Cycloaddition Approach Research Articles

Ni-Catalyzed Cycloaddition Approach to Coumarins by C-C σ-Bond Cleavage

Ni-Catalyzed Cycloaddition Approach to Coumarins by C-C σ-Bond Cleavage

A Palladium-Catalyzed Vinylcyclopropane (3 + 2) Cycloaddition Approach to the Melodinus Alkaloids

A palladium-catalyzed (3+2) cycloaddition of a vinylcyclopropane and a β-nitrostyrene is employed to rapidly assemble the cyclopentane core of the Melodinus alkaloids. The ABCD ring system of the natural product family is prepared in six steps from commercially available materials.

Alternative spiroketalization methods toward purpuromycin: a hemiketal conjugate addition strategy and use of an electron-rich isocoumarin precursor.

Two methods are presented that were designed to circumvent the persistent problem of benzofuran formation and instead yield a spiroketal of the rubromycin family type. First, using an alternative disconnection, a hemiketal conjugate addition to a naphthaquinone electrophile was investigated. Synthesis of the requisite electrophile provided insight into the selective oxidation and functionalization of the naphthalene portion. Second, the electronic features of the isocoumarin ring system were adjusted, and the corresponding reactivity further supports the hypothesis that electron-rich isocoumarins are capable of spiroketalization. Robust, flexible syntheses from simple precursors were developed that allowed multiple reduced isocoumarins to be generated. Combined, the data presented herein give insight into the sensitivities of this family and illuminate other potential methods of spiroketalization. In addition, the convergent assembly of substrates containing different naphthaquinone and isocoumarin subunits highlights the utility of our 1,3-dipolar cycloaddition approach to generate analogs of these structures for SAR, as well as chemical reactivity studies.

A Straightforward Approach towards Isoxazoline Amino Acid Esters by Domino Michael Additions/Nitrile Oxide Cycloadditions

AbstractThe syntheses of new heterocyclic isoxazoline amino acids are described based on a domino Michael addition/nitrile oxide formation/[3+2] cycloaddition approach. Chelated amino acid ester enolates can be added to nitroalkenes, and the generated nitronates are directly converted into nitrile oxides. These can be trapped intramolecularly by an alkene as a dipolarophile. The alkene can be introduced either via the nitroalkene or via the chelated enolate. Therefore, different types of heterocyclic amino acids can be obtained in a simple one‐pot protocol.

Progress in the total synthesis of rocaglamide.

The first cyclopenta[b]benzofuran derivative, rocaglamide, from Aglaia elliptifolia, was found to exhibit considerable insecticidal activities and excellent potential as a therapeutic agent candidate in cancer chemotherapy; the genus Aglaia has been subjected to further investigation. Both the structural complexity of rocaglamide and its significant activity make it an attractive synthetic target. Stereoselective synthesis of the dense substitution pattern of these targets is a formidable synthetic challenge: the molecules bear five contiguous stereocenters and cis aryl groups on adjacent carbons. In past years of effort, only a handful of completed total syntheses have been reported, evidence of the difficulties associated with the synthesis of rocaglate natural products. The advance on total synthesis of rocaglamide was mainly reviewed from intramolecular cyclization and biomimetic cycloaddition approach.

ChemInform Abstract: A Conjugate Addition—Dipolar Cycloaddition Approach Towards the Synthesis of Various Alkaloids

AbstractReview: 177 refs.

A [3 + 2] Dipolar Cycloaddition Route to 3-Hydroxy-3-alkyl Oxindoles: An Approach to Pyrrolidinoindoline Alkaloids

A [3 + 2] cycloaddition approach to the 3-hydroxy-3-alkyl oxindole scaffold is described. Isoxazolines obtained by cycloaddition of nitrile oxide 3 with 3-methylene oxindoles were elaborated to 3-hydroxy-3-cyanomethyl oxindoles employing a one-pot protocol en route to the pyrrolidinoindoline moiety which is found in many natural products. The total syntheses of alkaloids (±)-alline and (±)-CPC-1 were achieved using this methodology.

An IMDAF Cycloaddition Approach toward the Synthesis of the Lycopodium Alkaloid (±)-Fawcettidine

Using an intramolecular [4 + 2] cycloaddition/rearrangement cascade of 3-(1,4-dioxaspiro[4.4]non-7-en-7-yl)-N-furan-2-ylpropionamide (23) as the key step, the BCD core of the lycopodium alkaloid fawcettidine was constructed. Heating the initially formed Diels-Alder cycloadduct at 180 °C results in a nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the ensuing zwitterion to give a rearranged hexahydroindolinone. Our attempts to induce a related intramolecular furan Diels-Alder reaction (IMDAF) from the corresponding ketone of 23 failed to give any cycloaddition product. Instead, the only product obtained corresponded to a cyclopentenone derivative derived by isomerization of the double bond into the thermodynamically more stable α,β-position. Efforts toward construction of the final skeleton of fawcettidine by ring A closure of the rearranged cycloadduct derived from furanyl amide 23 are discussed.

Recent Developments in the [5+2] Cycloaddition

AbstractThe rapid generation of molecular complexity in a relatively easy manner has made the [5+2] cycloaddition approach a highly useful tool in the synthesis of a wide number of complex natural products and important biologically active products containing seven‐membered rings. Besides the common and highly efficient [5+2] cycloadditions of oxidopyrylium and oxidopyridinium ions with π‐systems which offer an easy access to a wide range of novel heterocyclic seven‐membered ring molecules with a oxygen or nitrogen bridge, and the less employed [5+2] photocycloadditions, the metal‐catalyzed [5+2] cycloadditions have attracted a lot of attention and have become one of the most popular ways of constructing seven‐membered ring products. All these cycloadducts can be synthetically manipulated easily toward a number of interesting molecular structures with high potential applications. Abbreviations: Ac: acetyl; Ar: aryl; BarF: tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate; BINAP: 2,2′‐bis(diphenylphosphanyl)‐1,1′‐binaphthyl; Bn: benzyl; Boc: tert‐butoxycarbonyl; Bu: butyl; Bz: benzoyl; Cbz: benzyloxycarbonyl; cod: cyclooctadiene; Cp: cyclopentadienyl; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCE: 1,2‐dichloroethane; de: diastereomeric excess; DFT: density functional theory; DMF: dimethylformamide; DMSO: dimethyl sulfoxide; dppb: 1,4‐bis(diphenylphosphino)butane; dppe: 1,2‐bis(diphenylphosphine)ethane; dppp: 1,3‐bis(diphenylphosphino)propane; ee: enantiomeric excess; Et: ethyl; HFIP: hexafluoroisopropyl alcohol; L: ligand; M: metal; Me: methyl; MOM: methoxymethyl; Ms: mesyl; Ph: phenyl; PMB: para‐methoxybenzoyl; Pr: propyl; Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole; TBDPS: tert‐butyldiphenylsilyl; TBS: tert‐butyldimethylsilyl; TEA: triethylamine; Tf: trifluoromethanesulfonyl; TFE: trifluoroethanol; THP: tetrahydropyran; TIPS: triisopropylsilyl; TMS: trimethylsilyl; Tol: tolyl; Tp: hydridotris(pyrazolyl)borate; Ts: 4‐toluenesulfonyl (tosyl); VCP: vinylcyclopropane.

1,3-Dipolar cycloaddition approach to pyrrolidine analogues of C-nucleosides related to pseudouridine

Pyrrolidine analogues of C-nucleosides related to pseudouridine have been synthesized by 1,3-dipolar cycloaddition reactions of uracil-5 and 2,4-dimethoxypyrimidine-5 nitrones with allyl alcohol and methyl acrylate, and subsequent reductive cleavage of the isoxazolidine cycloadducts. The dimethoxy derivatives have been easily deprotected to the corresponding uracils bearing the pyrrolidine ring instead of a sugar moiety. The regio and stereoselectivity of the reactions are discussed.

A rearrangement–cycloaddition approach to spiro-fused indanones

Spiro-fused indanones were constructed using a [4+2]-cycloaddition approach from α-methylene indanone dienophiles, which were elaborated from 4-chromanone in a number of steps including a key rearrangement process. This type of spiro-fused structure forms the central core ring system found in natural products such as coleophomone A. The cycloaddition reactions using an α-methylene indanone dienophile led to the exo diastereoisomer as the major cycloadduct, whereas the 1,4-dione based dienophile predominantly led to the endo diastereoisomer.

A conjugate addition-dipolar cycloaddition approach towards the synthesis of various alkaloids

The key element for the synthesis of several alkaloid skeletons consists of a conjugate additiondipolar cycloaddition of 2,3-bis(phenylsulfonyl)-1,3-butadiene with an appropriate oxime. The resulting cycloadducts are cleaved reductively to provide azapolycyclic scaffolds with strategically placed functionality for further manipulation to the target compounds.

ChemInform Abstract: Utility of Allylic Azides for the Synthesis of Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition.

AbstractStarting from Baylis—Hillman adducts, the synthesis of different annulated triazoles and tetrazoles using an intramolecular cycloaddition approach is described.

A modular, efficient, and stereoselective synthesis of substituted piperidin-4-ols.

A modular, efficient, and stereoselective synthesis of substituted piperidin-4-ols.

ChemInform Abstract: RuI‐Catalyzed Two‐Component [(5 + 2) + 1] Cycloaddition Approach Toward [5‐8‐5] Ring Systems.

AbstractAn atom‐economical cycloaddition reaction of a variety of ene‐vinylcyclopropanes with CO affords fused tricyclic cyclooctenones bearing three stereocenters.

ChemInform Abstract: A Cycloaddition Approach to Cyclopentenes via Metalladienes as 4π Partners.

ChemInform Abstract: A Cycloaddition Approach to Cyclopentenes via Metalladienes as 4π Partners.

RhI‐Catalyzed Two‐Component [(5+2)+1] Cycloaddition Approach toward [5‐8‐5] Ring Systems

Bringing it all together: [{Rh(CO)2Cl}2]-catalyzed two-component [(5+2)+1] cycloaddition of ene-vinylcyclopropanes with various tether types and substituents with CO has been designed for the one-pot synthesis of fused tricyclic cyclooctenones with atom and step economies. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Cover Picture: RhI‐Catalyzed Two‐Component [(5+2)+1] Cycloaddition Approach toward [5‐8‐5] Ring Systems (Chem. Asian J. 7/2010)

Cycloaddition Reactions…︁ …︁ catalyzed by transition metal complexes have been of continuing interest to chemists owing to their efficiency in constructing complicated molecules from much simpler starting materials in atom- and step-economical fashions. It has been found that eight-membered carbocycles in many natural products are fused or bridge-fused with one or more five- or six-membered carbocycles. In their Communication on page 1555 ff., Z.-X. Yu et al. present [Rh(CO)2Cl]2-catalyzed two-component [(5+2)+1] cycloaddition of ene-vinylcyclopropanes that have various tether types and substituents with CO designed for one-pot synthesis of fused tricyclic cyclooctenones with atom and step economies.

Utility of Allylic Azides for the Synthesis of Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition¹

The synthesis of a variety of annulated triazoles and tetrazoles from differently substituted allyl azides, afforded from the Baylis-Hillman adduct of acrylates, using intramolecular cycloaddition approach is described.

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

The synthesis of C3-carbocyclic spirooxindoles was realized by way of an intramolecular [2 + 2] cycloaddition reaction between a vinylidene indolin-2-one and an alkyne. The cycloaddition reaction occurs selectively with the distal double bond of the allene, is tolerant of a phenyl and trimethylsilyl group on the terminus of the alkyne, and can be used to access bicyclo[4.2.0]octadienes and bicyclo[5.2.0]nonadienes. The allene precursors are not observed, but are likely intermediates of an infrequently encountered thermal [3,3]-sigmatropic rearrangement of a propargylic acetate.