Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pd-catalyzed cross-electrophile Coupling/C-H alkylation reaction enabled by a mediator generated via C(sp³)-H activation.

ABSTRACT: Transition-metal-catalyzed cross-electrophile C(sp²)-(sp³) coupling and C-H alkylation reactions represent two efficient methods for the incorporation of an alkyl group into aromatic rings. Herein, we report a Pd-catalyzed cascade cross-electrophile coupling and C-H alkylation reaction of 2-iodo-alkoxylarenes with alkyl chlorides. Methoxy and benzyloxy groups, which are ubiquitous functional groups and common protecting groups, were utilized as crucial mediators via primary or secondary C(sp³)-H activation. The reaction provides an innovative and convenient access for the synthesis of alkylated phenol derivatives, which are widely found in bioactive compounds and organic functional materials.

SUBMITTER: Wu Z

PROVIDER: S-EPMC8221197 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Multimetallic Ni- and Pd-Catalyzed Cross-Electrophile Coupling To Form Highly Substituted 1,3-Dienes.

Project description:The synthesis of highly substituted 1,3-dienes from the coupling of vinyl bromides with vinyl triflates is reported for the first time. The coupling is catalyzed by a combination of (5,5'-bis(trifluoromethyl)-2,2'-bipyridine)NiBr2 and (1,3-bis(diphenylphosphino)propane)PdCl2 in the presence of a zinc reductant. This method affords tetra- and penta-substituted 1,3-dienes that would otherwise be difficult to access and tolerates electron-rich and -poor substituents, heterocycles, an aryl bromide, and a pinacol boronate ester. Mechanistically, the reaction appears to proceed by an unusual zinc-mediated transfer of a vinyl group between the nickel and palladium centers.

| S-EPMC5821523 | biostudies-literature

Direct C(sp2)-H alkylation of unactivated arenes enabled by photoinduced Pd catalysis.

Project description:Despite the fundamental importance of efficient and selective synthesis of widely useful alkylarenes, the direct catalytic C(sp2)-H alkylation of unactivated arenes with a readily available alkyl halide remains elusive. Here, we report the catalytic C(sp2)-H alkylation reactions of unactivated arenes with alkyl bromides via visible-light induced Pd catalysis. The reaction proceeds smoothly under mild conditions without any skeletal rearrangement of the alkyl groups. The direct syntheses of structurally diverse linear and branched alkylarenes, including the late-stage phenylation of biologically active molecules and an orthogonal one-pot sequential Pd-catalyzed C-C bond-forming reaction, are achieved with exclusive chemoselectivity and exceptional functional group tolerance. Comprehensive mechanistic investigations through a combination of experimental and computational methods reveal a distinguishable Pd(0)/Pd(I) redox catalytic cycle and the origin of the counter-intuitive reactivity differences among alkyl halides.

| S-EPMC7572399 | biostudies-literature

Synergistic Catalyst-Mediator Pairings for Electroreductive Cross-Electrophile Coupling Reactions.

Project description:Electroreductive cross-electrophile coupling (eXEC) represents an attractive approach for the direct C-C coupling of two electrophiles but generally suffers from limited scope compared to reactions with chemical reductants. This work demonstrates that mediator-assisted electrocatalysis is a general strategy for the enhancement of eXEC reactions. While eXEC reactions catalyzed by a variety of widely available ligand-nickel complexes are low yielding when applied to reductive couplings of challenging substrates, reactions with the same complexes generate products in near-quantitative yield when a redox-matched mediator is included. We identify a library of catalyst-mediator systems that provide complementary reactivity and enable coupling of a range of substrate classes in high yields. These catalyst systems are applicable to both chemical and electrochemical reduction, but some require electroreduction due to the low potentials required for activation. Finally, mechanistic studies offer insights that facilitate catalyst-mediator pairing.

| S-EPMC9635435 | biostudies-literature

Metallaphotoredox-Catalyzed Cross-Electrophile Csp3-Csp3 Coupling of Aliphatic Bromides.

Project description:A strategy for the installation of small alkyl fragments onto pharmaceutically relevant aliphatic structures has been established via metallaphotoredox catalysis. Herein, we report that tris(trimethylsilyl)silanol can be employed as an effective halogen abstraction reagent that, in combination with photoredox and nickel catalysis, allows a generic approach to Csp3-Csp3 cross-electrophile coupling. In this study, we demonstrate that a variety of aliphatic drug-like groups can be successfully coupled with a number of commercially available small alkyl electrophiles, including methyl tosylate and strained cyclic alkyl bromides. Moreover, the union of two secondary aliphatic carbon centers, a long-standing challenge for organic molecule construction, has been accomplished with a wide array of structural formats. Last, this technology can be selectively merged with Csp2-Csp3 aryl-alkyl couplings to build drug-like systems in a highly modular fashion.

| S-EPMC6697083 | biostudies-literature

ChemBead Enabled High-Throughput Cross-Electrophile Coupling Reveals a New Complementary Ligand.

Project description:High-throughput experimentation (HTE) methods are central to modern medicinal chemistry. While many HTE approaches to C-N and Csp2 -Csp2 bonds are available, options for Csp2 -Csp3 bonds are limited. We report here how the adaptation of nickel-catalyzed cross-electrophile coupling of aryl bromides with alkyl halides to HTE is enabled by AbbVie ChemBeads technology. By using this approach, we were able to quickly map out the reactivity space at a global level with a challenging array of 3×222 micromolar reactions. The observed hit rate (56 %) is competitive with other often-used HTE reactions and the results are scalable. A key to this level of success was the finding that bipyridine 6-carboxamidine (BpyCam), a ligand that had not previously been shown to be optimal in any reaction, is as general as the best-known ligands with complementary reactivity. Such "cryptic" catalysts may be common and modern HTE methods should facilitate the process of finding these catalysts.

| S-EPMC8554800 | biostudies-literature

Pd-catalyzed sp-sp3 cross-coupling of benzyl bromides using lithium acetylides.

Project description:Organolithium-based cross-coupling reactions have emerged as an indispensable method to construct C-C bonds. These transformations have proven particularly useful for the direct and fast coupling of various organolithium reagents (sp, sp2, and sp3) with aromatic (pseudo) halides (sp2). Here we present an efficient method for the cross-coupling of benzyl bromides (sp3) with lithium acetylides (sp). The reaction proceeds within 10 min at room temperature and can be performed in the presence of organolithium-sensitive functional groups such as esters, nitriles, amides and boronic esters. The potential application of the methodology is demonstrated in the preparation of key intermediates used in pharmaceuticals, chemical biology and natural products.

| S-EPMC8320736 | biostudies-literature

Coupling of Challenging Heteroaryl Halides with Alkyl Halides via Nickel-Catalyzed Cross-Electrophile Coupling.

Project description:Despite their importance, the synthesis of alkylated heterocycles from the cross-coupling of Lewis basic nitrogen heteroaryl halides with alkyl halides remains a challenge. We report here a general solution to this challenge enabled by a new collection of ligands based around 2-pyridyl-N-cyanocarboxamidine and 2-pyridylcarboxamidine cores. Both primary and secondary alkyl halides can be coupled with 2-, 3-, and 4-pyridyl halides as well as other more complex heterocycles in generally good yields (41 examples, 69% ave yield).

| S-EPMC5539790 | biostudies-literature

Synergistic Pd/Cu-catalyzed enantioselective Csp2-F bond alkylation of fluoro-1,3-dienes with aldimine esters.

Project description:Due to high bond dissociation energies of Csp2-F bonds, using fluorinated compounds in Csp2-Csp3 cross-coupling is difficult. Here the authors report a protocol for enantioselective Csp2-Csp3 coupling of dienyl fluorides with aldimine esters, enabled by synergistic copper and palladium catalysis. This reaction represents the first example of asymmetric Csp2-Csp3 cross-coupling involving an inert Csp2-F bond and provides expeditious access to chiral α-alkenyl α-amino acids with high enantioselectivity. Control experiments suggest that the Csp2-F bond activation occurs through a pathway involving PdH migratory insertion and subsequent allylic defluorination, rather than by direct oxidative addition of the Csp2-F bond to Pd(0). The detailed mechanism is further investigated by DFT calculation and the enantioselectivity is rationalized.

| S-EPMC9072389 | biostudies-literature

Ligand-Enabled Pd(II)-Catalyzed C(sp3)-H Lactonization Using Molecular Oxygen as Oxidant.

Project description:Pd(II)-catalyzed C-H lactonization of o-methyl benzoic acid substrates has been achieved using molecular oxygen as the oxidant. This finding provides a rare example of C-H oxygenation through Pd(II)/Pd(0) catalysis as well as a method to construct biologically important benzolactone scaffolds. The use of a gas mixture of 5% oxygen in nitrogen demonstrated the possibility for its application in pharmaceutical manufacturing.

| S-EPMC8023385 | biostudies-literature

Nickel-catalyzed cross-electrophile coupling of 2-chloropyridines with alkyl bromides.

Project description:The synthesis of 2-alkylated pyridines by the nickel-catalyzed cross-coupling of two different electrophiles, 2-chloropyridines with alkyl bromides, is described. Compared to our previously published conditions for aryl halides, this method uses the different, more rigid bathophenanthroline ligand and is conducted at high concentration in DMF solvent. The method displays promising functional group compatibility and the conditions are orthogonal to the Stille coupling.

| S-EPMC4006914 | biostudies-literature