A Cascade C(sp3)-H Annulation Involving C(alkyl),C(alkyl)-Palladacycle Intermediates.

C-H bond functionalization involving C,C-palladacycle intermediates provides a unique platform for developing novel reactions. However, the vast majority of studies have been limited to the transformations of C(aryl),C-palladacycles. In sharp contrast, catalytic reactions involving C(alkyl),C(alkyl)-palladacycles have rarely been reported. Herein, we disclose an unprecedented cascade C(sp3)-H annulation involving C(alkyl),C(alkyl)-palladacycles. In this protocol, alkene-tethered cycloalkenyl bromides undergo intramolecular Heck/C(sp3)-H activation to generate C(alkyl),C(alkyl)-palladacycles, which can be captured by α-bromoacrylic acids to afford tricyclic fused pyridinediones. In addition, this strategy can also be applied to indole-tethered cycloalkenyl bromides to construct pentacyclic fused pyridinediones via suquential Heck dearomatization/C(sp3)-H activation/decarboxylative cyclization. Notably, the removal of α-bromoacrylic acids in the reaction of alkene-tethered cycloalkenyl bromides can build an interesting tricyclic skeleton containing a four-membered ring. Preliminary mechanistic experiments indicate that five-membered C(alkyl),C(alkyl)-palladacycles serve as the key intermediates. Meanwhile, density functional theory (DFT) calculations have provided insights into the reaction pathway.

Norbornene Derivatives-Controlled Palladium-Catalyzed Divergent Synthesis of Dibenzo[a,c]cycloheptenones and Fluorenones from Aryl Iodides and α-Oxocarboxylic Acids.

A palladium-catalyzed divergent cascade decarboxylative annulation of aryl iodides and α-oxocarboxylic acids using norbornene (NBE) derivatives as a controlled switch is reported. When NBE is used as a mediator, fluorenones are synthesized with moderate to excellent yields via a Catellani reaction that involves sequential ortho-C-H arylation and ipso-decarboxylative acylation of aryl iodides. Employing oxanorbornadiene (ONBD) instead of NBE enables the assembly of dibenzo[a,c]cycloheptenones by a retro-Diels-Alder reaction rather than the release of an ONBD. Additionally, the synthetic utility of this method is demonstrated by the diversification of the products.

Versatile Tetrasilane for Time-Controlled Palladium-Catalyzed Divergent Synthesis of Silacycles via C-H Activation.

Transition-metal-catalyzed intermolecular annulation of silicon reagents with organic molecules is still underdeveloped due to the scarcity of silicon reagent types and their diverse reactivity. Herein, a readily accessible silicon reagent (octamethyl-1,4-dioxacyclohexasilane) has been developed for divergent synthesis of silacycles via time-controlled palladium-catalyzed cascade C-H silacyclization. This protocol enables the rapid and selective transformation of acrylamides into spirosilacycles with different ring sizes, including benzodioxatetrasilecines, benzooxadisilepines, and benzosiloles, in moderate to good yields through a time switch. Notably, the tetrasilane reagent can also be utilized for C-H silacyclization of 2-halo-N-methacryloylbenzamides and 2-iodobiphenyls, leading to diverse fused silacycles. Furthermore, several synthetic transformations of products are achieved. A series of mechanistic studies demonstrate the transformation relationships and possible pathways among ten-, seven-, and five-membered silacycles.

Pd(II)-Catalyzed Synthesis of Polycyclic Heteroarenes via an Aminopalladation/C-H Activation/Dealkylation/Decarboxylative Cyclization Cascade.

Until now, cascade reactions involving five-membered C,C-palladacycles rely heavily on Pd(0)-catalyzed C-H functionalization of aryl halides initiated by carbopalladation. Herein, we report a novel Pd(II)-catalyzed cascade decarboxylative cyclization of o-alkynylanilines initiated by aminopalladation. In this protocol, o-alkynylanilines undergo sequential anti aminopalladation, C-H activation, and dealkylation to form C,C-palladacycles, which are then trapped by o-bromobenzoic acids or 8-bromo-1-naphthoic acid to produce diverse polycyclic heteroarenes, such as dibenzo[a,c]carbazoles and multiple arene-fused cyclohepta[1,2-b]indoles.

Research advances in palladium-catalysed intermolecular C-H annulation of aryl halides with various aromatic ring precursors.

Transition-metal-catalysed C-H functionalization has emerged as a powerful approach for the transformation of organic molecules due to its high atom and step economy. Palladium-catalysed intermolecular C-H annulation of aryl halides, especially those involving annulation of a five-membered C,C-palladacycle with coupling reagents, have attracted considerable attention in the past decades. This review summarizes the progress on palladium-catalysed intermolecular C-H annulation of aryl halides with various aromatic ring precursors. Mechanistically, five-membered C,C-palladacycles as intermediates are involved in the majority of reactions.

Chemoselective Transformations of Cyclic ß-Bromoacrylic Acids with Palladacycles Formed by Aryl Iodides to Access Fused or Spiro Polycycles.

A palladium-catalyzed chemoselective decarboxylative annulation of different aryl iodides with cyclic ß-bromoacrylic acids for the construction of interesting fused and spiro polycycles is disclosed. Notably, cyclic ß-bromoacrylic acids can chemoselectively act as C1 or C2 insertion units by the use of different aryl iodides. 2-Iodo-N-methacryloylbenzamides can undergo a Heck/[4+2] annulation to afford hexahydrodibenzoisoquinoline-4,6(5H)-diones. Employing 2-iodobiphenyls or N-(2-iodophenyl)-2-phenylacrylamides as substrates enables the assembly of spirofluorenes and dispirooxindoles.

Double C-S bond formation via multiple Csp3-H bond cleavage: synthesis of 4-hydroxythiazoles from amides and elemental sulfur under metal-free conditions.

A novel and efficient approach for the synthesis of 4-hydroxythiazoles from amides and elemental sulfur has been developed. In the presence of P2O5, DMSO and HMPA, this metal-free protocol proceeds smoothly and tolerates a spectrum of functional groups. Furthermore, this strategy involves the process of double Csp3-S bond formation through the cleavage of multiple Csp3-H bonds for the first time.

Me3SiSiMe2(O n Bu): a disilane reagent for the synthesis of diverse silacycles via Brook- and retro-Brook-type rearrangement.

Herein, a readily available disilane Me3SiSiMe2(O n Bu) has been developed for the synthesis of diverse silacycles via Brook- and retro-Brook-type rearrangement. This protocol enables the incorporation of a silylene into different starting materials, including acrylamides, alkene-tethered 2-(2-iodophenyl)-1H-indoles, and 2-iodobiaryls, via the cleavage of Si-Si, Si-C, and Si-O bonds, leading to the formation of spirobenzosiloles, fused benzosiloles, and π-conjugated dibenzosiloles in moderate to good yields. Preliminary mechanistic studies indicate that this transformation is realized by successive palladium-catalyzed bis-silylation and Brook- and retro-Brook-type rearrangement of silane-tethered silanols.

Assembly of Furazan-Fused Quinolines via an Expeditious Metal-Free [2+2+1] Radical Tandem Cyclization Process.

A [2+2+1]-NO-segment-incorporating heteroannulative cascade is described. This versatile method, particularly using modular cyanoarylated ketimine substrates, allows efficient access to structurally diversified quinolines embedded with an oxadiazole core. This metal-free protocol proceeds smoothly at 30 °C, offers easy manipulation of substituents on the quinoline moiety, and tolerates a spectrum of functional groups. Density functional theory calculation revealed that the cyano moiety is crucial to facilitate the early cyclization step in this heteroannulation process and is different from the previously established late cyclization mechanistic interpretation.

Atmosphere-Controlled Palladium-Catalyzed Divergent Decarboxylative Cyclization of 2-Iodobiphenyls and α-Oxocarboxylic Acids.

A novel palladium-catalyzed divergent decarboxylative cyclization of 2-iodobiphenyls and α-oxocarboxylic acids utilizing the atmosphere as a controlled switch is reported. Under the protection of a nitrogen atmosphere, tribenzotropones are synthesized by a [4 + 3] decarboxylative cyclization. Employing a palladium/O2 system enables a [4 + 2] decarboxylative cyclization to assemble triphenylenes. Notably, preliminary mechanistic studies indicate that the formation of triphenylenes involves a double decarboxylation.

α-Bromoacrylic Acids as C1 Insertion Units for Palladium-Catalyzed Decarboxylative Synthesis of Diverse Dibenzofulvenes.

Herein α-bromoacrylic acids have been employed as C1 insertion units to achieve the palladium-catalyzed [4 + 1] annulation of 2-iodobiphenyls, which provides an efficient platform for the construction of diverse dibenzofulvenes. This protocol enables the formation of double C(aryl)-C(vinyl) bonds via a C(vinyl)-Br bond cleavage and decarboxylation. It is particularly noteworthy that the method features a broad substrate scope, and various interesting frameworks, such as bridged ring, fused (hetero)aromatic ring, and divinylbenzene, can be successfully incorporated into the products.

α-Oxocarboxylic Acids as Three-Carbon Insertion Units for Palladium-Catalyzed Decarboxylative Cascade Synthesis of Diverse Fused Heteropolycycles.

A novel palladium-catalyzed decarboxylative cascade cyclization for the assembly of diverse fused heteropolycycles by employing α-oxocarboxylic acids as three-carbon insertion units is reported. This protocol enables the synthesis of isoquinolinedione- and indolo[2,1-a]isoquinolinone-fused benzocycloheptanones in moderate to good yields by the use of different aryl iodides, including alkene-tethered 2-iodobenzamides and 2-(2-iodophenyl)-1H-indoles. Notably, the approach achieves simultaneous construction of both six- and seven-membered rings via sequential intramolecular carbopalladation, C-H activation, and decarboxylation.

Palladium-Catalyzed [4 + 3] or [2 + 2 + 3] Annulation via C-H Activation and Subsequent Decarboxylation: Access to Heptagon-Embedded Polycyclic Aromatic Hydrocarbons.

The construction of a seven-membered ring in the polycyclic aromatic hydrocarbon skeleton remains a notoriously difficult but attractive challenge. Herein a novel palladium-catalyzed [4 + 3] decarboxylative annulation of 2-iodobiphenyls with 2-(2-halophenyl)acrylic acids is reported, which provides an efficient approach for assembling various tribenzo[7]annulenes via a C-H activation and decarboxylation process. Moreover, tribenzo[7]annulenes can be also synthesized via a [2 + 2 + 3] decarboxylative annulation strategy by employing readily available 1,2-halobenzenes, phenylboronic acids, and 2-(2-halophenyl)acrylic acids.

Catalyst- and Additive-Free Method for the Synthesis of 2-Substituted Benzothiazoles from Aromatic Amines, Aliphatic Amines, and Elemental Sulfur.

Under catalyst- and additive-free conditions, a novel, convenient, environmentally friendly method was developed for the synthesis of 2-substituted benzothiazoles via the three-component one pot reaction from aromatic amines, aliphatic amines, and elemental sulfur. The reaction achieves double C-S and one C-N bond formations via cleavage of two C-N bonds and multiple C-H bonds. Furthermore, the mechanism research shows that DMSO acts as an oxidant in the cyclization reaction.

K2S as Sulfur Source and DMSO as Carbon Source for the Synthesis of 2-Unsubstituted Benzothiazoles.

We describe a three-component reaction of o-iodoanilines with K2S and DMSO that provides 2-unsubstituted benzothiazoles in moderate to good isolated yields with good functional group tolerance. Electron-rich aromatic amines and o-phenylenediamines instead of o-iodoanilines provided 2-unsubstituted benzothiazoles and 2-unsubstituted benzimidazoles with and without K2S under similar conditions. Notably, DMSO plays three vital roles: carbon source, solvent, and oxidant.

Iodine-Catalyzed Three-Component Cascade Reaction for the Synthesis of Substituted 2-Phenylnaphtho[1,3]selenazoles under Transition-Metal-Free Conditions.

An efficient molecular iodine-catalyzed three-component cascade reaction for the construction of 2-phenylnaphtho[2,1-d]selenazoles from naphthalen-2-amine, aldehydes, and selenium powder has been developed. The present approach has the advantages of metal-free conditions, simple operation, and available raw materials. Moreover, the mechanism of the study proved that the reaction underwent a radical process.

Palladium-Catalyzed Domino Heck/C-H Activation/Decarboxylation: A Rapid Entry to Fused Isoquinolinediones and Isoquinolinones.

A new palladium-catalyzed tandem cyclization of various alkene-tethered aryl iodides has been presented. In this protocol, o-bromobenzoic acids are employed as coupling parters to achieve the insertion of aromatic rings by the cleavage of C(sp2)-Br and decarboxylation, thus assembling various dibenzoisoquinolinediones and dibenzoisoquinolinones. In addition, a seven-membered ring can be constructed by the use of 8-bromo-1-naphthoic acid. Notably, this approach enables regioselective product formation and features broad substrate scope.

Palladium-Catalyzed Cascade Cyclization of Alkene-Tethered Aryl Halides with o-Bromobenzoic Acids: Access to Diverse Fused Indolo[2,1-a]isoquinolines.

A novel palladium-catalyzed cascade cyclization of alkene-tethered aryl halides with o-bromobenzoic acids is described, which provides an efficient avenue for building various fused hexacyclic scaffolds containing indolo[2,1-a]isoquinoline in moderate to excellent yield. The method enables the construction of three C-C bonds through an intramolecular carbopalladation, C-H activation, and a decarboxylation sequence. Furthermore, dihydrocyclohepta[de]naphthalene-fused indolo[2,1-a]isoquinolines can be synthesized in moderate yield by constructing a seven-membered ring.

NBE-Controlled Palladium-Catalyzed Interannular Selective C-H Silylation: Access to Divergent Silicon-Containing 1,1'-Biaryl-2-Acetamides.

A novel palladium-catalyzed interannular selective C-H silylation of 1,1'-biaryl-2-acetamides is described. The combination of palladium catalyst with copper oxidant enables meta- or ortho-selective C-H silylation by employing hexamethyldisilane as a trimethylsilyl source, which relies on the control of NBE derivatives as a switch, thus providing straightforward access to divergent silicon-containing 1,1'-biaryl-2-acetamides.

Transition-Metal-Free Sulfuration/Annulation of Alkenes: Economical Access to Thiophenes Enabled by the Cleavage of Multiple C-H Bonds.

A novel, atom economical, and transition-metal-free strategy for the synthesis of thiophenes from substituted buta-1-enes with potassium sulfide has been presented. The reaction achieves double C-S bond formations via cleavage of multiple C-H bonds and provides an efficient approach to access various functionalized thiophenes. Moreover, the strategy can also be used for the synthesis of thiophenes from 1,4-diaryl-1,3-dienes. Mechanistically, DMSO plays a role of oxidant and S3•- in situ generated from K2S is involved.