Palladium-catalyzed Heck Reaction Research Articles

Palladium catalyzed Heck reactions using 2,6-bis(1,2,4-diazaphosphol-1-yl)pyridine as a ligand

A new catalyst system for the Heck reaction consisting of PdCl2 and 2,6-bis(1,2,4-diazaphosphol-1-yl)pyridine as a ligand is proposed. This system is efficient for the coupling of styrene with aryl bromides (K3PO4, DMA, 130 °C) at 0.1 mol% catalyst loading.

Developing a straightforward route toward the synthesis of arylaminomaleimides by palladium-catalyzed arylation of one-pot synthesized aminomaleimides.

3-Aryl-4-aminomaleimides have well-demonstrated applications, such as being used as fluorophores and inhibitors. However, their previous synthesis methods have involved tedious multi-step procedures or methods that need pre-functionalized maleimides and toxic or unstable reagents. Here, a feasible method is developed to synthesize these useful compounds. This includes the one-pot preparation of 3-aminomaleimides, followed by their direct arylation through a palladium-catalyzed Heck reaction with various aryl iodides regioselectively at the β-position of their amine substituents. The results show that this method efficiently exhibits a broad scope.

Heck arylation of the natural pyrethrins

The natural pyrethrins have served as reliable active ingredients in insecticidal formulations and remain ideal due to their environmentally friendly characteristics. This work focussed on the elaboration of the pyrethrin scaffold utilising the palladium catalysed Heck reaction. Utilisation of cationic reaction conditions led to the production of 24 arylated pyrethrin derivatives with a range of substituted aromatic moieties containing (E,E) geometry of the rethrolone side chain.

What the Heck?-Automated Regioselectivity Calculations of Palladium-Catalyzed Heck Reactions Using Quantum Chemistry.

We present a quantum chemistry (QM)-based method that computes the relative energies of intermediates in the Heck reaction that relate to the regioselective reaction outcome: branched (α), linear (β), or a mix of the two. The calculations are done for two different reaction pathways (neutral and cationic) and are based on r 2SCAN-3c single-point calculations on GFN2-xTB geometries that, in turn, derive from a GFNFF-xTB conformational search. The method is completely automated and is sufficiently efficient to allow for the calculation of thousands of reaction outcomes. The method can mostly reproduce systematic experimental studies where the ratios of regioisomers are carefully determined. For a larger dataset extracted from Reaxys, the results are somewhat worse with accuracies of 63% for β-selectivity using the neutral pathway and 29% for α-selectivity using the cationic pathway. Our analysis of the dataset suggests that only the major or desired regioisomer is reported in the literature in many cases, which makes accurate comparisons difficult. The code is freely available on GitHub under the MIT open-source license: https://github.com/jensengroup/HeckQM.

Heck Reaction of N-Heteroaryl Halides for the Concise Synthesis of Chiral α-Heteroaryl-substituted Heterocycles.

The Heck reaction between N-heteroaryl halides and heterocyclic alkenes provides a convenient approach to biologically relevant α-heteroaryl functionalized heterocycles, yet reactions of this type have been challenging due to strong N-heteroaryl coordination to palladium metal, which causes catalyst poisoning. In this report, an efficient palladium-catalyzed Heck reaction between N-heteroaryl halides and heterocyclic olefins is established, leading to a variety of α-heteroaryl substituted heterocycles. The method features an unprecedented broad substrate scope and excellent functional group compatibility. The employment of a sterically bulky P, P=O ligand containing an anthryl moiety is crucial for this transformation due to the coordinative unsaturation facilitated by its steric bulkiness. The asymmetric variant of the Heck reaction is achieved with (S)-DTBM-SEGPHOS via a cationic palladium pathway, which has enabled an efficient asymmetric synthesis of (S)-nicotine and its analogues.

Heck Reaction of 2-Oxyacrylates with Aryl Bromides: A Common Route to Monoaryl Pyruvates and Ortho Ester-Protected Monoaryl Pyruvates.

A palladium-catalyzed Heck reaction between 2-oxyacrylates and aryl bromides was developed, where DavePhos was a unique ligand that efficiently promoted the reaction. The products, 2-oxycinnamates, served as excellent precursors, providing synthetically useful monoaryl pyruvates or ortho ester-protected monoaryl pyruvates depending on the nature of the 2-oxy group. The formation of such ortho esters via alkoxide addition is novel, and computational studies identified a plausible mechanism with an oxyallyl zwitterion as the key intermediate.

Palladium-catalyzed Heck reactions promoted by limonene-derived bicyclic phosphines

Tertiary bicyclic phosphines derived from (R)-(+)-limonene provided efficient palladium catalysts for Heck cross-coupling reactions. Overall, high yields of the desired aryl alkenes products were obtained for cross-coupling of sterically and electronically diverse substrates. The efficiency of the catalysts was further demonstrated in the synthesis of commercial ketones, such as raspberry ketone and its derivatives.

Visible-Light-Driven, Palladium-Catalyzed Heck Reaction of Internal Vinyl Bromides with Styrenes.

Functionalized 1,3-dienes were efficiently accessed from visible-light-driven, palladium-catalyzed Heck reaction of S,S-functionalized internal vinyl bromides with styrenes under mild conditions. This Heck reaction showcased tolerance of a wide array of functional groups, afforded the target products in moderate to excellent yields through a radical reaction pathway. The resultant diene products could be further transformed to highly functionalized trisubstituted furan derivatives.

Synthesis of 9, 10-Dihydrophenanthrene, Phenanthrene, Mono- and Dialkyl Phenanthrene and Octa-hydro Phenanthrene by Palladium-catalyzed Heck Reactions

Methodology for the synthesis of 9, 10-dihydrophenanthrene, alkyl phenanthrene and Octahydro-phenanthrene has been developed via a palladium- catalyzed Heck reaction followed by Reverse Diels-Alder reaction of formaldehyde elimination. Reported methods are useful for the synthesis of higher homologous of polynuclear aromatic hydrocarbons.

Palladium-Catalyzed Heck Reaction of Endocyclic Conjugated C=C Bonds of Pyrroles

Palladium-Catalyzed Heck Reaction of Endocyclic Conjugated C=C Bonds of Pyrroles

Synthesis of Selenopyrano[2,3-c]pyrazol-4(1H)-ones and Their C–H Activation

AbstractWe disclose the synthesis of selenopyrano[2,3-c]pyrazol-4(1H)-ones and their aryl derivatives for the first time by using selenopyran ring formation via an in situ-generated selenide that reacts directly with α-halo-β-ynone-bearing substituted pyrazoles to provide the corresponding selenopyrano[2,3-c]pyrazol-4(1H)-ones. Subsequent direct C–H arylation of the latter compounds effected by palladium-catalyzed Heck reactions permits the incorporation of arene substituents onto the selenopyrano[2,3-c]pyrazol-4(1H)-ones scaffolds with moderate to good yields, and might be useful for biological screenings.

Visible-Light-Induced Pd-Catalyzed Radical Strategy for Constructing C-Vinyl Glycosides.

A novel visible-light-induced palladium-catalyzed Heck reaction for bromine sugars and aryl olefins with high regio- and stereochemistry selectivity for the preparation of C-glycosyl styrene is described. This reaction takes place in one step at room temperature by using a simple and readily available starting material. This protocol can be scaled up to a wide range of glycosyl bromide donors and aryl olefin substrates. Mechanistic studies indicate that a radical addition pathway is involved.

Synthesis and Antiproliferative Activity of 9‐Formyl and 9‐Ethynyl Noscapines

AbstractAppending functional groups to the core skeleton of natural α‐noscapine, an FDA approved cough medicine, resulted in analogues with anticancer activity. In this study, we report the synthesis and antiproliferative activity of 9‐formyl and 9‐ethynylnoscapines. 9‐Formylnoscapine 5 was synthesized from 9‐bromonoscapine 2c via a three‐step reaction sequence involving palladium catalysed Heck reaction with ethyl acrylate leading to noscapinoid 7, dihydroxylation of 7 with OsO4 and oxidative cleavage of diol 8. Further, Seyferth‐Gilbert homologation of 9‐formylnoscapine using Bestmann‐Ohira reagent resulted in 9‐ethynylnoscapine 6 in excellent yield. Antiproliferative activity screening of new noscapinoids 5‐7 against NCI60 human tumor cell lines resulted in 9‐ethynylnoscapine 6 as a potent anticancer agent with the lowest mean percentage growth against the full 60‐cell line panel.

Deaminative (Carbonylative) Alkyl-Heck-type Reactions Enabled by Photocatalytic C-N Bond Activation.

The palladium-catalyzed Heck reaction is a well-known, Nobel Prize winning transformation for producing alkenes. Unlike the alkenyl and aryl variants of the Heck reaction, the alkyl-Heck reaction is still underdeveloped owing to the competitive side reactions of alkyl-palladium species. Herein, we describe the development of a deaminative alkyl-Heck-type reaction that proceeds through C-N bond activation by visible-light photoredox catalysis. A variety of aliphatic primary amines were found to be efficient starting materials for this new process, affording the corresponding alkene products in good yields under mild reaction conditions. Moreover, this strategy was successfully applied to deaminative carbonylative alkyl-Heck-type reactions.

Deciphering the conformation of C-linked α-D-mannopyranosides and their application toward the synthesis of low nanomolar E. coli FimH ligands

Some symboles could not be reproduce. For the full abstract, please consult the original article C-Allyl –D-mannopyranosideswere preparedvia a variety of routesto determine an optimal route to the -anomers. The relative conformational energies of the key intermediate was evaluated by molecular modelingwhich showed the conventional 4C1chair conformation to be the lowest energy conformer. This finding was also confirmed by NMR and X-ray crystallography. The perbenzoylated C-allyl mannoside was also converted into 1,1’-biphenyl analogues using a palladium-catalyzed Heck reaction. Two of the resulting minor reaction products were co-crystallized with the uropathogenic E. coliFimH. Alternatively, the KDof the major and expected Heck product was in the low nM range as measured by SPR. Crystal data showed that the C-linked derivatives efficiently bind in the FimH binding cavity near the so-called hydrophobic tyrosine gate.

Regioselective synthesis of 2,3-disubstituted 1-alkyl pyrrolo[2,3-b] quinoxalines through palladium-catalyzed Heck reaction of chalcones and evaluation of their anti-bacterial activities

The regioselective synthesis of 1-alkyl-2-aryl-3-acyl pyrrolo[2,3-b]quinoxalines through palladium-catalyzed Heck coupling reaction/heteroannulation was reported. The reaction of N-alkyl/benzyl-3-chloroquinoxaline-2-amines with chalcones catalyzed by Pd(OAc)2 in the presence of KOtBu, as the base, in DMSO afforded the desired products in good-to-high yields. The MIC and MBC determinations revealed that these compounds could be used in the future research works for the development of antibiotics.

The Heck reaction as a tool to expand polyoxovanadates towards thiol-sensitive organic-inorganic hybrid fluorescent switches.

Among the Lindqvist-type hexavanadates synthesised herein by the palladium-catalysed Heck reactions a C-C cross-coupled organic-inorganic hybrid with the largest conjugated, stilbene-derivatised π ligands is reduced in the presence of thiols producing a remarkable increase in fluorescence intensity with respect to the fully-oxidised variant. This enhanced emission (ON-state) of the reduced species can be switched OFF if the solution is subjected to e.g. air where the species is re-oxidised.

Synthesis of Cyclobutenes via a Palladium-Catalyzed Asymmetric Heck Reaction

Synthesis of Cyclobutenes via a Palladium-Catalyzed Asymmetric Heck Reaction

9-Vinylanthracene Based Fluorogens: Synthesis, Structure-Property Relationships and Applications.

Fluorescent dyes with aggregation-induced emission (AIE) properties exhibit intensified emission upon aggregation. They are promising candidates to study biomolecules and cellular changes in aqueous environments when aggregation formation occurs. Here, we report a group of 9-position functionalized anthracene derivatives that were conveniently synthesized by the palladium-catalyzed Heck reaction. Using fluorometric analyses, these dyes were confirmed to show AIE behavior upon forming aggregates at high concentrations, in viscous solvents, and when poorly solubilized. Their photophysical properties were then further correlated with their structural features, using density functional theory (DFT) calculation. Finally, we demonstrated their potential applications in monitoring pH changes, quantifying globular proteins, as well as cell imaging with confocal microscopy.

Irradiation-Induced Heck Reaction of Unactivated Alkyl Halides at Room Temperature.

The palladium-catalyzed Mizoroki-Heck reaction is arguably one of the most significant carbon-carbon bond-construction reactions to be discovered in the last 50 years, with a tremendous number of applications in the production of chemicals. This Nobel-Prize-winning transformation has yet to overcome the obstacle of its general application in a range of alkyl electrophiles, especially tertiary alkyl halides that possess eliminable β-hydrogen atoms. Whereas most palladium-catalyzed cross-coupling reactions utilize the ground-state reactivity of palladium complexes under thermal conditions and generally apply a single ligand system, we report that the palladium-catalyzed Heck reaction proceeds smoothly at room temperature with a variety of tertiary, secondary, and primary alkyl bromides upon irradiation with blue light-emitting diodes in the presence of a dual phosphine ligand system. We rationalize that this unprecedented transformation is achieved by utilizing the photoexcited-state reactivity of the palladium complex to enhance oxidative addition and suppress undesired β-hydride elimination.