A Formal [3+3] Cycloaddition Approach To Natural Product Synthesis

Deng, Jun; Wang, Xiaona; Hsung, Richard P.

doi:10.1002/9781118778173.ch12

Cited by 11 publications

(15 citation statements)

References 540 publications

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“…Nucleophilic addition of the sulfur ylide onto the electrophilic vinylogous carbon of the metal carbene generates the proposed vinylcopper intermediate ( 6 ). A striking feature of this pathway, and one not seen in previously reported metallo-vinylcarbene cycloaddition reactions, is the requirement for displacement of the R 2 S leaving group ( 6 → 7 ) rather than addition–elimination that occurs in [3+3]- and [3+2]-cycloaddition processes, [3a] which opens a new cycloaddition reaction pathway and also suggests leaving group requirements.…”

mentioning

confidence: 85%

“…[1] The development of [4+2]-cycloaddition reactions have provided the most advantageous scheme for the formation of organic compounds having six-membered rings, [2] and recently available [3+3]-cycloaddition processes have added complimentary methodologies. [3] Dipolar cycloaddition reactions, especially those that combine a 1,3-dipole with an alkene or alkyne, have offered access to five- and seven-membered-ring systems. [4] The synthesis of four-membered rings have used [2+2]-cycloaddition, [5] but alternative [3+1]-cycloaddition processes have rarely been reported.…”

mentioning

confidence: 99%

“…[3a,11] These versatile intermediates have emerged as a synthetically useful class of three-carbon adducts when paired with a broad spectrum of dipoles and nucleophilic unsaturated compounds to construct cyclic molecules through [3+3]-cycloaddition [3a,11a,b] or by [3+2]-cycloaddition. [11c–f] Our intent was now to use these versatile intermediates for [3+1]-cycloaddition reactions by addition/elimination with stable ylides whose nucleophilic reactivity would allow bond formation at the electrophilic vinylogous position of metallo-enolcarbenes that, with displacement of a leaving group from the intermediate adduct, would form the desired [3+1]-cycloaddition product.…”

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confidence: 99%

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Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

et al. 2017

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The first asymmetric [3+1]-cycloaddition was successfully achieved by copper(I) triflate/double-sidearmed bisoxazoline complex catalyzed reactions of β-triisopropyl-silyl-substituted enoldiazo compounds with sulfur ylides. This methodology delivered a series of chiral cyclobutenes in good yields with high enantio- and diastereoselectivities (up to 99% ee, and >20:1 d.r.). Additionally, the [3+1]-cycloaddition of catalytically generated metallo-enolcarbenes was successfully extended to reaction with a stable benzylidene dichlororuthenium complex.

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confidence: 85%

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confidence: 99%

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confidence: 99%

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Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

et al. 2017

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“…In addition, diverse enamine methods have been developed that utilize enones and enals in combination with acid catalysts for the construction of six-membered ring heterocyclic 7,15 and carbocyclic 13d,16 compounds. Reactants other than enamines that include acrylic acid chlorides and esters 17 as well as allenes 18 and phosphorus ylides 19 and dipolar species that include aziridines 15a,20 and cyclopropanes 21 have been employed.…”

Section: Organocatalysismentioning

confidence: 99%

“…There are two basic catalytic pathways with which to enter [3 + 3]-cycloaddition transformations: organocatalysis and transition metal catalysis. Organocatalysis is commonly based on vinyliminium ion chemistry, 7 but phosphine catalysis might also be compatible, 8 and N -heterocyclic carbene catalysis has been reported. 9 Its formal relationship to [3 + 3]-cycloaddition is similar to that of the linkage of the Robinson annulation reaction to [4 + 2]-cycloaddition in that the overall process is stepwise, rather than concerted, involving addition and condensation.…”

Section: Organocatalysismentioning

confidence: 99%

The [3 + 3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts

2014

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ConspectusThe combination of two or more unsaturated structural units to form cyclic organic compounds is commonly referred to as cycloaddition, and the combination of two unsaturated structural units that forms a six-membered ring is formally either a [5 + 1]-, [4 + 2]-, [2 + 2 + 2]-, or [3 + 3]-cycloaddition. Occurring as concerted or stepwise processes, cycloaddition reactions are among the most useful synthetic constructions in organic chemistry. Of these transformations, the concerted [4 + 2]-cycloaddition, the Diels–Alder reaction, is by far the best known and most widely applied. However, although symmetry disallowed as a concerted process and lacking certifiable examples until recently, stepwise [3 + 3]-cycloadditions offer advantages for the synthesis of a substantial variety of heterocyclic compounds, and they are receiving considerable attention.In this Account, we present the development of stepwise [3 + 3]-cycloaddition reactions from virtual invisibility in the 1990s to a rapidly growing synthetic methodology today, involving organocatalysis or transition metal catalysis. With origins in organometallic or vinyliminium ion chemistry, this area has blossomed into a viable synthetic transformation for the construction of six-membered heterocyclic compounds containing one or more heteroatoms. The development of [3 + 3]-cycloaddition transformations has been achieved through identification of suitable and compatible reactive dipolar adducts and stable dipoles. The reactive dipolar species is an energetic dipolar intermediate that is optimally formed catalytically in the reaction. The stepwise process occurs with the reactive dipolar adduct reacting as an electrophile or as a nucleophile to form the first covalent bond, and this association provides entropic assistance for the construction of the second covalent bond and the overall formal [3 + 3]-cycloaddition. Organocatalysis is well developed for both inter- and intramolecular synthetic transformations, but the potential of transition metal catalysis for [3 + 3]-cycloaddition has only recently emerged. The key to the rapid development of the transition metal-based methodology has been recognition that certain catalytically generated vinylcarbenes are effective dipolar adducts for reactions with stable dipolar compounds, including aryl and vinyl ylides. In particular, metallo-enolcarbenes that are generated catalytically from conveniently prepared stable enoldiazoacetates or from donor–acceptor cyclopropenes are highly effective dipolar adducts for [3 + 3]-cycloaddition. The electron-donating oxygen of the silyl ether enhances electrophilic ring closure to the metal-bound carbon of the initial adduct from vinylogous addition, and this enhancement inhibits the alternative [3 + 2]-cycloaddition across the carbon–carbon double bond of the vinylcarbene.Catalytically generated metallo-enolcarbenes react under mild conditions with a broad spectrum of compatible stable dipoles, including nitrones, azomethine imines, ylides, and certain covalent precursors of s...

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Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

et al. 2017

View full text Add to dashboard Cite

The first asymmetric [3+1]‐cycloaddition was successfully achieved by copper(I) triflate/double‐sidearmed bisoxazoline complex catalyzed reactions of β‐triisopropylsilyl‐substituted enoldiazo compounds with sulfur ylides. This methodology delivered a series of chiral cyclobutenes in good yields with high enantio‐ and diastereoselectivities (up to 99 % ee, and >20:1 d.r.). Additionally, the [3+1]‐cycloaddition of catalytically generated metallo‐enolcarbenes was successfully extended to reaction with a stable benzylidene dichlororuthenium complex.

show abstract

A Formal [3+3] Cycloaddition Approach To Natural Product Synthesis

Cited by 11 publications

References 540 publications

Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

The [3 + 3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts

Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

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