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.

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.

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

The development of a 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.

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,β-unsaturated olefins under mild reaction conditions. This transformation addresses the chemoselectivity issue in the dearomatizative transformation of phenol scaffolds (6π-electron) caused by the SE 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 S1 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-β-naphthol with -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 was found to exhibit mechanoresponsive luminescence, which can be applied to optical memory devices.

In(OTf)-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) Lewis acid that differs from the well-known [4 + 2] cycloaddition version 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-β-naphthol and Nitroolefin.

A novel [4 + 1] dearomative spiroannulation of α-halo-β-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(sp)-X bond cleavage.

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 -functionalized tetraarylpyrroles as new fluorophores.

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

A dearomatization/deiodination/rearomatization strategy for the [3 + 2] cyclization of -iodophenolic substrates with -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.

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.

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

Polar disconnection of the C(sp )-N bond of N,N-dialkyl-substituted tertiary amines via ammonium species conventionally favored the loss of the smaller alkyl group by an S 2 displacement, while selective C(sp )-N bond cleavage by cutting off the larger alkyl group is still underdeveloped. Herein, we present a novel Pd -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(sp )-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 S 1 pathway, in the presence of a smaller alkyl group (Me, Et, Pr).

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 , making them to work as promising functional materials in optical-related fields.

Two-in-one strategy for fluorene-based spirocycles Pd(0)-catalyzed spiroannulation of -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 -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 -coumarins and exhibit excellent spectroscopic properties.

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,β-Unsaturated Imines.

A novel [4+1] spiroannulation of o- & p-bromophenols with α,β-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 Sc /Py-Box catalyst.

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 -membered ( > 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.

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

A novel palladium-catalyzed [4+1] spiroannulation was developed by using a C(sp )-H activation/naphthol dearomatization approach. This bimolecular domino reaction of two aryl halides was realized through a sequence of cyclometallation-facilitated C(sp )-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.

Highly Chemoselective Construction of Spiro[4,5]decane-Embedded Polycyclic Scaffolds by a Palladium/Norbornene-Catalyzed C-H Activation/Arene Dearomatization Reaction.

A highly chemoselective intermolecular annulation reaction of phenol-based biaryls with bromoalkyl alkynes has been successfully developed by palladium/norbornene catalysis. This domino process was accomplished by following a cascade of Catellani-type C-H functionalization, alkyne migratory insertion, and arene dearomatization, thus leading to a large number of spiro[4,5]decane-embedded polycyclic molecules bearing various functional groups in moderate to excellent yields.

Palladium/Norbornene-Catalyzed C-H Alkylation/Alkyne Insertion/Indole Dearomatization Domino Reaction: Assembly of Spiroindolenine-Containing Pentacyclic Frameworks.

Reported is a highly chemoselective intermolecular annulation of indole-based biaryls with bromoalkyl alkynes by using palladium/norbornene (Pd/NBE) cooperative catalysis. This reaction is realized through a sequence of Catellani-type C-H alkylation, alkyne insertion, and indole dearomatization, by forming two C(sp )-C(sp ) and one C(sp )-C(sp ) bonds in a single chemical operation, thus providing a diverse range of pentacyclic molecules, containing a spiroindolenine fragment, in good yields with excellent functional-group tolerance. Preliminary mechanistic studies reveal that C-H bond cleavage is likely involved in the rate-determining step, and the indole dearomatization might take place through an olefin coordination/insertion and β-hydride elimination Heck-type pathway.

Pd(0)-Catalyzed Intermolecular Dearomatizing [3 + 2] Spiroannulation of Phenol-Based Biaryls and Allenes.

Readily available phenol-derived biaryls reacted with allenes under palladium catalysis to provide a variety of highly valuable spiro[cyclohexane-1,1'-indene]-2,5-dien-4-ones. This new catalytic process, involving a key step of regioselective allylative dearomatization of phenol, proceeded efficiently through a [3 + 2] spiroannulation pathway by overcoming undesired β-hydride elimination. Preliminary asymmetric studies showed that high enantioselectivity could be realized by using a commercially available PHOX ligand.

Catalytic Enantioselective Tautomerization of Metastable Enamines.

The first example of catalytic enantioselective tautomerization of structurally labile but isolable enamines for accessing their chiral imine-tautomers is described. Kinetically stable enamine-based dibenzo[b,d]azepines were tautomerized by a simple chiral BINOL-phosphoric acid, providing a variety of seven-membered imine products bearing both central and axial stereogenic elements in good yields (up to 96%) with excellent enantio- and diastereoselectivities (up to 97% ee, >20:1 dr).

Rapid Assembly of Diversely Functionalized Spiroindenes by a Three-Component Palladium-Catalyzed C-H Amination/Phenol Dearomatization Domino Reaction.

A novel palladium-catalyzed three-component reaction of phenol-derived biaryls with N-benzoyloxyamines and norbornadiene (NBD) has been developed for the assembly of highly functionalized spiroindenes. This domino process was realized through NBD-assisted C-H amination and phenol dearomatization by forming one C-N bond and two C-C bonds in a single step. Preliminary studies indicated that asymmetric control of this transformation was feasible with chiral ligands.