Tandem Catalysis:  The Sequential Mediation of Olefin Metathesis, Hydrogenation, and Hydrogen Transfer with Single-Component Ru Complexes

Louie, Janis; Bielawski, Christopher W.; Grubbs, Robert H.

doi:10.1021/ja016431e

Cited by 427 publications

(237 citation statements)

References 33 publications

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“…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%

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

Scheiper

Glorius

Leitner

et al. 2004

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

129

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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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Section: Resultsmentioning

confidence: 99%

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

Scheiper

Glorius

Leitner

et al. 2004

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

129

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“…Treatment of the diene 13 with the Grubbs N-heterocyclic carbene catalyst at 40 8C gave the desired cyclic ether, which was reduced in situ and deprotected with acid to afford the primary alcohol 14 in 75 % overall yield. [18] The hydrogenation of the alkene in the metathesis product was necessary at this juncture because of its propensity to undergo oxidation. Oxidation of the primary alcohol 14 by pyridinium dichromate, [19] followed by palladium-catalyzed hydrogenation of the benzyl ether, furnished gaur acid (7) in 79 % yield (two steps).…”

Section: Methodsmentioning

confidence: 99%

Stereodivergent Construction of Cyclic Ethers by a Regioselective and Enantiospecific Rhodium‐Catalyzed Allylic Etherification: Total Synthesis of Gaur Acid

et al. 2004

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The transition-metal-catalyzed intermolecular allylic etherification is a fundamentally important cross-coupling strategy for the construction of enantiomerically enriched allylic ethers. [1] Although there are numerous examples of the use of simple primary alcohols as nucleophiles, secondary or tertiary alcohols have been used in relatively few studies, [2] partially because of the poor nucleophilicity of these alcohols and the high basicity of the corresponding alkali-metal alkoxides. In response to these underlying problems, we recently reported a regioselective and enantiospecific rhodium-catalyzed allylic etherification with copper(i) alkoxides as nucleophiles. [3] The transmetalation of an alkali-metal alkoxide served to diminish its basicity, thereby promoting the etherification of a soft metal-allyl electrophile. [4] Herein, we now describe a two-step stereodivergent synthesis of cyclic ethers. The stereospecific etherification of the acyclic enantiomerically enriched allylic carbonate I with secondary alkenyl alcohols (R)-and (S)-II followed by ringclosing metathesis (RCM) affords the cis-and trans-disubstituted cyclic ethers III and IV, respectively (Scheme 1; n = 0-3). [5][6][7] The inherent advantage of this approach is the ability to vary both ring size and relative configuration as a direct Scheme 1. General approach for the stereodivergent construction of cyclic ethers. LG = leaving group.

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“…Mais recentemente, Grubbs e colaboradores publicaram uma síntese alternativa da mesma (R)-(-)-muscona 78 a partir do álcool 79, através de um elegante processo em uma etapa ("one pot") envolvendo três reações seqüenciais (RCM -desidrogenação por transferência de H -hidrogenação) mediadas pelo mesmo complexo de rutênio, o catalisador de Grubbs de segunda geração 5 (Esquema 23) 69 . O rendimento deste processo de catálise em cascata ("tandem") foi de 56% e, como esperado, mostrou-se melhor a partir da cetona 76a (75%).…”

Section: Musconaunclassified

“…No caso da síntese do macrolido de 14 membros (S)-(-)-zearalenona 90, a ciclização foi realizada ao nível da ligação dupla pouca reativa do sistema estirênico presente no precursor 88 (Esquema 26). Apenas o catalisador de rutênio de 2 a geração 4, pouco (69) …”

Section: Zearalenonaunclassified

Metátese de olefinas aplicada ao fechamento de anéis: uma ferramenta poderosa para a síntese de macrociclos naturais

Santos¹,

Kaiser²,

Férézou³

2008

Quím. Nova

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Recebido em 7/3/07; aceito em 30/8/07; publicado na web em 26/2/08 RING-CLOSING OLEFIN METATHESIS: A POWERFUL TOOL FOR THE SYNTHESIS OF NATURAL MACROCYCLES. For a quarter of a century, metathesis has become indispensable for the synthesis of natural and non-natural products, particularly of biologically active compounds. This review illustrates through a maximum of appropriate examples the power and the versatility of the metathesis ring-closure (RCM) reaction as a key ring-closure methodology for the synthesis of natural macrocycles. Its high functional group compatibility as well as the possibility of further transformations makes this reaction a powerful tool in the cases where the structural framework and function requirements are difficult to meet.

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Tandem Catalysis: The Sequential Mediation of Olefin Metathesis, Hydrogenation, and Hydrogen Transfer with Single-Component Ru Complexes

Cited by 427 publications

References 33 publications

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

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

Stereodivergent Construction of Cyclic Ethers by a Regioselective and Enantiospecific Rhodium‐Catalyzed Allylic Etherification: Total Synthesis of Gaur Acid

Metátese de olefinas aplicada ao fechamento de anéis: uma ferramenta poderosa para a síntese de macrociclos naturais

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