Gold‐Catalyzed Reactions of 1,5‐ and 1,6‐Enynes with Carbonyl Compounds: Cycloaddition vs. Metathesis

Escribano-Cuesta, Ana; López‐Carrillo, Verónica; Janssen, D. B.; Echavarren, Antonio M.

doi:10.1002/chem.200900668

Cited by 100 publications

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References 51 publications

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“…Cyclopropyl gold( i ) carbene intermediates can also be trapped by carbonyl groups inter- 99,100 or intramolecularly. 101,102 Thus, oxo-1,6-enynes 75 undergo a [2+2+2] cycloaddition to form oxatricyclic compounds 76 (Scheme 26).…”

Section: Evolution Of the Key Gold Intermediatesmentioning

confidence: 99%

Intriguing mechanistic labyrinths in gold(i) catalysis

2014

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Section: Evolution Of the Key Gold Intermediatesmentioning

confidence: 99%

Intriguing mechanistic labyrinths in gold(i) catalysis

2014

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Section: Gold(i)-catalyzed Cascade Reactions Of Oxoenynesmentioning

confidence: 99%

“…83−85 Thus, for example, 1,6-enyne 13y reacts with 2,4,6-trimethylbenzaldehyde to give the product of formal [2 + 2 + 2] cycloaddition 59a , along with diene 60a , resulting from a metathesis-type reaction (Scheme 14). 83 When the reaction was performed with 13z and 1-pyrenecarboxaldehyde, 1,3-diene 60b was obtained as the major compound. Formation of the [2 + 2 + 2] cycloaddition products of type 59 can be explained by attack of the aldehyde to cyclopropyl gold(I) intermediate 61 to give oxonium cation 62 , followed by Prins cyclization to form tetrahydropyranyl cation 63 and metal elimination.…”

Section: Gold(i)-catalyzed Cascade Reactions Of Oxoenynesmentioning

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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“…In contrast to that found with 1,6-enynes with propargyl alcohols, ethers, and silyl ethers (Scheme 8), 1,6-enynes 36 with a carbonyl group at the alkenyl side chain react in the presence of Au(I) catalysts to give oxatricyclic skeletons 37 by a domino process in which two C-C and one C-O bonds are assembled by a formal [2?2?2] alkyne/alkene/ carbonyl cycloaddition [72,83]. We have recently applied this cyclization for the synthesis of orientalol F (38) [92], a sesquiterpene isolated from the rhizomes of the Chinese plant Alisma orientalis [93].…”

Section: Gold-catalyzed Cyclization Of Simple 16-enynesmentioning

confidence: 83%

“…Enynes 25c-d react with catalyst A gave 32a-c and 33a-c by 1,5-migration followed by a formal C-H insertion (Scheme 7). Related formal C-H insertions have been observed in other reaction proceeding through Au or Pt carbenes [83][84][85][86][87][88][89][90]. These results are consistent with a mechanism in which the intermediate a,b-unsaturated gold carbene/allyl-gold cation 34 abstracts a hydride from the ArCH 2 O group to form a g 1 -allyl-gold(I) 35, which reacts at C-1 or C-3 with the oxonium cation to give 32a-c or 33a-c, respectively.…”

Section: Gold-catalyzed Cyclization Of Simple 16-enynesmentioning

confidence: 95%

Complexity via Gold-Catalyzed Molecular Gymnastics

Echavarren

Jiménez‐Núñez

2010

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Reactions of 1,6-enynes catalyzed by gold(I) complexes usually proceed stereospecifically through highly distorted cyclopropyl gold carbenes. Substrates with an alkoxy substituent at the propargylic position undergo stereoselective transformations through intermediates in which the OR group and the gold carbene are anti-oriented. Intramolecular attack of carbonyl groups to the cyclopropyl gold carbene is faster than the 1,5-migration of the OR groups, which itself is faster than the intramolecular cyclopropanation by a pendant alkenyl group. The intramolecular attack of carbonyl groups is the key transformation in the [2?2?2] gold-catalyzed cycloaddition, which has been applied in the total synthesis of (?)-orientalol F.Electrophilic metals catalyze the cyclization of 1,n-enynes to give a variety of cyclic structures (recent reviews in [1-4]) [5][6][7][8][9][10][11][12][13][14][15][16]. In the absence of nucleophiles, simple 1,6-enynes 1 undergo skeletal rearrangement to give products 2 (single exo-cleavage) and 3 (double exo-cleavage) ( Fig. 1) . In a third type skeletal rearrangement, dienes 4 (single endo-cleavage) were found using cationic Au(I) catalysts [5,38]. Products of type 4 were later found in reactions catalyzed by InCl 3 [27, 28], Fe(III) [6], or Ru(II) [39]. Cyclobutenes resulting from a [2?2] cycloaddition process have also been obtained from 1,6-[40], 1,7-[25, 29-31, 34, 41], and 1,8-enynes [42, 43]. Other type of cyclobutenes have been obtained in the palladium-[17, 18], platinum-[44], and gold-catalyzed cyclization of enynes [15,16,[45][46][47].Although dienes 2 obtained by the single exo-cleavage are identical to those formed by the metal-catalyzed metathesis of enynes [48,49], the mechanism of the skeletal rearrangement is very different [50,51]. For Au(I), the rearrangement was proposed to proceed via intermediates 5 (Fig. 2) [52]. On the other hand, the double-cleavage skeletal rearrangement usually leads to dienes 3 with predominant [1-4, 17-21, 38], or exclusive Z [53, 54] configuration. For Au(I), products of type 3 are obtained via rearranged carbene 6, followed by 1,2-H shift and protodemetalation [52]. Experimental support for the involvement of 6 has been obtained in reactions in which these intermediates have been trapped with alkenes [55], indoles, allyl silanes [56][57][58], and carbonyl compounds [59,60]. Proton loss from 6 can form 1,4-dienes in InCl 3 -catalyzed reactions of substrate in which R 0 is an alkyl group [27].The dual character of intermediates 5 as metal carbenes and carbocationic species has been recently discussed [1][2][3][4][61][62][63]. Conventionally, these complexes are often depicted as cyclopropyl gold carbenes 5, although DFT calculations show that these species have highly distorted structures, intermediate between cyclopropyl gold carbenes and gold-stabilized homoallylic carbocations [38,52]. A gold carbene has been formed in the gas phase, see [64,65]. Intermediates of type 5 are involved in other processes such as nucleophilic additions of heteronucleo...

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Gold‐Catalyzed Reactions of 1,5‐ and 1,6‐Enynes with Carbonyl Compounds: Cycloaddition vs. Metathesis

Abstract: Gold and rings: The gold(I)-catalyzed addition of aldehydes to 1,6-enynes gives 1,3-dienes, by a cycloaddition/fragmentation process. 1,5-Enynes react with aldehydes and ketones by the 5-endo-dig pathway to give the corresponding cycloadducts.

Cited by 100 publications

References 51 publications

Intriguing mechanistic labyrinths in gold(i) catalysis

Intriguing mechanistic labyrinths in gold(i) catalysis

Gold-Catalyzed Rearrangements and Beyond

Complexity via Gold-Catalyzed Molecular Gymnastics

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