Synthesis Of Small Organic Molecules Research Articles

Photoredox Product Selectivity Controlled by Persistent Radical Stability.

The use of photoredox catalysis for the synthesis of small organic molecules relies on harnessing and converting the energy in visible light to drive reactions. Specifically, photon energy is used to generate radical ion species that can be harnessed through subsequent reaction steps to form a desired product. Cyanoarenes are widely used as arylating agents in photoredox catalysis because of their stability as persistent radical anions. However, there are marked, unexplained variations in product yields when using different cyanoarenes. In this study, the quantum yield and product yield of an α-aminoarylation photoredox reaction between five cyanoarene coupling partners and N-phenylpyrrolidine were characterized. Significant discrepancies in cyanoarene consumption and product yield suggested a chemically irreversible, unproductive pathway in the reaction. Analysis of the side products in the reaction demonstrated the formation of species consistent with radical anion fragmentation. Electrochemical and computational methods were used to study the fragmentation of the different cyanoarenes and revealed a correlation between product yield and cyanoarene radical anion stability. Kinetic modeling of the reaction demonstrates that cross-coupling selectivity between N-phenylpyrrolidine and the cyanoarene is controlled by the same phenomenon present in the persistent radical effect.

Recent synthetic strategies of small heterocyclic organic molecules with optoelectronic applications: a review.

Over the past few years, there have been tremendous developments in the design and synthesis of organic optoelectronic materials with appealing applications in device fabrication of organic light-emitting diodes, superconductors, organic lasers, organic field-effect transistors, clean energy-producing organic solar cells, etc. There is an increasing demand for the synthesis of green, highly efficient organic optoelectronic materials to cope with the issue of efficiency roll-off in organic semiconductor-based devices. This review systematically summarized the recent progress in the design and synthesis of small organic molecules having promising optoelectronic properties for their potential applications in optoelectronic devices during the last 10-year range (2010-early 2021).

Engineering single–atom active sites anchored covalent organic frameworks for efficient metallaphotoredox C[sbnd]N cross–coupling reactions

Photoredox catalysis has become an indispensable solution for the synthesis of small organic molecules. However, the precise construction of single-atomic active sites not only determines the catalytic performance, but also avails the understanding of structure–activity relationship. Herein, we develop a facile approach to immobilize single-atom Ni sites anchored porous covalent organic framework (COF) by use of 4,4′,4″-(1,3,5-triazine-2,4,6-triyl)trianiline and 2,6-diformylpyridine (Ni SAS/TD-COF). Ni SAS/TD-COF catalyst achieves excellent catalytic performance in visible-light-driven catalytic carbon–nitrogen cross-coupling reaction between aryl bromides and amines under mild conditions. The reaction provides amine products in excellent yields (71%–97%) with a wide range of substrates, including aryl and heteroaryl bromides with electron-deficient, electron-rich and neutral groups. Notably, Ni SAS/TD-COF could be recovered from the reaction mixture, corresponding to the negligible loss of photoredox performance after several cycles. This work provides a promising opportunity upon rational design of single-atomic active sites on COFs and the fundamental insight of photoredox mechanism for sustainable organic transformation.

Highly Regio‐ and Enantioselective Hydrosilylation of gem‐Difluoroalkenes by Nickel Catalysis

AbstractThe synthesis of small organic molecules with a difluoromethylated stereocenter is particularly attractive in drug discovery. Herein, we have developed an efficient method for the direct generation of difluoromethylated stereocenters through Ni0‐catalyzed regio‐ and enantioselective hydrosilylation of gem‐difluoroalkenes. The reaction also represents the enantioselective construction of carbon(sp3)−silicon bonds with nickel catalysis, which provides an atom‐ and step‐economical synthesis route of high‐value optically active α‐difluoromethylsilanes. This protocol features readily available starting materials and commercial chiral catalysis, broad substrates spanning a range of functional groups with high yield (up to 99 % yield) and excellent enantioselectivity (up to 96 % ee). The enantioenriched products undergo a variety of stereospecific transformations. Preliminary mechanistic studies were performed.

Highly Regio- and Enantioselective Hydrosilylation of gem-Difluoroalkenes by Nickel Catalysis.

The synthesis of small organic molecules with a difluoromethylated stereocenter is particularly attractive in drug discovery. Herein, we have developed an efficient method for the direct generation of difluoromethylated stereocenters through Ni0 -catalyzed regio- and enantioselective hydrosilylation of gem-difluoroalkenes. The reaction also represents the enantioselective construction of carbon(sp3 )-silicon bonds with nickel catalysis, which provides an atom- and step-economical synthesis route of high-value optically active α-difluoromethylsilanes. This protocol features readily available starting materials and commercial chiral catalysis, broad substrates spanning a range of functional groups with high yield (up to 99 % yield) and excellent enantioselectivity (up to 96 % ee). The enantioenriched products undergo a variety of stereospecific transformations. Preliminary mechanistic studies were performed.

Identification of the Tyrosine- and Phenylalanine-Derived Soluble Metabolomes of Sorghum.

The synthesis of small organic molecules, known as specialized or secondary metabolites, is one mechanism by which plants resist and tolerate biotic and abiotic stress. Many specialized metabolites are derived from the aromatic amino acids phenylalanine (Phe) and tyrosine (Tyr). In addition, the improved characterization of compounds derived from these amino acids could inform strategies for developing crops with greater resilience and improved traits for the biorefinery. Sorghum and other grasses possess phenylalanine ammonia-lyase (PAL) enzymes that generate cinnamic acid from Phe and bifunctional phenylalanine/tyrosine ammonia-lyase (PTAL) enzymes that generate cinnamic acid and p-coumaric acid from Phe and Tyr, respectively. Cinnamic acid can, in turn, be converted into p-coumaric acid by cinnamate 4-hydroxylase. Thus, Phe and Tyr are both precursors of common downstream products. Not all derivatives of Phe and Tyr are shared, however, and each can act as a precursor for unique metabolites. In this study, 13C isotopic-labeled precursors and the recently developed Precursor of Origin Determination in Untargeted Metabolomics (PODIUM) mass spectrometry (MS) analytical pipeline were used to identify over 600 MS features derived from Phe and Tyr in sorghum. These features comprised 20% of the MS signal collected by reverse-phase chromatography and detected through negative-ionization. Ninety percent of the labeled mass features were derived from both Phe and Tyr, although the proportional contribution of each precursor varied. In addition, the relative incorporation of Phe and Tyr varied between metabolites and tissues, suggesting the existence of multiple pools of p-coumaric acid that are fed by the two amino acids. Furthermore, Phe incorporation was greater for many known hydroxycinnamate esters and flavonoid glycosides. In contrast, mass features derived exclusively from Tyr were the most abundant in every tissue. The Phe- and Tyr-derived metabolite library was also utilized to retrospectively annotate soluble MS features in two brown midrib mutants (bmr6 and bmr12) identifying several MS features that change significantly in each mutant.

Electrochemical Installation of CFH2 -, CF2 H-, CF3 -, and Perfluoroalkyl Groups into Small Organic Molecules.

Electrosynthesis can be considered a powerful and sustainable methodology for the synthesis of small organic molecules. Due to its intrinsic ability to generate highly reactive species under mild conditions by anodic oxidation or cathodic reduction, electrosynthesis is particularly interesting for otherwise challenging transformations. One such challenge is the installation of fluorinated alkyl groups, which has gained significant attention in medicinal chemistry and material science due to their unique physicochemical features. Unsurprisingly, several electrochemical fluoroalkylation methods have been established. In this review, we survey recent developments and established methods in the field of electrochemical mono-, di-, and trifluoromethylation, and perfluoroalkylation of small organic molecules.

Electrochemical Assembly for Synthesis of Middle-Sized Organic Molecules.

Electrochemical methods offer a powerful, reliable, and environmentally benign approach for the synthesis of small organic molecules, and such methods are useful not only for the transformation of small molecules, but also for the preparation of oligomers and polymers. Electrochemical assembly is a concept that allows structurally well-defined middle-sized organic molecules to be synthesized by applying electrochemical methods. The preparation of dendrimers, dendronized polymers, and oligosaccharides are introduced as examples of such an approach. Automated electrochemical assembly of oligosaccharides is also demonstrated using the electrochemical synthesizer developed by our group.

Green Synthesis of Triazole-Based Chemosensors and their Efficacy Towards Mercury Sensing

Background: The synthesis of small organic molecules based Hg2+ ions receptors have gained considerable attention because it is one of the most prevalent toxic metals which is continuously discharged into the environment by different natural and industrial activities. 1,4-Disubstituted 1,2,3-triazoles have been reported as good chemosensors for the detection of various metal ions including Hg2+ ions. Methods: The synthesis of 1,2,3-triazoles (4a-4c) was achieved by Cu(I)-catalyzed azide-alkyne cycloaddition, and their binding affinity towards various metal ions and anions were studied by UVVisible titration experiments. The perchlorate salts of metal ions and tetrabutylammonium salts of anions were utilized for the UV-Visible experiments. DFT studies were performed to understand the binding and mechanism on the sensing of 4a toward Hg2+ using the B3LYP/6-311G(d,p) method for 4a and B3LYP/LANL2DZ for 4a-Hg2+ species on the Gaussian 09W program. Results: The UV-visible experiments indicated that the compounds 4a-4c show a selective response towards Hg2+ ion in UV-Visible spectra, while other ions did not display such changes in the absorption spectra. The binding stoichiometry was evaluated by Job’s plot which indicated the 1:1 binding stoichiometry between receptors (4a-4c) and Hg2+ ion. The detection limit of 4a, 4b and 4c for the Hg2+ ions was found to be 29.1 nM, 3.5 μM and 1.34 μM, respectively. Conclusion: Some 1,2,3-triazole derivatives were synthesized (4a-4c) exhibiting high selectively and sensitivity towards Hg2+ ions in preference to other ions. Compound 4a has a low detection limit of 29.1 nM and the binding constant of 2.3×106 M-1. Similarly, 4b and 4c also showed selective sensing towards Hg2+ ions in the μM range. The observed experimental results were corroborated by density functional theory (DFT) calculations.

Thermodiffusion and hydrolysis of 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC).

Presently, microfluidic traps are designed mimicking the environment of hydrothermal pores, where a combination of thermophoresis and convection leads to accumulation so that high concentrations of organic matter can be reached. Such a setup is interesting in the context of the origin of life to observe accumulation and possible further synthesis of small organic molecules or prebiotic molecules such as nucleotides or RNA-fragments, but could also be used to replicate DNA-strands. The addition of coupling agents for the activation of carboxyl or phosphate groups such as 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and EDC-hydrochloride (EDC-HCl) is necessary in order to speed up the process. This work characterizes the thermophoretic properties of EDC and EDC-HCl needed to optimize the design of the traps. At p H 4-6 spontaneous hydrolysis of EDC is observed, which also leads to a neutralisation of the p H. In order to evaluate the thermodiffusion measurements the rate constants were measured at 23 and [Formula: see text] C and the activation energy of the hydrolysis calculated.

Current Parallel Solid-Phase Synthesis of Drug-like Oxadiazole and Thiadiazole Derivatives for Combinatorial Chemistry.

Solid-phase organic synthesis is a powerful tool in the synthesis of small organic molecules and building of libraries of compounds for drug discovery. Heterocyclic compounds are important components of the drug discovery field as well and serve as a core for hundreds of marketed drugs. In particular, oxadiazole and thiadiazole cores are compounds of great interest due to their comprehensive biological activities and structural features. Therefore, a plethora of oxadiazole and thiadiazole synthesis methodologies have been reported to date, including solution and solid-phase synthesis methodologies. In this review, we concentrate on and summarize solid-phase synthetic approaches of the oxadiazole and thiadiazole derivatives.

Pd-Catalyzed Mizoroki-Heck Reactions Using Fluorine-Containing Agents as the Cross-Coupling Partners

The Mizoroki-Heck reaction represents one of the most convenient methods for carbon-carbon double bond formation in the synthesis of small organic molecules, natural products, pharmaceuticals, agrochemicals, and functional materials. Fluorine-containing organic compounds have found wide applications in the research areas of materials and life sciences over the past several decades. The incorporation of fluorine-containing segments into the target molecules by the Mizoroki-Heck reactions is highly attractive, as these reactions efficiently construct carbon-carbon double bonds bearing fluorinated functional groups by simple procedures. This review summarizes the palladium-catalyzed Mizoroki-Heck reactions using various fluorine-containing reagents as the cross-coupling partners. The first part of the review describes the Pd-catalyzed Mizoroki-Heck reactions of aryl halides or pseudo-halides with the fluorinated alkenes, and the second part discusses the Pd-catalyzed Mizoroki-Heck reactions of the fluorinated halides or pseudo-halides with alkenes. Variants of the Pd-catalyzed Mizoroki-Heck reactions with fluorine-containing reagents are also briefly depicted. This work supplies an overview, as well as a guide, to both younger and more established researchers in order to attract more attention and contributions in the realm of Mizoroki-Heck reactions with fluorine-containing participants.

Mechanochemical synthesis of small organic molecules.

With the growing interest in renewable energy and global warming, it is important to minimize the usage of hazardous chemicals in both academic and industrial research, elimination of waste, and possibly recycle them to obtain better results in greener fashion. The studies under the area of mechanochemistry which cover the grinding chemistry to ball milling, sonication, etc. are certainly of interest to the researchers working on the development of green methodologies. In this review, a collection of examples on recent developments in organic bond formation reactions like carbon–carbon (C–C), carbon–nitrogen (C–N), carbon–oxygen (C–O), carbon–halogen (C–X), etc. is documented. Mechanochemical syntheses of heterocyclic rings, multicomponent reactions and organometallic molecules including their catalytic applications are also highlighted.

Application of visible-light photosensitization to form alkyl-radical-derived thin films on gold.

Visible-light irradiation of phthalimide esters in the presence of the photosensitizer [Ru(bpy)3]2+ and the stoichiometric reducing agent benzyl nicotinamide results in the formation of alkyl radicals under mild conditions. This approach to radical generation has proven useful for the synthesis of small organic molecules. Herein, we demonstrate for the first time the visible-light photosensitized deposition of robust alkyl thin films on Au surfaces using phthalimide esters as the alkyl radical precursors. In particular, we combine visible-light photosensitization with particle lithography to produce nanostructured thin films, the thickness of which can be measured easily using AFM cursor profiles. Analysis with AFM demonstrated that the films are robust and resistant to mechanical force while contact angle goniometry suggests a multilayered and disordered film structure. Analysis with IRRAS, XPS, and TOF SIMS provides further insights.

Abstract PL04-01: G-quadruplexes and DNA dynamics

Abstract DNA is structurally dynamic in ways that have a consequence for biologic processes. A class of four-stranded DNA structure, called the G-quadruplexes, can be formed from G-rich single-stranded DNA. There is now a good level of understanding of the structural biophysics of G-quadruplexes along with a large body of work on the design and synthesis of small organic molecules that can target such structures. Some such molecules have been found to have antiproliferative effects on human cancer cells along with specific effects on the activity of certain genes, raising intriguing hypotheses about their existence and function in cells. Recent results from my laboratory provide new insights into when and where such non-Watson-Crick structures may exist in cellular DNA, together with a perspective on whether this structural motif in DNA presents new opportunities to think about intervention and future therapeutics. Citation Format: Shankar Balasubramanian. G-quadruplexes and DNA dynamics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr PL04-01. doi:10.1158/1538-7445.AM2017-PL04-01

Blue‐Light‐Emitting Triazolopyridinium and Triazoloquinolinium Salts

AbstractCompounds that emit blue light are of interest for applications that include optoelectronic devices and chemo/biosensing and imaging. The design and synthesis of small organic molecules that can act as high‐efficiency deep‐blue‐light emitters in the solid state and can be easily processed from solutions represents a significant challenge. Herein we present the preparation and photophysical, photochemical and electrochemical properties of a series of triazolopyridinium and triazoloquinolinium compounds. The compounds are soluble in water or polar organic solvents and exhibit photoluminescence in the blue region of the spectrum in fluid solution, in the solid state and in a frozen matrix.

Transition metal-catalyzed C-H bond functionalization in multicomponent reactions: a tool toward molecular diversity.

Transition metal-catalyzed C-H bond functionalization has numerous applications in organic synthesis as a powerful type of bond transformation. In particular, the combination of C-H functionalization with other types of chemical transformations in the manner of multicomponent reactions is an even more beneficial tool in the synthesis of small organic molecules because such reactions provide a platform for the rapid generation of high molecular diversity and complexity by making use of the advantages of both latent C-H bond transformation and the multicomponent reaction. Herein, we provide a review highlighting the research advances in the multicomponent reactions built upon transition metal-catalyzed C-H bond functionalization. The content spans from the reactions featuring the functionalization of C(sp3)-H, C(sp2)-H and C(sp)-H bonds over the last decade.

β-Diketiminate complexes of the first row transition metals: applications in catalysis.

Although β-diketiminate complexes have been widely explored in stoichiometric studies, their use as catalysts is largely underdeveloped. With growing interest in the catalytic activity of complexes of the first row transition metals, primarily due to the untapped potential of such metal centers, along with the growing global focus on sustainable chemistry with earth abundant metals, this Perspective focuses on the use of β-diketiminate complexes of the first row transition metals as catalysts for the synthesis of small organic molecules.

ChemInform Abstract: Reaction Screening in Continuous Flow Reactors

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Catalyst-dependent selectivity in the relay catalytic branching cascade.

The synthesis of small organic molecules as probes for discovering new therapeutic agents has been an important aspect of chemical biology. One of the best ways to access collections of small molecules is to use various techniques in diversity-oriented synthesis (DOS). Recently, a new form of DOS, namely "relay catalytic branching cascades" (RCBCs), has been introduced, wherein a common type of starting material reacts with several scaffold-building agents (SBAs) to obtain structurally diverse molecular scaffolds under the influence of catalysts. Herein, the RCBC reaction of a common type of substrate with SBAs is reported to give two different types of molecular scaffolds and their formation is essentially dependent on the type of catalyst used.