Synthesis of (+)‐Schisanwilsonene A by Tandem Gold‐Catalyzed Cyclization/1,5‐Migration/Cyclopropanation

Gaydou, Morgane; Miller, Ricarda; Delpont, Nicolas; Ceccon, Julien; Echavarren, Antonio M.

doi:10.1002/anie.201302411

Cited by 54 publications

(27 citation statements)

References 52 publications

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“…73 By appending the alkene to the 1,6-enyne through a silicon tether in substrate 13t , we also obtained cyclic siloxane 48b with high stereoselectivity. 78 In an intermolecular variant of this process, reaction of 1,6-enyne 13u with alkene 49 gave 50 , which was converted into the antiviral sesquiterpene (+)-schisanwilsonene ( 51 ) by a stereoselective route that includes a divinyl cyclopropane rearrangement. In this last example, it is interesting to remark that the cyclization/1,5-acetoxy migration is faster that the alternative 1,2-acyloxy migration that would lead to racemization.…”

Section: Gold(i)-catalyzed Cyclopropanation Of Enynesmentioning

confidence: 99%

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Gold-Catalyzed Rearrangements and Beyond

2013

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Cycloisomerizations of enynes are probably the most representative carbon–carbon bond forming reactions catalyzed by electrophilic metal complexes. These transformations are synthetically useful because chemists can use them to build complex architectures under mild conditions from readily assembled starting materials. However, these transformations can have complex mechanisms. In general, gold(I) activates alkynes in the presence of any other unsaturated functional group by forming an (η2-alkyne)–gold complex. This species reacts readily with nucleophiles, including electron-rich alkenes. In this case, the reaction forms cyclopropyl gold(I) carbene-like intermediates. These can come from different pathways depending on the substitution pattern of the alkyne and the alkene. In the absence of external nucleophiles, 1,n-enynes can form products of skeletal rearrangement in fully intramolecular reactions, which are mechanistically very different from metathesis reactions initiated by the [2 + 2] cycloaddition of a Grubbs-type carbene or other related metal carbenes.In this Account, we discuss how cycloisomerization and addition reactions of substituted enynes, as well as intermolecular reactions between alkynes and alkenes, are best interpreted as proceeding through discrete cationic intermediates in which gold(I) plays a significant role in the stabilization of the positive charge. The most important intermediates are highly delocalized cationic species that some chemists describe as cyclopropyl gold(I) carbenes or gold(I)-stabilized cyclopropylmethyl/cyclobutyl/homoallyl carbocations. However, we prefer the cyclopropyl gold(I) carbene formulation for its simplicity and mnemonic value, highlighting the tendency of these intermediates to undergo cyclopropanation reactions with alkenes.We can add a variety of hetero- and carbonucleophiles to the enynes in the presence of gold(I) in intra- or intermolecular reactions, leading to the corresponding adducts with high stereoselectivity through stereospecific anti-additions. We have also developed stereospecific syn-additions, which probably occur through similar intermediates. The attack of carbonyl groups at the cyclopropyl carbons of the intermediate cyclopropyl gold(I) carbenes initiates a particularly interesting group of reactions. These trigger a cascade transformation that can lead to the formation of two C–C and one C–O bonds. In the fully intramolecular process, this stereospecific transformation has been applied for the synthesis of natural sesquiterpenoids such as (+)-orientalol F and (−)-englerin A.Intra- and intermolecular trapping of cyclopropyl gold(I) carbenes with alkenes leads to the formation of cyclopropanes with significant increase in the molecular complexity, particularly in cases in which this process combines with the migration of propargylic alkoxy and related OR groups. We have recently shown this in the stereoselective total synthesis of the antiviral sesquiterpene (+)-schisanwilsonene by a cyclization/1,5-acetoxy migration/intermolecular cyclo...

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Section: Gold(i)-catalyzed Cyclopropanation Of Enynesmentioning

confidence: 99%

“…In this last example, it is interesting to remark that the cyclization/1,5-acetoxy migration is faster that the alternative 1,2-acyloxy migration that would lead to racemization. 78 …”

Section: Gold(i)-catalyzed Cyclopropanation Of Enynesmentioning

confidence: 99%

Gold-Catalyzed Rearrangements and Beyond

2013

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“…We will finish this review by another remarkable reaction of a propargylic acetate. At the occasion of the total synthesis of (+)‐schisanwilsonene A, Echavarren devised a very elegant cascade involving a 5‐ exo ‐ tri g cyclization – 1,5‐ O ‐acyl migration – cyclopronation converting propargyl acetate 63 in the presence of olefin 64 into advanced cyclopropyl precursor 65 . The latter could be transformed into the final natural product in 11 steps including a divinylcyclopropane‐cycloheptadiene rearrangement.…”

Section: Miscellaneousmentioning

confidence: 99%

Gold‐Catalyzed Migration of Propargyl Acetate as an Entry into the Total Synthesis of Natural Products

Fensterbank

2018

Israel Journal of Chemistry

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Gold catalysis has emerged over the last two decades as a protocole of choice for the efficient and selective activation of a variety of organic functional groups. This has served to the total synthesis of natural products at several occasions. In this context, the gold‐catalyzed migration (1,2‐ or 1,3‐) of propargyl acetates has been particularly used. This review highlights these different synthetic developments which are presented according to the involved mechanisms.

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“…The migration is proposed to proceed through an allyl gold cation intermediate 78 formed by a syn addition of both the alkyne and the OR group to the alkene. An application of this methodology toward the synthesis of (+)-Schisanwilsonene A via tandem gold-catalyzed cyclization/1,5-migration/cyclopropanation from 1,6-enynes has been recently reported 75 .…”

Section: Ether Migrationsmentioning

confidence: 99%

Gold‐Catalyzed Migrations and Ring Expansions

Merino

Fernández

Nevado

2014

Patai's Chemistry of Functional Groups

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Gold complexes have been used to π‐activate alkynes, alkenes, and related moieties due to their strong affinity for these carbon systems. In this chapter we have summarized first, the most representative examples of gold‐catalyzed migrations occurring in propargylic systems and classified them according to the nature of the migrating group. In the second part, we have compiled the most relevant gold‐catalyzed ring expansions according to ring size. The current mechanistic understanding of these transformations is also presented.

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Synthesis of (+)‐Schisanwilsonene A by Tandem Gold‐Catalyzed Cyclization/1,5‐Migration/Cyclopropanation

Abstract: Going (anti)viral: The first total synthesis of the antiviral (+)‐schisanwilsonene A has been completed using a fully stereoselective tandem cyclization/1,5‐migration/intermolecular cyclopropanation. The key reaction sequence is catalyzed by gold.

Cited by 54 publications

References 52 publications

Gold-Catalyzed Rearrangements and Beyond

Gold-Catalyzed Rearrangements and Beyond

Gold‐Catalyzed Migration of Propargyl Acetate as an Entry into the Total Synthesis of Natural Products

Gold‐Catalyzed Migrations and Ring Expansions

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