Chromenes through Metal-Catalyzed Reactions of Styrenyl Ethers. Mechanism and Utility in Synthesis

Schuster M., Blechert S.

Transition metal catalyzed CC bond formations belong to the most important reactions in organic synthesis. One particularly interesting reaction is olefin metathesis, a metal-catalyzed exchange of alkylidene moieties between alkenes. Olefin metathesis can induce both cleavage and formation of CC double bonds. Special functional groups are not necessary. Although this reaction—which can be catalyzed by numerous transition metals—is used in industry, its potential in organic synthesis was not recognized for many years. The recent abrupt end to this Sleeping-Beauty slumber has several reasons. Novel catalysts can effect the conversion of highly fictionalized and sterically demanding olefins under mild reaction conditions and in high yields. Improved understanding of substrate–catalyst interaction has greatly contributed to the recent establishment of olefin metathesis as a synthetic method. In addition to the preparation of polymers with fine-tuned characteristics, the metathesis today also provides new routes to compounds of low molecular weight. The highly developed ring-closing metathesis has been proven to be key step in the synthesis of a growing number of natural products. At the same time interesting applications can be envisioned for newly developed variants of bimolecular metathesis. Improvements in the selective cross-metathesis of acyclic olefins as well as promising attempts to include alkynes as viable substrates provide for a vivid development of the metathesis chemistry.

Marsella M.J., Maynard H.D., Grubbs R.H.

A highly efficient combination: template directing and olefin metathesis. The polyether dienes 1 react in good yields to give crown ethers 2 in the presence of LiClO4 and the Ru catalyst 3 (Cy = cyclohexyl). Ring-opening metathesis polymerization (ROMP) of the cyclic olefins 2 results in polymers that are capable of regenerating 2 by template-directed methathesis depolymerization.

Crowe W.E., Goldberg D.R., Zhang Z.J.

Allylsilanes are prepared by simple metathetical cross-coupling of terminal olefins with allyltrimethylsilane. Allytrimethylsilane coupling with π-substituted terminal olefins (styrenes, 1-phenyl-1,3-butadiene, and acrylonitrile) proceeds in excellent yield and very high selectivity. Lower, but still useful, selectivities are observed for allyltrimethylsilane/alkyl olefin cross-metathesis reactions.

Schwab P., Grubbs R.H., Ziller J.W.

The reactions of RuCl2(PPh3)3 with a number of diazoalkanes were surveyed, and alkylidene transfer to give RuCl2(CHR)(PPh3)2 (R = Me (1), Et (2)) and RuCl2(CH-p-C6H4X)(PPh3)2 (X = H (3), NMe2 (4), OMe (5), Me (6), F (7), Cl (8), NO2 (9)) was observed for alkyl diazoalkanes RCHN2 and various para-substituted aryl diazoalkanes p-C6H4XCHN2. Kinetic studies on the living ring-opening metathesis polymerization (ROMP) of norbornene using complexes 3−9 as catalysts have shown that initiation is in all cases faster than propagation (ki/kp = 9 for 3) and that the electronic effect of X on the metathesis activity of 3−9 is relatively small. Phosphine exchange in 3−9 with tricyclohexylphosphine leads to RuCl2(CH-p-C6H4X)(PCy3)2 10−16, which are efficient catalysts for ROMP of cyclooctene (PDI = 1.51−1.63) and 1,5-cyclooctadiene (PDI = 1.56−1.67). The crystal structure of RuCl2(CH-p-C6H4Cl)(PCy3)2 (15) indicated a distorted square-pyramidal geometry, in which the two phosphines are trans to each other, and the alkyli...

Grubbs R.H., Miller S.J., Fu G.C.

Carbon-carbon bond forming reactions remain among the most important for the synthesis of organic structures. The transition metal alkylidene-catalyzed olefin metathesis reaction (eq 1) and the related transition metal alkylidene-mediated carbonyl olefination reaction (eq 2) are two such processes. Historically, olefin metathesis has been studied extensively both from the mechanistic standpoint and in the context of polymer synthesis. In contrast, its application to the synthesis of complex organic molecules and natural products has been limited. The related reaction, transition metal-mediated carbonyl olefination, is not as extensively studied mechanistically nor in synthetic applications. Among the reasons for this gap in methodology has been the incompatibility of traditional catalysts with the polar functional groups typically encountered in organic synthesis.

Schwab P., France M.B., Ziller J.W., Grubbs R.H.

Morken J.P., Didiuk M.T., Visser M.S., Hoveyda A.H.

Crowe W.E., Zhang Z.J.

Grossman R.B., Doyle R.A., Buchwald S.L.

Treatment of (EBTHI)MCl 2 [M=Zr, 1; M=Hf, 2; EBTHI=ethylene-1,2-bis(η 5 -4,5,6,7-tetrahydro-1-indenyl)] with 2 equiv of NaEt 3 BH in C 6 H 6 produces the hydride dimers [(EBTHI)MH(μ-H)] 2 (M=Zr, 3; M=Hf, 4). The dimethylhafnium complex (EBTHI)HfMe 2 (5) is formed when 2 is treated with MeLi in C 6 H 6 . Complexes 3 and 4 can be protonated with the weak acid [PhMe 2 NH][Co(C 2 B 9 H 11 ) 2 ] to give monomeric cationic hybrides [(EBTHI)M(H)(NPhMe 2 )][Co(C 2 B 9 H 11 ) 2 ] (M=Zr, 6; M=Hf, 7), in which the N,N-dimethylaniline ligand is very weakly coordinated to the metal

Tricot M.

Emploi de la relation de Yamakawa Fujii pour obtenir la longueur de persistance a partir de la viscosite

Bezuidenhoudt B.C., Marais C.

Ekeli J.B., Foscato M., Blanco C.O., Occhipinti G., Fogg D.E., Jensen V.R.

Niu Y., Gao S., Liu X., Xin H., Duan X., Guo L., Gao P., Li P.

Visible-light-induced palladium-catalyzed formal [3 + 3] cyclization of 2-iodophenols and cyclopropenes for the synthesis of 2,2-disubstituted 2H-chromenes with a quaternary carbon center in moderate to good yields.

Antonova Alexandra S., Zubkov Fedor I.

Catalytic olefin metathesis using Hoveyda-Grubbs type ruthenium complexes is a powerful tool for creating complex molecules possessing a variety of practically useful properties. This method is also applied for obtaining modern polymer materials from low-demand petroleum products. Among all ruthenium complexes containing five- or six-membered chelate rings, the commercially available HG-II catalyst is the most common. In addition, other Hoveyda-Grubbs type complexes, which include a Het→Ru donor–acceptor bond in the chelate ring, often exhibit metathesis activity equal to or superior to that of HG-II. This review considers second-generation N-heterocyclic ruthenium carbene Hoveyda-Grubbs type complexes with donor–acceptor bonds such as O→Ru, S→Ru, Se→Ru, N→Ru, P→Ru and Hal→Ru in the chelate ring. Methods of preparation, analysis of stability and catalytic activity of such complexes are compared, and examples of the application of these organometallic ruthenium derivatives in the synthesis of practically relevant products are provided. The literature from 2010 to 2023 is summarized, making this review useful for a broad audience of chemists working in heterocyclic and organometallic chemistry, as well as practitioners involved in the production of catalysts and polymers.The bibliography includes 174 references.

Cheng-Sánchez I., Moya-Utrera F., Sarabia F.

Nadirova M., Zieliński A., Malinska M., Kajetanowicz A.

Two new ruthenium complexes with chelating-ether benzylidene ligands bearing a furan moiety were synthesized and characterized, including X-ray crystallography. They initiated fast, also at 0 °C, and were found to be highly active in a variety of ring-closing, ene-yne, and cross-metathesis reactions, including an active pharmaceutical ingredient (API) model, which makes them good candidates for the transformation of complex polyfunctional compounds that require mild reaction conditions.

Zheng S., Wen Z., Yang K., Zeng Y., Chen L., Deng J.

The first copper-catalyzed direct dehydrative alkynylation of 2H-chromene hemiketals with terminal alkynes has been uncovered. The use of cheap and readily available CuCl2 as the catalyst allowed the preparation of various 2,2-disubstituted 2-alkynylated 2H-chromenes in moderate to good yields, which compensates for the limitation of the current methods only suited for the synthesis of 2-monosubsituted 2-alkynylated 2H-chromenes.

Nechmad N.B., Lemcoff N.G., Delaude L.

This chapter surveys the various types of ruthenium benzylidene complexes that were described in the literature within the years 1995–2021. The emphasis is placed on their synthesis, characterization, and chemical reactivity rather than their catalytic activity. Some remarkable structure/activity relationships that helped tailoring the coordination sphere of the metal center through ligand design in order to achieve the highest possible activities and selectivities toward various kinds of olefin metathesis reactions are nonetheless highlighted. A brief overview of the few ruthenium benzylidyne complexes that have been reported thus far is also included.

Ahmed W., Jayant V., Alvi S., Ahmed N., Ahmed A., Ali R.

The passion of total- and fragments syntheses of natural products always remained one of the top priorities among the synthetic chemists worldwide. Due their curiosity toward the complexity of molecules of living nature and their endeavour to imitate them in laboratory; limitless arrays of natural products have been extracted, architecturally-elucidated, synthesized, and chronicled by utilizing various synthetic methodologies in different fashions. Frequently, the synthesis of complex natural products proceed with inscrutable synthetic challenges, which can be circumvented either by modification of previously developed synthetic methods or by formulating a new one. In this way, a myriad of powerful synthetic reactions have been developed since the genesis of the logic of chemical synthesis. Amongst them, metathesis tactics discovered unexpectedly in the 1950s (Nobel Prize in 2005), have incredibly influenced and changed the landscape of the art of the total and formal synthesis in the last three decades thereby achieved the fame abruptly as compared to other developed transformations or their modified forms. In this particular review article, we envisioned to report a comprehensive detail of the metathetic tools involved in both total and fragments synthesis of natural products in the years 2018 and 2019 along with an overview of 2017.

Zheng S., Zou Y., Wen Z., Lin J., Gu L., Chen L.

A facile synthesis of 2-phosphorylated 2H-chromenes has been accomplished herein via a Y(OTf)3-catalyzed dehydrative coupling of 2H-chromene hemiacetals with P(O)-H compounds. This protocol features low catalyst loading, mild reaction conditions, broad substrate scope and easy elaboration of the products.

Grela K., Kajetanowicz A., Szadkowska A., Czaban‐Jóźwiak J.

This chapter describes olefin cross‐metathesis (CM) reactions catalyzed by ruthenium, molybdenum, and tungsten complexes and surveys the literature from 1993 through 2020. Cross‐metathesis has been applied to the synthesis of a wide range of functionalized alkenes, including natural and biologically active products. Due to its simplicity and inherit atom economy, CM has found applications in the preparation of fine chemicals and various building blocks, and in transformations of biomass. Tandem reactions involving CM as the key step are also reviewed. Examples discussed in this chapter serve to illustrate how the reactivity of alkene substrates in CM depends on the presence of functional groups and steric congestion in the proximity of the reacting double bonds. A discussion of the mechanism of olefin metathesis is also included.

Blacquiere J.M.

Hemilabile ligands that undergo reversible changes in denticity have long been exploited to enable catalyst activation and to increase lifetime. However, this common description does not fully refl...

Zhang J., Qiu Y., Zhang B., Huang Z., He Z.

In this report, a P(NMe2)3-mediated reductive intramolecular annulation reaction has been developed with benzoyl formates bearing a trisubstituted alkene unit. It provides a facile synthesis of highly functionalized 2,2-disubstituted 2H-chromenes with a broad substrate scope and high efficiency. Experimental results suggest this annulation reaction proceeds via a cascade of alkene isomerization/vinyl o-quinone methide formation/6π-electrocyclization. As a key intermediate, the vinyl-substituted o-quinone methide is presumably generated by a Kukhtin-Ramirez adduct initiated O → C vinyl migration.

Hoveyda A.H., Liu Z., Qin C., Koengeter T., Mu Y.

Hoveyda A.H., Liu Z., Qin C., Koengeter T., Mu Y.

Ethylene is the byproduct of olefin metathesis reactions that involve one or more terminal alkenes. Its volatility is one reason why many cross-metathesis or ring-closing metathesis processes, which are reversible transformations, are efficient. However, because ethylene can be converted to a methylidene complex, which is a highly reactive but relatively unstable species, its concentration can impact olefin metathesis in other ways. In some cases, introducing excess ethylene can increase reaction rate owing to faster catalyst initiation. Ethylene and a derived methylidene complex can also advantageously inhibit substrate or product homocoupling, and/or divert a less selective pathway. In other instances, a methylidene's low stability and high activity may lead to erosion of efficiency and/or kinetic selectivity, making it preferable that ethylene is removed while being generated. If methylidene decomposition is so fast that there is little or no product formation, it is best that ethylene and methylidene complex formation is avoided altogether. This is accomplished by the use of di- or trisubstituted alkenes in stereoretentive processes, which includes adopting methylene capping strategy. Here, we analyze the different scenarios through which ethylene and the involvement of methylidene complexes can be manipulated and managed so that an olefin metathesis reaction may occur more efficiently and/or more stereoselectively.