H-Bonding as a Control Element in Stereoselective Ru-Catalyzed Olefin Metathesis

Hoveyda, Amir H.; Lombardi, Pamela J.; O’Brien, Robert V.; Zhugralin, Adil R.

doi:10.1021/ja9030903

Cited by 121 publications

(72 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent work has highlighted the enhanced metathesis efficiency of allylic alcohols compared to their corresponding ethers (26,27), and our own preliminary observations are consistent with these findings. As evidenced by Hoveyda, it is possible that hydrogen bonding between the allylic alcohol derived carbene and a ruthenium chloride ligand is crucial in expediting subsequent CM to the electron deficient enone (27).…”

Section: Resultssupporting

confidence: 90%

An expedient route to substituted furans via olefin cross-metathesis

Donohoe

Bower

2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The olefin cross-metathesis (CM) reaction is used extensively in organic chemistry and represents a powerful method for the selective synthesis of differentially substituted alkene products. Surprisingly, efforts to integrate this remarkable process into strategies for aromatic and heteroaromatic construction have not been reported. Such structures represent key elements of the majority of small molecule drug compounds; methods for the controlled preparation of highly substituted derivatives are essential to medicinal chemistry. Here we show that the olefin CM reaction, in combination with an acid cocatalyst or subsequent Heck arylation, provides a concise and flexible entry to 2,5-di-or 2,3,5-tri-substituted furans. These cascade processes portend further opportunities for the regiocontrolled preparation of other highly substituted aromatic and heteroaromatic classes.catalysis | cembranolide | Heck reaction R uthenium catalyzed olefin metathesis has become a remarkably powerful tool for organic chemistry (1-5). In recent years, the potential of ring-closing olefin metathesis (RCM) as a key step for the preparation of aromatic and heteroaromatic compounds has begun to be realized (6-8). Studies from our own laboratory have delineated versatile RCM-based protocols for the regiodefined synthesis of pyridines, pyridazines, furans, and pyrroles (9-15). Despite the evident potential of these methods it is notable that any RCM-based approach is reliant upon the a priori construction of a suitable precursor, which necessarily detracts from synthetic convergency and flexibility. A related approach involves the use of olefin cross-metathesis (CM) as a key step. Here both fragment coupling and strategic C=C bond formation are unified and, as such, potentially greater efficiencies are afforded. Despite this potential, and presumably due to perceived problems associated with double bond geometry, olefin CM-based methodologies for aromatic and heteroaromatic construction have not, to the best of our knowledge, been disclosed. Herein we report the successful implementation of this concept in terms of a versatile and direct entry to disubstituted and trisubstituted furans. It is likely that these studies will set the stage for the development of general olefin CM-based entries to other aromatic and heteroaromatic classes of varying ring sizes (Scheme 1, top).Substituted furans are prevalent in natural products and pharmaceuticals and also represent useful intermediates in synthesis. Convergent de novo approaches to furans that embody high levels of flexibility and predictable regiocontrol are of particular value yet are relatively uncommon (16)(17)(18)(19)(20)(21)(22). Specifically, methods that employ simple starting materials, enable facile substituent introduction, and are concise are likely to be of significance to both medicinal chemistry and total synthesis. Our approach to furans relies upon the intermediacy of trans-γ-hydroxyenones 3 that are accessible via the established olefin CM of readily available allylic alcohol...

show abstract

Section: Resultssupporting

confidence: 90%

An expedient route to substituted furans via olefin cross-metathesis

Donohoe

Bower

2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In contrast, cross metathesis of homoallylic alcohol 14a with vinyl dioxinone 10 gave dioxinone 15a in an 81% yield (Scheme 3). 23 Subsequently, we examined the oxidation of the cross metathesis product 15a to give enone-dioxinone 16a (Table 1). Our initial attempts involving pyridinium chlorochromate and manganese dioxide were unsuccessful with unreacted starting material being recovered (Table 1, entries 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 6-substituted salicylates via biomimetic aromatization utilizing the cross metathesis of a vinyl dioxinone with homoallylic alcohols

Blencowe

BarrettAnthony

2012

Can. J. Chem.

View full text Add to dashboard Cite

We herein report biomimetic syntheses of 6-substituted salicylates from the cross metathesis of 2,2-dimethyl-6-vinyl-1,3-dioxin-4-one with homoallylic alcohols, oxidation, and aromatization of the intermediate enone-dioxinones. Of particular note is the use of the catalyst 1,4-diazabicyclo[2.2.2]octane in the microwave thermolytic ketene generation and trapping, cyclization, and dehydration reaction sequence.Résumé : Dans ce travail, on rapporte les synthèses biomimétiques de salicylates substitués en position-6, par le biais d'une réaction de métathèse croisée de la 2,2-diméthyl-6-vinyl-1,3-dioxin-4-one avec des alcools homoallyliques, suivie d'une oxydation et d'une aromatisation de l'intermédiaire énone-dixoinones. Il est important de noter l'utilisation du 1,4-diazabicyclo[2.2.2]octane comme catalyseur dans la génération thermolytique du cétène, de son piégeage, de sa cyclisation et de sa déshydrogénation dans la séquence réactionnelle.Mots-clés : salicylates, synthèse biomimétique, dioxinone, synthèse d'un polycétide.[Traduit par la Rédaction]

show abstract

“…Presumably, protecting groups around the reacting centres might act as temporary constraints to adequately shape this particular diene and simultaneously confer selectivity upon the stereochemistry of the newly formed double bond, while substrates with free allylic hydroxyl groups could accelerate the RCM reaction rates. This could be explained by anticipating co-operative O-H•••Cl-Ru hydrogen bonding [80]. As shown in Fig.…”

Section: Second the Selection Of Protecting Groups To Be Attached Tomentioning

confidence: 94%

Nonanolides of Natural Origin: Structure, Synthesis, and Biological Activity

Sun¹,

Lu²,

Ree³

et al. 2012

curr med chem

View full text Add to dashboard Cite

Naturally occurring nonanolides (synonym decanolides) are a large family of secondary metabolites with an interesting 10- membered macrolide subunit. Metabolites of the nonanolide family have been found to have various biological activities, including cytotoxic, phytotoxic, antimalarial, antifungal, antibacterial, and antimicrofilament activities. An early review of the chemistry and bioactivity of nonanolides was presented in 1996, covering the literature published between 1975 and 1995. During the past decades, the broad spectrum of bioactivity and the intriguing structure of the medium-sized ring in nonanolide analogues have continuously drawn the attention of biologists and natural product and synthetic chemists, resulting in a great number of publications. This review summarizes in whole the recent progress in the field of the nonanolides of natural origin, aiming to give the readers a brief view of the compounds, concerning their natural occurrence, structural elucidation, biological activities, total synthesis, and structure-activity relationships. The article covers the literature published in the period from the beginning of 1996 to July 2011.

show abstract

H-Bonding as a Control Element in Stereoselective Ru-Catalyzed Olefin Metathesis

Cited by 121 publications

References 18 publications

An expedient route to substituted furans via olefin cross-metathesis

An expedient route to substituted furans via olefin cross-metathesis

Synthesis of 6-substituted salicylates via biomimetic aromatization utilizing the cross metathesis of a vinyl dioxinone with homoallylic alcohols

Nonanolides of Natural Origin: Structure, Synthesis, and Biological Activity

Contact Info

Product

Resources

About