ChemInform Abstract: N‐KETOVINYLATION OF AMIDES

Khokhlov, P. S.; Savenkov, N. F.; Sokolova, G. D.; Strepikheev, Yu. A.; Kolesova, V. A.

doi:10.1002/chin.198238180

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“…The synthesis of racemic tabersonine began with the preparation of 1-amino-3-siloxy-1,3-butadiene 16 , which was equipped with the carbomethoxy group, to temper the reactivity of the amino group, and the allyl group, chosen to provide the necessary handle for constructing the piperidine ring. We expected to prepare diene precursor 15 by the reported acid-catalyzed condensation of a secondary amide with the commercially available monoacetal 13 . The required N -allylcarbamate 14 was prepared in 96% crude yield by the reaction of 2 equiv of allylamine with methyl chloroformate in dichloromethane.…”

Section: Resultsmentioning

confidence: 99%

An Efficient Approach to Aspidosperma Alkaloids via [4 + 2] Cycloadditions of Aminosiloxydienes: Stereocontrolled Total Synthesis of (±)-Tabersonine. Gram-Scale Catalytic Asymmetric Syntheses of (+)-Tabersonine and (+)-16-Methoxytabersonine. Asymmetric Syntheses of (+)-Aspidospermidine and (−)-Quebrachamine

et al. 2002

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Described is a concise, highly stereocontrolled strategy to the Aspidosperma family of indole alkaloids, one that is readily adapted to the asymmetric synthesis of these compounds. The strategy is demonstrated by the total synthesis of (+/-)-tabersonine (rac-1), proceeding through a 12-step sequence. The basis for this approach was provided by a highly regio- and stereoselective [4 + 2] cycloaddition of 2-ethylacrolein with 1-amino-3-siloxydiene developed in our laboratory. Subsequent elaboration of the initial adduct into the hexahydroquinoline DE ring system was accomplished efficiently by a ring-closing olefin metathesis reaction. A novel ortho nitrophenylation of an enol silyl ether with (o-nitrophenyl)phenyliodonium fluoride was developed to achieve an efficient, regioselective introduction of the requisite indole moiety. The final high-yielding conversion of the ABDE tetracycle into pentacyclic target rac-1 relied on intramolecular indole alkylation and regioselective C-carbomethoxylation. Our approach differs strategically from previous routes and contains built-in flexibility necessary to access many other members of the Aspidosperma family of indole alkaloids. The versatility of the synthetic strategy was illustrated through the asymmetric syntheses of the following Aspidosperma alkaloids: (+)-aspidospermidine, (-)-quebrachamine, (-)-dehydroquebrachamine, (+)-tabersonine, and (+)-16-methoxytabersonine. Of these, (+)-tabersonine and (+)-16-methoxytabersonine were synthesized in greater than 1-g quantities and in enantiomerically enriched form ( approximately 95% ee). The pivotal asymmetry-introducing step was a catalyzed enantioselective Diels-Alder reaction, which proceeded to afford the cycloadducts in up to 95% ee. Significantly, the synthetic sequence was easy to execute and required only four purifications over the 12-step synthetic route.

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Section: Resultsmentioning

confidence: 99%

An Efficient Approach to Aspidosperma Alkaloids via [4 + 2] Cycloadditions of Aminosiloxydienes: Stereocontrolled Total Synthesis of (±)-Tabersonine. Gram-Scale Catalytic Asymmetric Syntheses of (+)-Tabersonine and (+)-16-Methoxytabersonine. Asymmetric Syntheses of (+)-Aspidospermidine and (−)-Quebrachamine

et al. 2002

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“…The carbomethoxy group was selected to temper the reactivity of the amino group, and the allyl group was chosen to provide a means to construct the piperidine ring. The condensation of commercially available acetylacetaldehyde dimethylacetal ( 4 ) with methyl N -(2-propenyl)carbamate in the presence of a catalytic amount of p- toluenesulfonic acid in refluxing chloroform afforded vinylogous imide 5 in 90% yield. The treatment of a slight excess of the imide with KHMDS followed by quenching of the resulting enolate with TBSCl gave the desired diene ( 6 ) in quantitative yield, even on a multigram scale .…”

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A General Strategy to Aspidosperma Alkaloids: Efficient, Stereocontrolled Synthesis of Tabersonine

Kozmin

Rawal

1998

J. Am. Chem. Soc.

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ChemInform Abstract: N‐KETOVINYLATION OF AMIDES

Abstract: Die Ketoacetale (I) werden mit den Amiden (II) bzw. (IV) durch säurekatalysierte Kondensation in die ungesättigten Carbonsäureamide (IIIa) und (IIIb), die Carbaminsäureamide (IIIc) bis (IIIe) bzw. in das Sulfonamid (V) übergeführt.

Cited by 2 publications

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A General Strategy to Aspidosperma Alkaloids: Efficient, Stereocontrolled Synthesis of Tabersonine

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