Organic Chemistry Research Articles

Dual-Catalysis-Enabled Construction of Vicinal Stereogenic Centers through Diastereo- and Enantioselective Allylic Substitution

AbstractVicinal stereogenic centers represent prevalent structural motifs in organic synthetic chemistry, and their construction poses a longstanding challenge. Transition-metal-catalyzed asymmetric allylic substitution has become a well-established enantioselective C–C bond-forming reaction. When these reactions involve a prochiral nucleophile and an allylic electrophile with a terminal substituent, the creation of vicinal stereogenic centers becomes feasible. However, despite remarkable achievements having been accomplished, realizing this transformation with precise control over both the enantio- and diastereoselectivity remains a significant challenge. To address the stereoselective challenges, the introduction of a second catalyst to the transition-metal-catalyzed asymmetric allylic alkylation to control the diastereoselectivity during C–C bond formation has proven particularly fruitful. In this short review, we aim to highlight recent advances in dual catalysis that enable diastereo- and enantioselective allylic substitutions.1 Introduction2 Construction of Vicinal Stereogenic Centers by Organo and Metal Dual Catalysis2.1 Chiral Phase-Transfer Catalysis and Transition-Metal Dual Catalysis2.2 Chiral Amine and Transition-Metal Dual Catalysis2.3 NHC and Transition-Metal Dual Catalysis2.4 Chiral Aldehyde and Transition-Metal Dual Catalysis2.5 Chiral Lewis Base and Transition-Metal Dual Catalysis3 Construction of Vicinal Stereogenic Centers by Metal and Metal Dual Catalysis3.1 Lewis Acidic Metal and Iridium Dual Catalysis3.2 Lewis Acidic Metal and Palladium Dual Catalysis3.3 Palladium and Ruthenium Dual Catalysis3.4 Other Advancements in the Construction of Vicinal Stereogenic Centers through Synergistic Bimetallic Catalysis Enabling Asymmetric Allylic Alkylation4 Conclusions and Future Outlook

Ungrading in organic chemistry: students assessing themselves and reflecting on their learning

The focus on grades has diminished the focus on learning. One strategy that aims to return students’ attention to what they are actually learning (and not just earning) is ungrading. Ungrading is thought of as any strategy in which instructors do not assign a number or letter grade to students’ assignments and assessments. Instead, faculty may (1) provide thorough feedback and engage in dialogue with students about their work, and perhaps, (2) allow students to assign their own grade. Whichever style of ungrading they choose, the scholars that have been forging the path for ungrading come from a variety of fields and perspectives, including STEM instructors in more recent years. The focus on incorporating ungrading practices into the organic chemistry curriculum provided here is adapted from a variety of practitioners, and especially the foundational work of chemistry professor Clarissa Sorensen-Unruh. In addition to discussing the current ungrading practices in various fields, we will use this perspective article to share our own experience with and lessons learned from beginning to incorporate ungrading in the undergraduate organic chemistry curriculum, both as it relates to the implementation of the practice and our own perceptions of the student experience and learning outcomes. Ultimately, the goal is to allow students to see the significance of the process of learning and to engage in some metacognitive work that they can apply to different assignments, whether in our class or not. If we want students to focus on learning, perhaps they should do the grading themselves.

Modifying an Organic Chemistry Esterification Teaching Lab to Be Accessible to Blind and Visually Impaired (BVI) Students

Modifying an Organic Chemistry Esterification Teaching Lab to Be Accessible to Blind and Visually Impaired (BVI) Students

Advancements in hydrochlorination of alkenes

The hydrochlorination of alkenes has been extensively studied in research and is commonly featured in organic chemistry textbooks as an exemplification of the Markovnikov rule. However, the application of this reaction is typically limited to specific alkenes, such as highly substituted ones, styrenes, or strained systems. Conversely, monosubstituted or 1,2-disubstituted alkenes do not readily react with HCl gas or solutions of HCl gas at practical rates. The challenges associated with hydrochlorination reactions for these "non-activated" alkenes have spurred considerable research efforts over the past 30 years, which constitute the primary focus of this review. The discussion begins with classical polar hydrochlorinations, followed by metal-promoted radical hydrochlorinations, and concludes with a brief overview of recent anti-Markovnikov hydrochlorinations.

Crafting British medicine in the Empire: the establishment of medical schools in India and Canada, 1763-1837.

In the early nineteenth century, medical schools became a growing means of regulating medicine in the British Empire, both in the metropole and in two colonies: India and Canada. By examining the establishment of medical schools in Calcutta, Bombay, Madras, Quebec City, Montreal and Toronto between the end of the Seven Years' War and the beginning of the Victorian era, this article argues that the rise of the British Empire was a key factor in the gradual replacement of private medical apprenticeships with institutional medical education. Although the imperial state did not implement a uniform medical policy across the British Empire, the medical schools established under its jurisdiction were instrumental in devising a curriculum that emphasised human dissection, bedside training in hospitals and organic chemistry as criteria of medical competence.

Exploring student perceptions: Factors influencing academic performance in a school of pharmacy in Nigeria

Background: The failure and success rate of students in pharmacy school has been shown to be dependent on some courses that predict academic performance. The study identified factors that could impact failure and academic performances of pharmacy students at Obafemi Awolowo University. Methods: The study was a cross-sectional study of 219 undergraduate pharmacy students from third, fourth and fifth years of a school of pharmacy in Nigeria. A pre-tested questionnaire gathered data on demographics, course perceptions and academic factors. Descriptive and inferential statistics such as percentages, weighted averages, and Chi squared tests were used to analyse the data obtained at p < 0.05. Results: Financial constraints, family challenges, and a lack of peer interaction were significantly associated with repeating a year. Specific courses perceived as difficult included “Pharmaceutical organic chemistry” (PHC 202), “Practical pharmaceutics I” (PHA 201) and “Medicinal chemistry II” (PHC 402). Courses perceived as difficult, particularly in the fourth year, were notably linked to academic stress. Conclusion: The study identified specific factors and courses that affect pharmacy students’ performance in the Nigerian context. Policy makers and faculty can take vital feedback to adjust the training content, methods and assessment system to possibly deliver a holistic education to pharmacy students.     

From Ground-State to Excited-State Activation Modes: Flavin-Dependent "Ene"-Reductases Catalyzed Non-natural Radical Reactions.

ConspectusEnzymes are desired catalysts for chemical synthesis, because they can be engineered to provide unparalleled levels of efficiency and selectivity. Yet, despite the astonishing array of reactions catalyzed by natural enzymes, many reactivity patterns found in small molecule catalysts have no counterpart in the living world. With a detailed understanding of the mechanisms utilized by small molecule catalysts, we can identify existing enzymes with the potential to catalyze reactions that are currently unknown in nature. Over the past eight years, our group has demonstrated that flavin-dependent "ene"-reductases (EREDs) can catalyze various radical-mediated reactions with unparalleled levels of selectivity, solving long-standing challenges in asymmetric synthesis.This Account presents our development of EREDs as general catalysts for asymmetric radical reactions. While we have developed multiple mechanisms for generating radicals within protein active sites, this account will focus on examples where flavin mononucleotide hydroquinone (FMNhq) serves as an electron transfer radical initiator. While our initial mechanistic hypotheses were rooted in electron-transfer-based radical initiation mechanisms commonly used by synthetic organic chemists, we ultimately uncovered emergent mechanisms of radical initiation that are unique to the protein active site. We will begin by covering intramolecular reactions and discussing how the protein activates the substrate for reduction by altering the redox-potential of alkyl halides and templating the charge transfer complex between the substrate and flavin-cofactor. Protein engineering has been used to modify the fundamental photophysics of these reactions, highlighting the opportunity to tune these systems further by using directed evolution. This section highlights the range of coupling partners and radical termination mechanisms available to intramolecular reactions.The next section will focus on intermolecular reactions and the role of enzyme-templated ternary charge transfer complexes among the cofactor, alkyl halide, and coupling partner in gating electron transfer to ensure that it only occurs when both substrates are bound within the protein active site. We will highlight the synthetic applications available to this activation mode, including olefin hydroalkylation, carbohydroxylation, arene functionalization, and nitronate alkylation. This section also discusses how the protein can favor mechanistic steps that are elusive in solution for the asymmetric reductive coupling of alkyl halides and nitroalkanes. We are aware of several recent EREDs-catalyzed photoenzymatic transformations from other groups. We will discuss results from these papers in the context of understanding the nuances of radical initiation with various substrates.These biocatalytic asymmetric radical reactions often complement the state-of-the-art small-molecule-catalyzed reactions, making EREDs a valuable addition to a chemist's synthetic toolbox. Moreover, the underlying principles studied with these systems are potentially operative with other cofactor-dependent proteins, opening the door to different types of enzyme-catalyzed radical reactions. We anticipate that this Account will serve as a guide and inspire broad interest in repurposing existing enzymes to access new transformations.

Oxide Solid‐Solution Catalysts with Good Redox Properties for Liquid Phase Reactions: A Review

In this review, we discuss liquid‐phase redox reactions using oxide solid‐solution catalysts. These oxide solid solutions are readily prepared by introducing various elements into the foundational metal oxide template. Doping with metal species leads to the formation of [MOx] clusters with unique coordination structures, which is a remarkable feature that deserves attention. Consequently, oxide solid solutions exhibit catalytic capabilities that extend beyond those of conventional metal‐oxide catalysts. Notably, these [MOx] clusters occasionally exhibit exceptional redox activities that can be used to catalyze liquid‐phase redox reactions. Hence, we conjecture that a connection exists between catalyst structure and activity. This review delves into oxide solid‐solution catalysts through the lenses of organic chemistry, solid catalysts, and computational chemistry, thereby collectively shaping our understanding and prospects in this field.

Organic Synthesis: When and Why─An Entrepreneurial-Minded Learning Activity for Organic Chemistry Undergraduates

Organic Synthesis: When and Why─An Entrepreneurial-Minded Learning Activity for Organic Chemistry Undergraduates

Metal Complexes in Biology and Medicine: The System Cadmium ((II))/ Iron ((II))/ Zinc ((II)) - α - Aminobutenoic Acid

Metal ions play an important role in biological system. The importance of metal ions to essential functions of living systems and for wellbeing of living organisms is well known. Metal ions are fundamental elements for the maintenance of life spans of the human, animals, and plants. Recent advances in inorganic chemistry have made possible formation of number of transition metal complexes with organic ligand of interest, which can be used as therapeutic agent. In coordination compounds studies, knowledge of the stability constants of complexes is necessary for preliminary quantitative treatment. The present technique involving the use of paper electrophoresis is described for the study of equilibria in binary complex systems in solution. The method is based on the movement of a spot of a metal ion in an electric field at various pH’s of background electrolyte. A graph of pH versus mobility was used to obtained information in the binary complexes and to calculate its stability constants. Using this method , the stability constants of binary complexes metal (II) – α – aminobutenoic acid have been determined to be ( 3.78 ± 0.01, 2.48 ± 0.03 ); ( 3.27 ± 0.04, 2.33 ± 0.07 ); and (4.45 ± 0.02, 2.66 ± 0.05); (logarithm stability constant values) for cadmium (II), iron (II) and zinc (II) complexes, respectively, at ionic strength 0.01 Mol / L and a temperature of 35º C.

Ortho C-H Bond Activations in an Atmospheric Microwave Plasma Ion Source.

C-H bond ortho-substitution reaction has always been a significant and challenging topic in organic chemistry. We proposed a synthesis method based on microwave plasma torches. High-resolution mass spectrometry was used to monitor rapid reaction products. 2-Alkylbenzimidazole can be formed through the reaction of phenylnitrenium ion and nitriles on a millisecond scale. This reaction can achieve the one-step formation of benzimidazoles from benzene ring single-substituted compounds without the addition of external oxidants or catalysts. A similar C-H bond activation reaction can be accomplished with ketones. Meanwhile, the microwave plasma reactor was modified, and the resulting 2-methylbenzimidazole was successfully collected, indicating the device has good application potential in organic reactions such as C-H bond activation reaction.

Artificial Intelligence for Retrosynthetic Planning Needs Both Data and Expert Knowledge.

Rapid advancements in artificial intelligence (AI) have enabled breakthroughs across many scientific disciplines. In organic chemistry, the challenge of planning complex multistep chemical syntheses should conceptually be well-suited for AI. Yet, the development of AI synthesis planners trained solely on reaction-example-data has stagnated and is not on par with the performance of "hybrid" algorithms combining AI with expert knowledge. This Perspective examines possible causes of these shortcomings, extending beyond the established reasoning of insufficient quantities of reaction data. Drawing attention to the intricacies and data biases that are specific to the domain of synthetic chemistry, we advocate augmenting the unique capabilities of AI with the knowledge base and the reasoning strategies of domain experts. By actively involving synthetic chemists, who are the end users of any synthesis planning software, into the development process, we envision to bridge the gap between computer algorithms and the intricate nature of chemical synthesis.

Optimal Oriented External Electric Fields to Trigger a Barrierless Oxaphosphetane Ring Opening Step of the Wittig Reaction.

The Wittig reaction is one of the most important processes in organic chemistry for the asymmetric synthesis of olefinic compounds. In view of the increasingly acknowledged potentiality of the electric fields in promoting reactions, here we will consider the effect of the oriented external electric field (OEEF) on the second step of Wittig reaction (i. e. the ring opening oxaphosphetane) in a model system for non-stabilized ylides. In particular, we have determined the optimal direction and strength of the electric field that should be applied to annihilate the reaction barrier of the ring opening through the polarizable molecular electric dipole (PMED) model that we have recently developed. We conclude that the application of the optimal external electric field for the oxaphosphetane ring opening favours a Bestmann-like mechanism.

Incorporating Green Chemistry into Undergraduate Organic Chemistry Laboratory: Synthesis of Banana Oil

Incorporating Green Chemistry into Undergraduate Organic Chemistry Laboratory: Synthesis of Banana Oil

"Naked life": the vital meaning of nutrition in ClaudeBernard's physiology.

The aim of this paper is to elucidate the vital meaning and strategic role that nutrition holds in Claude Bernard's "biological philosophy", in the sense Auguste Comte gave to this expression, i.e. the theoretical part of biology. I propose that Bernard's nutritive perspective on life should be thought of as an "interfield" object, following Holmes' category. Not only does nutrition bridge disciplines like physiology and organic chemistry, as well as levels of inquiry ranging from special physiology to the organism's total level, including the cell and protoplasm, but it also forms the genetic and structural foundation for Bernard's two fundamental axioms in general physiology: the necessary complementarity of destruction and creation (1) and the uniformity of this physiological law across all life forms, be it plants or animals (2). Because Bernard's nutritive theory is a major pivot for the re-ordering of life and its characterization, I argue that it must be located and understood in the scientific and metaphysical context of his time, of which he claims to be the heir and challenger-what I propose to characterize as the "epistemic space" of nutrition, on the background of which Bernard builds his own "logic". I then set out this logic of nutrition, focusing on three interrelated bernardian theses: the establishment of the theory of indirect nutrition as the basis for the notion of "milieu intérieur"; the enduring conception of nutrition as a continuous generation; the emphasis on nutrition as a way of reshaping the form/matter relationship.

Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Recent Advances in the Total Synthesis of Spirotryprostatin Alkaloids.

Spirotryprostatin alkaloids, a class of alkaloids with a unique spirocyclic indoledionepiperazine structure, were first extracted from the fermentation broth of Aspergillus fumigatus and have garnered significant attention in the fields of biology and pharmacology. The investigation into the pharmacological potential of this class of alkaloids has unveiled promising applications in drug discovery and development. Notably, certain spirotryprostatin alkaloids have demonstrated remarkable anti-cancer activity, positioning them as potential candidates for anti-tumor drug development. In recent years, organic synthetic chemists have dedicated efforts to devise efficient and viable strategies for the total synthesis of spirotryprostatin alkaloids, aiming to meet the demands within the pharmaceutical domain. The construction of the spiro-C atom within the spirotryprostatin scaffold and the chirality control at the spiro atomic center emerge as pivotal aspects in the synthesis of these compounds. This review categorically delineates the synthesis of spirotryprostatin alkaloids based on the formation mechanism of the spiro-C atom.

Recent Advances on Diarylethene-Based Photoswitching Materials: Applications in Bioimaging, Controlled Singlet Oxygen Generation for Photodynamic Therapy and Catalysis.

Diarylethenes (DAE), a class of best performing photoswitchable compounds, where the key features of stability, photoisomerization wavelengths, quantum yield and variability in the photoisomers significantly depend on their derivatization. The last decade has witnessed a surge in the engagement of DAEs to different areas of chemical and biological impacts like catalysis in synthetic organic chemistry, biological markers for in vivo imaging of live cells, chemosensing within cells to photo-dynamic therapy by controlled generation of singlet oxygen. Previous reviews on applications of DAE-based systems did not predominantly cover all the aspects of biological and industrial implementations. They have covered only one field of application either in the biological science or the synthetic aspect or photochromic aspects only. This review is a coalition of all those aspects in last six years. Here the variation of properties of the DAE systems with respect to structural diversifications have been discussed in detail along with their potential applications in catalysis, regulating singlet oxygen generation, photodynamic therapy, bioimaging and their future prospects. We hope that this review will certainly motivate researchers to generate new DAE architectures with superior bioimaging or catalyzing properties in future.

Chemodivergence in Fluorine Source-Controlled Cascade Reaction of Aryne Precursors to Synthesize Pyrrolo[3,4-b]indoles and 3-Arylated Maleimides.

Reactions allowing chemodivergence prove to be attractive strategies in synthetic organic chemistry. We herein described a highly practical, transition-metal-free, highly regioselective and chemodivergent cascade reaction controlled by fluorine sources, which involved a [3 + 2] cycloaddition or C-arylation process between aryne precursors and 3-aminomaleimides. These two pathways led to a wide scope of structurally diverse pyrrolo[3,4-b]indoles (19 examples) and 3-arylated maleimides (25 examples) in good-to-excellent yields. Furthermore, the reaction could be scaled up, and several synthetic transformations were accomplished for the preparation of functionalized molecules and might provide new opportunities for the discovery of N-heterocyclic drugs.

Recent Progress in Haloalkene Synthesis by Hydrohalogenation (HX=HCl, HBr, HI) of Alkynes

AbstractHydrohalogenation of alkynes is one of the fundamental reactions in organic chemistry, as described in textbooks that begins from old time as Reppe's chemistry. This method, which directly affords haloalkenes in a single step, is attractive from both industrial and academic viewpoints. Despite the long history of this reaction, novel efficient catalysts and regioselective and/or stereoselective controlled reactions are still a challenging topic. This review addresses the recent (past decade) advances in this field of organic chemistry.