Ene Cyclization Research Articles

A Concise Asymmetric Total Synthesis of (+)-8-Epigrosheimin via Catalyst-Free Tandem Allylboration–Lactonization

AbstractA concise and scalable asymmetric synthesis of (+)-8-epigrosheimin is reported in nine steps using only three column chromatographic purifications with an overall yield 47.0% from (R)-(–)-carvone. Two synthetic routes are evaluated by catalyst-free tandem allylboration–lactonization of two carvone-derived aldehydes and subsequent ene cyclization, where strategy via Lee–Lay aldehyde is found to be more effective for 8-epigrosheimin.

Palladium‐Catalyzed Cycloisomerization of 1,6‐Allene‐Ene via [1,8]‐Sigmatropic Hydrogen Shift of Allylic C−H

AbstractA ligand‐free palladium‐promoted [1,8]‐sigmatropic hydrogen shift reaction of 1,6‐allene‐ene was reported, which went through an intramolecular Ene cyclization using base as a hydrogen shuttle. Notably, the transformation could realize the HAT process via the hydrogen shift from an old allylic C−H bond to a new one in the presence of oxidant, between which have low BDE distinction. The mild reaction conditions, high atom economy and good chemo/regioselectivity proved the valuable of this strategy. The control experiments using acetone‐D6/D2O proved that neither solvent nor water were involved in the cycloisomerization process and HAT process was more convincible. The target products could achieve more valuable molecules via convenient synthetic transformation.

Correction: A sequential Ugi–Smiles/transition-metal-free endo-dig Conia–ene cyclization: the selective synthesis of saccharin substituted 2,5-dihydropyrroles

Correction for ‘A sequential Ugi–Smiles/transition-metal-free endo-dig Conia–ene cyclization: the selective synthesis of saccharin substituted 2,5-dihydropyrroles’ by Hassan Seyrani et al., New J. Chem., 2021, 45, 15647–15654, https://doi.org/10.1039/D1NJ01159F.

BF3*OEt2 catalyzed synthesis of spiropyrrolidine frameworks via (3,5)-oxonium-ene cyclization

γ-Hydroxyolefin derived from proline undergoes a smooth ene cyclization with aldehydes to produce the 7-oxa-1-azaspiro[4.5]decane scaffolds in good yields. Whereas the condensation of γ-hydroxyalkene with 2-hydroxybenzaldehyde affords the corresponding tetrahydro-2H-spiro[pyrano[3,2-c]chromene-3,2′-pyrrolidine derivatives in excellent yields. This is the first report on the ene cyclization of aldehydes with γ-hydroxyalkene derived from the α-amino acid, proline.

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions.

The hexameric resorcin[4]arene capsule as a self-assembled organocatalyst promotes a series of reactions like the carbonyl–ene cyclization of (S)-citronellal preferentially to isopulegol, the water elimination from 1,1-diphenylethanol, the isomerization of α-pinene and β-pinene preferentially to limonene and minor amounts of camphene. The role of the supramolecular catalyst consists in promoting the protonation of the substrates leading to the formation of cationic intermediates that are stabilized within the cavity with consequent peculiar features in terms of acceleration and product selectivity. In all cases the catalytic activity displayed by the hexameric capsule is remarkable if compared to many other strong Brønsted or Lewis acids.

Thermal Degradation of Linalool-Chemotype Cinnamomum osmophloeum Leaf Essential Oil and Its Stabilization by Microencapsulation with β-Cyclodextrin.

The thermal degradation of linalool-chemotype Cinnamomum osmophloeum leaf essential oil and the stability effect of microencapsulation of leaf essential oil with β-cyclodextrin were studied. After thermal degradation of linalool-chemotype leaf essential oil, degraded compounds including β-myrcene, cis-ocimene and trans-ocimene, were formed through the dehydroxylation of linalool; and ene cyclization also occurs to linalool and its dehydroxylated products to form the compounds such as limonene, terpinolene and α-terpinene. The optimal microencapsulation conditions of leaf essential oil microcapsules were at a leaf essential oil to the β-cyclodextrin ratio of 15:85 and with a solvent ratio (ethanol to water) of 1:5. The maximum yield of leaf essential oil microencapsulated with β-cyclodextrin was 96.5%. According to results from the accelerated dry-heat aging test, β-cyclodextrin was fairly stable at 105 °C, and microencapsulation with β-cyclodextrin can efficiently slow down the emission of linalool-chemotype C. osmophloeum leaf essential oil.

A sequential Ugi–Smiles/transition-metal-free endo-dig Conia–ene cyclization: the selective synthesis of saccharin substituted 2,5-dihydropyrroles

A convenient, transition-metal-free access to a series of unprecedented saccharin substituted 2,5-dihydropyrroles is reported.

Total Syntheses of Norrisolide-Type Spongian Diterpenes Cheloviolene C, Seconorrisolide B, and Seconorrisolide C.

The first total syntheses of three unusual norrisolide-type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late-stage ring-scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans-hydrindane system, and a crucial retro Diels-Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3-b]furan system, which is commonly seen in rearranged spongian diterpenes.

Total Syntheses of Norrisolide‐Type Spongian Diterpenes Cheloviolene C, Seconorrisolide B, and Seconorrisolide C

AbstractThe first total syntheses of three unusual norrisolide‐type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late‐stage ring‐scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans‐hydrindane system, and a crucial retro Diels–Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3‐b]furan system, which is commonly seen in rearranged spongian diterpenes.

Ene cyclization reaction in heterocycle synthesis.

The ene cyclization has evolved to become an indispensable tool for the synthesis of various ring size heterocyclic compounds. In the past and recent years, many exciting reports have demonstrated the broad scope and synthetic utility of ene cyclization and the versatility of oxonium ion, iminium ion and thionium ion intermediates. Moreover, the ease of regio- and stereoselectivity of ene cyclization has led to the development of new types of heterocyclic compounds. This article aims at reviewing the utilities of ene cyclization reactions for the synthesis of various ring sizes of oxygen, nitrogen and sulfur heterocycles. It also covers some applications in natural product synthesis. The mechanism of the reactions is discussed wherever necessary. The review article covers the time period from 1986 to 2017.

Construction of Morphan Derivatives by Nitroso–Ene Cyclization: Mechanistic Insight and Total Synthesis of (±)‐Kopsone

AbstractA type II nitroso–ene cyclization was developed for the construction of morphan derivatives with good functional‐group tolerance. DFT calculations revealed that the nitroso–ene reaction proceeds in a stepwise manner involving diradical or zwitterionic intermediates. The rate‐determining step is C−N bond formation, followed by a rapid hydrogen‐transfer step with a chair‐conformation transition state. The current approach was also successfully applied in the first total synthesis of (±)‐kopsone, a highly strained yet simple morphan‐type alkaloid isolated from Kopsia macrophylla.

Total Synthesis of Homodimericin A.

We report the concise total synthesis of homodimericin A (1), a recently identified fungal metabolite bearing an unprecedented molecular architecture. The success of the approach hinges on a series of rationally designed and bioinspired transformations, including a Moore rearrangement to assemble the monomeric hydroquinone precursor, homodimerization through double Michael addition to construct the planar A/B/C tricyclic framework, and a tandem Diels-Alder reaction/carbonyl-ene cyclization to forge the congested D/E/F tricyclic cage motif. Unequivocal evidence for the elucidated structure of homodimericin A was also provided by this study.

Total Synthesis of Homodimericin A

AbstractWe report the concise total synthesis of homodimericin A (1), a recently identified fungal metabolite bearing an unprecedented molecular architecture. The success of the approach hinges on a series of rationally designed and bioinspired transformations, including a Moore rearrangement to assemble the monomeric hydroquinone precursor, homodimerization through double Michael addition to construct the planar A/B/C tricyclic framework, and a tandem Diels–Alder reaction/carbonyl–ene cyclization to forge the congested D/E/F tricyclic cage motif. Unequivocal evidence for the elucidated structure of homodimericin A was also provided by this study.

ChemInform Abstract: Ligand‐Controlled Gold‐Catalyzed Cycloisomerization of 1,n‐Enyne Esters Toward Synthesis of Dihydronaphthalene.

We describe herein a gold-catalyzed rearrangement of propargyl esters followed by allene–ene cyclization to afford substituted bicyclic [4.4.0] dihydronaphthalene compounds. This method is also applied to vinylethers and vinylamines of 1,7-enyne esters to form dihydroquinoline and dihydrobenzopyran structures. The basis of this transformation is the ligand-controlled preferential activation of the alkene over the allene, affording the desired aromatic bicyclic structures in moderate to excellent yields.

Total Synthesis of Plakilactones C, B and des-Hydroxyplakilactone B by the Oxidative Cleavage of Gracilioether Furanylidenes.

A chemoselective oxidative cleavage of synthetic gracilioether B, 11-epi-gracilioether C benzoate, and des-hydroxygracilioether C with pyridinium chlorochromate, which proceeds with loss of the furanyl acetate, has enabled total synthesis and stereochemical elucidation of the marine sponge metabolites (4R,6R)-plakilactone C, (4R,6R,9R)-plakilactone B, and (4R,6R)-des-hydroxyplakilactone B. des-Hydroxygracilioether C, the putative biosynthetic precursor to hippolachnin A, was also found to undergo a facile ene cyclization on treatment with SnCl4.

ChemInform Abstract: Enantioselective Total Synthesis of (—)‐Hosieine A.

AbstractIn the approach to the title compound (IV), a bioactive constituent of Ormosia hosier, the unprecedented nitroso—ene cyclization of hydroxamic acid (II) represents the main step with formation of the 2‐azabicyclo[3.2.1]octane core.

Ligand-controlled gold-catalyzed cycloisomerization of 1,n-enyne esters toward synthesis of dihydronaphthalene.

We describe herein a gold-catalyzed rearrangement of propargyl esters followed by allene-ene cyclization to afford substituted bicyclic [4.4.0] dihydronaphthalene compounds. This method is also applied to vinylethers and vinylamines of 1,7-enyne esters to form dihydroquinoline and dihydrobenzopyran structures. The basis of this transformation is the ligand-controlled preferential activation of the alkene over the allene, affording the desired aromatic bicyclic structures in moderate to excellent yields.

Organocatalytic Carbonyl–Ene Cyclization

Organocatalytic Carbonyl–Ene Cyclization

Enantioselective Total Synthesis of (−)‐Hosieine A

AbstractThe first total synthesis of (−)‐hosieine A was accomplished and features an unprecedented nitroso–ene cyclization to construct the 2‐azabicyclo[3.2.1]octane ring system. Phosphine‐enabled stereoselective bromohydrination provided interesting mechanistic insights into the anti‐Markovnikov process. Also noteworthy is the retention of stereochemistry at C9 in the facile radical debromination initiated by Et3B/air.

Total synthesis of (±)-hippolachnin A.

The first total synthesis of the marine polyketide (±)-hippolachnin A has been achieved in nine linear steps and an overall yield of 9%. Rapid access to the oxacyclobutapentalene core structure was secured by strategic application of an ene cyclization.