Recent Advances in Homogeneous Metal-Catalyzed Aerobic C–H Oxidation of Benzylic Compounds

Csp(3)-H oxidation of benzylic methylene compounds is an established strategy for the synthesis of aromatic ketones, esters, and amides. The need for more sustainable oxidizers has encouraged researchers to explore the use of molecular oxygen. In particular, homogeneous metal-catalyzed aerobic oxidation of benzylic methylenes has attracted much attention. This account summarizes the development of this oxidative strategy in the last two decades, examining key factors such as reaction yields, substrate: catalyst ratio, substrate scope, selectivity over other oxidation byproducts, and reaction conditions including solvents and temperature. Finally, several mechanistic proposals to explain the observed results will be discussed.(IT-774-13 (Basque Government) and CTQ2017-86630-P (Spanish Ministry of Economy and Competitiveness) projects

Palladium-Catalyzed Domino Cycloisomerization/Double Condensation of Acetylenic Acids with Dinucleophiles

first_page settings Open AccessArticle Palladium-Catalyzed Domino Cycloisomerization/Double Condensation of Acetylenic Acids with Dinucleophiles by Nerea Conde , María Teresa Herrero , Garazi Urgoitia and Raul SanMartin * [ORCID] Department of Organic and Inorganic Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain * Author to whom correspondence should be addressed. Academic Editors: Thomas J. J. Müller and Eelco Ruijter Catalysts 2022, 12(2), 127; https://doi.org/10.3390/catal12020127 Received: 18 December 2021 / Revised: 13 January 2022 / Accepted: 17 January 2022 / Published: 21 January 2022 (This article belongs to the Special Issue Metal-Catalyzed Processes in One-Pot Syntheses of Heterocycles) Download PDF Browse Figures Citation Export Abstract Metal-catalyzed cascade processes based on hydrofunctionalization of alkynes are receiving much more attention because of their potential to provide advantageous approaches to otherwise synthetically challenging compounds. An alternative catalyst system has been found for the domino cycloisomerization/cyclocondensation reaction involving acetylenic acids and heterodinucleophiles. A CNN pincer palladium(II) complex, acting as a homogeneous catalyst, provides the corresponding polyheterocycles with a higher substrate/catalyst ratio. Other palladium sources were also tested and discarded, and a number of mechanistic studies including poisoning assays, kinetic plots, TEM images, XRD spectra and UPLC-MS analysis of reaction intermediates were conducted in order to shed light on the role of this pincer catalyst and the catalytic cycle involved in the cascade reaction. As a result, a more nuanced mechanism is tentatively proposed.This research was funded by the Basque Government (IT1405-19) and the Spanish Ministry of Economy and Competitiveness (CTQ2017-86630-P)

Direct Arylation in the Presence of Palladium Pincer Complexes

Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved efficiency, higher reaction yields, and advantageous reaction conditions. In addition to a revision of the literature concerning intra- and intermolecular direct arylation reactions performed in the presence of palladium pincer complexes, the role of these remarkably active catalysts will also be discussed.This research was funded by the Basque Government (IT1405-19) and the Spanish Ministry of Economy and Competitiveness (CTQ2017-86630-P)

Iron-catalyzed cascade synthesis of nitrogen polycycles from alkynoic acids and functionalized amines

Catalysis by first-row transition metals is of increasing interest in the context of the scarcity of chemical resources. For instance, iron is promising due to its abundance, low toxicity and unique electronic features. Here we synthesized quinazoline alkaloids from alkynoic acids and functionalized amines in the presence of iron dibromide and pyridine in toluene or, alternatively, in a solventless reaction system. We studied iron sources, reaction media and the effect of additives. Results show 39-99% yields and regioselective preparation of nitrogen- and oxygen-containing scaffolds. This is the first example of a cascade process involving alkynoic acids catalyzed by iron. Fe is more abundant, cheaper and less toxic than other Au, Cu and Ru catalysts previously reported for similar transformations.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded by the Basque Government (IT1405-19) and the Spanish Ministry of Economy and Competitiveness (CTQ2017-86630-P). JD thanks the Basque Government for a predoctoral scholarship. Finally, technical and human support provided by SGIker of UPV/EHU is gratefully acknowledged

Metal-Catalyzed Cascade Reactions between Alkynoic Acids and Dinucleophiles: A Review

Cascade reactions provide a straightforward access to many valuable compounds and reduce considerably the number of steps of a synthetic sequence. Among the domino and multicomponent processes that involve alkynes, the cascade reaction between alkynoic acids and C-, N-, O- and S-aminonucleophiles stands out as a particularly powerful tool for the one-pot construction of libraries of nitrogen-containing heterocyclic compounds with scaffold diversity and molecular complexity. This reaction, based on an initial metal-catalyzed cycloisomerization that generates an alkylidene lactone intermediate, was originally catalyzed by gold(I) catalysts, along with silver salts or Brönsted acid additives, but other alternative metal catalysts have emerged in the last decade as well as different reaction media. This review examines the existing literature on the topic of metal-catalyzed cascade reactions of acetylenic acids and dinucleophiles and discusses aspects concerning substrate/catalyst ratio for every catalyst system, nature of the aminonucleophile involved and substrate scope. In addition, alternative solvents are also considered, and an insight into the pathway of the reaction and possible intermediates is also provided.This research was funded by the Basque Government (IT1583-22) and the Spanish Ministry of Economy and Competitiveness (CTQ2017-86630-P)

An unprecedented photochemical reaction for anthracene-containing derivatives

A series of anthracene-containing derivatives have been synthesised and characterised. The photochemical behaviour of these derivatives have been investigated by 1 H NMR spectroscopy. An unprecedented photolysis reaction for anthracene-containing derivatives was observed in the case of anthracenes directly armed with a -CH 2 O-R group upon UV irradiation. The photolysis reaction process has been demonstrated to occur in three steps. Firstly, the anthracene-containing derivatives are converted into the corresponding endoperoxide intermediate upon UV irradiation in the presence of air; then, the endoperoxide intermediate is decomposed to the corresponding starting compound and 9-anthraldehyde; finally, 9-anthraldehyde is further oxidised to anthraquinone. Additionally, the photolysis reaction of anthracene-containing derivatives is significantly promoted in the presence of a thiacalix[4]arene platform

Recent Advances in Homogeneous Metal-Catalyzed Aerobic C–H Oxidation of Benzylic Compounds

Csp3⁻H oxidation of benzylic methylene compounds is an established strategy for the synthesis of aromatic ketones, esters, and amides. The need for more sustainable oxidizers has encouraged researchers to explore the use of molecular oxygen. In particular, homogeneous metal-catalyzed aerobic oxidation of benzylic methylenes has attracted much attention. This account summarizes the development of this oxidative strategy in the last two decades, examining key factors such as reaction yields, substrate:catalyst ratio, substrate scope, selectivity over other oxidation byproducts, and reaction conditions including solvents and temperature. Finally, several mechanistic proposals to explain the observed results will be discussed