An Expeditious Asymmetric Synthesis of Polyfunctional 1,7‐Dioxaspiro[5.5]undecanes

Gerber‐Lemaire, Sandrine; Vogel, Pierre

doi:10.1002/ejoc.200400514

Cited by 9 publications

(4 citation statements)

References 89 publications

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“…Following another approach based on the simultaneous functionalization of diolefin 39 , the same authors reported a sequence of ozonolysis / reductive treatment to afford bis-hemiketal 40 ( Scheme 6 ) [ 30 ]. Subsequent acidic treatment, first with aqueous HF and then with CSA, induced spirocyclization to the tricyclic intermediate 41 , in high yield.…”

Section: Synthesis Of Naturally Occurring [66]-spiroketalsmentioning

confidence: 99%

Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products

2008

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Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.

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Section: Synthesis Of Naturally Occurring [66]-spiroketalsmentioning

confidence: 99%

Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products

2008

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“…[34] Simultaneous ozonolysis of the olefins followed by reductive treatment afforded a mixture of bis(hemiketals) 55 which was directly treated under acidic conditions to cleave the silyl ethers and induce cyclization to the tricyclic hemiketal 56 in high yield (72%, four steps). Interestingly, this sequence provided the less energetically favorable kinetic axial/equatorial spiroketal by trapping in a tricyclic structure.…”

Section: From 11'-methylenedi(3-oxo-8-oxabicyclo[321]oct-6-ene) Tomentioning

confidence: 99%

Preparation and Synthetic Applications of 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives

Favre¹,

Gerber‐Lemaire²,

Vogel³

2008

Chimia

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The development of efficient routes to multi-gram quantities of chiral synthons is a key issue in the total synthesis of natural products and analogues. The conformationally defined and rigid 8-oxabicyclo[3.2.1]oct-6-en-3-one template is an appealing starting material for the development of non-iterative approaches to polyoxygenated fragments that are found in a large variety of biologically relevant natural compounds. Desymmetrization and resolution procedures, stereoselective functionalizations and double-chain elongations represent attractive strategies for such synthetic challenges.adducts. Further stereoselective functionalization of the rigid bicyclic templates then provides an efficient access to stereodefined polyketides. We give here an overview of noniterative approaches to polyoxygenated compounds from 8-oxabicyclo[3.2.1]oct-6-en-3-one derivatives that are generated through [4+3] cycloaddition reactions. [4+3]-Cycloadditions of Oxyallyl Cations to Furan and DerivativesThe generation of the 8-oxabicyclo[3.2.1]oct-6-en-3-one template can be achieved by a [4+3] cycloaddition of furan to oxyallyl cations of type 3 (Scheme 1). These stabilized cations 3 can be produced from tetrahalogenoketones 1 in the presence of a reducing metal [1] or a tertiary amine in an ionizing solvent. [2] The resulting rigid bicyclic system is a synthon of choice for stereoselective transformations as illustrated by the reduction of ketone 4 , with L-selectride or SmI 2 which provides the endo-alcohol 5 and the exo -alcohol 6 , respectively. In the late 1990s Vo gel and co-workers extended this powerful strategy to a double [4+3] cycloaddition of 2,2-methylenebis(furan) 7 to oxyallyl cations which gives rise to a mixture of bisbicycloadducts meso-8 and threo-8 in a 45:55 ratio (60% yield). [3] Several other precursors of oxyallyl cations were inves-

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“…In addition to seminal reports by the groups of Evans,5 Kishi,6 Paterson,7 Smith,8 Crimmins,9 Heathcock,10 and Ley11 on the total syntheses of spongistatins 1 and 2, much effort has been devoted to the implementation of straightforward and high‐yielding pathways towards the ABCD “northern” hemisphere12 and the EF tetrahydropyran subunits 13. Our group has presented an early synthesis of the C29–C51 fragments of spongistatin 114 and has developed a noniterative approach to the asymmetric synthesis of fifteen‐carbon polyketides, including advanced precursors of AB15 and CD16 spiroacetals of spongistatin 1–3 starting from 2,2'‐methylidenedifuran 17. Because of their limited supply from nature18 any clinical evaluation of spongistatins must rely upon synthetic sources.…”

Section: Introductionmentioning

confidence: 99%

Short Diastereoselective Synthesis of the C1–C13 (AB Spiroacetal) and C17–C28 Fragments (CD Spiroacetal) of Spongistatin 1 and 2 through Double Chain‐Elongation Reactions

Flowers

Vogel

2010

Chemistry A European J

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A unique and practical synthetic sequence for rapid access to polyketides and to further the spiroacetals derived from them, which utilizes a bidirectional Hosomi-Sakurai allylation approach around key allylsilanes in the synthesis of the AB and CD ring systems of spongistatin 1 and 2, is reported. The synthesis of the AB spiroacetal 9 requires 13 steps, with a longest linear sequence of seven steps in an overall yield of 27%. The synthesis of the CD spiroacetal 13 requires 15 steps, with a longest linear sequence of 11 steps in an overall yield of 30%. Both syntheses start from but-3-enol.

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An Expeditious Asymmetric Synthesis of Polyfunctional 1,7‐Dioxaspiro[5.5]undecanes

Cited by 9 publications

References 89 publications

Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products

Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products

Preparation and Synthetic Applications of 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives

Short Diastereoselective Synthesis of the C1–C13 (AB Spiroacetal) and C17–C28 Fragments (CD Spiroacetal) of Spongistatin 1 and 2 through Double Chain‐Elongation Reactions

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