Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reversing conventional site-selectivity in C(sp3)-H bond activation.

ABSTRACT: One of the core barriers to developing C-H activation reactions is the ability to distinguish between multiple C-H bonds that are nearly identical in terms of electronic properties and bond strengths. Through recognition of distance and molecular geometry, remote C(sp2)-H bonds have been selectively activated in the presence of proximate ones. Yet achieving such unconventional site selectivity with C(sp3)-H bonds remains a paramount challenge. Here we report a combination of a simple pyruvic acid-derived directing group and a 2-pyridone ligand that enables the preferential activation of the distal ?-C(sp3)-H bond over the proximate ?-C(sp3)-H bonds for a wide range of alcohol-derived substrates. A competition experiment between the five- and six-membered cyclopalladation step, as well as kinetic experiments, demonstrate the feasibility of using geometric strain to reverse the conventional site selectivity in C(sp3)-H activation.

SUBMITTER: Xia G

PROVIDER: S-EPMC6628918 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Reversing conventional site-selectivity in C(sp3)-H bond activation.

Xia Guoqin G Weng Jiang J Liu Luoyan L Verma Pritha P Li Ziqi Z Yu Jin-Quan JQ

Nature chemistry 20190415 6

One of the core barriers to developing C-H activation reactions is the ability to distinguish between multiple C-H bonds that are nearly identical in terms of electronic properties and bond strengths. Through recognition of distance and molecular geometry, remote C(sp2)-H bonds have been selectively activated in the presence of proximate ones. Yet achieving such unconventional site selectivity with C(sp3)-H bonds remains a paramount challenge. Here we report a combination o ...[more]

PMID: 30988418

Similar Datasets

meta C-H Arylation of Electron-Rich Arenes: Reversing the Conventional Site Selectivity.

Project description:Controlling site selectivity of C-H activation without using a directing group remains a significant challenge. While Pd(II) catalysts modulated by a mutually repulsive pyridine-type ligand have been shown to favor the relatively electron-rich carbon centers of arenes, reversing the selectivity to favor palladation at the relatively electron-deficient positions has not been possible. Herein we report the first catalytic system that effectively performs meta C-H arylation of a variety of alkoxy aromatics including 2,3-dihydrobenzofuran and chromane with exclusive meta site selectivity, thus reversing the conventional site selectivity governed by native electronic effects. The identification of an effective ligand and modified norbornene (NBE-CO2Me), as well as taking advantage of the statistics, are essential for achieving the exclusive meta selectivity.

| S-EPMC6750962 | biostudies-literature

C(spn )-X (n=1-3) Bond Activation by Palladium.

Project description:We have studied the palladium-mediated activation of C(spn )-X bonds (n = 1-3 and X = H, CH3 , Cl) in archetypal model substrates H3 C-CH2 -X, H2 C=CH-X and HC≡C-X by catalysts PdLn with Ln = no ligand, Cl- , and (PH3 )2 , using relativistic density functional theory at ZORA-BLYP/TZ2P. The oxidative addition barrier decreases along this series, even though the strength of the bonds increases going from C(sp3 )-X, to C(sp2 )-X, to C(sp)-X. Activation strain and matching energy decomposition analyses reveal that the decreased oxidative addition barrier going from sp3 , to sp2 , to sp, originates from a reduction in the destabilizing steric (Pauli) repulsion between catalyst and substrate. This is the direct consequence of the decreasing coordination number of the carbon atom in C(spn )-X, which goes from four, to three, to two along this series. The associated net stabilization of the catalyst-substrate interaction dominates the trend in strain energy which indeed becomes more destabilizing along this same series as the bond becomes stronger from C(sp3 )-X to C(sp)-X.

| S-EPMC9306469 | biostudies-literature

Silver Catalyzed Site-Selective C(sp3)-H Bond Amination of Secondary over Primary C(sp3)-H Bonds.

Project description:Sulfamates are widespread in numerous pharmacologically active molecules. In this paper, Silver/Bathophenanthroline catalyzed the intramolecular selective amination of primary C(sp3)-H bonds and secondary C(sp3)-H bonds of sulfamate esters, to produce cyclic sulfamates in good yields and with a high site-selectivity. DFT calculations revealed that the interaction between sulfamates and L10 makes the molecule more firmly attached to the catalyst, benefiting the catalysis reaction. The in vitro anticancer activity of the final products was evaluated in MCF-7 breast cancer cells.

| S-EPMC9571442 | biostudies-literature

Hydrodealkenylative C(sp3)-C(sp2) bond fragmentation.

Project description:Chemical synthesis typically relies on reactions that generate complexity through elaboration of simple starting materials. Less common are deconstructive strategies toward complexity-particularly those involving carbon-carbon bond scission. Here, we introduce one such transformation: the hydrodealkenylative cleavage of C(sp3)-C(sp2) bonds, conducted below room temperature, using ozone, an iron salt, and a hydrogen atom donor. These reactions are performed in nonanhydrous solvents and open to the air; reach completion within 30 minutes; and deliver their products in high yields, even on decagram scales. We have used this broadly functionality tolerant transformation to produce desirable synthetic intermediates, many of which are optically active, from abundantly available terpenes and terpenoid-derived precursors. We have also applied it in the formal total syntheses of complex molecules.

| S-EPMC6625654 | biostudies-literature

The site-selectivity and mechanism of Pd-catalyzed C(sp2)-H arylation of simple arenes.

Project description:Control over site-selectivity is a critical challenge for practical application of catalytic C-H functionalization reactions in organic synthesis. Despite the seminal breakthrough of the Pd-catalyzed C(sp2)-H arylation of simple arenes via a concerted metalation-deprotonation (CMD) pathway in 2006, understanding the site-selectivity of the reaction still remains elusive. Here, we have comprehensively investigated the scope, site-selectivity, and mechanism of the Pd-catalyzed direct C-H arylation reaction of simple arenes. Counterintuitively, electron-rich arenes preferably undergo meta-arylation without the need for a specifically designed directing group, whereas electron-deficient arenes bearing fluoro or cyano groups exhibit high ortho-selectivity and electron-deficient arenes bearing bulky electron-withdrawing groups favor the meta-product. Comprehensive mechanistic investigations through a combination of kinetic measurements and stoichiometric experiments using arylpalladium complexes have revealed that the Pd-based catalytic system works via a cooperative bimetallic mechanism, not the originally proposed monometallic CMD mechanism, regardless of the presence of a strongly coordinating L-type ligand. Notably, the transmetalation step, which is influenced by a potassium cation, is suggested as the selectivity-determining step.

| S-EPMC8178950 | biostudies-literature

Activation of perfluoroalkyl iodides by anions: extending the scope of halogen bond activation to C(sp3)-H amidation, C(sp2)-H iodination, and perfluoroalkylation reactions.

Project description:A simple, efficient, and convenient activation of perfluoroalkyl iodides by tBuONa or KOH, without expensive photo- or transition metal catalysts, allows the promotion of versatile α-sp3 C-H amidation reactions of alkyl ethers and benzylic hydrocarbons, C-H iodination of heteroaryl compounds, and perfluoroalkylations of electron-rich π bonds. Mechanistic studies show that these novel protocols are based on the halogen bond interaction between perfluoroalkyl iodides and tBuONa or KOH, which promote homolysis of perfluoroalkyl iodides under mild conditions.

| S-EPMC9930934 | biostudies-literature

Diverse secondary C(sp3)-H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines.

Project description:We describe a coinage-metal-catalyzed site-selective oxidation of secondary C(sp3)-H bonds for aliphatic amine substrates. Broad amine scope, good functional compatibility and late-stage diversification are demonstrated with this method. The steric demand of the ?-substituents controlled diastereoselectivities under this catalytic system. The site selectivity favors secondary C(sp3)-H bonds over tertiary ones underscoring the unique synthetic potential of this method.

| S-EPMC6115674 | biostudies-literature

Synthesis of Asthma Drug Zafirlukast (Accolate) Using Intramolecular Oxidative Coupling via sp3 C-H Bond Activation.

Project description:The FDA-approved drug for the treatment of asthma, zafirlukast, is synthesized engaging multiple catalytic reactions including a new method for the construction of 3-aroylindoles via oxidative cyclization. The highlights include transition-metal and peroxide free C-H bond activation using the stoichiometric amount of sodium persulfate as an oxidizing agent in the construction of 3-aroylindole, avoiding transition metal, with over 28% overall yield. The complete process has a turnaround time of 28 h to get the target molecule starting from substituted aniline, with practically no protecting groups.

| S-EPMC6641481 | biostudies-literature

β-Ketoallylic methylsulfones synthesis via inert C(sp3)-H bond activation by magnetic Ag-Cu MOF.

Project description:Herein, the one-pot tandem synthesis of β-ketoallylic methylsulfones has been achieved from readily available dimethyl sulfoxide and acetophenones as coupling partners in one step. In this procedure, dimethyl sulfoxide serves as a triple role including solvent, dual synthon and as an oxidant agent. The use of magnetic Ag-Cu MOF as a bimetallic catalyst is the key to the progress of the reaction due to its accessible active sites. It provides facile access to various β-ketoallylic methylsulfone derivatives from direct C(sp3)-H bond activation and functionalization of aromatic methyl ketones especially acetophenones with electron-rich and electron-poor groups. Moreover, the present work offers a synthetically powerful strategy to form products in good to excellent yields (74-96%) with the atom, step, and pot economics. It has also delivered a new chromane-4-one derivative from 2-hydroxy acetophenone with intramolecular Michael-addition of related β-ketoallyl methylsulfone product. In the final step, the electronic properties of some products have been predicted with the theoretical studies.

| S-EPMC10728156 | biostudies-literature

Enantioselective palladium-catalyzed C(sp2)-C(sp2) σ bond activation of cyclopropenones by merging desymmetrization and (3 + 2) spiroannulation with cyclic 1,3-diketones.

Project description:Catalytic asymmetric variants for functional group transformations based on carbon-carbon bond activation still remain elusive. Herein we present an unprecedented palladium-catalyzed (3 + 2) spiro-annulation merging C(sp2)-C(sp2) σ bond activation and click desymmetrization to form synthetically versatile and value-added oxaspiro products. The operationally straightforward and enantioselective palladium-catalyzed atom-economic annulation process exploits a TADDOL-derived bulky P-ligand bearing a large cavity to control enantioselective spiro-annulation that converts cyclopropenones and cyclic 1,3-diketones into chiral oxaspiro cyclopentenone-lactone scaffolds with good diastereo- and enantio-selectivity. The click-like reaction is a successful methodology with a facile construction of two vicinal carbon quaternary stereocenters and can be used to deliver additional stereocenters during late-state functionalization for the synthesis of highly functionalized or more complex molecules.

| S-EPMC8549799 | biostudies-literature