Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Metal-free deoxygenative coupling of alcohol-derived benzoates and pyridines for small molecules and DNA-encoded libraries synthesis.

ABSTRACT: Alcohols are among the most widely occurring functional groups found in naturally abundant, biologically relevant organic compounds, which in many cases are considered feedstock chemicals. Herein, we report a metal-free method for the deoxygenative coupling of alcohol-derived benzoates and pyridines promoted by visible light. Given the practical, mild and water-compatible conditions, small molecules and DNA headpieces can be successfully functionalized with a range of primary, secondary and tertiary alcohols. This protocol is distinguished by its wide substrate scope and broad applicability, even in the context of late-stage functionalization and DNA-drug coupling reactions.

SUBMITTER: Kolusu SRN

PROVIDER: S-EPMC9200129 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Metal-free deoxygenative coupling of alcohol-derived benzoates and pyridines for small molecules and DNA-encoded libraries synthesis.

Kolusu Sai Rohini Narayanan SRN Nappi Manuel M

Chemical science 20220510 23

Alcohols are among the most widely occurring functional groups found in naturally abundant, biologically relevant organic compounds, which in many cases are considered feedstock chemicals. Herein, we report a metal-free method for the deoxygenative coupling of alcohol-derived benzoates and pyridines promoted by visible light. Given the practical, mild and water-compatible conditions, small molecules and DNA headpieces can be successfully functionalized with a range of primary, secondary and tert ...[more]

PMID: 35774170

Similar Datasets

Phosphasilene mediated CO activation and deoxygenative homo coupling of CO molecules in reactions with metal carbonyls.

Project description:Herein, we report the synthesis of a new sterically demanding hyper-coordinate phosphasilene (Mes*PSi(SiMe3)(PhC(N t Bu)2) (1) and its unprecedented reactivity with metal carbonyls (M = Fe, Mo, W). The reaction of 1 with Fe(CO)5 involves the deoxygenative homocoupling of two CO molecules, forming a rare ketene (μ-CCO) inserted Fe complex 2. Contrastingly, reactions with M(CO)6 (M = Mo, W) entail the deoxygenated activation of one CO molecule, with the second CO molecule being trapped between Si and P atoms. All the compounds including their crystal structures, are thoroughly characterized and potential energy profiles for the reaction mechanisms are also explored.

| S-EPMC11485134 | biostudies-literature

Transition Metal-Free Regioselective Phosphonation of Pyridines: Scope and Mechanism.

Project description:Regioselective phosphonation of pyridines is an interesting transformation in synthesis and medicinal chemistry. We report herein a metal-free approach enabling access to various 4-phosphonated pyridines. The method consists of simply activating the pyridine ring with a Lewis acid (BF3·OEt2) to facilitate the nucleophilic addition of a phosphine oxide anion. The formed sigma complex is subsequently oxidized with an organic oxidant (chloranil) to yield the desired adducts in good to excellent yields. We furthermore showed that access to C2-phosphoinated pyridines can be achieved in certain cases with strong Lewis basic phosphorus nucleophiles or with strong Lewis acidic pyridines. Both experimental and computational mechanistic investigations were undertaken and allowed us to understand the factors controlling the reactivity and selectivity of this reaction.

| S-EPMC10251503 | biostudies-literature

High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries.

Project description:DNA encoding facilitates the construction and screening of large chemical libraries. Here, we describe general strategies for the stepwise coupling of coding DNA fragments to nascent organic molecules throughout individual reaction steps as well as the first implementation of high-throughput sequencing for the identification and relative quantification of the library members. The methodology was exemplified in the construction of a DNA-encoded chemical library containing 4,000 compounds and in the discovery of binders to streptavidin, matrix metalloproteinase 3, and polyclonal human IgG.

| S-EPMC2584757 | biostudies-literature

Light-enabled metal-free pinacol coupling by hydrazine.

Project description:Efficient carbon-carbon bond formation is of great importance in modern organic synthetic chemistry. The pinacol coupling discovered over a century ago is still one of the most efficient coupling reactions to build the C-C bond in one step. However, traditional pinacol coupling often requires over-stoichiometric amounts of active metals as reductants, causing long-lasting metal waste issues and sustainability concerns. A great scientific challenge is to design a metal-free approach to the pinacol coupling reaction. Herein, we describe a light-driven pinacol coupling protocol without use of any metals, but with N2H4, used as a clean non-metallic hydrogen-atom-transfer (HAT) reductant. In this transformation, only traceless non-toxic N2 and H2 gases were produced as by-products with a relatively broad aromatic ketone scope and good functional group tolerance. A combined experimental and computational investigation of the mechanism suggests that this novel pinacol coupling reaction proceeds via a HAT process between photo-excited ketone and N2H4, instead of the common single-electron-transfer (SET) process for metal reductants.

| S-EPMC7066673 | biostudies-literature

Stealth polymeric vesicles via metal-free click coupling.

Project description:The strain-promoted azide-alkyne cycloaddition represents an optimal metal-free method for the modular coupling of amphiphilic polymer blocks. Hydrophilic poly(oxazoline) (PMOXA) or poly(ethylene glycol) (PEG) A-blocks were coupled with a hydrophobic poly(siloxane) B-block to provide triblock copolymers capable of self-assembling into vesicular nanostructures. Stealth properties investigated via a complement activation assay revealed the superior in vitro stealth attributes of polymeric vesicles synthesized via a metal-free approach to those coupled via the widely used copper-catalyzed click method. Furthermore, the ability to change a single parameter, such as the hydrophilic block, allowed the direct comparison of the biocompatibility properties of triblock copolymers containing PMOXA or PEG. Our studies convincingly demonstrate the need for a metal-free approach, both in preventing cytotoxicity while imparting optimal stealth properties for potential biomedical applications.

| S-EPMC3817994 | biostudies-literature

In-solution direct oxidative coupling for the integration of sulfur/selenium into DNA-encoded chemical libraries.

Project description:Sulfur/selenium-containing electron-rich arenes (ERAs) exist in a wide range of both approved and investigational drugs with diverse pharmacological activities. These unique chemical structures and bioactive properties, if combined with the emerging DNA-encoded chemical library (DEL) technique, would facilitate drug and chemical probe discovery. However, it remains challenging, as there is no general DNA-compatible synthetic methodology available for the formation of C-S and C-Se bonds in aqueous solution. Herein, an in-solution direct oxidative coupling procedure that could efficiently integrate sulfur/selenium into the ERA under mild conditions is presented. This method features simple DNA-conjugated electron-rich arenes with a broad substrate scope and a transition-metal free process. Furthermore, this synthetic methodology, examined by a scale-up reaction test and late-stage precise modification in a mock peptide-like DEL synthesis, will enable its utility for the synthesis of sulfur/selenium-containing DNA-encoded libraries and the discovery of bioactive agents.

| S-EPMC8890091 | biostudies-literature

Deoxygenative Coupling of CO with a Tetrametallic Magnesium Hydride Complex.

Project description:Addition of CO to a tetrametallic magnesium hydride cluster results in both carbon-carbon bond formation and deoxygenation to generate an acetaldehyde enolate [C2OH3]- which remains coordinated to the cluster. To the best of our knowledge, this is the first example of formation of an isolable complex containing an [C2OH3]- fragment from reaction of CO with a metal hydride, and the first example of CO homologation and deoxygenation at a main group metal. DFT studies suggest that key steps in the mechanism involve nucleophilic attack of an oxymethylene on a formyl ligand to generate an unstable [C2O2H3]3- fragment, which undergoes subsequent deoxygenation.

| S-EPMC11497278 | biostudies-literature

Sustainable Synthetic Approach for (Pyrazol-4-ylidene)pyridines By Metal Catalyst-Free Aerobic C(sp<sup>2</sup>)-C(sp<sup>3</sup>) Coupling Reactions between 1-Amino-2-imino-pyridines and 1-Aryl-5-pyrazolones.

Project description:A novel, metal catalyst-free, and efficient method has been developed for the synthesis of (pyrazol-4-ylidene)pyridine derivatives. The process involves dehydrogenative coupling of 1-amino-2-imino-pyridines with 1-aryl-5-pyrazolone derivatives utilizing O2 as the sole oxidant. The new method benefits from a high atom economy, efficiency, and substrate scope, as well as the simplicity of reaction and product purification procedures.

| S-EPMC6682090 | biostudies-literature

Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers.

Project description:The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. The scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless sulfonamide linker (photosplicing) are reported. Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C-C bond is formed by an intramolecular photochemical process that involves an excited singlet state and traversal of a five-membered transition state, and thus consistent ipso-ipso coupling results. These results demonstrate that photosplicing is a unique aryl cross-coupling method in the excited state that can be applied to synthesize a broad range of biaryls.

| S-EPMC6973076 | biostudies-literature

Transition metal-free cross-coupling of furan ring with haloacetylenes.

Project description:On the example of menthofuran, a naturally abundant compound, it has been shown for the first time that the furan ring can be readily cross-coupled with acylhaloacetylenes in the solid Al2O3 powder at room temperature to afford the corresponding 2-ethynyl derivatives in up to 88% yield. The reaction represents a ring closing/ring opening process that includes reversible formation of the intermediate cycloadducts further producing acetylene derivatives with elimination of HHal.

| S-EPMC7127138 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data