decoding in the string representations, because human experts tend to interpret reactions by analyzing substructures that comprise a molecule. It is well-established that some substructures are stable and remain unchanged in reactions. In this paper, we developed a substructure-level decoding model, where commonly preserved portions of product molecules were automatically extracted with a fully data-driven approach. Our model achieves improvement over previously reported models, and we demonstrate that its performance can be boosted further by enhancing the accuracy of these substructures. Analyzing substructures extracted from our machine learning model can provide human experts with additional insights to assist decision-making in retrosynthesis analysis.

Electrochemical Reduction of Diarylketones and Aryl Alkenes

AbstractThe reduction of ketones or alkenes is an attractive and challenging task in organic chemistry and has widespread applications in the production of fine chemicals, fragrances, pharmaceuticals, vitamins, and functional materials. Classical reduction methods usually require the use of potentially dangerous hydrogen and the reaction under high temperature and pressure conditions, so environmentally friendly, economical, simple, and safe reduction methods are urgently needed. This paper innovatively reports a method for the electrochemical reduction of diarylketones or aryl alkenes in a mixed solvent system of CH3CN/THF. The reaction proceeds smoothly, and the corresponding products are obtained in high yields. The mechanistic study shows that the reaction is a free radical reaction, and reveals the necessity of CH3CN solvent, which plays the three roles of solvent, proton donors, and reactant at the same time. Furthermore, the high yield of the gram‐scale experiment successfully confirmed the potential industrial application of this electrochemical method.

Modular synthesis of 1,4-diketones through regioselective bis-acylation of olefins by merging NHC and photoredox catalysis

Efficient and modular synthesis of structurally diverse 1,4-diketones from readily available building blocks represents an essential but challenging task in organic chemistry. Herein, we report a multi-component, regioselective bis-acylation of olefins by merging NHC organocatalysis and photoredox catalysis. With this protocol, a broad range of 1,4-diketones could be rapidly assembled using bench-stable feedstock materials. The robustness of this method was further evaluated by sensitivity screening, and good reproductivity was observed. Moreover, the diketone products could be readily converted into functionalized heterocycles, such as multi-substituted furan, pyrrole, and pyridazine. Mechanistic investigations shed light on the NHC and photoredox dual catalytic radical reaction mechanism.

Expanded Kekulenes.

The synthesis of kekulene and its higher homologues is a challenging task in organic chemistry. The first successful synthesis and characterization of the parent kekulene were reported by Diederich and Staab in 1978. Herein, we report the facile preparation of a series of edge-extended kekulenes by bismuth(III) triflate-catalyzed cyclization of vinyl ethers from the properly designed macrocyclic precursors. Their molecular structures were confirmed by X-ray crystallographic analysis and NMR spectroscopy. Their size- and symmetry-dependent electronic structures (frontier molecular orbitals, aromaticity) and physical properties (optical and electrochemical) were investigated by various spectroscopic measurements, assisted by theoretical calculations. Particularly, the acene-like units along each zigzag edge demonstrate a dominant local aromatic character. Our studies provide an easy synthetic strategy toward various fully fused carbon nanostructures and give some insights into the electronic properties of cycloarenes.

The Task Navigator Following the STRAKNAP Concept: Development, Application, and Evaluation of a New Scaffold to Support Nonmajor Chemistry Students while Solving Tasks in Organic Chemistry

Educational Scaffolding was first mentioned in 1976 by Wood et al. Several examples for scaffolding in chemistry are also known from the literature. As written scaffolds, stepped supporting tools to support students while solving problems in organic chemistry were developed, applied, and evaluated. Although the students rated the tool as very helpful, a think-aloud study showed that the support given by this scaffold was not sufficient. As a further development of stepped supporting tools, task navigators were therefore developed, applied, and evaluated. This new scaffold gives tips on strategy, knowledge, and application of knowledge after the STRAKNAP concept. The evaluation of this tool shows that the students rated the tool as being very helpful. A think-aloud study showed that the scaffold supports the students while they solve a problem. Because of the stepwise construction of the task navigators and the providing of the knowledge needed for the application, the students can solve parts of the task successfully even if they do not solve all parts correctly; the students can always start from scratch. When students use the tool regularly, their knowledge of organic chemistry increases compared to students who did not use the tool at all. The task navigator is not only a scaffold for the content of the task but also for the development of methodological competences on the field of strategies and applying knowledge.

Silver in C(sp2)‐H Functionalization

AbstractThe direct functionalization of C−H bonds is a fundamental task in organic chemistry. Because of the extraordinary catalysis performance, reaction selectivity, stability, and relatively lower cost than other noble transition metals, silver catalysts had successfully captured lots of interest and been widely in C−H bond functionalization. In this review, the development in the last decade of silver‐mediated C(sp2)‐H bond functionalization is summarized, categorized by the type of newly formed bond, C−C bond, C−N bond, C−O bond, etc. The mechanism, scope, and limitations of the reported references were introduced.

Valid, Plausible, and Diverse Retrosynthesis Using Tied Two-Way Transformers with Latent Variables.

Retrosynthesis is an essential task in organic chemistry for identifying the synthesis pathways of newly discovered materials, and with the recent advances in deep learning, there have been growing attempts to solve the retrosynthesis problem through transformer models, which are the state-of-the-art in neural machine translation, by converting the problem into a machine translation problem. However, the pure transformer provides unsatisfactory results that lack grammatical validity, chemical plausibility, and diversity in reactant candidates. In this study, we develop tied two-way transformers with latent modeling to solve those problems using cycle consistency checks, parameter sharing, and multinomial latent variables. Experimental results obtained using public and in-house datasets demonstrate that the proposed model improves the retrosynthesis accuracy, grammatical error, and diversity, and qualitative evaluation results verify its ability to suggest valid and plausible results.

Synthesis of a Sidewall Fragment of a (12,0) Carbon Nanotube

AbstractSynthesis of a carbon nanobelt (CNB) is a very challenging task in organic chemistry. Herein, we report the successful synthesis of an octabenzo[12]cyclacene based CNB (6), which can be regarded as a sidewall fragment of a (12,0) carbon nanotube. The key intermediate compound, a tetraepoxy nanobelt (5), was first synthesized by Diels–Alder reaction, and subsequent reductive aromatization gave the fully conjugated CNB 6. X‐ray crystallographic analysis unambiguously confirmed the belt‐shaped structure of 6. 1H NMR spectrum and theoretical calculations (ACID, NICS, and 2D/3D ICSS) revealed localized aromaticity and stronger shielding chemical environment in the inner region of the belt. The optical properties (absorption and emission) of 6 were studied and correlated to its electronic structure. Strain analysis indicates that the phenyl substituents at the zigzag edges are crucial to the successful synthesis of 6. This report presents a new strategy towards highly strained CNBs.

Synthesis of a Sidewall Fragment of a (12,0) Carbon Nanotube.

Synthesis of a carbon nanobelt (CNB) is a very challenging task in organic chemistry. Herein, we report the successful synthesis of an octabenzo[12]cyclacene based CNB (6), which can be regarded as a sidewall fragment of a (12,0) carbon nanotube. The key intermediate compound, a tetraepoxy nanobelt (5), was first synthesized by Diels-Alder reaction, and subsequent reductive aromatization gave the fully conjugated CNB 6. X-ray crystallographic analysis unambiguously confirmed the belt-shaped structure of 6. 1 H NMR spectrum and theoretical calculations (ACID, NICS, and 2D/3D ICSS) revealed localized aromaticity and stronger shielding chemical environment in the inner region of the belt. The optical properties (absorption and emission) of 6 were studied and correlated to its electronic structure. Strain analysis indicates that the phenyl substituents at the zigzag edges are crucial to the successful synthesis of 6. This report presents a new strategy towards highly strained CNBs.

Perceived relevance of tasks in organic chemistry by preservice chemistry teachers

Abstract In this article the development, use and evaluation of tasks in organic chemistry is discussed. These tasks are designed following the concept of school-related content knowledge. In this study the perceived relevance of these new tasks by preservice chemistry teachers was evaluated. Of special interest was the question how new tasks should be designed to be perceived as relevant; are some features of the tasks more suitable than others? To answer all research questions a mixed methods study was conducted. To understand the students’ rating of the new tasks by using questionnaires, in addition focus group interviews were conducted. The suitability of these new tasks for use in written exams was also evaluated. The results show that the students perceived the tasks as relevant for their future profession if they included contents of the school curriculum, realistic situations and were personalized. They perceived the new tasks also as relevant for practicing skills in communication and explanations.

Condensation of Malonic Diethyl Ester with Acrylamide

The purposeful synthesis of polyfunctional organic substances is an important task in organic chemistry, as well as for solving practical problems in technologies of fine organic chemistry and biochemistry. Here presents the results of studies on the synthesis of polyfunctional substances as possible ligand based on with malonic acid diethyl ester. The condensation of malonic acid diethyl ether with acrylamide in phase transfer catalysis conditions leads to new derivative of malonic acid-1,1-dicarbethoxy-3-carbamoilpropane. The formation of mentioned compound has been followed by the method of UV spectrometry. The complexatation of the received substance investigated in relation to iron ions also.

Modular Synthesis of Functionalized Butenolides by Oxidative Furan Fragmentation

The development of new chemical transformations to simplify the synthesis of valuable building blocks is a challenging task in organic chemistry and has been the focus of considerable research effort. Here we report a chemical transformation that enables the facile and modular synthesis of synthetically challenging yet biologically important functionalized butenolides from easily accessible furans. Specifically, Diels–Alder reactions between furans and singlet oxygen generate versatile hydroperoxide intermediates, which undergo iron(II)‐mediated radical fragmentation in the presence of Cu(OAc)2 or various radical trapping reagents to afford butenolides bearing a wide variety of appended remote functional groups, including olefins, halides, azides, and aldehydes. The practical utility of this transformation is demonstrated by easy diversification of the products by means of cross‐coupling reactions and, most importantly, by its ability to simplify the syntheses of known building blocks of eight biologically active natural products.