The role of cyclobutenes in gold(i)-catalysed skeletal rearrangement of 1,6-enynes

Escribano-Cuesta, Ana; Pérez‐Galán, Patricia; Herrero‐Gómez, Elena; Sekine, Masaki; Braga, Ataualpa Albert Carmo; Maseras, Feliu; Echavarren, Antonio M.

doi:10.1039/c2ob25419k

Cited by 59 publications

(65 citation statements)

References 77 publications

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“…3,46 In the case of 1,6-enynes that bear an aryl substituted alkyne and a terminally unsubstituted alkene, which react sluggishly with electrophilic metal catalysts, the initial gold( i )-activated substrate 61 could evolve by three pathways: anti -5- exo-dig ( via 62 ), 6- endo-dig ( via 63 ), and syn -5- exo-dig ( via 64 ) (Scheme 24). 91 In general agreement with previous mechanistic work, 58,92 recent DFT calculations show that the syn -5- exo-dig cyclization does not compete with the other two pathways, whose relative preference depends on the substitution pattern of the enyne. 91 Products of double-cleavage rearrangement 66 could be formed through intermediate 65 , in which the methylene is formally inserted into the alkyne carbons.…”

Section: Evolution Of the Key Gold Intermediatessupporting

confidence: 87%

“…91 In general agreement with previous mechanistic work, 58,92 recent DFT calculations show that the syn -5- exo-dig cyclization does not compete with the other two pathways, whose relative preference depends on the substitution pattern of the enyne. 91 Products of double-cleavage rearrangement 66 could be formed through intermediate 65 , in which the methylene is formally inserted into the alkyne carbons. On the other hand, dienes 70 of single-cleavage rearrangement can be formed by expansion of the cyclopropane of 63 to form cyclobutene–Au( i ) complex 67 , followed by cleavage to give diene–Au( i ) complex 68 .…”

Section: Evolution Of the Key Gold Intermediatessupporting

confidence: 87%

“…Only a few examples of highly strained bicyclo[3.2.0]hept-5-enes have been reported in gold( i ) catalysed isomerisations, 91,94,95 whereas products of formal [2+2] cycloaddition have been observed in the parent intermolecular reactions of alkynes with alkenes, 54 as well as in the cyclisation of 1,7-, 1,8- 46,96 and higher enynes. 55 Alternatively, 67 could give the product of alkene isomerisation 69 .…”

Section: Evolution Of the Key Gold Intermediatesmentioning

confidence: 99%

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Intriguing mechanistic labyrinths in gold(i) catalysis

2014

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Section: Evolution Of the Key Gold Intermediatessupporting

confidence: 87%

Section: Evolution Of the Key Gold Intermediatessupporting

confidence: 87%

Section: Evolution Of the Key Gold Intermediatesmentioning

confidence: 99%

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Intriguing mechanistic labyrinths in gold(i) catalysis

2014

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“…30,31 Exocyclic carbene intermediate 2 , formed in the anti -5- exo - dig pathway, can also give rise to products of single-cleavage rearrangement 9 through transition state TS 2 – 12 and intermediates 12 . 30 …”

Section: Gold(i)-catalyzed Cyclization Of Enynesmentioning

confidence: 99%

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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“…2 Much less attention was given initially to the corresponding intermolecular reactions, which, in principle, are more challenging. In an intermolecular process involving two unsaturated substrates, their possible competitive binding with the gold complex should be considered,3 as well as the fact that gold catalysts are inherently acidic and therefore can promote the polymerization of alkenes by cationic mechanisms 4.…”

Section: Introductionmentioning

confidence: 99%