A Catalytic Approach to (<i>R</i>)‐(+)‐Muscopyridine with Integrated “Self‐Clearance”

Fürstner, Alois; Leitner, Andrea

doi:10.1002/anie.200390103

Cited by 238 publications

(81 citation statements)

References 48 publications

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“…A similar pyridinophane cyclization reaction was recently reported by Fürst-ner. [16] Template-directed RCM of the less active bis-styrene derivative 4e, on the other hand, was only possible in the presence of large amounts (15 mol %) of the more active second-generation Grubbs catalyst, [Cl 2 (PCy 3 )(IMes)-…”

Section: Dedicated Cluster Full Papersmentioning

confidence: 99%

General Approach for Template‐Directed Synthesis of Macroheterocycles by Ring‐Closing Metathesis (RCM)

et al. 2005

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Dedicated to Prof. Dr. Richard Schrock on the occasion of his 60 th birthday and in recognition of his highly appreciated contribution to chemistry in general and his pioneering studies on ofefin metathesis in particular.Abstract: A general method to prepare macroheterocycles is reported in which a rigid symmetric platinated tris-pincer tricationic complex (3) is used as a template. The system uses bisolefin functionalized pyridine ligands (1, 2) which selectively bind to the three platinum centers of the template resulting in pre-organization of the olefinic tails. By subjecting these pre-organized complexes (4) to olefin metathesis reaction conditions, the olefinic tails were interconnected affording several macroheterocycles of different compositions and sizes. Various pyridines with different substitution patterns (2,6-and 3,5-disubstituted) and different olefinic tails (aliphatic, polyether, and styryl) were synthesized and used in the cyclization reactions, showing the diversity of this method. It was found that only the use of 2,6-disubstituted pyridines resulted in the formation of the desired macrocycles while 3,5-difunctionalized pyridines gave only pyridinophane formation. Furthermore, the length of the olefinic tails needs to be at least eleven atoms (C or O) in order to suppress oligomerization in favor of macrocycle formation. Yields of up to 70% of the macrocycles were obtained using the first-generation [Cl 2 (Cy 3 P) 2 Ru ¼ CHPh] or second-generation [Cl 2 (Cy 3 P)(IMes)Ru ¼ CHPh] Grubbs catalysts. Reactions of the platinated pincer pyridines with Schrock Mo-based metathesis catalysts results in exclusive olefin isomerization and no productive metathesis. The generated macrocycles (hosts) could effectively be separated from the template by addition of aqueous sodium chloride and reattached to the (recycled) template (guest). The X-ray structure determination of host-guest complex 10 is the definite proof for this reattachment and the perfect cyclic structure of the macrocycle.

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Section: Dedicated Cluster Full Papersmentioning

confidence: 99%

General Approach for Template‐Directed Synthesis of Macroheterocycles by Ring‐Closing Metathesis (RCM)

et al. 2005

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“…They are able to catalyze, for example, the cross coupling of aromatic and heteroaromatic chlorides or sulfonates with various Grignard reagents with exceptional ease and unprecedentedly high reaction rates. When applied to substrates bearing more than one leaving group, this method allows one to perform selective, serial, or exhaustive alkylation reactions (24,30).…”

Section: Resultsmentioning

confidence: 99%

“…It is also important to note that the 22-membered cycloalkene formed by RCM does not have to be ‡ Slow addition of the Grignard reagent over 30 min is essential, resulting in the exclusive formation of the monosubstitution product, whereas more rapid addition affords product mixtures. isolated but can be converted into isooncinotine by stirring the crude reaction mixture in an autoclave under H 2 (50 bars, 70°C) for 12 h. Under these conditions, the alkylidene complex is converted into a ruthenium hydride, which serves as homogeneous catalyst saturating the double bond (30,41,42). The analytical and spectroscopic data of (Ϫ)-isooncinotine 1 thus obtained from diene 13 in 76% over three steps in ''one pot'' are in excellent agreement with those reported in the literature (6).…”

Section: Resultsmentioning

confidence: 99%

“…The approach is largely catalysis-based and scrutinizes methodology developed previously in our laboratories. Thus, it shows that cheap and nontoxic iron salts warrant consideration as substitutes for established palladium and nickel catalysts in alkyl-aryl cross-coupling reactions of (hetero)aryl chlorides (24,25,30). Likewise, the potential of an entry into optically active piperidines by asymmetric hydrogenation of substituted pyridines (23) is demonstrated by the conversion of 9 into compound 10.…”

Section: Discussionmentioning

confidence: 99%

“…The resulting bright-yellow solution was added to a solution of the aldehyde described above (260 mg, 0.44 mmol) in THF (5 ml) at Ϫ78°C. The mixture was stirred at that temperature for 5 min and then for 30 …”

Section: (R)-hex-5-enoic Acid (3-{[4-(2-hept-6-enylpiperidinyl)butyl]mentioning

confidence: 99%

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Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine

Scheiper

Glorius

Leitner

et al. 2004

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

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128

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A concise and efficient total synthesis of the spermidine alkaloid (؊)-isooncinotine (1) incorporating a 22-membered lactam ring is outlined. The approach is largely catalysis-based, involving a selective iron-catalyzed alkyl-aryl cross-coupling reaction of a difunctionalized pyridine substrate, a heterogeneous asymmetric hydrogenation step to set the chiral center of the target, and a highly integrated ring-closing metathesis͞hydrogenation sequence to forge the saturated macrocyclic edifice in a single operation. Despite the prevalence of the biogenetic bases spermidine and spermine in nature and their widespread use as tools in biochemical research (1), little is known about the physiological properties of the small but structurally rather unique class of alkaloids incorporating these polyamines into their macrocyclic skeletons (2-4). This may be due, in part, to the difficulties in obtaining pure samples of these compounds from the natural sources † as well as to the fact that most syntheses described thus far provided only racemic material. Prototype spermidine alkaloids are (Ϫ)-isooncinotine (1), (Ϫ)-oncinotine (2), (Ϫ)-neooncinotine (3), and oncinodin-12-one (4), which were isolated from the stem bark of Oncinotis nitida and Oncinotis tenuiloba (Apocynaceae) (5-7) and have been repeatedly targeted in the past (8-12) (Fig. 1). Only recently has one member of this series (i.e., compound 2) been made available in an optically active form through total synthesis by using a diastereoselective 1,3-dipolar cycloaddition for the formation of the stereogenic center at the junction of the piperidine and the macrocyclic ring (13).In pursuit of previous work in the field of polyamine alkaloids (14, 15), we were prompted to develop a complementary, practical, and potentially scaleable entry into this family of natural products, choosing the 22-membered macrolactam (Ϫ)-isooncinotine 1 as our initial target. The envisaged route, however, should not only provide material for further evaluation but also meet a set of stringent chemical criteria. Specifically, it is felt that contemporary organic chemistry must (i) prioritize catalysis-based bond formations, (ii) try to control absolute stereochemistry by asymmetric catalysis, and (iii) aim at high convergence combined with an overall ''economy of steps'' (16). Furthermore, the total synthesis of 1 should provide us with the possibility to scrutinize methodology developed in our laboratories. Outlined below is the successful reduction of this plan to practice. Materials and MethodsGeneral. All reactions were carried out under Ar in flame-dried glassware. The solvents used were purified by distillation over the drying agents indicated and were transferred under Ar: tetrahydrofuran (THF) (Na), CH 2 Cl 2 (P 4 O 10 ), MeCN, Et 3 N, pyridine, NMP, hexamethylphosphoramide (HMPA), tetramethylethylenediamine (CaH 2 ), dimethylformamide (DMF) (dibutyltin dilaurate͞Desmodur), MeOH, EtOH (Mg), and toluene (Na͞K). For flash chromatography, Merck silica gel 60 (230-400 mesh) was used. F...

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Alkaline Earth Metals: Organometallic Chemistry

Alexander

Guino-o

Zuniga

et al. 2005

Encyclopedia of Inorganic Chemistry

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The organometallic chemistry of the alkaline earth metals has undergone a renaissance during the last decade with exciting novel uses of the organomagnesium reagents in synthetic chemistry to significantly extend the utility of these well‐developed reagents. With the development of the organometallic chemistry of the heavier metals significantly lagging behind, and past work mainly focusing on and establishing π‐bonded metal–ligand systems, intense research efforts during the last decade have contributed significantly to expand the understanding of the organometallic compounds of these metals, establishing σ‐bonded organometallic compounds for the heavy alkaline earth metals. This improved insight did not only provide the basis for a more detailed understanding of the metal–ligand bonding characteristics, but also paved the way towards the successful applications of the compounds as polymerization initiators and in organic synthetic chemistry. This article summarizes some of the recent, exciting developments in regards to alkaline earth organometallics.

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A Catalytic Approach to (R)‐(+)‐Muscopyridine with Integrated “Self‐Clearance”

Cited by 238 publications

References 48 publications

General Approach for Template‐Directed Synthesis of Macroheterocycles by Ring‐Closing Metathesis (RCM)

General Approach for Template‐Directed Synthesis of Macroheterocycles by Ring‐Closing Metathesis (RCM)

Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine

Alkaline Earth Metals: Organometallic Chemistry

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