Synthesis of a C(22)−C(34) Halichondrin B Precursor via Ring Opening−Double Ring Closing Metathesis

Burke, Steven D.; Quinn, Kevin J.; Chen, Victor

doi:10.1021/jo981342e

Cited by 60 publications

(28 citation statements)

References 42 publications

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“…Stereocenters are easily established in a ring and transferred to the side chain. RRM has been applied in the synthesis of fused carbocycles2 and polycyclic ethers3 as well as piperidines,4, 5 pyrrolidines,5 and various natural products 6…”

Section: Methodsmentioning

confidence: 99%

Diastereoselective Ring‐Rearrangement Metathesis

2006

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A new stereocenter is formed by ring‐rearrangement metathesis (RRM), which has now been extended to diastereoselective processes. Selectivities are catalyst‐ and substrate‐dependent. In these conversions yielding carbo‐ and heterocycles, d.r. values of up to 14:1 were obtained. For example, cyclooctadiene 1 was converted into piperideine 2 at room temperature and with high diastereoselectivity (Ts=toluene‐4‐sulfonyl).

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Section: Methodsmentioning

confidence: 99%

Diastereoselective Ring‐Rearrangement Metathesis

2006

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“…The second class of reactions that will be discussed here (scenario 1b in Scheme 43) proceeds with liberation of ethylene and has thus an additional, entropic driving force. The formation of bicyclic products from cycloalkenes bearing two pendant olefinic moieties was already reported in the early days of ruthenium-catalyzed olefin metathesis by Grubbs et al: [121] bond occurs, resulting in an interruption of the catalytic cycle (Scheme 52) [122].…”

Section: Scheme 46mentioning

confidence: 77%

"Ring Closing Metathesis of Substrates Containing more than two C-Cdouble Bonds: Rapid Access to Functionalized Heterocycles"

Schmidt¹,

Hermanns

2006

COC

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In most cases where ring closing metathesis is applied to the synthesis of heterocycles, α,ω-dienes are used as precursors. If substrates containing more than two double bonds are subjected to a metathesis reaction, carba-or heterocycles bearing additional exocyclic alkene functionality result, or multiple ring closing processes occur. This offers interesting and potentially very useful synthetic perspectives. On the other hand, selectivity problems need to be addressed as the cyclization of substrates with more than two double bonds available for olefin metathesis may result in constitutional isomers or stereoisomers. This review highlights problems and opportunities evolving from ring closing metathesis of tri-, tetra-, and polyenes as a strategy for the selective synthesis of functionalized heterocycles. The chapter on RCM of trienes is subdivided according to the symmetry of the metathesis precursor. The following two chapters deal with the double or multiple RCM of tetra-or polyenes. These processes are further classified according to the preferred cyclization mode. Finally, the application of cascade or domino metathesis reactions to the synthesis of heterocycles will be discussed. These processes can be classified into those where exclusively C-C-double bonds take part in the metathesis reaction, and those where one or more C-C-triple bonds are involved.

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“…Scheme 73 Synthesis of swainsonine (378) via RRM of cyclopentene 375 [157] Scheme 74 Synthesis of bis-dihydropyran fragment 380 of halichondrin by tandem ROM-double RCM of cyclopentene 379 [158] Scheme 75 Synthesis of astrophylline (384) via RRM of cyclopentene 382 [159] dihydropyran ring was formed and the reaction led to a mixture of the isomeric compounds 381a and 381b in low yield.…”

Section: Metathesis On Solid Supportmentioning

confidence: 99%

“…An early example of cyclopentene-opening/double RCM leading to bis-dihydropyran 380 (the C22-C34 segment of the potent antitumor agent halichondrin A) was disclosed by Burke et al (Scheme 74) [158]. In this case, the ROM-RCM sequence was performed with catalyst B, leading from cyclopentene 379 to 380 in 71% yield.When metathesis precursor 379 was exposed to catalyst A, only one An important variation of CM methodology is ring-opening cross metathesis (ROCM) where one of the reacting substrates is a (strained) cycloalkene.…”

Section: Domino Metathesis Reactionsmentioning

confidence: 99%