Annulation Strategy Research Articles

Silver(i)-catalyzed sequential hydroamination and Prins type cyclization for the synthesis of fused benzo-δ-sultams.

An intramolecular annulation strategy has been developed for the synthesis of tetrahydrobenzo[e]pyrano[4,3-c][1,2]thiazine derivatives by means of coupling of aldehydes with 2-(4-hydroxybut-1-yn-1-yl)-N-arylsulfonamides using a catalytic amount of silver hexafluoroantimonate in toluene at 80 °C. This is the first report on the synthesis of fused benzo-δ-sultam derivatives through C-N, C-O, and C-C bond formations. The reaction proceeds through a cascade of hydroamination and Prins type cyclization.

Expansion of the aromatic part of Cinchona alkaloids. Annulation of quinolines with phenoxazine motifs

An oxidative cross-coupling strategy for quinoline ring annulation in Cinchona alkaloids has been developed. Key-reaction optimization by changing oxidants and adjusting the nucleophilicity of the 2-aminophenols led to cupreine and cupreidine expanded with the phenoxazinone unit in 56–75% yield. The stereochemical integrity of the obtained alkaloid structures was confirmed by combined experimental and computed CD and NMR data. The conformational study revealed a fast equilibrium of the three conformers, differing in the orientation of the pyrido[a-3,2]phenoxazine moiety.

Synthesis of 2,2-Difluorinated 4-Isoflavanols/4-Thioisoflavanols via a Base-Catalyzed [4 + 2] Annulation Reaction of gem-Difluoroolefins.

DBU-catalyzed sequential intermolecular and intramolecular nucleophilic addition reactions between gem-difluoroolefins and o-hydroxy/mercapto benzaldehydes have been developed to provide a [4 + 2] annulation strategy for facile synthesis of gem-difluorinated isoflavanol derivatives. The competitive addition-elimination reaction of gem-difluoroolefins with nucleophiles was avoided under mild conditions, affording 2,2-difluorinated 4-isoflavanols or 2,2-difluoriated 4-thioisoflavanols in good to excellent yields.

Arylative Cyclization of Indole‐1‐carboxamides with 1,6‐Enynes for the Synthesis of Polycyclic Indole Scaffolds

A new alkyne annulation strategy has been developed for the synthesis of polycyclic indole derivatives through a cascade of C–H annulation and Michael addition reactions. This is the first report on sequential alkyne annulation and aza‐Michael addition reactions of indole‐1‐carboxamides with alkyne tethered substrates.

Efficient Synthesis of Highly Functionalized Spirocarbocyclic Oxindoles through Hauser Annulation

The synthesis of highly functionalized spirocarbocyclic oxindoles was accomplished for the first time, using a Hauser annulation strategy. A reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate gave access to a new class of biologically important spiro[indoline‐3,2′‐naphthalene] derivatives in very good yields.

A Tandem Oxidative Annulation Strategy for the Synthesis of Tetracyclic 3-Spirooxindole Benzofuranones.

A simple and efficient method was developed for the construction of the medicinally important tetracyclic 3-spirooxindole benzofuranones. In this highly atom- and step-economical one-pot protocol, one quaternary carbon center, two new cycles, and four new bonds (C-C/C-O/C-N) were formed under simple ligand-free copper-catalyzed conditions through a novel tandem oxidative annulation strategy.

Switchable Access to Different Spirocyclopentane Oxindoles by N-Heterocyclic Carbene Catalyzed Reactions of Isatin-Derived Enals and N-Sulfonyl Ketimines.

A novel NHC-catalyzed annulation protocol for the asymmetric synthesis of biologically important β-lactam fused spirocyclopentane oxindoles with four contiguous stereocenters, including two quaternary carbon centers, was developed. Alternatively, spirocyclopentane oxindoles containing an enaminone moiety can be achieved using the same starting materials, isatin-derived enals, and N-sulfonyl ketimines, in the presence of a slightly different NHC catalytic system. This switchable annulation strategy enables the selective assembly of both heterocyclic scaffolds with good yields and excellent enantioselectivities for a broad range of substrates.

Switchable Access to Different Spirocyclopentane Oxindoles by N‐Heterocyclic Carbene Catalyzed Reactions of Isatin‐Derived Enals and N‐Sulfonyl Ketimines

AbstractA novel NHC‐catalyzed annulation protocol for the asymmetric synthesis of biologically important β‐lactam fused spirocyclopentane oxindoles with four contiguous stereocenters, including two quaternary carbon centers, was developed. Alternatively, spirocyclopentane oxindoles containing an enaminone moiety can be achieved using the same starting materials, isatin‐derived enals, and N‐sulfonyl ketimines, in the presence of a slightly different NHC catalytic system. This switchable annulation strategy enables the selective assembly of both heterocyclic scaffolds with good yields and excellent enantioselectivities for a broad range of substrates.

Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H.

Total syntheses of three different lamellarins have been accomplished using a Ru(II)-catalyzed (3 + 2) annulation strategy to construct the central pyrrole ring. The striking features of this synthesis are the use of PEG-400 as a green solvent for the (3 + 2) annulation reaction and multiple catalytic reactions with excellent overall yield. The present route also enables the synthesis of various lamellarin analogues devoid of a B ring.

Rapid Access to Indeno[1,2‐c]quinolines via Brønsted Acid‐ Catalyzed Cascade Reaction

AbstractA Brønsted acid‐catalyzed annulation strategy has been developed to construct indeno[1,2‐c]quinolines. This tandem synthetic method proceeds through a sequential electrophilic addition followed by a Friedel–Crafts‐type reaction. A variety of tetracyclic compounds was obtained in moderate to high yields under mild reaction conditions in a short time.magnified image

Catalytic Enantioselective Syntheses of Isoxazolidin-5-ones

This short review provides an overview concerning the developments toward the catalytic enantioselective syntheses of isoxazolidin-5-one derivatives making use of metal-based or organocatalytic conditions. The subsequent use and chemical transformations of these valuable chiral oxazole heterocycles will also be described. 1 Introduction 2 Aza-Michael Strategy 3 Nitroso-Based Annulation Strategy 4 Nitrone-Based Annulation Strategy 5 Functionalization Reactions of Isoxazolidin-5-ones 6 Miscellaneous 7 Conclusion

New thiophene-functionalized pyrene, peropyrene, and teropyrene via a two- or four-fold alkyne annulation and their photophysical properties

We synthesized thiophene-functionalized pyrene, peropyrene, and teropyrene through a two- or four-fold alkyne annulation reaction promoted by triflic acid. All of the target compounds were fully characterized spectroscopically, and the structure of the peropyrene analogue was unambiguously confirmed by X-ray crystallography. A significant red shift in the absorption and emission properties as a function of extended conjugation was observed by UV–vis and fluorescence spectroscopy. This alkyne annulation strategy is a useful method for the conversion of smaller polycyclic aromatics to larger ones, such as nanographenes.

ChemInform Abstract: A Green Synthesis of Unsymmetrical 9‐Arylxanthenes in a One‐Pot Cascade Benzylation/Annulation/Dehydration Strategy.

Abstract A green synthesis of unsymmetrical 9-arylxanthenones is described using Ca(OTf)2 in one-pot cascade benzylation, annulation and dehydration strategy starting from readily accessible π-activated carbinols. 4-Hydroxycoumarin/cyclohexane-1,3-dione required to be refluxed in water with 2-(hydroxy(phenyl)methyl)phenol derivatives in the presence of 5 mol % of Ca(OTf)2 to yield the unsymmetrical 9H-xanthenes, whereas α/β-naphthols reacted under solvent free-microwave irradiation conditions. Use of ecofriendly alkaline earth catalyst, water as the solvent, mw-irradiation, substrate scope and high yields make this methodology more amenable.

Frontispiece: A Pd‐Catalyzed Synthesis of Functionalized Piperidines

Pd Catalysis A readily available cyclic carbamate functions as a general precursor to a range of functionalized piperidine products using a new Pd-catalyzed annulation strategy. An asymmetric catalytic variant provides a rapid and efficient means to access these heterocycles with high to excellent levels of enantiocontrol. In addition, these richly functionalized compounds are amenable to further chemoselective elaboration. For more information, see the Communication by J. P. A. Harrity et al. on page 13000 ff.

ChemInform Abstract: Rh‐ and Cu‐Cocatalyzed Aerobic Oxidative Approach to Quinazolines via [4 + 2] C—H Annulation with Alkyl Azides.

A novel and efficient rhodium- and copper-co-catalyzed C–H bond activation and annulation for the construction of bioactively important quinazolines has been developed. This [4 + 2] annulation strategy utilizing alkyl azides as the carbon–heteroatom synthons shows high efficiency in the synthesis of six-membered benzoheterocycles containing two heteroatoms. This aerobic oxidative protocol provides a useful application of simple alkyl azides in N-heterocycle synthesis with N2 and H2O as byproducts.

Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro‐1,2‐Diazepinones by NHC‐Catalyzed [3+4] Annulation Reactions

AbstractA strategy for the NHC‐catalyzed asymmetric synthesis of spirobenzazepinones, spiro‐1,2‐diazepinones, and spiro‐1,2‐oxazepinones has been developed via [3+4]‐cycloaddition reactions of isatin‐derived enals (3C component) with in‐situ‐generated aza‐o‐quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven‐membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all‐carbon spiro stereocenter is generated.

Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro-1,2-Diazepinones by NHC-Catalyzed [3+4] Annulation Reactions.

A strategy for the NHC-catalyzed asymmetric synthesis of spirobenzazepinones, spiro-1,2-diazepinones, and spiro-1,2-oxazepinones has been developed via [3+4]-cycloaddition reactions of isatin-derived enals (3C component) with in-situ-generated aza-o-quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven-membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all-carbon spiro stereocenter is generated.

A Pd-Catalyzed Synthesis of Functionalized Piperidines.

A readily available cyclic carbamate 1 functions as a general precursor to a range of functionalized piperidine products via a new Pd-catalyzed annulation strategy. An asymmetric catalytic variant provides a rapid and efficient means to access these heterocycles with high to excellent levels of enantiocontrol. Finally, these richly functionalized compounds are amenable to further chemoselective elaboration.

ChemInform Abstract: An Air‐Stable Half‐Sandwich RuII Complex as an Efficient Catalyst for [3 + 2] Annulation of 2‐Arylcyclo‐2‐enones with Alkynes.

AbstractA novel ruthenium complex HSRC is prepared and successfully applied for the synthesis of spiro carbocyclic indenes via a [3 + 2] annulation strategy.

ChemInform Abstract: Synthesis of Poly‐Substituted Benzene from Morita—Baylis—Hillman Adducts via [3 + 1 + 2] Annulation Strategy: Palladium‐Catalyzed Domino Cyclization (5‐exo/3‐exo), Ring‐Expansion by Palladium Rearrangement, and Aromatization.

ChemInform Abstract: Synthesis of Poly‐Substituted Benzene from Morita—Baylis—Hillman Adducts via [3 + 1 + 2] Annulation Strategy: Palladium‐Catalyzed Domino Cyclization (5‐exo/3‐exo), Ring‐Expansion by Palladium Rearrangement, and Aromatization.