Tandem Intramolecular Nicholas and Pauson−Khand Reactions for the Synthesis of Tricyclic Oxygen-Containing Heterocycles

Quintal, Miriam M.; Closser, Kristina D.; Shea, Kevin M.

doi:10.1021/ol0479141

Cited by 36 publications

(6 citation statements)

References 20 publications

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“…The Co–alkyne complexes obtained were then used as substrates for the intramolecular Nicholas reaction. The cyclization was performed under the conditions reported earlier, that is, in DCM with BF 3 · Et 2 O as Lewis acid under high dilution ( C = 0.001 m ) . For the synthesis of 10‐ and 11‐membered macrocycles 20a and 20b , Co–alkyne complexes 16a and 16b were used, respectively, without separation from the regioisomers 17a , b (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Oxaenediynes through the Nicholas‐Type Macrocyclization Approach

et al. 2016

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The Nicholas‐type macrocyclization has been used for the first time for the synthesis of 10‐ and 11‐membered oxaenediynes fused to a benzothiophene. The acyclic starting materials were easily synthesized by electrophilic cyclization of o‐(buta‐1,3‐diynyl)thioanisoles followed by a Sonogashira coupling of the resulting 2‐ethynyl‐3‐iodobenzothiophenes with functionalized alkynes. A high reactivity of the 10‐membered oxacycles in the Bergman cyclization was predicted by DFT calculations and confirmed by differential scanning calorimetry. The ability of enediynes to induce single‐strand PM2 DNA scissions was also found.

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Section: Resultsmentioning

confidence: 99%

Oxaenediynes through the Nicholas‐Type Macrocyclization Approach

et al. 2016

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“…Initially we used 12a N -methyl morpholine N -oxide (NMO) in CH 2 Cl 2 to effect cleavage of the cobalt complex, and we obtained 5 in 70% yield. However, to our surprise, the reaction was sluggish (3 days) and sensitive to the quality of NMO; hence, we sought alternate protocols . Heating the Co 2 (CO) 6 −alkyne complex in the presence of other cleavage reagents such as cyclohexylamine 12b or acetonitrile 12c did not result in the formation of the 5 but led to the decomposition of the cobalt complex.…”

Section: Introductionmentioning

confidence: 99%

“…Treatment of the Co 2 (CO) 6 −alkyne complex with H 2 O 2 furnished the desired tricyclic enone 5 in 30% yield. Use of dimethoxyethane and acetonitrile at 70 °C as the Co 2 (CO) 6 −alkyne complex cleavage cocktail afforded the enone 5 in 92% yield 12d…”

Section: Introductionmentioning

confidence: 99%

Diversity Oriented Synthesis of Tricyclic Compounds from Glycals Using the Ferrier and the Pauson−Khand Reactions

and

Tripathi

2005

J. Comb. Chem.

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Diversity oriented synthesis of tricyclic compounds was achieved using a combination of the Ferrier reaction and the Pauson-Khand reaction. Ferrier reaction was effected using NbCl5, and the Pauson-Khand reaction was carried out using Co2(CO)8, acetonitrile-dimethoxyethane. Michael additions using various alkyl, aryl, and heterocyclic thiols were also performed successfully. The Ferrier, Pauson-Khand, and Michael addition reactions were found to be highly diastereoselective.

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“…Decomplexation is generally effected oxidatively, using cerium ammonium nitrate or iodine. Recent developments in this area include a tandem Nicholas-Pauson-Khand sequence, 2 the use of montmorillonite K-10 to generate the stabilized cation, 3 a solid-phase version of the reaction, 4 as well as the synthesis of natural product hybrids, 5 and bioactive polyether structures. 6 Recently, related reactions involving the use of rhenium 7 or ruthenium 8 catalysts have been developed, and successful enantioselective versions of these reaction have in some cases been carried out, 9 although their full scope has not yet been investigated.…”

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The Development of an Asymmetric Nicholas Reaction Using Chiral Phosphoramidite Ligands

Ljungdahl¹,

Pera²,

Andersson³

et al. 2008

Synlett

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An asymmetric version of the Nicholas reaction involving the use of chiral phosphoramidite ligands has been developed. Treatment of a cobalt carbonyl complexed propargylic alcohol with two equivalents of the chiral ligand, followed by reaction with a silyl enol ether in the presence of a Lewis acid, afforded, after decomplexation, the desired product in up to 74% ee for the carbon-carbon bond forming step.The Nicholas reaction (Scheme 1) is a versatile transformation, involving the reaction of a cobalt carbonyl stabilized propargylic cation 1 with different nucleophiles. 1 The scope of nucleophiles that can be applied in the Nicholas reaction is wide, including alcohols, amines, thiols, fluoride, hydride, phosphines, as well as various types of carbon nucleophiles in the form of enol ethers, electron-rich aromatics, allyl silanes, allyl stannanes, and trialkyl aluminum reagents. 1a Complexation of the precursor propargylic alcohols or ethers with dicobalt octacarbonyl proceeds smoothly at room temperature, and the dark red complex formed is subsequently treated with a Lewis acid to generate the cation prior to addition of the nucleophile. Decomplexation is generally effected oxidatively, using cerium ammonium nitrate or iodine. Recent developments in this area include a tandem Nicholas-Pauson-Khand sequence, 2 the use of montmorillonite K-10 to generate the stabilized cation, 3 a solid-phase version of the reaction, 4 as well as the synthesis of natural product hybrids, 5 and bioactive polyether structures. 6 Recently, related reactions involving the use of rhenium 7 or ruthenium 8 catalysts have been developed, and successful enantioselective versions of these reaction have in some cases been carried out, 9 although their full scope has not yet been investigated. In this communication we report the successful development of an asymmetric version of the Nicholas reaction using chiral phosphoramidites as ligands to cobalt.Asymmetric versions of the Nicholas reaction have in general involved the use of chiral nucleophiles 10 or chiral substrates. 11 Chirality transfer has also been performed. 12 However, to our knowledge the use of racemic propargylic alcohols in conjunction with chiral ligands coordinated to cobalt have not been reported for the Nicholas reaction, and we thus embarked on an investigation into this matter. Our initial screening of chiral phosphine ligands in the Nicholas reaction showed that the propargylic cobalt complexes formed suffered from low reactivity, in agreement with earlier reports by Nicholas 13 and Mayr. 14 Phosphites showed more promise in activating the complex for nucleophilic attack. 12b Although chiral phosphite ligands have been used in asymmetric reactions, 15 we instead opted for the structurally similar class of phosphoramidite ligands that have been extensively employed lately. Chiral phosphoramidites are versatile ligands employed in a number of asymmetric transformations, 16-18 having the additional advantage that such compounds are facile to prepare in a parallel format...

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Tandem Intramolecular Nicholas and Pauson−Khand Reactions for the Synthesis of Tricyclic Oxygen-Containing Heterocycles

Abstract: [reaction: see text] Simple acyclic enynes can be easily converted into tricyclic ethers upon treatment with Co2(CO)8 followed by Nicholas and Pauson-Khand reactions. Tricyclic [5,8,5]- and [5,7,5]-systems can be prepared in high overall yields in only seven synthetic steps.

Cited by 36 publications

References 20 publications

Oxaenediynes through the Nicholas‐Type Macrocyclization Approach

Oxaenediynes through the Nicholas‐Type Macrocyclization Approach

Diversity Oriented Synthesis of Tricyclic Compounds from Glycals Using the Ferrier and the Pauson−Khand Reactions

The Development of an Asymmetric Nicholas Reaction Using Chiral Phosphoramidite Ligands

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