Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Electrocatalytic C(sp³)-H/C(sp)-H cross-coupling in continuous flow through TEMPO/copper relay catalysis.

ABSTRACT: Electrocatalytic dehydrogenative C(sp³)-H/C(sp)-H cross-coupling of tetrahydroisoquinolines with terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward and sustainable access to 2-functionalized tetrahydroisoquinolines.

SUBMITTER: Guo B

PROVIDER: S-EPMC8561139 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Electrocatalytic C(sp3)-H/C(sp)-H cross-coupling in continuous flow through TEMPO/copper relay catalysis.

Guo Bin B Xu Hai-Chao HC

Beilstein journal of organic chemistry 20211028

Electrocatalytic dehydrogenative C(sp3)-H/C(sp)-H cross-coupling of tetrahydroisoquinolines with terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward and sustainable access to 2-functionalized tetrahydroisoquinolines. ...[more]

PMID: 34795802

Similar Datasets

Decarboxylative sp3 C-N coupling via dual copper and photoredox catalysis.

Project description:Over the past three decades, considerable progress has been made in the development of methods to construct sp2 carbon-nitrogen (C-N) bonds using palladium, copper or nickel catalysis1,2. However, the incorporation of alkyl substrates to form sp3 C-N bonds remains one of the major challenges in the field of cross-coupling chemistry. Here we demonstrate that the synergistic combination of copper catalysis and photoredox catalysis can provide a general platform from which to address this challenge. This cross-coupling system uses naturally abundant alkyl carboxylic acids and commercially available nitrogen nucleophiles as coupling partners. It is applicable to a wide variety of primary, secondary and tertiary alkyl carboxylic acids (through iodonium activation), as well as a vast array of nitrogen nucleophiles: nitrogen heterocycles, amides, sulfonamides and anilines can undergo C-N coupling to provide N-alkyl products in good to excellent efficiency, at room temperature and on short timescales (five minutes to one hour). We demonstrate that this C-N coupling protocol proceeds with high regioselectivity using substrates that contain several amine groups, and can also be applied to complex drug molecules, enabling the rapid construction of molecular complexity and the late-stage functionalization of bioactive pharmaceuticals.

| S-EPMC6106865 | biostudies-literature

Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp3-sp2 Cross-Coupling of Oxalates with Aryl Halides.

Project description:Alkyl oxalates, prepared from their corresponding alcohols, are engaged for the first time as carbon radical fragments in metallaphotoredox catalysis. In this report, we demonstrate that alcohols, native organic functional groups, can be readily activated with simple oxalyl chloride to become radical precursors in a net redox-neutral Csp3-Csp2 cross-coupling with a broad range of aryl halides. This alcohol-activation coupling is successfully applied to the functionalization of a naturally occurring steroid and the expedient synthesis of a medicinally relevant drug lead.

| S-EPMC5464990 | 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

Enantioselective C(sp3)-C(sp3) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis.

Project description:Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp3-hybridized carbon centres, which are attractive candidate compounds in drug discovery. Enantioselective C(sp3)-C(sp3) coupling is challenging, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl). Here, we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalysed alkyl-alkyl coupling. This strategy enables the enantioselective cross-coupling of non-activated alkyl halides with alkenyl boronates to produce chiral alkyl boronates. Employing readily available and stable olefins as pro-chiral nucleophiles, the coupling proceeds under mild conditions and exhibits broad scope and high functional-group tolerance. Applications for the functionalization of natural products and drug molecules, as well as the synthesis of chiral building blocks and a key intermediate to (S)-(+)-pregabalin, are demonstrated.

| S-EPMC7610379 | biostudies-literature

Visible-Light-Promoted Iron-Catalyzed C(sp2 )-C(sp3 ) Kumada Cross-Coupling in Flow.

Project description:A continuous-flow, visible-light-promoted method has been developed to overcome the limitations of iron-catalyzed Kumada-Corriu cross-coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes' residence time, considerably enhancing the applicability of this iron-catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application.

| S-EPMC6771604 | biostudies-literature

Benzylic C(sp3)-C(sp2) cross-coupling of indoles enabled by oxidative radical generation and nickel catalysis.

Project description:A mechanistically unique functionalization strategy for a benzylic C(sp3)-H bond has been developed based on the facile oxidation event of indole substrates. This novel pathway was initiated by efficient radical generation at the benzylic position of the substrate, with subsequent transition metal catalysis to complete the overall transformation. Ultimately, an aryl or an acyl group could be effectively delivered from an aryl (pseudo)halide or an acid anhydride coupling partner, respectively. The developed method utilizes mild conditions and exhibits a wide substrate scope for both substituted indoles and C(sp2)-based reaction counterparts. Mechanistic studies have shown that competitive hydrogen atom transfer (HAT) processes, which are frequently encountered in conventional methods, are not involved in the product formation process of the developed strategy.

| S-EPMC8179435 | biostudies-literature

Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence.

Project description:The dual catalysis strategy is an efficient and powerful tool to fulfill the stereodivergent synthesis of stereoisomeric products from the same set of starting materials. Great attention has been given to the construction of chiral compounds with two contiguous stereocenters. However, the synthesis of two remote noncontiguous stereocenters is more challenging and is less developed, despite the high demand for synthetic tactics. We herein developed an unprecedented example of the stereodivergent preparation of synthetically useful and biologically important chiral ζ-hydroxy amino ester derivatives containing remote 1,6-noncontiguous stereocenters and a unique β,γ-unsaturation moiety. This cascade dehydrogenation/1,6-Michael addition/hydrogenation protocol between readily-available ketoimine esters and racemic branched dienyl carbinols was rationally realized with bimetallic copper/ruthenium relay catalysis. The key features of the process were atom economy, step economy, and redox-neutrality. All four stereoisomers of chiral ζ-hydroxy amino ester derivatives were easily achieved by the orthogonal permutations of a chiral copper catalyst and chiral ruthenium catalyst. Importantly, a much more challenging stereodivergent synthesis of all eight stereoisomers of chiral peptide products containing three remote stereocenters was accomplished with excellent results through the cooperation of two chiral catalyst pairs and substrate enantiomers.

| S-EPMC11220595 | biostudies-literature

Copper-catalyzed oxidative C(sp3)-H/C(sp2)-H cross-coupling en route to carbocyclic rings.

Project description:Copper-catalyzed selective coupling of C(sp3)-H bonds with C(sp2)-H bonds has been developed. An aniline module was used as a directing group to generate an aminyl radical, which selectively cleaves the secondary and tertiary C(sp3)-H bonds via a 1,5-HAT process to forge six-membered carbocyclic rings.

| S-EPMC5577718 | biostudies-literature

Visible-Light-Driven Intermolecular Reductive Ene-Yne Coupling by Iridium/Cobalt Dual Catalysis for C(sp3 )-C(sp2 ) Bond Formation.

Project description:A new methodology to form C(sp3 )-C(sp2 ) bonds by visible-light-driven intermolecular reductive ene-yne coupling has been successfully developed. The process relies on the ability of the Hantzsch ester to contribute in both SET and HAT processes through a unified cobalt and iridium catalytic system. This procedure avoids the use of stoichiometric amounts of reducing metallic reagents, which is translated into high functional-group tolerance and atom economy.

| S-EPMC6916364 | biostudies-literature

Ni-electrocatalytic Csp3-Csp3 doubly decarboxylative coupling.

Project description:Cross-coupling between two similar or identical functional groups to form a new C-C bond is a powerful tool to rapidly assemble complex molecules from readily available building units, as seen with olefin cross-metathesis or various types of cross-electrophile coupling1,2. The Kolbe electrolysis involves the oxidative electrochemical decarboxylation of alkyl carboxylic acids to their corresponding radical species followed by recombination to generate a new C-C bond3-12. As one of the oldest known Csp3-Csp3 bond-forming reactions, it holds incredible promise for organic synthesis, yet its use has been almost non-existent. From the perspective of synthesis design, this transformation could allow one to agnostically execute syntheses without regard to polarity or neighbouring functionality just by coupling ubiquitous carboxylates13. In practice, this promise is undermined by the strongly oxidative electrolytic protocol used traditionally since the nineteenth century5, thereby severely limiting its scope. Here, we show how a mildly reductive Ni-electrocatalytic system can couple two different carboxylates by means of in situ generated redox-active esters, termed doubly decarboxylative cross-coupling. This operationally simple method can be used to heterocouple primary, secondary and even certain tertiary redox-active esters, thereby opening up a powerful new approach for synthesis. The reaction, which cannot be mimicked using stoichiometric metal reductants or photochemical conditions, tolerates a range of functional groups, is scalable and is used for the synthesis of 32 known compounds, reducing overall step counts by 73%.

| S-EPMC9248350 | biostudies-literature