Extracurricular laboratory:new discovery of (1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium

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Rapid and high yielding synthesis of medium ring lactams was made possible through the use of a benzoylurea auxiliary that serves to stabilize a cisoid amide conformation, facilitating cyclization. The auxiliary is released after activation under the mild conditions required to deprotect a primary amine, such as acidolysis of a Boc group in the examples given here. This methodology is a promising tool for the synthesis of medium ring lactams, macrocyclic natural products and peptides.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination/ cyclization sequence. They serve as a versatile platform for the annellation of five- to seven-membered rings using ring-closing olefin metathesis (RCM). Furano-, pyrano-, oxepino- and azepinocoumarins were synthesized from the same set of precursors using Ru-catalyzed double bond isomerizations and RCM in a defined order. One class of products, pyrano[2,3-f]chromene-2,8-diones, were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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The combination of enzymes with traditional chemical catalysts unifies the high selectivity of the former with the versatility of the latter. A major challenge of this approach is the difference in the optimal reaction conditions for each catalyst type. In this work, we combined a cofactor-free decarboxylase with a ruthenium metathesis catalyst to produce high-value antioxidants from bio-based precursors. As suitable ruthenium catalysts did not show satisfactory activity under aqueous conditions, the reaction required the use of an organic solvent, which in turn significantly reduced enzyme activity. Upon encapsulation of the decarboxylase in a cryogel, the decarboxylation could be conducted in an organic solvent, and the recovery of the enzyme after the reaction was facilitated. After an intermediate drying step, the subsequent metathesis in pure organic solvent proved to be straightforward. The synthetic utility of the cascade was demonstrated by the synthesis of the antioxidant 4,4?-dihydroxystilbene in an overall yield of 90 %.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Ru K-edge XAS data indicate that second generation ruthenium-based olefin metathesis precatalysts (L = N-heterocyclic carbene) possess a more electron-deficient metal center than in the corresponding first generation species (L = tricyclohexylphosphine). This surprising effect is also observed from DFT calculations and provides a simple rationale for the slow phosphine dissociation kinetics previously noted for second-generation metathesis precatalysts. Copyright

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Aromatic fluorinated hydrocarbons, used as solvents for olefin metathesis reactions, catalysed by standard commercially available Ru precatalysts, allow substantially higher yields to be obtained, especially of challenging substrates, including natural and biologically active compounds. The Royal Society of Chemistry 2008.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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A systematic study on ring-closing metathesis with Grubbs II catalyst to cembranoid macrocycles is described. Acyclic terpenoids with a functional group X in the homoallylic position relative to an RCM active terminus and substituents R, R1 directly attached to the other terminal double bond were prepared from geraniol derived trienes and fragments that are based on bromoalkenes and dimethyl malonate. Such terpenoids were suitable precursors, despite the presence of competing double bonds in their framework. The size of R and R1 is crucial for successful macrocyclization. Whereas small alkyl substituents at the double bond directed the RCM towards six-membered ring formation, cross metathesis leading to dimers dominated for bulkier alkyl groups. A similar result was obtained for precursors without functional group X. In the case of unsymmetrically substituted terpenoid precursor (R=Et, R1=Me) with homoallylic OTBS or OMe group, the RCM could be controlled towards formation of macrocyclic cembranoids, which were isolated with excellent E-selectivity. The role of the substituents was further studied by quantum chemical calculations of simplified model substrates. Based on these results a mechanistic rationale is proposed.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Biomimetic epoxide-opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide-opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2O was applied to the synthesis of a new nerolidol-type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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We described the highly efficient synthesis of cis-hydrindenols from 2-allylbicyclo[2.2.2]octenol derivatives using the Diels-Alder adducts of masked o-benzoquinones (MOBs) with suitable dienophiles, as precursors for ring-rearrangement metathesis (RRM). These facile, versatile, and operationally simple transformation strategies produced cis-hydrindenol products with four stereo-centers and a tertiary hydroxyl functional group.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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An efficient total synthesis of the antiproliferative macrolide and cell migration inhibitor lactimidomycin (3) is reported, which relies on the performance of ring closing alkyne metathesis (RCAM). The strained 12-membered 1,3-enyne 21 as the key intermediate was forged with the aid of [(Ph 3SiO)3Mo?CPh]?OEt2 (27) as the most effective member of a new generation of powerful alkyne metathesis catalysts. 21 was elaborated to the target by a ruthenium catalyzed trans-hydrosilylation/ proto-desilylation sequence and a highly diastereoselective Mukaiyama aldol reaction controlled by oxazaborolidinone 29 as strategic operations.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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The four diastereomers of 2,5-bis[(3-guanidino)propyl]-1-[3-(4- hydroxyphenyl)propionyl]-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (54-57) and of 2,5-bis[(3-guanidino)propyl]-1-(4-hydroxyphenylacetyl)-7-(2- naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (58-61) were synthesized by a divergent methodology from l- and d-glutamic acids. The 11-membered ring core was made by ring closing metathesis of linear bis(allylamines), and the guanidyl functions were introduced by a simultaneous double Mitsunobu reaction using bis(Boc)guanidine. These compounds were designed to mimic cyclic pentapeptide FC131 (c[Gly-d-Tyr-Arg-Arg-Nal]). The Royal Society of Chemistry.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI