Total synthesis of (±)-aspercyclide A and its C19 methyl ether

Carr, James L.; Offermann, Daniel A.; Holdom, Mary D.; Dusart, Philip; White, Andrew J. P.; Beavil, Andrew J.; Leatherbarrow, Robin J.; Lindell, Stephen D.; Sutton, Brian J.; Spivey, Alan C.

doi:10.1039/b923528k

Cited by 30 publications

(27 citation statements)

References 26 publications

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“…Upon reaction with sodium iodide and catalytic amounts of copper(I) iodide and (±)- trans - N , N ′-dimethyl-1,2-cyclohexanediamine in dioxane at 110°C, a variety of aryl bromides 11 Br could be smoothly converted to their iodinated analogs 11 I with excellent yields. The scope of the reaction was shown to be remarkably broad and this process clearly is one of the most efficient to date, as exemplified with representative synthetic application of this process that will be overviewed in section Synthetic Applications of Halogen Exchanges in Aryl Halides and its use in natural product synthesis (Fürstner and Kennedy, 2006 ; Carr et al, 2010 ). It was later on extended to other (hetero)aryl bromides (Lützen et al, 2014 ) and to continuous flow chemistry using a sodium iodide packed-bed reactor (Chen et al, 2014 ) and recent studies demonstrated that the reaction time could be shortened using microwave irradiation (Cannon et al, 2011 ) and that other diamines and some triamines (Jin and Davies, 2017 ) could also be used as ligands.…”

Section: Halogen Exchange In Aryl Halidesmentioning

confidence: 99%

Metal-Mediated Halogen Exchange in Aryl and Vinyl Halides: A Review

et al. 2018

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Halogenated arenes and alkenes are of prime importance in many areas of science, especially in the pharmaceutical, agrochemical, and chemical industries. While the simplest ones are commercially available, some of them are still hardly accessible depending on their substitution patterns and the nature of the halogen atom. Reactions enabling the selective and efficient replacement of the halogen atom of an aryl or alkenyl halide by another one, lighter, or heavier, are therefore of major importance since they can be used for example to turn a less reactive aryl/alkenyl chloride into the more reactive iodinated derivatives or, in a reversed sense, to block an undesired reactivity, for late-stage modifications or for the introduction of a radionuclide. If some halogen exchange reactions are possible with activated substrates, they usually require catalysis with metal complexes. Remarkably efficient processes have been developed for metal-mediated halogen exchange in aryl and vinyl halides: they are overviewed, in a comprehensive manner, in this review article.

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Section: Halogen Exchange In Aryl Halidesmentioning

confidence: 99%

Metal-Mediated Halogen Exchange in Aryl and Vinyl Halides: A Review

et al. 2018

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“…In recent years, a wide array of metal-catalyzed coupling reactions has been effectively applied to C-C bond formation, including the C-C bond formation for the construction of macrocycle [7][8][9][10]. We next set out to explore ring-closing strategy via palladium-catalyzed intramolecular C-C bond formation.…”

Section: Evaluation Of Alternative Ring-closing Strategymentioning

confidence: 99%

Application of Ring-Closing Metathesis Strategy to the Synthesis of Vaniprevir (MK-7009), a 20-Membered Macrocyclic HCV Protease Inhibitor

Chen

2012

Organometallics as Catalysts in the Fine Chemical Industry

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Vaniprevir (MK-7009) bearing a 20-membered macrocycle and chiral components is a highly efficacious HCV protease inhibitor aiming for the treatment of chronic infection of hepatitis C virus. The efficient macrocyclization coupled with the assembling of key chiral components is of great challenge for the large-scale production of this structurally complex molecule. In this chapter, a convergent synthesis with a longest sequence of nine steps featuring highly efficient macrocyclization via ring-closing metathesis (RCM) along with the improvement in the syntheses of key components will be described. RCM for the construction of 20-membered macrocycle using low catalyst loading (0.2 mol%) and practically high concentration (0.13 M) was achieved by simultaneous and slow addition of ruthenium catalyst and the diene substrate. The strategy of using RCM in this costeffective synthesis sets a new paradigm for the synthesis of several other macrocyclic HCV protease inhibitors at Merck Research Laboratories.

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“…The palladium complexes 10a,b are thermally considerably more stable than palladium complexes with triorganylphosphine ligands. In addition, the Pd 0 -carbene complex 10b has an extremely high activity with long-term stability in the Heck reaction: with only 4 × 10 −4 mol% of catalyst, Pd(OTfa) 2 Coupling of benzoic acids [53] Air stable [54] PdCl 2 Coupling of aryl or vinyl arenecarboxylates [55] Least expensive Pd salt [56a] [Pd(acac) 2 ] Aryl iodides - [45,57] [Pd(dba) 2 ] Aryl and alkenyl halides, benzyl acetates…”

Section: 22 the Catalystsmentioning

confidence: 99%

Cross‐Coupling of Organyl Halides with Alkenes – The Heck Reaction

Bräse¹,

Meijere²

2013

Metal‐Catalyzed Cross‐Coupling Reactions and More

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The carbopalladation of an alkene by an organylpalladium halide is the essential step in one of the major contemporary metal-catalyzed C-C coupling reactions. About 45 years ago, a Japanese and an American group almost simultaneously designed and executed palladium-mediated coupling reactions of aryl and alkenyl halides with alkenes [1]. In subsequent investigations, Richard Heck and his group developed this reaction into a catalytic transformation and started to demonstrate its usefulness as well as its rather broad scope. The real push to utilize this powerful C-C-bondforming process, however, started only around the mid-1980s, and by now, an impressive number of publications have established the meanwhile so-called Heck reaction [2] 1) as an indispensable method in Organic Synthesis [3][4][5][6][7]. The universal recognition of the importance of the Heck reaction and the Negishi as well as the Suzuki coupling eventually won the Nobel Prize for Richard Heck along with Ei-ichi Negishi and Akira Suzuki in 2010. The applications of the Heck reaction range from the preparation of -functionalized and unfunctionalized -hydrocarbons, novel polymers, and dyes to new advanced enantioselective syntheses of natural products and biologically active nonnatural compounds. The more or less simultaneous developments of mechanistically related variants, namely, the Kumada, Suzuki, Stille, Hiyama, and Negishi coupling reactions (Chapters 12, 2, 3, 4, and 15, respectively) of metallated alkenes and arenes with aryl and alkenyl halides or the metal-catalyzed formation and cycloisomerization of enynes have drawn profit from the improvement of and mechanistic insights into the Heck reaction. This, of course, applies vice versa as well. Using only a catalytic amount of a palladium(0) complex or a precursor to a palladium species, the Heck reaction can bring about unprecedented structural changes, particularly when conducted intramolecularly. The full potential of this palladium-catalyzed process is still being further explored as demonstrated by a total of over 7000 publications in the past 40 years by 1) The alkynylation of aryl and alkenyl halides, frequently also considered as Heck reactions, is described in Chapter 6.

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Total synthesis of (±)-aspercyclide A and its C19 methyl ether

Abstract: The total syntheses of (±)-aspercyclide A (1) and its C19 methyl ether derivative (15a) are described. ELISA studies show that both compounds display comparable antagonist activity against the IgE–FcεRI protein–protein interaction.

Cited by 30 publications

References 26 publications

Metal-Mediated Halogen Exchange in Aryl and Vinyl Halides: A Review

Metal-Mediated Halogen Exchange in Aryl and Vinyl Halides: A Review

Application of Ring-Closing Metathesis Strategy to the Synthesis of Vaniprevir (MK-7009), a 20-Membered Macrocyclic HCV Protease Inhibitor

Cross‐Coupling of Organyl Halides with Alkenes – The Heck Reaction

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