Intramolecular Diels-Alder reactions of furans with a merely strain-activated tetrasubstituted alkene: Bicyclopropylidene

Heiner, Thomas; Kozhushkov, Sergei I.; Noltemeyer, Mathias; Haumann, Thomas; Boese, Roland; Meijere, Armin de

doi:10.1016/0040-4020(96)00720-x

Cited by 54 publications

(22 citation statements)

References 20 publications

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“…They involved furans tethered by bicyclopropylidene and methylene cyclopropane moieties (Scheme 8). [35][36][37] When R in 2 and 3 is changed from H to OMe, the pressure sensitivity of the cycloaddition increases ( Table 4). …”

Section: Correlation Between Pressure and Steric Hindrancementioning

confidence: 93%

Correlation between pressure and steric interactions in organic reactions

Jenner

2005

Tetrahedron

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Section: Correlation Between Pressure and Steric Hindrancementioning

confidence: 93%

Correlation between pressure and steric interactions in organic reactions

Jenner

2005

Tetrahedron

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“…[16] An ab initio calculation at the MP6-31+G* level of the two transition states leading to the trans-and cis-ring fusion products in the IMDAMC [17] reaction revealed that the trans-stereochemistry in 13 ‡ is only slightly favored (<0.5 kcal/mol), rationalizing the relatively modest diastereoselectivity (4.8:1 dr) observed for this process.…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 99%

Eight‐Step Enantioselective Total Synthesis of (−)‐Cycloclavine

McCabe

Wipf

2016

Angewandte Chemie

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The first enantioselective total synthesis of (−)-cycloclavine has been accomplished in 8 steps and 7.1% overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by dirhodium catalyst Rh 2 (S-TBPTTL) 4 , and the enone 1,2-addition of a new TEMPOcarbamate methyl carbanion. An intramolecular strain-promoted Diels-Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate in >99% ee after crystallization. The synthesis of (−)-1 was completed by a late stage intramolecular Diels-Alder furan (IMDAF) cycloaddition to install the indole. Graphical Abstract KeywordsClavine alkaloids; allene; enantioselective; cyclopropanation; sequential cycloadditions Cycloclavine (1) was originally isolated from the seeds of the African morning glory shrub Ipomoea hildebrandtii and later from Aspergillus japonicus, a species of filamentous fungus. [1,2] In preliminary biological evaluations, it demonstrated promising insecticidal and anti-parasitic activity. [3] Cycloclavine belongs to the clavine subset of ergot alkaloids, a prominent group of natural products that share a fused indole core (Figure 1). Members of this family have long served as an inspiration for the design of therapeutic agents and agrochemicals due to their potent and diverse biological activities. [4] In recent years, major advances in elucidating the biogenetic origin of ergot alkaloids have been made. [4] A unique Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript structural feature of cycloclavine is a pyrrolidine-fused cyclopropane in place of the piperidine that is typical for other clavine and lysergic acid alkaloids.While its biological properties remain largely unexplored, cycloclavine's unusual pentacyclic scaffold has attracted the interest of synthetic chemists. Particularly, the assembly of three consecutive stereogenic carbons at C(5), C(8) and C(10), two of them allcarbon quaternary stereocenters, requires robust synthetic methodologies and high stereochemical control.To date, three total syntheses and three formal syntheses of racemic cycloclavine have been reported, including a prior total synthesis accomplished by our group. [5,6,7,[8][9] However, no enantioselective total synthesis of cycloclavine has been accomplished. In order to meet this objective and establish a concise route to either enantiomer as well as analogs of the natural product, we fundamentally revised our previous 14-steps/1.2% yield approach to racemic product and developed a streamlined asymmetric total synthesis of the unnatural enantiomer (−)-cycloclavine, (−)-(1) (Figure 2). Our main goals were: (a) to introduce the enone moiety in 2 directly from the ketone product of the methylenecyclopropane (MCP)-Diels-Alder reaction; (b) to develop an asymmetric cyclopropanation of unsubstituted allene 5 to install the quaternary stereocenter that directs the formation of the two neighboring stereogenic carbons in (−)-1; and (c) to generate the amide linkage in 3 by direct amino...

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“…The 2-[trans-(1Ј,1ЈЈ-bicycloprop-2Ј-yl)]acetic acid (14) was easily available from 2-(1Ј,1ЈЈ-bicyclopropyliden-2Ј-yl)ethanol (16) which had previously been prepared by the reaction of lithiobicyclopropylidene with ethylene oxide. [21] Subsequent reduction of 16 under the same Birch conditions applied to 7b؊g gave the corresponding 2-(1Ј,1ЈЈ-bicycloprop-2Ј-yl)ethanol (17) in 85% yield, but only with 85% trans diastereoselectivity. Finally, Jones oxidation of 17 gave 2-[trans-(1Ј,1ЈЈ-bicycloprop-2Ј-yl)]acetic acid (14) in 74% yield (Scheme 5).…”

Section: Introductionmentioning

confidence: 99%

Convenient Syntheses and Biological Activity of Novel ω-trans-(Bicyclopropyl)- and ω-(Bicyclopropylidenyl)-Substituted Fatty Acids and Their Derivatives

et al. 2000

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A series of ω-trans-(bicyclopropyl)-substituted fatty acids 9 has been synthesized from bicyclopropylidene (5) starting by deprotonation with n-butyllithium. Electrophilic substitution of lithiobicyclopropylidene with THP-protected ω-iodoalkanols 6 gave the THP-protected (bicyclopropylidenyl)alkanols 7 in 63−88% yield. A reasonably diastereoselective reduction of the bicyclopropylidene moiety in 7 was achieved with lithium in liquid ammonia, and deprotection of the resulting trans-(bicyclopropyl)alkanol derivatives 8 followed by Jones oxidation provided the fatty acids 9 in yields ranging from 59 to 75%. ω-Bicyclopropylidenyl-substituted fatty acids 11 were prepared by deprotection and oxidation of the THP-

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Intramolecular Diels-Alder reactions of furans with a merely strain-activated tetrasubstituted alkene: Bicyclopropylidene

Cited by 54 publications

References 20 publications

Correlation between pressure and steric interactions in organic reactions

Correlation between pressure and steric interactions in organic reactions

Eight‐Step Enantioselective Total Synthesis of (−)‐Cycloclavine

Convenient Syntheses and Biological Activity of Novel ω-trans-(Bicyclopropyl)- and ω-(Bicyclopropylidenyl)-Substituted Fatty Acids and Their Derivatives

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