Highly Effective Conditions for Nickel-Mediated Heck Cyclization Cascades Starting from Aryl and Vinyl Triflates

In contrast to the tremendous power of Pd-based Mizoroki–Heck reactions, methods to achieve such processes with other metals, particularly Ni, are generally lacking. Herein, we delineate specific conditions that can enable cascade variants of these C–C bond forming events to proceed smoothly under Ni catalysis. Critically, these reactions work with equal facility as their Pd-initiated counterparts when conducted intramolecularly, and in many cases are devoid of any Ni–H-mediated alkene isomerization within the starting materials and/or products as has typically been observed with previous Ni-based protocols. When conducted intermolecularly, the developed variant affords unique regioselectivity in product formation, substantively favoring 6-endo additions over the more standard 5-exo counterparts observed under Pd-based conditions. Finally, applications of the developed procedures to two different natural product syntheses are described

From Theory to Experiment: Transformer-based Generation Enables Rapid Discovery of Novel Reactions

Deep learning methods have been proven their potential roles in the chemical field, such as reaction prediction and retrosynthesis analysis. However, the de novo generation of unreported reactions using artificial intelligence technology remains not be completely explored. Inspired by molecular generation, we proposed the task of novel reaction generation. In this work, we applied the Heck reactions to train the transformer model, state-of-art natural language process model and obtained 4717 generated reactions after sampling and processing. We then confirmed that 2253 novel Heck reactions by organizing chemists to judge the generated reactions, and adopted organic synthesis experiment to verify the feasibility of unreported reactions. In this process, it only took 15 days from Heck reaction generation to experimental verification, proving that our model learns reaction rules in-depth and can make great contributions in the novel reaction discovery.

How to Make a Cocktail of Palladium Catalysts with Cola and Alcohol: Heteroatom Doping vs. Nanoscale Morphology of Carbon Supports

Sparkling drinks such as cola can be considered an affordable and inexpensive starting material consisting of carbohydrates and sulfur- and nitrogen-containing organic substances in phosphoric acid, which makes them an excellent precursor for the production of heteroatom-doped carbon materials. In this study, heteroatom-doped carbon materials were successfully prepared in a quick and simple manner using direct carbonization of regular cola and diet cola. The low content of carbon in diet cola allowed reaching a higher level of phosphorus in the prepared carbon material, as well as obtaining additional doping with nitrogen and sulfur due to the presence of sweeteners and caffeine. Effects of carbon support doping with phosphorus, nitrogen and sulfur, as well as of changes in textural properties by ball milling, on the catalytic activity of palladium catalysts were investigated in the Suzuki–Miyaura and Mizoroki–Heck reactions. Contributions of the heteroatom doping and specific surface area of the carbon supports to the increased activity of supported catalysts were discussed. Additionally, the possibility of these reactions to proceed in 40% potable ethanol was studied. Moreover, transformation of various palladium particles (complexes and nanoparticles) in the reaction medium was detected by mass spectrometry and transmission electron microscopy, which evidenced the formation of a cocktail of catalysts in a commercial 40% ethanol/water solution.

Palladium-Catalyzed Mizoroki–Heck and Copper-Free Sonogashira Coupling Reactions in Water Using Thermoresponsive Polymer Micelles

A few kinds of thermoresponsive diblock copolymers have been synthesized and utilized for palladium-catalyzed coupling reactions in water. Poly(N-isopropylacrylamide) (PNIPAAm) and poly(N,N-diethylacrylamide) (PDEAAm) are employed for thermoresponsive segments and poly(sodium 4-styrenesulfonate) (PSSNa) and poly(sodium 2-acrylamido-methylpropanesulfonate) (PAMPSNa) are employed for hydrophilic segments. Palladium-catalyzed Mizoroki–Heck reactions are performed in water and the efficiency of the extraction process is studied. More efficient extraction was observed for the PDEAAm copolymers when compared with the PNIPAAm copolymers and conventional surfactants. In the study of the Sonogashira coupling reactions in water, aggregative precipitation of the products was observed. Washing the precipitate with water gave the product with satisfactory purity with a good yield.

Ferrocenylimine Palladium (II) Complexes: Synthesis, Characterization and Application in Mizoroki-Heck and Suzuki-Miyaura Cross-Coupling Reactions

Carbon-carbon cross-coupling reactions are essential synthetic tools for synthesizing polymers, natural products, agrochemicals, and pharmaceuticals. Therefore, new catalysts that function with greater efficiency and functional group tolerance are being researched. We have prepared new ferrocenylimine monodentate N and P donor ligands and N^N and N^P bidentate chelating ligands (L1 to L4) employed in stabilizing palladium ions for application in Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions. The ferrocenylimine ligands were successfully synthesized by Schiff base condensation reactions of acetyl ferrocene with hydrazine monohydrate to afford ferrocenyl hydrazone (L1). Ligand L1 was further treated with aldehydes to give ferrocenyl(2-diphenylphosphino)imine (L3) and ferrocenyl(pyridyl)imine (L3), while phosphination of L1 with chlorodiphenylphosphine afforded L2. The ligands were used to prepare new palladium(II) complexes (C1 to C4) by complexation with [PdCl2(MeCN)2]. All the ligands and complexes were fully characterized using standard spectroscopic and analytical techniques, including 1H NMR and 13C NMR spectroscopy, FT-IR spectroscopy, mass spectrometry and elemental analysis. The complexes (C1 to C4) were tested for efficacies in catalyzing Mizoroki-Heck and Suzuki-Miyaura C-C cross-coupling reactions and proved to be suitable catalyst precursors. Ferrocenyl(2-diphenylphosphine)imino and ferrocenyl-methyl hydrazone palladium(II) complexes C2 and C3 showed the best activities at TONs of up to 201. The ferrocenyl palladium(II) (pre)catalysts demonstrated moderate activity in Mizoroki-Heck reactions involving substrates with substituents on the olefin and aryl halide (including 4-Cl, 4-CH3, -CO2Me and -CO2Et). Density Functional Theory was used to study the mechanism of the Mizoroki-Heck cross-coupling reactions and have led to confirmation of the widely accepted catalytic cycle. Catalyst precursors (C1 to C4) also displayed good activity and selectivity in Suzuki-Miyaura cross-coupling reactions, at 0.5 mol% catalyst loading, with good tolerance to functional groups present on the aryl halide and boronic acid substrates (such as 4-Cl, 4-CHO, 4-COOH, 3-NO2, 3,5-dimethoxy and 4-CH3).