Diversification of Naphthol Skeletons Triggered by Aminative Dearomatization.

A silver-catalyzed aminative dearomatization of naphthols has been developed and integrated into a stepwise approach for subsequent skeletal diversifications including ring expansion, ring opening, ring contraction, and atom transmutation of aryl scaffolds. This approach enables the synthesis of a diverse array of azepinones, unsaturated amides, isoquinolines, and indenones from naphthol substrates. Its application in the synthesis of bioactive and functional molecules as well as the conversion of complex molecular skeletons underscores its broad potential applicability. Mechanistic investigations suggest the intermediacy of the dearomatized intermediates.

Cooperative Photoredox and Cobalt-Catalyzed Acceptorless Dehydrogenative Functionalization of Cyclopropylamides towards Allylic N,O-Acyl-acetal Derivatives.

We disclose herein a novel photoredox and cobalt co-catalyzed ring-opening/acceptorless dehydrogenative functionalization of mono-donor cyclopropanes. This sustainable and atom-economic approach allows the rapid assembly of a wide range of allylic N,O-acyl-acetal derivatives. The starting materials are readily available and the reaction features mild conditions, broad substrate scope, and excellent functional group compatibility. The optimized conditions accommodate assorted cycloalkylamides and primary, secondary, and tertiary alcohols, with applications in late-stage functionalization of pharmaceutically relevant compounds, stimulating further utility in medicinal chemistry. Moreover, selective nucleophilic substitutions with various carbon nucleophiles were achieved in a one-pot fashion, offering a reliable avenue to access some cyclic and acyclic derivatives.

Highly Selective 1,4-Diacylation/Cycloisomerization of 1,3-Enynes: De Novo Synthetic Strategy to Polysubstituted Furans.

The development of a de novo synthetic strategy for rapid assembly of biologically relevant multisubstituted furans is an appealing but challenging task. Herein, we disclose NHC and organophotocatalysis cocatalyzed three-component radical 1,4-diacylation/cycloisomerization cascade process of readily available 1,3-enynes, which provides an efficient and straightforward entry to a wide range of polysubstituted furans with good yields and excellent regio- and chemoselectivities. The reaction features mild conditions, broad substrate scopes, and good functional group compatibilities.

Rapid Assembly of Spironaphthalenones by Dearomative Spiroannulation of Naphthols and Dielectrophiles.

A novel [4 + 1] and [5 + 1] dearomative spiroannulation has been developed by the use of commercial naphthols and phenols with dielectrophiles. Various spirocycles, including spiro[4.5] and spiro[5.5] have been constructed successfully by employing four-atom or five-atom dielectrophilic synthons. This transformation was realized through a sequence of site-selective C-alkylation/dearomative spiroannulation. Moreover, the potential application of this method was exemplified by several further transformation.

Dearomatization/Spiroannulation of Halophenols Enables the Forging of Contiguous Quaternary Carbon Cyclohexadienones.

A dearomatization/spiroannulation process has been successfully achieved between simple halophenols and α,ß-unsaturated olefins under mild reaction conditions. This transformation addresses the chemoselectivity issue in the dearomatizative transformation of phenol scaffolds (6π-electron) caused by the SEAr process, enabling the construction of versatile cyclohexadienone frameworks containing contiguous quaternary all-carbon centers in high yields. Further studies have provided valuable insights into the process, revealing that debromination/spiroannulation occurs through the SRN1 pathway.

Palladium-Catalyzed C-H Arylation/Arene Dearomatization Domino Reaction: Expeditious Access to Spiro[4,5]fluorenes.

A palladium-catalyzed C-H arylation/arene dearomatization of α-aryl-ß-naphthol with o-dihalobenzenes was realized in a redox-neutral manner. This bimolecular domino reaction was initiated by an in situ-formed Pd(II) species generated from the dihalobenzene, followed by phenolic-group-directed C-H activation, biaryl cross-coupling, and naphthol dearomatization, thus rendering the rapid assembly of a class of spiro[4,5]fluorenes in high yields with good chemoselectivity. Remarkably, malononitrile-derived spirofluorene 6 was found to exhibit mechanoresponsive luminescence, which can be applied to optical memory devices.

In(OTf)3-catalyzed reorganization/cycloaddition of two imine units and subsequent modular assembly of acridinium photocatalysts.

Herein, we disclose a novel reorganization/cycloaddition between two imine units catalyzed by In(OTf)3 Lewis acid that differs from the well-known [4 + 2] cycloaddition version via the Povarov reaction. By means of this unprecedented imine chemistry, a collection of synthetically useful dihydroacridines has been synthesized. Notably, the obtained products give rise to a series of structurally novel and fine-tuneable acridinium photocatalysts, offering a heuristic paradigm for synthesis and efficiently facilitating several encouraging dihydrogen coupling reactions.

Rapid Assembly of Spiroisoxazolidines by [4 + 1] Dearomative Spiroannulation of α-Bromo-ß-naphthol and Nitroolefin.

A novel [4 + 1] dearomative spiroannulation of α-halo-ß-naphthol and nitroolefin has been developed for the direct construction of various spiroisoxazolidines in high chemo- and diastereoselectivity. Notably, halophenols (X = Cl and I) were also tolerated by this reaction. This transformation was realized through a sequence of electrophilic dearomatization/dehalogenation, and mechanistic studies revealed that different routes occurred for C(sp3)-X bond cleavage. Moreover, the potential application of this method was exemplified by several further transformations.

Palladium-Catalyzed Alkenyl C-H Activation/Diamination toward Tetrahydrocarbazole and Analogs Using Hydroxylamines as Single-Nitrogen Sources.

A palladium-catalyzed alkenyl C-H activation/diamination reaction of cycloalkenyl bromoarenes with hydroxylamines is described. A wide range of tetrahydrocarbazoles and analogs has been prepared using fine-tuning bifunctional secondary hydroxylamines as the single-nitrogen sources. Mechanistic investigations suggest that the selective alkenyl C-H activation/diamination cascade process should build the N-heterocycles.

Palladium(II)-Catalyzed [2+2+1] Annulation of Alkynes and Hydroxylamines: A Rodox-Neutral Approach to Fully Substituted Pyrroles.

A palladium-catalyzed [2+2+1] annulation of alkynes and hydroxylamines has been developed for the rapid construction of fully substituted pyrroles. This transformation involves sequential nucleophilic-addition of hydroxylamine to alkyne, alkyne migratory insertion, and synergistic demetallization cyclization, which provides a redox-neutral annulation approach to pyrrole derivatives. Moreover, the strategy enabled alteration of the photophysical properties of pyrrole products by varying the aryl substituents, thus leading to the development of N-functionalized tetraarylpyrroles as new fluorophores.

Dearomatization/Deiodination of o-Iodophenolic Compounds with α,ß-Unsaturated Imines for Accessing Benzofuran Derivatives.

A dearomatization/deiodination/rearomatization strategy for the [3 + 2] cyclization of o-iodophenolic substrates with α,ß-unsaturated imines to construct various dihydrobenzofuran-related skeletons has been established. Tolerance to different functional groups has been tested. Mechanistic studies revealed that this domino reaction was possibly realized by the deiodination and tautomerization of the key dearomatized intermediate to generate a free phenolic O radical. Moreover, an anticancer agent 4 and an α-glucosidase inhibitor 5 with high bioactivities were successfully synthesized using this novel protocol.

Selective C(sp3 )-N Bond Cleavage of N,N-Dialkyl Tertiary Amines with the Loss of a Large Alkyl Group via an SN 1 Pathway.

Polar disconnection of the C(sp3 )-N bond of N,N-dialkyl-substituted tertiary amines via ammonium species conventionally favored the loss of the smaller alkyl group by an SN 2 displacement, while selective C(sp3 )-N bond cleavage by cutting off the larger alkyl group is still underdeveloped. Herein, we present a novel Pd0 -catalyzed [2+2+1] annulation, proceeding through an alkyne-directed palladacycle formation and consecutive diamination with a tertiary hydroxylamine by cleaving its N-O bond and one C(sp3 )-N bond, for the rapid assembly of tricyclic indoles in a single-step transformation. Noteworthy, experimental results indicated that large tert-butyl and benzyl groups were selectively cleaved via an SN 1 pathway, in the presence of a smaller alkyl group (Me, Et, i Pr). Under the guidance of this new finding, tricyclic indoles bearing a removable alkyl group could be exclusively obtained by using a (α-methyl)benzyl/benzyl or tert-butyl/2-(methoxycarbonyl)ethyl mixed amino source.

Total Synthesis of Dalesconol A by Pd(0)/Norbornene-Catalyzed Three-Fold Domino Reaction and Pd(II)-Catalyzed Trihydroxylation.

Herein, we describe a concise total synthesis of dalesconol A through a "polycyclization/oxidation" approach. In the polycyclization stage, a Pd(0)/NBE-catalyzed 3-fold domino reaction and a subsequent intramolecular Michael addition have been utilized for the one-step assembly of the heptacyclic molecular skeleton. In the late stage of oxidation state adjustments, a stepwise sequence including site-selective benzylic oxidation, Pd(II)-catalyzed oxime ether directed trihydroxylation, and desaturation has been adopted to introduce the oxygen functionalities and furnish the synthesis of dalesconol A. With the advantage of the late-stage amidation of three C-H bonds in a single step, the amino analogue of dalesconol A has also been obtained with high efficiency.

Construction of Structurally Rigid Azulen-6-ones via Migratory Rearrangement of Spirocycles and Their Photophysical Studies.

We report the synthesis of polysubstituted 1,1,2,3-tetraarylazulen-6-ones through the ring opening and scaffold rearrangement of spirocycles in the presence of ferric chloride under ambient conditions. Control experiments shown that this reaction may proceeded through a radical cation mechanism and futher theoretical calculation revealed that the electronic distribution of the radical cation intermediate dominated this oxidative rearrangement instead of dehydrogenation. It is noteworthy that some interesting photophysical properties, including aggregation-induced emission, halochromism, and two-photon fluorescence, were discovered for the azulen-6-one 2a, making them to work as promising functional materials in optical-related fields.

A chemo- and regioselective Pd(0)-catalyzed three-component spiroannulation.

A chemo- and regioselective Pd(0)-catalyzed spiroannulation has been successfully developed. The key feature of this method is the use of readily available 1,2-dihaloarenes, alkynes and 2-naphthols for the rapid assembly of spirocarbocyclic molecules. Mechanistic studies revealed that this domino reaction proceeded through a cascade of oxidative addition to Pd(0), alkyne migratory insertion, and 2-naphthol-facilitated dearomatizing [4+1] spiroannulation.

A Dearomatization/Debromination Strategy for the [4+1] Spiroannulation of Bromophenols with α,ß-Unsaturated Imines.

A novel [4+1] spiroannulation of o- & p-bromophenols with α,ß-unsaturated imines has been developed for the direct synthesis of a new family of azaspirocyclic molecules. Notably, several other halophenols (X=Cl, I) were also applicable for this transformation. Moreover, a catalytic asymmetric version of the reaction was realized with 1-bromo-2-naphthols by using a chiral ScIII /Py-Box catalyst. Mechanistic studies revealed that this domino reaction proceeded through electrophile-triggered dearomatization of phenol derivatives at their halogenated positions and followed by halogen-displacement with N-nucleophiles via a radical-based SRN 1 mechanism.

Hydroxylamines As Bifunctional Single-Nitrogen Sources for the Rapid Assembly of Diverse Tricyclic Indole Scaffolds.

Conventional approaches on using hydroxylamine derivatives as single nitrogen sources, for the construction of n-membered (n > 3) N-heterocycles, rely upon two chemical operations by involving sequential nucleophilic and electrophilic C-N bond formations. Here, we report a highly efficient cascade of alkyne insertion/C-H activation/amination for the rapid preparation of a myriad of tricyclic indoles, in a single-step transformation, by using bifunctional secondary hydroxylamines. It is noteworthy that judicious selection of applicable amino agents, for enabling the prior oxidative addition of aryl iodide to initial Pd(0) species and subsequent two C-N bonds formation, was the key to the success of this reaction. Control experiments indicated that a five-membered palladacyclic intermediate played a crucial role in promoting the final aminative ring closure.

Palladium-Catalyzed [2+2+1] Spiroannulation via Alkyne-Directed Remote C-H Arylation and Subsequent Arene Dearomatization.

Palladium-catalyzed alkene-directed cross-coupling of aryl iodide with another aryl halide through C-H arylation opens a unique avenue for unsymmetrical biaryl-derived molecules. However, homo-coupling of aryl iodides often erodes the overall synthetic efficiency. Reported herein is a highly chemoselective Pd0 -catalyzed alkyne-directed cross-coupling of aryl iodides with bromophenols, which was subsequently followed by phenol dearomatization to furnish a very attractive [2+2+1] spiroannulation. Notably, possible homo-coupling of aryl iodides was not observed at all. Mechanistic studies indicated that a five-membered aryl/vinyl palladacycle most likely accounts for promoting the key step of biaryl cross-coupling.

Two-in-one strategy for fluorene-based spirocycles via Pd(0)-catalyzed spiroannulation of o-iodobiaryls with bromonaphthols.

Rapid assembly of fluorene-based spirocycles represents a highly significant but challenging task in organic synthesis. Reported herein is a novel Pd(0)-catalyzed [4+1] spiroannulation of simple o-iodobiaryls with bromonaphthols for the one-step construction of [4,5]-spirofluorenes in high yields with excellent functional group tolerance. Noteworthily, these valuable fluorene-based coumarin skeletons can enrich the database of C-coumarins and exhibit excellent spectroscopic properties.

Palladium-Catalyzed Intermolecular [4+1] Spiroannulation by C(sp3 )-H Activation and Naphthol Dearomatization.

A novel palladium-catalyzed [4+1] spiroannulation was developed by using a C(sp3 )-H activation/naphthol dearomatization approach. This bimolecular domino reaction of two aryl halides was realized through a sequence of cyclometallation-facilitated C(sp3 )-H activation, biaryl cross-coupling, and naphthol dearomatization, thus rendering the rapid assembly of a new class of spirocyclic molecules in good yields with broad functional-group tolerance. Preliminary mechanistic studies indicate that C-H cleavage is likely involved in the rate-determining step, and a five-membered palladacycle was identified as the key intermediate for the intermolecular coupling.