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Journal ArticleDOI

A short and convenient way to produce the Taxol A-ring utilizing the Shapiro reaction

TL;DR: In this paper, a Taxol A-ring building block was converted in three simple steps to various arenesulfonylhydrazones and then to the target molecule with the Shapiro reaction.
About: This article is published in Tetrahedron.The article was published on 2002-03-11 and is currently open access. It has received 27 citations till now. The article focuses on the topics: Shapiro reaction.

Summary (1 min read)

1. Introduction

  • The authors have earlier reported their entries to the side chain 2 6 and the C-ring precursor 4.
  • The use of intramolecular electrophiles allows preparation of cyclic products with high stereoselectivity.
  • The route involves only four steps and proceeds with high yields.

2. Results and discussion

  • Methylation (13a!14a) was incomplete in these experiments.
  • Also, TMEDA/hexane was impracticable here because of strong salt formation between CH 3 I and TMEDA.

3. Conclusions

  • Taxole A-ring building block 10 was synthesized with a novel and short method consisting of only four steps with high 38% overall yield.
  • Tosylhydrazone 9a was found to be the best of the studied arylhydrazones in Shapiro reaction allowing the formation of stable dianions and complete methylation.
  • Evidence of the possible effect of steric hindrance was observed in the preparation and reactivity of hydrazones.
  • Protonation of the vinyl anion by THF remained problematic to some extent giving always some protonated vinyl anion.
  • This can be minimized with rapid decomposition of dianion 15a at room temperature followed by immediate addition of the electrophile.

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Citations
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Journal ArticleDOI
TL;DR: In this paper, the influence of the chiral base and electrophiles on the regioselectivity and double stereodifferentiation of the silyl-protected allylhydropentalenone derivative was investigated.

6 citations

Journal ArticleDOI
TL;DR: In this article, a cross-linked polystyrene divinyl benzene sulfonic acid (SPS) as a heterogeneous catalyst has been used for the protection of one carbonyl group of two identical carbonyls of 2,2-dialkyl-1,3-cyclohexanedione.

5 citations

Journal ArticleDOI
TL;DR: In this paper, a detailed DFT-level mechanism elucidation of the two-step reaction of tosylhydrazones with alkyllithium reagents (the Shapiro reaction) is presented.
Abstract: A detailed DFT-level mechanism elucidation of the two-step reaction of tosylhydrazones with alkyllithium reagents (the Shapiro reaction) is presented. A rationale of the experimental regioselectivity is offered together with some suggestions for modifying the experimental main regioisomer. Also, the proposed general mechanism was checked with a recent modification of the Shapiro reaction involving a fluorination reaction.

4 citations

Book ChapterDOI
01 Jan 2005
TL;DR: A review of the literature dealing with the construction of olefinic double bonds by elimination of S, Se, N, P, As, Sb, Si, Ge, B, including transition metals can be found in this article.
Abstract: This chapter is a review of the literature during the period 1995–2003 (earlier work being included when needed) dealing with the construction of olefinic double bonds by elimination of S, Se, N, P, As, Sb, Si, Ge, B, or metals, including transition metals. We have focused on the eliminations involving isolable precursors as opposed to spontaneous eliminations as they occur in various coupling reactions. Accordingly, synthetically important reactions like the Wittig, Horner—Wadsworth–Emmons, or Peterson reactions are only briefly mentioned and dealt with in details in chapter 1.16. In addition, reactions such as the Julia olefination (in its original version) or the Horner–Wittig reaction, which involve the formation of well-defined intermediates and their chemical modification, are more extensively discussed.

3 citations

Book ChapterDOI
01 Jan 2019
TL;DR: The Eschenmoser fragmentation reaction as discussed by the authors was first proposed by Leonard at Illinois in the early 1970s, and has been shown to give allylic amines with known stereochemistry.
Abstract: From the early observation by Kizhner that heteroatom substituents at the α position of a ketone were lost during the reaction to give an olefinic product, the reduction of such compounds has been the focus of research into the reaction, especially after the advent of the Huang-Minlon modification made the reaction experimentally simple. From these researches, Nelson Leonard at Illinois played a leading early role in defining the scope and limitations of the reaction. Later, the hyrazinolysis of α-epoxyketones under acid catalysis was shown by Wharton at the University of Wisconsin-Madison to provide a valuable method for the 1,3-transposition of oxygen functionality. The reaction, which proceeds with predictable stereochemistry, now bears his name. More recently, the aza analog of the reaction, using 2-acylaziridines in place of the epoxyketones, has attracted interest due to its ability to give allylic amines with known stereochemistry. The reaction of the α, b-epoxyketones with tosylhydrazine leads to fragmentation to give an acetylenic ketone in a reaction now known as the Eschenmoser fragmentation.

2 citations

References
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Book
01 Jun 1977
TL;DR: Localized Chemical bonding Delocalized Chemical Bonding Bonding Weaker than Covalent Stereochemistry Carbocations, Carbanions, Free Radicals, Carbenes and Nitrenes Mechanisms and Methods of Determining them Photochemistry Acids and Bases Effects of Structure on Reactivity Aliphatic Nucleophilic Substitution Aromatic Electrophilic Substitutes Aliphatically Electrophilic Substitution Free-Radical Substitution Addition to Carbon-Carbon Multiple Bonds Adding to Carbon Hetero Multiple Bonds Eliminations Rearrangements Ox
Abstract: Localized Chemical bonding Delocalized Chemical Bonding Bonding Weaker than Covalent Stereochemistry Carbocations, Carbanions, Free Radicals, Carbenes and Nitrenes Mechanisms and Methods of Determining Them Photochemistry Acids and Bases Effects of Structure on Reactivity Aliphatic Nucleophilic Substitution Aromatic Electrophilic Substitution Aliphatic Electrophilic Substitution Free-Radical Substitution Addition to Carbon-Carbon Multiple Bonds Addition to Carbon- Hetero Multiple Bonds Eliminations Rearrangements Oxidations and Reductions The Literature of Organic Chemistry Classifications of Reactions by Type of Compound Synthesized.

4,885 citations

Journal ArticleDOI
TL;DR: This account attempts to bring together in a cogent overview the chemistry and biology of taxol, one of the few organic compounds, which, like benzene and aspirin, is recognizable by name to the average citizen.
Abstract: One can view plants as a reference library of compounds waiting to be searched by a chemist who is looking for a particular property. Taxol, a complex polyoxygenated diterpene isolated from the Pacific Yew, Taxus brevifolia, was discovered during extensive screening of plant materials for antineoplastic agents during the late 1960s. Over the last two decades, interest in and research related to taxol has slowly grown to the point that the popular press now seems poised to scoop each new development. What was once an obscure compound, of interest only to the most masochistic of synthetic chemists and an equally small number of cellular biologists, has become one of the few organic compounds, which, like benzene and aspirin, is recognizable by name to the average citizen. In parallel, the scientific study of taxol has blossomed. Physicians are currently studying its effects on nearly every known neoplasm. Biologists are using taxol to study the mechanisms of cell function by observing the effects of its interactions with the cellular skeletal systems. Synthetic chemists, absorbed by the molecule's unique and sensitive structure and functionality, are exploring seemingly every available pathway for its synthesis. Indeed, the demand for taxol has risen so in the last five years that alternative sources to the extraction of T. brevifolia are being vigorously pursued. Because of the rapidly expanding scope of research in the multifaceted study of taxol, those who are interested in the field may find acquisition of a reasonable base of knowledge an arduous task. For this reason, this account attempts to bring together, for the first time, in a cogent overview the chemistry and biology of this unique molecule.

554 citations

Journal ArticleDOI
TL;DR: The chemistry of the potent anticancer diterpenoid taxol is reviewed, with an emphasis on isolation and analysis, structural modifications, partial synthesis, and structure-activity relationships.

275 citations

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