Cascade Annulation Strategy for Expeditious Assembly of Hydroxybenzo[c]chromen-6-ones and Their Photophysical Property Studies.

A 1,8-diazabicyclo[5.4.0]undec-7-ene-promoted cascade double-annulation of ortho-alkynyl quinone methide (in situ generated from modular propargylamine) for constructing of 2-aryl-4-hydroxybenzo[c]chromen-6-ones is developed. This synthetic strategy offers remarkable operational simplicity as it allows the use of benchtop-grade solvents without the need for predrying measures and inert atmosphere protection. Additionally, it demonstrates good functional group compatibility. The photophysical properties of these compounds were also examined, revealing bright fluorescence with high quantum yields.

Recent Expedition in Pd- and Rh-Catalyzed C(Ar) -B Bond Formations and Their Applications in Modern Organic Syntheses.

Transition metal-catalyzed borylation has emerged as a powerful and versatile strategy for synthesizing organoboron compounds. These compounds have found widespread applications in various aspects, including organic synthesis, materials science, and medicinal chemistry. This review provides a concise summary of the recent advances in palladium- and rhodium-catalyzed borylation from 2013 to 2023. The review covers the representative examples of catalysts, substrates scope and reaction conditions, with particular emphasis on the development of catalyst systems, such as phosphine ligands, NHC-carbene, and more. The diverse array of borylative products obtained for further applications in Suzuki-Miyaura coupling, and other transformations, are also discussed. Future directions in this rapidly evolving field, with the goal of designing more efficient, selective borylation methodologies are highlighted, too.

Facile Assembly of Modular-Type Phosphines for Tackling Modern Arylation Processes.

This Account presents an overview of a promising collection of phosphine ligands simply made from the modular Fischer indolization process and their applications in modern arylation processes. Using one easily accessible 2-arylindole scaffold, three major phosphino-moiety-positioned ligand series can be readily generated. We have attempted to explore challenging electrophilic and nucleophilic partners for the coupling reaction using the modular ligand tool. For the electrophilic partner study, CM-phos-type ligands, where the phosphino group is located at the 2-arene position of 2-arylindole, allow the successful cross-coupling of aryl mesylates. The CM-phos ligand forms a palladacycle before entering the cross-coupling catalytic cycle. For the nucleophilic partner investigation, the indole C3-positioned phosphines show the first accomplishment of Pd-catalyzed organotitanium nucleophile arylation. Indeed, the aryl-titanium nucleophile undergoes cross-coupling more efficiently than does the organoboron coupling partner in particular cases. Moreover, in the indole C3-positioned phosphine series, the -PPh2-containing ligands perform better in the highly sterically hindered cross-coupling of aryl chlorides than do ligands containing the -PCy2 moiety. The catalyst loading can even be reduced to 0.2 mol % Pd for tetra-ortho-substituted biaryl synthesis. This finding offers a new perspective on the next-generation design of phosphine ligands in which the sterically bulky and electron-rich -PR2 group (R = alkyl) may not be necessary for the cross-coupling of aryl chlorides. In general, we hypothesize that a good balance of steric and electronic properties for entertaining the oxidative addition and reductive elimination steps is crucial to the success of the reaction. For the steric factor, the highly sterically congested -PR2 group normally favors the reductive elimination, yet we conjecture that this sterically bulky group would serve as an obstacle for the incoming aryl halides. For the electronic factor, the electron rich -PR2 group is believed to support the oxidative cleavage of the C(Ar)-Cl bond by donating more electron density to the corresponding σ* orbital. Nevertheless, the high electron richness of the -PR2 group may disfavor the reductive elimination electronically. Overall, an appropriate balance of both electron density and steric bulkiness is suggested to allow the sterically hindered cross-coupling to proceed smoothly. We have found that the -PPh2-containing ligand is a good starting point for this investigation. The formation of aromatic carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds from aryl chlorides was successfully realized using our proprietary phosphines.In addition to the indole-core-bearing ligand skeleton, we also explored the relevant imidazolyl and carbazolyl phosphines for their unique applications. Interestingly, the carbazolyl ligand, having more flexible C-N axial chirality, displays particular interchangeable Pd-N and Pd-arene coordination, which facilitates both oxidative addition and reductive elimination processes. Moreover, this C-N axially chiral ligand allows the successful asymmetric Suzuki-Miyaura coupling for attaining the most sterically hindered tetra-ortho-substituted biaryls with excellent enantioselectivity. The rationale behind these scientifically interesting findings is presented in detail.

An expeditious FeCl3-catalyzed cascade 1,4-conjugate addition/annulation/1,5-H shift sequence for modular access of all-pyrano-moiety-substituted chromenes.

ortho-Alkynyl quinone methides are well-known four-atom synthons for direct [4 + n] cycloaddition in constructing useful oxa-heterocyclic compounds owing to their high reactivity as well as the thermodynamically favored aromatization nature of this process. Herein we report an operationally simple and eco-friendly protocol for the modular and regioselective access of (E)-4-(vinyl or aryl or alkynyl)iminochromenes from propargylamines and S-methylated ß-ketothioamides in the presence of FeCl3, and particularly under undried acetonitrile and air atmosphere conditions. This method exhibits a broad substrate scope and displays nice functional group compatibility, thus providing an efficient access of 3,4-disubstituted iminochromenes.

N-Difluoromethylation of N-pyridyl-substituted anilines with ethyl bromodifluoroacetate.

A general protocol for N-difluoromethylation of aniline derivatives is developed. Commercially available ethyl bromodifluoroacetate serves as a difluorocarbene source in the presence of a base. This carbene surrogate is attractive owing to its favorable stability, environmental friendliness and inexpensiveness. This reaction system features notable operational simplicity (bench top-grade solvents can be used without any pre-drying and do not require inert atmosphere protection). A wide range of functional groups in aniline derivatives are well-tolerated, and good-to-excellent product yields are generally obtained.

Cascade Lactonization/Benzannulation of Propargylamines with Dimethyl 3-Oxoglutarate for Modular Assembly of Hydroxylated/Arene-Functionalized Benzo[c]chromen-6-ones.

A DBU-mediated cascade strategy of propargylamines with dimethyl 3-oxoglutarate for constructing a functionalized benzo[c]chromen-6-one core has been achieved. This cascade process presumably involves a sequence of 1,4-conjugate addition, followed by lactonization, alkyne-allene isomerization, enol-keto tautomerization, 6π-electrocyclization, and aromatization. This protocol features mild reaction conditions, simple operation, rich structural diversity, and good functional group tolerance. A photophysical survey reveals that the benzo[c]chromen-6-one products exhibit fluorescence properties and show potential for exploring fluorescent material applications.

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.

A cascade double 1,4-addition/intramolecular annulation strategy for expeditious assembly of unsymmetrical dibenzofurans.

Existing synthetic routes for accessing dibenzofuran core have intrinsic regioselectivity, limiting the substitution patterns available in heteropolycyclic arene products. Here we report a double 1,4-conjugate addition/intramolecular annulation cascade reaction between propargylamines and two equivalents of imidazolium methylides that allows efficient access of structurally versatile dibenzofurans. This transition metal-free protocol proceeds smoothly under bench-top air atmosphere and offers easy manipulation of substituents on the dibenzofuran core, and also provides good-to-excellent product yields with good functional group tolerance, particularly the -Br and -Cl groups which are often incompatible with existing metal-catalyzed C-C and/or C-O bond ring-forming processes. It is worth noting that ladder-type π-systems with all-arene quarternary carbon structure can be straightforwardly generated upon simple late-stage functionalization.

DMAP-Catalyzed Annulation Approach for Modular Assembly of Furan-Fused Chromenes.

With a tandem DMAP-catalyzed reaction between o-AQM, in which it is generated in situ from propargylic amine, and acyl carbene surrogate (from pyridinium ylide), a variety of polyarylated chromenes are assembled in good yields. This process does not require transition-metal catalyst and exhibits easy manipulation of the arene group and good functional group compatibility, particularly the -Br group which can be further transformed to other functionalities by cross-coupling reactions. The modular feature of o-AQM substrates and the simple operation procedures add further advantages to this synthetic method.

Palladium-Catalyzed Monoarylation of Arylhydrazines with Aryl Tosylates.

A palladium-catalyzed C-N bond coupling reaction between arylhydrazines and aryl tosylates for facile synthesis of unsymmetrical N,N-diarylhydrazines has been developed. Employing the catalyst system of Pd(TFA)2 associated with newly developed phosphine ligand L1, the monoarylation of arylhydrazine proceeds smoothly to afford desired products in good-to-excellent yields (up to 95%) with good functional group compatibility. This method provides an alternative synthetic pathway for accessing structurally diversified N,N-diarylhydrazines from simple and easily accessible coupling components.

Rapid Access of Alkynyl and Alkenyl Coumarins via a Dipyridinium Methylide and Propargylamine Cascade Reaction.

A DMAP-catalyzed cascade approach allowing facile assembly of alkynyl coumarins is reported. By virtue of reactive o-AQM (in situ generated from modular propargylamine) and a new synthetic equivalent of acyl carbene (from pyridinium ylide), the reaction proceeds smoothly to afford a variety of alkynyl coumarins in good-to-excellent yields. This transition-metal-free and oxidant-free process features moderate functional group tolerance, particularly the -Br group; thus, this protocol circumvents the inherent shortcomings of the existing Sonogashira coupling of coumarin triflates. This versatile method is also found to be applicable to the preparation of ß-alkenyl coumarins, resembling the outcomes of the current Heck-type coupling reaction.

Organocatalytic Approach for Assembling Flavanones via a Cascade 1,4-Conjugate Addition/oxa-Michael Addition between Propargylamines with Water.

A DBU-catalyzed one-pot cascade reaction of propargylamines and water for the synthesis of flavanones has been developed. This process proceeds via a sequence of 1,4-conjugate addition of water to alkynyl o-quinone methide (o-AQM), followed by the alkyne-allene isomerization and subsequent intramolecular oxa-Michael addition. This strategy provides a convenient method for accessing a broad range of flavanones in good to excellent yields with good functional-group tolerance, in particular, the reactive halo functional groups.

A ZnI2-catalyzed regioselective cascade 1,4-conjugate addition/5-exo-dig annulation pathway for one-pot access to heterobiaryl frameworks.

Facile access to π-extended heterobiaryl compounds via a non-cross-coupling strategy has been achieved. In the presence of an inexpensive ZnI2 catalyst and versatile propargylamine and ß-naphthol (or ß-naphthylamine and ß-naphthyl mercaptan) starting materials, a variety of sterically hindered heterobiaryl frameworks can be easily obtained. The present catalytic system offers excellent selectivity, good-to-excellent product yields, and good functional group tolerance including, for instance, -CN, -COOH, -C(O)R, -Br and -Cl groups. This cyclization process is proposed to proceed via in situ generated alkynyl o-quinone methides (o-AQMs), following a cascade intermolecular 1,4-conjugate addition/5-exo-dig annulation/1,3-H shift pathway.

Palladium-Catalyzed N-Arylation of Sulfoximines with Aryl Sulfonates.

Palladium-catalyzed C-N bond coupling reaction between NH-sulfoximines and aryl halides (e.g., -Br, -I, and -Cl and pseudohalides -OTf and -ONf) was successfully achieved. Nevertheless, aryl tosylates/mesylates left much to be achieved. In this report, a general N-arylation of sulfoximines with aryl sulfonates is described. Using Pd(OAc)2/MeO-CM-phos complex, the N-aryl sulfoximine products can be obtained in good-to-excellent yields (up to 99%) with good common functional group compatibility. In addition to arene moieties, alkenyl tosylates are shown to be successful coupling partners.

A General Palladium-Phosphine Complex To Explore Aryl Tosylates in the N-Arylation of Amines: Scope and Limitations.

The scope and limitations of the monoselective N-arylation of various amines by using aryl and hetaryl tosylates are presented. The air-stable and easily accessible Pd(OAc)2 /CM-phos {CM-phos=2-[2-(dicyclohexylphosphino)phenyl]-1-methyl-1H-indole}catalyst system was able to deal with a wide range of aryl tosylate substrates as well as amine nucleophiles, including primary and secondary cyclic/acyclic aliphatic amines and anilines. NH-Bearing heterocycles such as indole, carbazole, pyrrole, 10-phenothiazine, and 10-phenoxazine were shown to be feasible coupling partners under this catalytic system. The described reaction conditions tolerate a wide range of functional groups and allow an array of aromatic amines as well as unsymmetrical amine products to be easily accessed from the various phenolic derivatives. Interestingly, this catalyst system even offers the opportunity to perform the reaction in water medium. We also report the intermolecular coupling of optically active α-central chiral amines with aryl tosylates without erosion of the enantiomeric purity.

Palladium-catalysed mono-α-alkenylation of ketones with alkenyl tosylates.

The first example of palladium-catalysed selective mono-α-alkenylation of ketones with alkenyl tosylates is described. In the presence of a Pd/XPhos catalyst system (0.1-1.0 mol%), the reaction provides mono-α-alkenylated ketones in good yields and exhibits excellent substrate tolerance. Highly congested, tri- and tetra-substituted alkenyl tosylates react smoothly and even problematic heteroaryl and aliphatic ketones are applicable substrates. Notably, small ß,γ-unsaturated ketones are successfully prepared using acetone as a simple three-carbon feedstock.

Oxidative coupling between C(sp²)-H and C(sp³)-H bonds of indoles and cyclic ethers/cycloalkanes.

Cross-dehydrogenative-coupling (CDC) between C-H/C-H bonds of indoles and cyclic ethers/cycloalkanes is made viable through a simple transition-metal-free pathway. With the aid of only di-tert-butyl peroxide, a number of inactive cyclic ethers and cycloalkanes can be directly coupled with indole derivatives in satisfactory yields.

Copper-Catalyzed Oxidative C-H Amination of Tetrahydrofuran with Indole/Carbazole Derivatives.

A simple α-C-H amination of cyclic ether with indole/carbazole derivatives has been accomplished by employing copper(II) chloride/bipy as the catalyst system. In the presence of the di-tert-butyl peroxide oxidant, cyclic ethers such as tetrahydrofuran, 1,4-dioxane, and tetrahydropyran successfully undergo C-H/N-H cross dehydrogenative coupling (CDC) with various carbazole or indole derivatives in good-to-excellent yields.

Regioselective direct C-3 arylation of imidazo[1,2-a]pyridines with aryl tosylates and mesylates promoted by palladium-phosphine complexes.

Direct C-3 arylation of imidazo[1,2-a]pyridines with aryl tosylates and mesylates has been accomplished by employing palladium(II) acetate associated with SPhos (2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl) or L1 (2-(2-(diisopropylphosphino)phenyl)-1-methyl-1H-indole). This catalyst system can be applied to a wide range of aryl sulfonates and shows excellent C-3 regioselectivity of imidazo[1,2-a]pyridine. These results represent the first examples of using tosylate- and mesylate-functionalized arenes as the electrophile partners for this regioselective direct arylation.

Direct intermolecular C-H arylation of unactivated arenes with aryl bromides catalysed by 2-pyridyl carbinol.

Direct intermolecular C-H arylation employing aryl bromide as the arene source has been developed. This process proceeds via a simple transition-metal-free pathway. With the aid of inexpensive and commercially available 2-pyridyl carbinol and potassium tert-butoxide, various unactivated arene C-H bonds can be directly arylated by aryl bromides through homolytic aromatic substitution.