A General Method for the Synthesis of 5H‐Benzo[b]‐, Carbazolo[2,3‐b]‐ and Indolo[2,3‐b]carbazole Derivatives via Copper(II) Triflate‐Catalyzed Heteroannulation

A straightforward approach for the construction of 5H‐benzo[b]‐, carbazolo[2,3‐b]‐ and indolo[2,3‐b]carbazole derivatives has been developed by using copper(II) triflate‐catalyzed heteroannulation.     

Microwave‐Assisted Facile Synthesis of Furo[3,2‐b]indole Derivatives via Silver(I)‐Mediated [3+2] Cycloaddition

A robust one‐pot process has been developed for the synthesis of a variety of furo[3,2‐b]indoles from readily available o‐propargylaminoacetophenones via silver(I)‐mediated [3+2] cycloaddition.     

Gold(I)‐Catalyzed Cascade for Synthesis of Pyrrolo[1,2‐a:2′,1′‐c]‐/Pyrido[2,1‐c]pyrrolo[1,2‐a]quinoxalinones

An efficient and convenient method was developed for the one‐pot construction of the complex polycyclic heterocycles pyrrolo[1,2‐a:2′,1′‐c]‐/pyrido[2,1‐c]pyrrolo[1,2‐a]quinoxalinones from two simple starting materials via a gold(I)‐catalyzed domino reaction. This strategy presents an atom economical and environmentally friendly transformation, in which two new C N bonds and one new C C bond are formed in a one‐pot reaction process.     

Copper‐Catalyzed Domino Synthesis of Benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones using Cyanamide as a Building Block

An efficient and practical copper‐catalyzed domino synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones has been developed. The protocol uses N‐(2‐halophenyl)‐3‐alkylpropiolamides and cyanamide as the starting materials, inexpensive copper(I) iodide and pipecolinic acid as the catalyst and ligand, and the corresponding products were obtained in moderate to good yields.

     

Copper‐Catalyzed Domino Synthesis of Isoquinolino[2,3‐a]quinazolinones

A copper‐catalyzed domino method for synthesis of isoquinolino[2,3‐a]quinazolinones has been developed using readily available, substituted methyl 2‐(2‐haloobenzamido)benzoates and nitriles as the starting materials. The domino process comprises an Ullmann‐type C‐arylation, intramolecular addition of NH with CN, and nucleophilic attack of amino to ester group. The inexpensive, convenient and efficient copper‐catalyzed method should provide a new and useful strategy for constructing nitrogen heterocycles.     

Assembly of Enantioenriched cis‐3a,8a‐Hexahydropyrrolo[2,3‐b]indole Scaffolds by Silver(I)‐Catalyzed Asymmetric Domino Reaction of Isocyanoacetates in the Presence of Cinchona‐Derived Chiral Phosphorus Ligands

By using Cinchona‐derived chiral phosphines as catalytic ligands, enantioenriched cis‐3a,8a‐hexahydropyrrolo[2,3‐b]indoles (ent‐HPIs), which are core scaffolds in a large array of biologically active natural products, can be convergently assembled under mild conditions through the silver(I)‐catalyzed asymmetric domino reaction of readily available isocyanoacetates and 2‐(2‐aminophenyl)acrylates. Various functionalities can be tolerated in the reaction, affording enantioenriched HPIs in high overall yields and good enantioselectivities (up to 92% ees).

     

Synthesis of Optically Active 2H‐Thiopyrano[2,3‐b]quinolines with Three Contiguous Stereocenters via an Organocatalytic Asymmetric Tandem Michael–Henry Reaction

Optically active 2H‐thiopyrano[2,3‐b]quinolines with three contiguous stereocenters have been synthesized via a chiral bifunctional squaramide‐catalyzed tandem Michael–Henry reaction between 2‐mercaptoquinoline‐3‐carbaldehydes and nitroolefins. The reactions proceed with excellent diastereo‐ and enantioselectivity to give the title compounds in high yields with high levels of diastereo‐ and enantioselectivity (up to >99/1 dr and >99% ee, respectively).     

Efficient Synthesis of Chiral Isoquinoline and Pyrido[1,2‐b]‐isoquinoline Derivatives via Intramolecular Heck Reactions

The palladium(0)‐catalyzed reaction of derivatives of γ‐amino‐α,β‐unsaturated esters bearing an N‐(2‐iodobenzoyl) substituent results in an intramolecular Heck reaction, the outcome of which depends on the structure of the substrate as well as on the experimental conditions. The methodology developed has been applied to the efficient syntheses of chiral isoquinoline and pyrido[1,2‐b]–isoquinoline derivatives.     

Microwave‐Assisted Synthesis of Pyrazino[2,1‐b]quinazolines and 3‐Indolyl‐2(1H)‐pyrazinones Employing a Chemoselective Silver(I)‐ and Gold(I)‐Catalyzed Reaction

Novel microwave‐assisted syntheses of pyrazino[2,1‐b]quinazolines and 3‐indolyl‐2(1H)‐pyrazinones employing silver(I)‐ or gold(I)‐catalyzed protocols have been elaborated. The scope and limitations of these processes have been investigated.     

Benzo[b]tryptanthrin Inhibits MDR1, Topoisomerase Activity,and Reverses Adriamycin Resistance in Breast Cancer Cells

Tryptanthrin is an indoloquinazoline alkaloid isolated from indigo. Tryptanthrin and its benzo‐annulated derivative, benzo[b]tryptanthrin, inhibit both topoisomerases I (topo I) and II (topo II) and cause cytotoxicity in several human cancer cell lines. From diverse assessment methods, including cleavage complex stabilization, comet, DNA unwinding/intercalation, topo II ATPase inhibition, ATP competition for topo II, and wound‐healing assays, we determined that the mode of action of benzo[b]tryptanthrin is as a DNA non‐intercalative and ATP‐competitive topo I and II dual catalytic inhibitor. Benzo[b]tryptanthrin induced apoptosis through the cleavage of caspase‐3 and PARP in HCT15 colon cancer cells. Additionally, benzo[b]tryptanthrin reversed adriamycin resistance by down‐regulation of multidrug resistance protein 1 (MDR1) in adriamycin‐resistant MCF7 breast cancer cells (MCF7adr) with more potent inhibitory activity than tryptanthrin. Taken together, derivatization by benzo‐annulation of tryptanthrin ameliorated the MDR‐reversing effect of tryptanthrin and may pave the way to the discovery of a novel potent adjuvant agent for chemotherapy.     

Palladium‐Catalyzed Intramolecular Annulation of 3‐[2‐(2‐Iodobenzylamino)aryl]‐N‐arylpropiolamides: Synthesis of 3‐[5H‐Dibenzo[b,e]azepin‐11(6H)‐ylidene]indolin‐2‐ones

A novel palladium‐catalyzed intramolecular tandem annulation method is presented for the synthesis of 3‐[5H‐dibenzo[b,e]azepin‐11(6H)‐ylidene]indolin‐2‐ones. This method allows the conversion of various 3‐[2‐(2‐iodobenzylamino)aryl]‐N‐arylpropiolamides to the corresponding 3‐[5H‐dibenzo[b,e]azepin‐11(6H)‐ylidene]indolin‐2‐ones through the diarylation of an alkyne.     

Facile Palladium‐Catalyzed Synthesis of 3‐Arylpyrazolo[1,5‐a]pyrimidines

An efficient palladium‐catalyzed synthesis of 3‐arylpyrazolo[1,5‐a]pyrimidines has been investigated. The key step in the synthesis is a Suzuki biaryl coupling of 3‐bromo‐2,5‐dimethyl‐7‐aminopyrazolo[1,5‐a]pyrimidines with arylboronic acids to provide 3‐arylpyrazolo[1,5‐a]pyrimidines in moderate to good yield. The synthetic utility of this methodology has been demonstrated by a concise and convergent synthesis of R121920, a potent CRHR₁ antagonist recently undergoing clinical evaluations.     

Studies on Palladium‐Catalyzed Synthesis of Dihydrocycloocta‐ [b]indoles and their Thermal Reactivities with Maleimide or Maleic Anhydride

A palladium(0)‐catalyzed reaction of 2‐allyl‐3‐indolyl boronates/propargylic carbonates was observed to afford dihydrocycloocta[b]indoles highly efficiently via carbon‐carbon coupling, [1,5]‐hydrogen migration involving dearomatization, and electrocyclization involving rearomatization. Their thermal reactions with the addition of dienophiles involving eletrocyclization and [4+2] cycloaddition have been studied.

     

Impact of alkyl side chain on the photostability and optoelectronic properties of indacenodithieno[3,2‐b]thiophene‐alt‐naphtho[1,2‐c:5,6‐ c′]bis[1,2,5]thiadiazole medium bandgap copolymers

Three donor‐π‐acceptor (D‐π‐A) type alternating conjugated polymers, namely PIDTT‐DTNT‐C16, PIDTT‐DTNT‐HD and PIDTT‐DTNT‐OD bearing the same backbone of indacenodithieno[3,2‐b]thiophene (IDTT) as the D unit and naphtho[1,2‐c:5,6‐c′]bis[1,2,5]thiadiazole (NT) as the A moiety but with different flexible side chain (n‐hexadecyl (C16), 2‐hexyldecyl (HD) and 2‐octyldodecyl (OD)) substituted thiophene employed as π‐bridges, were synthesized and characterized. The effects of the side chain on absorption, photostability, energy levels, aggregation, backbone conformation, morphology and photovoltaic properties were systematically investigated. Because moderate D and strong A units were selected to construct the polymer backbone, a medium optical bandgap (ca. 1.66 eV) and low‐lying highest occupied molecular orbital energy level (E_HOMO ≈ ?5.36 V), thus resulting in a relatively higher open‐circuit voltage (V_OC) of 0.80–0.83 V, were achieved. It was found that the side chain gave rise to an insignificant impact on absorption, aggregation and photostability in chlorobenzene solution and energy levels but a non‐negligible influence on absorption, photostability and aggregation behavior in the film state. It was found that PIDTT‐DTNT‐C16 with the densest and most ordered packing structure exhibited the best photostability. Inverted bulk heterojunction polymer solar cells based on PIDTT‐DTNT‐HD:PC₆₁BM ([6,6]‐phenyl‐C₆₁‐butyric acid methyl ester) showed at least a 1.5‐fold increase in power conversion efficiency, chiefly originating from its slightly improved absorption, more balanced μ_h/μ_e ratio and favorable morphology of the active layer as a result of incorporating branched HD side chains into the IDTT‐alt‐DTNT backbone. © 2019 Society of Chemical Industry     

Synthesis of 2,3‐Diarylbenzo[b]thiophenes via Nickel‐Catalyzed Suzuki–Miyaura Cross‐Coupling and Palladium‐Catalyzed Decarboxylative Arylation

We report a new approach to 2,3‐diarylbenzo[b]thiophenes based on the nickel‐catalyzed Suzuki–Miyaura cross‐coupling/palladium‐catalyzed decarboxylative arylation sequence of 3‐chloro‐2‐methoxycarbonylbenzo[b]thiophenes, which are readily accessible from the corresponding cinnamic acids. In addition, this methodology can be applied to the concise synthesis of π‐extended 2,3,6,7‐tetraarylbenzo[1,2‐b;4,5‐b′]dithiophenes. Their optical properties are also described.     

Palladium‐Catalyzed Direct Arylations of 1,2‐Azolo[1,5‐a]pyridines using Copper(I) Chloride as a Lewis Acid Activator and the Synthesis of 2,6‐Disubstituted Pyridines

A direct method for the arylation of 1,2‐azolo[1,5‐a]pyridines has been developed. In the process, the fused pyridines react with aryl halides in the presence of the palladium complex Pd(OAc)₂(Phen) as a catalyst and copper(I) chloride (CuCl) as a Lewis acid to form arylated derivatives. While pyrazolo[1,5‐a]pyridines and [1,2,4]triazolo[1,5‐a]pyridines are arylated at ortho‐positions of their pyridine rings using this method, in situ ring‐opening of the formed C‐7 arylated [1,5‐a]pyridine takes place to generate the 2,6‐disubstituted pyridine. Also, upon treatment with lithium diisopropylamide (LDA), C‐7 arylated pyrazolo[1,5‐a]pyridine‐3‐carboxylates react to produce diversely substituted 2,6‐disubstituted pyridines. Finally, a sequential C‐3 arylation was accomplished through a two‐step sequence involving hydrolysis of pyrazolo[1,5‐a]pyridine‐3‐carboxylates followed by the bimetallic Pd/Cu‐catalyzed decarboxylative coupling reaction with aryl bromide.

     

2,3‐Disubstituted Benzo[b]thiophenes from Diarylalkynes via Electrophilic Addition‐Cyclization and Palladium‐Catalyzed Cross‐Coupling

Diarylalkynes are readily transformed in 3‐chlorobenzo[b]thiophenes in a two‐step electrophilic addition‐cyclization procedure that runs highly efficiently in solution or in the solid phase. The heteroaromatic carbon‐chlorine bond participates in palladium‐catalyzed Suzuki–Miyaura or Buchwald–Hartwig cross‐couplings to give, in a single step, 2,3‐disubstituted derivatives of pharmacological relevance .     

Copper(I)‐Catalyzed Synthesis of Novel 4‐(Trifluoromethyl)‐[1,2,3]triazolo[1,5‐a]quinoxalines via Cascade Reactions of N‐(o‐Haloaryl)alkynylimine with Sodium Azide

Novel tricyclic 4‐(trifluoromethyl)‐[1,2,3]triazolo[1,5‐a]quinoxalines were readily prepared from N‐(o‐haloaryl)alkynylimines and sodium azide via copper(I)‐catalyzed tandem reactions. This synthetic strategy provides an efficient way to access a library of novel heterocyclic compounds that are of interest in drug discovery.     

Copper(I)‐Catalyzed [3+2] Cycloaddition/Ring‐Opening Rearrangement/[4+2] Cycloaddition/Aromatization Cascade: An Unprecedented Chemo‐ and Stereoselective Three Component Coupling of Sulfonyl Azide,Alkyne and N‐Arylidenepyridin‐2‐ amine to Pyrido[1,2‐a]pyrimidin‐4‐imine

A novel synthetic protocol for the one‐pot chemo‐ and stereoselective construction of diversely functionalized pyrido[1,2‐a]pyrimidin‐4‐imines via copper(I)‐catalyzed [3+2] cycloaddition/ring‐opening rearrangement/[4+2] cycloaddition/aromatization cascade of sulfonyl azides, alkynes and N‐arylidenepyridin‐2‐amines under mild reaction conditions is reported. In addition, the catalytic activity of copper(I)‐modified zeolite, a recyclable, heterogeneous catalyst is also investigated, which gives improved yield compared to its homogeneous equivalents.     

Simple and Efficient Copper(I)‐Catalyzed Access to Three Versatile Aminocoumarin‐Based Scaffolds using Isocyanoacetate

An efficient method has been developed for the one‐pot copper(I)‐catalyzed synthesis of 3‐aminocoumarin and its derivatives, such as 3‐substituted methylideneaminocoumarins and chromeno[3,4‐d]imidazol‐4(1H)‐ones. Significantly, the strategy presents a straightforward and efficient approach to constructing biologically useful molecular scaffolds.