Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Practical Catalytic Cleavage of C(sp³ )-C(sp³ ) Bonds in Amines.

ABSTRACT: The selective cleavage of thermodynamically stable C(sp³ )-C(sp³ ) single bonds is rare compared to their ubiquitous formation. Herein, we describe a general methodology for such transformations using homogeneous copper-based catalysts in the presence of air. The utility of this novel methodology is demonstrated for C_? -C_? bond scission in >70 amines with excellent functional group tolerance. This transformation establishes tertiary amines as a general synthon for amides and provides valuable possibilities for their scalable functionalization in, for example, natural products and bioactive molecules.

SUBMITTER: Li W

PROVIDER: S-EPMC6771714 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Practical Catalytic Cleavage of C(sp3 )-C(sp3 ) Bonds in Amines.

Li Wu W Liu Weiping W Leonard David K DK Rabeah Jabor J Junge Kathrin K Brückner Angelika A Beller Matthias M

Angewandte Chemie (International ed. in English) 20190701 31

The selective cleavage of thermodynamically stable C(sp3 )-C(sp3 ) single bonds is rare compared to their ubiquitous formation. Herein, we describe a general methodology for such transformations using homogeneous copper-based catalysts in the presence of air. The utility of this novel methodology is demonstrated for Cα -Cβ bond scission in >70 amines with excellent functional group tolerance. This transformation establishes tertiary amines as a general ...[more]

PMID: 31125156

Similar Datasets

Synthesis of (diarylmethyl)amines using Ni-catalyzed arylation of C(sp3)-H bonds.

Project description:The first nickel catalyzed deprotonative cross coupling between C(sp3)-H bonds and aryl chlorides is reported, allowing the challenging arylation of benzylimines in the absence of directing group or stoichiometric metal activation. This methodology represents a convenient access to the (diarylmethyl)amine moiety, which is widespread in pharmaceutically relevant compounds.

| S-EPMC4786957 | biostudies-literature

Aminodealkenylation: Ozonolysis and copper catalysis convert C(sp3)-C(sp2) bonds to C(sp3)-N bonds.

Project description:Great efforts have been directed toward alkene π bond amination. In contrast, analogous functionalization of the adjacent C(sp3)-C(sp2) σ bonds is much rarer. Here we report how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp3)-C(sp2) σ bond-rupturing cross-coupling reactions for the construction of new C(sp3)-N bonds. We have used this unconventional transformation for late-stage modification of hormones, pharmaceutical reagents, peptides, and nucleosides. Furthermore, we have coupled abundantly available terpenes and terpenoids with nitrogen nucleophiles to access artificial terpenoid alkaloids and complex chiral amines. In addition, we applied a commodity chemical, α-methylstyrene, as a methylation reagent to prepare methylated nucleosides directly from canonical nucleosides in one synthetic step. Our mechanistic investigation implicates an unusual copper ion pair cooperative process.

| S-EPMC10753956 | biostudies-literature

Photoredox-catalyzed C-C bond cleavage of cyclopropanes for the formation of C(sp3)-heteroatom bonds.

Project description:Sterically congested C-O and C-N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)-heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C-C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.

| S-EPMC9547854 | biostudies-literature

Oxidative coupling of sp 2 and sp 3 carbon-hydrogen bonds to construct dihydrobenzofurans.

Project description:Metal-catalyzed cross-couplings provide powerful, concise, and accurate methods to construct carbon-carbon bonds from organohalides and organometallic reagents. Recent developments extended cross-couplings to reactions where one of the two partners connects with an aryl or alkyl carbon-hydrogen bond. From an economic and environmental point of view, oxidative couplings between two carbon-hydrogen bonds would be ideal. Oxidative coupling between phenyl and "inert" alkyl carbon-hydrogen bonds still awaits realization. It is very difficult to develop successful strategies for oxidative coupling of two carbon-hydrogen bonds owning different chemical properties. This article provides a solution to this challenge in a convenient preparation of dihydrobenzofurans from substituted phenyl alkyl ethers. For the phenyl carbon-hydrogen bond activation, our choice falls on the carboxylic acid fragment to form the palladacycle as a key intermediate. Through careful manipulation of an additional ligand, the second "inert" alkyl carbon-hydrogen bond activation takes place to facilitate the formation of structurally diversified dihydrobenzofurans.Cross-dehydrogenative coupling is finding increasing application in synthesis, but coupling two chemically distinct sites remains a challenge. Here, the authors report an oxidative coupling between sp 2 and sp 3 carbons by sequentially activating the more active aryl site followed by the alkyl position.

| S-EPMC5552783 | biostudies-literature

Controlled Synthesis of Oligomers Containing Main-Chain B(sp2 )-B(sp2 ) Bonds.

Project description:A number of novel alkynyl-functionalized diarylbis(dimethylamino)diboranes(4) are prepared by salt metathesis, and the appended alkynyl groups are subjected to hydroboration. Their reactions with monohydroboranes lead to discrete boryl-appended diborane(4) species, while dihydroboranes induce their catenation to oligomeric species, the first known examples of well-characterized macromolecular species with B-B bonds. The oligomeric species were found to comprise up to ten repeat units and are soluble in common organic solvents. Some of the oligomeric species have good air stability and all were characterized by NMR and vibrational spectroscopy and size-exclusion chromatography techniques.

| S-EPMC9292976 | biostudies-literature

Palladium-Catalyzed C(sp3 )-H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group.

Project description:C-H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C-H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ-C-H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2-dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off-cycle free-amine directed ϵ-cyclopalladation of the arylation product is reported.

| S-EPMC6391947 | biostudies-literature

Photocatalytic aerobic oxidation of C(sp3)-H bonds.

Project description:In modern industries, the aerobic oxidation of C(sp3)-H bonds to achieve the value-added conversion of hydrocarbons requires high temperatures and pressures, which significantly increases energy consumption and capital investment. The development of a light-driven strategy, even under natural sunlight and ambient air, is therefore of great significance. Here we develop a series of hetero-motif molecular junction photocatalysts containing two bifunctional motifs. With these materials, the reduction of O2 and oxidation of C(sp3)-H bonds can be effectively accomplished, thus realizing efficient aerobic oxidation of C(sp3)-H bonds in e.g., toluene and ethylbenzene. Especially for ethylbenzene oxidation reactions, excellent catalytic capacity (861 mmol g cat-1) is observed. In addition to the direct oxidation of C(sp3)-H bonds, CeBTTD-A can also be applied to other types of aerobic oxidation reactions highlighting their potential for industrial applications.

| S-EPMC10789790 | biostudies-literature

Biomimetic catalytic aerobic oxidation of C-sp(3)-H bonds under mild conditions using galactose oxidase model compound CuIIL.

Project description:Developing highly efficient catalytic protocols for C-sp(3)-H bond aerobic oxidation under mild conditions is a long-desired goal of chemists. Inspired by nature, a biomimetic approach for the aerobic oxidation of C-sp(3)-H by galactose oxidase model compound CuIIL and NHPI (N-hydroxyphthalimide) was developed. The CuIIL-NHPI system exhibited excellent performance in the oxidation of C-sp(3)-H bonds to ketones, especially for light alkanes. The biomimetic catalytic protocol had a broad substrate scope. Mechanistic studies revealed that the CuI-radical intermediate species generated from the intramolecular redox process of CuIILH2 was critical for O2 activation. Kinetic experiments showed that the activation of NHPI was the rate-determining step. Furthermore, activation of NHPI in the CuIIL-NHPI system was demonstrated by time-resolved EPR results. The persistent PINO (phthalimide-N-oxyl) radical mechanism for the aerobic oxidation of C-sp(3)-H bond was demonstrated.

| S-EPMC9400635 | biostudies-literature

Multicomponent double Mannich alkylamination involving C(sp2)-H and benzylic C(sp3)-H bonds.

Project description:Alkylamines are ubiquitous in pharmaceuticals, materials and agrochemicals. The Mannich reaction is a well-known three-component reaction for preparing alkylamines and has been widely used in academic research and industry. However, the nucleophilic components in this process rely on C(sp2)-H and activated C(sp3)-H bonds while the unactivated C(sp3)-H bonds involved Mannich alkylamination is a long-standing challenge. Here, we report an unprecedented multicomponent double Mannich alkylamination for both C(sp2)-H and unactivated benzylic C(sp3)-H bonds. In this process, various 3-alkylbenzofurans, formaldehyde and alkylamine hydrochlorides assemble efficiently to furnish benzofuran-fused piperidines. Mechanistic studies and density functional theory (DFT) calculations revealed a distinctive pathway that a multiple Mannich reaction and retro-Mannich reaction of benzofuran and dehydrogenation of benzylic C(sp3)-H bonds were key steps to constitute the alkylamination. This protocol furnishes a Mannich alkylamine synthesis from unusual C-H inputs to access benzofuran-fused piperidines with exceptional structural diversity, molecular complexity and drug-likeness. Therefore, this work opens a distinctive vision for the alkylamination of unactivated C(sp3)-H bonds, and provides a powerful tool in diversity-oriented synthesis (DOS) and drug discovery.

| S-EPMC8782832 | biostudies-literature

Copper-promoted site-selective carbonylation of sp3 and sp2 C-H bonds with nitromethane.

Project description:Copper-promoted direct carbonylation of unactivated sp3 C-H and aromatic sp2 C-H bonds of amides was developed using nitromethane as a novel carbonyl source. The sp3 C-H functionalization showed high site-selectivity by favoring the C-H bonds of α-methyl groups. The sp2 C-H carbonylation featured high regioselectivity and good functional group compatibility. Kinetic isotope effect studies indicated that the sp3 C-H bond breaking step is reversible, whereas the sp2 C-H bond cleavage is an irreversible but not the rate-determining step. Control experiments showed that a nitromethyl intermediate should be involved in the present reaction.

| S-EPMC6020547 | biostudies-literature