Total Synthesis of ( ± )-α-Cubebene and ( ± )-β-Cubebene

Piers, Edward; Britton, Ronald W.; Waal, William De

doi:10.1139/v71-003

Cited by 34 publications

(3 citation statements)

References 7 publications

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“…The gross structure of cubebol was originally proposed by Sorm and co-workers in 1960, with the structure and full stereochemistry subsequently being supported by the first total synthesis of (−)-cubebol by Yoshikoshi and co-workers in 1969 . The early syntheses of cubebol , and closely related, by formal dehydration, α- and β-cubebenes ,, proceed by way of norcubebanone ( 2 ) as a common late stage intermediate. In all these syntheses, an unsaturated α-diazoketone (eg, 3 ) was used to generate the embedded cyclopropane; however, cyclopropanation yields were moderate, and the diastereofacial selectivities were poor and in favor of undesired isomer.…”

Section: Introductionmentioning

confidence: 93%

Stereocontrolled Syntheses of (−)-Cubebol and (−)-10-Epicubebol Involving Intramolecular Cyclopropanation of α-Lithiated Epoxides

2010

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Formylation of (-)-menthone (11) with LDA and HCO(2)CH(2)CF(3) avoids loss of configurational integrity at the isopropyl group, giving hydroxymethylenementhone 12. Lithium 2,2,6,6-tetramethylpiperidide-induced intramolecular cyclopropanation of derived unsaturated terminal epoxide 17 (and chlorohydrin 16), efficiently generates a substituted tricyclo[4.4.0.0(1,5)]decan-4-ol 18, which is used in a concise synthesis of (-)-cubebol (1). In contrast, isopropyl group inversion during formylation of menthone with NaOMe and HCO(2)Et led, by a similar strategy, to syntheses of 7-epicubebol (33) and (from (+)-menthone) of naturally occurring (-)-10-epicubebol (39), confirming the original structural assignment. Computational studies support the origin of the inversion as being rate-determining formylation of cis-enolate 27 from a mixture of rapidly interconverting enolates. In the synthesis of 7-epicubebol (33), allylic tertiary C-H insertion is observed as a significant competing reaction in the intramolecular cyclopropanation of unsaturated terminal epoxide 22.

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Section: Introductionmentioning

confidence: 93%

Stereocontrolled Syntheses of (−)-Cubebol and (−)-10-Epicubebol Involving Intramolecular Cyclopropanation of α-Lithiated Epoxides

2010

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“…Except for two recent syntheses by Fürstner and Hannen and Fehr and co-workers, , all previous routes have highlighted an α-diazoketone to generate the internal cyclopropane (Scheme ). − However, these approaches suffer from moderate yields for the cyclopropanation reaction as well as low diastereoselectivities. In 2010, Hodgson et al .…”

Section: Recent Applications In Total Synthesismentioning

confidence: 99%

Cyclopropanation Strategies in Recent Total Syntheses

2017

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Complex molecular architectures containing cyclopropanes present significant challenges for any synthetic chemist. This review aims to highlight the strategic considerations for introduction of the cyclopropane motif in a collection of recent total syntheses. At first, an overview of the most important and widely used cyclopropanation techniques is presented, followed by a discussion of elegant approaches and clever solutions that have been developed to enable the synthesis of various unique cyclopropane natural products or use of cyclopropanes as versatile strategic intermediates.

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“…Other terpenoid natural products contain the bicyclo[4.1.0]heptane ring substructure (see Chart ). The terpenoid natural products (−)-α-cubebene, (−)-β-cubebene, and (−)-cubebol (all found in Piper cubeba L.) have been synthesized via α-diazoketone as well as Ohloff–Rautenstrauch approaches. , The tricyclic (+)-isovelleral found in Lactifus vellereus is reported to exhibit cytotoxic effects (enhanced by demethylation), making it an attractive anticancer agent …”

Section: Introductionmentioning

confidence: 99%

One Lump or Two? A Plurality of Pathways in Gold(III)-Catalyzed Cyclization Transforming Propargyl Acetates to a Carene-like Bicyclo[4.1.0]heptane

2017

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The bicyclo[4.1.0]heptane substructure, featured in a number of natural products, is economically formed via gold(III)-mediated cycloisomerization of a 5-acetoxy-1,6-enyne. This Ohloff−Rautenstrauch rearrangement takes place with high regio-and stereocontrol and purportedly proceeds through either of two pathways that differ in the order of major events: cyclization followed by ester migration ("cyclization first") or its transpose ("migration first"). Implicit solvent-phase (dichloroethane) electronic structure calculations [IEFPCM-B2PLYP-D3/def2-TZVP//IEFPCM-B2PLYP/6-31G(d)-LANL2DZ] aimed at elucidation of the minimum energy pathway corresponding to the "cyclization first" and "migration first" pathways are presented herein. Both pathways feature multiple steps and are characterized by low-energy barriers, indicating that facile interconversion of structures on the surface is possible. In addition, the highest-energy structures for each of the two pathways are very close in energy (ΔΔE ⧧ < 3.0 kcal/mol). Relative turnover frequency (TOF) and degree of TOF control (X TOF ) calculations indicate that although a cyclization first pathway may dominate, both cyclization and acyl migration processes influence the rate of this reaction.

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Total Synthesis of ( ± )-α-Cubebene and ( ± )-β-Cubebene

Cited by 34 publications

References 7 publications

Stereocontrolled Syntheses of (−)-Cubebol and (−)-10-Epicubebol Involving Intramolecular Cyclopropanation of α-Lithiated Epoxides

Stereocontrolled Syntheses of (−)-Cubebol and (−)-10-Epicubebol Involving Intramolecular Cyclopropanation of α-Lithiated Epoxides

Cyclopropanation Strategies in Recent Total Syntheses

One Lump or Two? A Plurality of Pathways in Gold(III)-Catalyzed Cyclization Transforming Propargyl Acetates to a Carene-like Bicyclo[4.1.0]heptane

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