Quinoxaline-based azamacrocycles: synthesis, AIE behavior and acidochromism.

The development of luminescent molecular materials has advanced rapidly in recent decades, primarily driven by the synthesis of novel emissive compounds and a deeper understanding of excited-state mechanisms. Herein, we report a streamlined synthetic approach to light-emitting diazapolyoxa- and polyazamacrocycles N2CnOxQ and NyCnQ (n = 3-10; x = 2, 3; y = 2-5), incorporating a 2,3-diphenylquinoxaline residue (DPQ). This synthetic strategy based on macrocyclization through Pd-catalyzed amination reaction yields the target macrocycles in good or high yields (46-92%), enabling precise control over their structural parameters. A key role of the PhPF-tBu ligand belonging to the JosiPhos series in this macrocyclization was elucidated through DFT computation. This macrocyclization reaction eliminates the need for complex protecting-deprotecting procedures of secondary amine groups, offering a convenient and scalable method for the preparation of target compounds. Moreover, it boasts a potentially broad substrate scope, making it promising for structure-properties studies within photophysics, sensor development, and material synthesis. Photophysical properties of representative macrocycles were investigated, employing spectroscopic techniques and DFT computation. It was demonstrated that DPQ-containing macrocycles display aggregation-induced emission in a DCM-hexane solvent mixture despite the presence of flexible tethers within their structures. Single-crystal X-ray diffraction analysis of a representative compound N2C8O3Q allowed us to gain deeper insight into its molecular structure and AIE behaviour. The emissive aggregates of the N2C10O3Q macrocycle were immobilized on filter paper yielding AIE-exhibiting test strips for measuring acidity in vapors and in aqueous media.

Ruthenium(II) complexes with phosphonate-substituted phenanthroline ligands as reusable photoredox catalysts.

Ru(II) complexes with polypyridyl ligands (2,2'-bipyridine = bpy, 1,10-phenanthroline = phen) play a central role in the development of photocatalytic organic reactions. In this work, we synthesized four mixed-ligand [Ru(phen)(bpy)2]2+-type complexes (Ru-Pcat-A) bearing two phosphonate substituents P(O)(OH)(OR) (R = H, Et) attached to the phen core at positions 3,8 (Ru-3,8PH and Ru-3,8PHEt) and 4,7 (Ru-4,7PH and Ru-4,7PHEt) of the heterocycle in high yields (87-99%) and characterized them using spectral methods. Single crystal X-ray diffraction was employed to determine the coordination mode of the ditopic phen ligand in Ru-4,7PH. This complex exists as the neutral species and forms a 1D hydrogen-bonded framework in the crystals. The light absorption characteristics were found to be similar for all complexes prepared in this work. However, the emission maxima in aqueous solutions were significantly affected by the substitution of the heterocycle, ranging from 629 nm for Ru-4,7PH to 661 nm for Ru-3,8PHEt. The emission quantum yields in Ar-saturated deionized water showed a strong dependence on the substitution pattern of the phen ligand, with maximal values reaching approximately 0.11 for Ru-4,7PHEt and Ru-4,7PH, which is twice as high as that of the classical [Ru(bpy)3]2+ complex (Ru-bpy). The photocatalytic performance of Ru-Pcat-A was investigated using visible light photoredox catalytic transformations of tertiary amines. With Ru-Pcat-A, we achieved the phosphonylation of N-aryl-1,2,3,4-tetrahydroisoquinolines (THIQs) and cyanation of THIQs and N,N-dimethylaniline in methanol, while a mixture of nitromethane/methanol (1 : 1 v/v) proved to be the optimal solvent for conducting the nitromethylation of THIQs. In the majority of the studied reactions, Ru-4,7PHEt exhibited greater efficiency compared to Ru-bpy, and it could be easily separated from the products using water extraction and reused in the next catalytic cycle. We successfully performed seven consecutive nitromethylation and phosphonylation of N-phenyl-1,2,3,4-tetrahydroisoquinoline using the recycled homogeneous photoredox catalyst.

Switchable Selectivity in the Annulation of o-Trifluoroacetylanilines and Activated Terminal Alkynes Based on Transition Metal and Phosphine Catalysis.

In this work, we have developed selective methods for the synthesis of quinoline-2-carboxylates and quinoline-3-carboxylates as well as (indolin-2-ylidene)acetates through copper-, silver-, or phosphine-catalyzed reaction of propiolates with 2'-amino-2,2,2-trifluoroacetophenones. The approaches proposed ensure synthesis of substituted quinoline carboxylates and (indolin-2-ylidene)acetates in good yields. Introduction of alkynones into the reaction with 2'-amino-2,2,2-trifluoroacetophenones gives acyl substituted derivatives in good yields.

Synthesis of ß-iodovinyl sulfones via direct photoinitiated difunctionalization of internal alkynes.

The reaction of direct photoinitiated iodosulfonylation of internal acetylenes with p-tolylsulfonyl iodide and its regioselectivity of the products was studied. Methods for the subsequent functionalization of ß-iodovinylsulfones using cross-coupling reactions to obtain valuable and non-available compounds are proposed.

Polyoxa- and Polyazamacrocycles Incorporating 6,7-Diaminoquinoxaline Moiety: Synthesis and Application as Tunable Optical pH-Indicators in Aqueous Solution.

Synthetic approach to fluorescent polyaza- and polyoxadiazamacrocycles comprising a structural fragment of 6,7-diamino-2,3-diphenylquinoxaline has been elaborated using Pd-catalyzed amination providing target compounds in yields up to 77%. A series of nine novel N- and N,O-containing macrocyclic ligands differing by the number of donor sites and cavity size has been obtained. These compounds possess well-pronounced fluorescent properties with emission maxima in a blue region in aprotic solvents and high quantum yields of fluorescence, while in proton media, fluorescence shifts towards the green region of the spectrum. Using macrocycles 5c and 5e as examples, we have shown that such compounds can serve as dual-channel (colorimetric and fluorimetric) pH indicators in water media, with pH transition point and response being dependent on the macrocycle structure due to different sequences of protonation steps.

Regiodivergent Metal-Controlled Synthesis of Multiply Substituted Quinolin-2-yl- and Quinolin-3-ylphosphonates.

In this study, we developed a selective method for synthesis of multi-substituted quinoline-2-ylphosphonates and quinoline-3-ylphosphonates by copper- or gold-catalyzed reactions of phosphoryl-substituted conjugated ynones with 2'-amino-2,2,2-trifluoroacetophenones. The approach proposed makes it possible to obtain various substituted quinolines in good yields. It is also shown that (4,4,4-trifluoro-3-oxobut-1-yn-1-yl)phosphonate reacts with 2-aminoaryl ketones under non-catalytic conditions with formation of 4-substituted quinoline-2-ylphosphonates in high yields.

Transition-Metal-Catalyzed C-S, C-Se, and C-Te Bond Formations via Cross-Coupling and Atom-Economic Addition Reactions. Achievements and Challenges.

In the present review, we discuss recent progress in the field of C-Z bond formation reactions (Z = S, Se, Te) catalyzed by transition metals. Two complementary methodologies are considered─catalytic cross-coupling reactions and catalytic addition reactions. The development of advanced catalytic systems is aimed at improved catalyst efficiency, reduced catalyst loading, better cost efficiency, environmental concerns, and higher selectivity and yields. The important rise of research efforts in sustainability and green chemistry areas is critically assessed. The paramount role of mechanistic studies in the development of a new generation of catalytic systems is addressed, and the key achievements, problems, and challenges are summarized for this field.

Copper-catalyzed deacetonative Sonogashira coupling.

A convenient Pd- and phosphine-free protocol for assembling internal alkynes from tertiary propargyl alcohols and (het)aryl halides has been developed. The proposed tandem approach includes the base-promoted retro-Favorskii fragmentation followed by Cu-catalyzed C(sp)-C(sp2) cross-coupling. The use of inexpensive reagents (e.g. a catalyst, additives, a base, and a solvent) and good functional group tolerance make the procedure practical and cost-effective. The synthetic utility of the method was demonstrated by a smooth alkynylation of vinyl iodides derived from natural steroidal hormones.

Domino assembly of dithiocarbamates via Cu-catalyzed denitrogenative thiolation of iodotriazole-based diazo precursors.

An efficient domino approach to assemble benzoxazoles and anthranilamides bearing dithiocarbamate moieties has been developed. The proposed route represents a Cu-catalyzed three-component reaction between readily available 5-iodo-1,2,3-triazoles, amines, and CS2. The cascade transformation is based on a denitrogenative coupling of in situ formed dithiocarbamic acids with diazo intermediates, generated via annulation-triggered triazole ring-opening. This method is applicable to nucleophilic secondary amines and features good functional group compatibility.

Ruthenium(II) complexes with phosphonate-substituted phenanthroline ligands: synthesis, characterization and use in organic photocatalysis.

Ru(II) complexes with polypyridyl ligands play a central role in the development of photocatalytic organic reactions. This work is aimed at the structural modification of such complexes to increase their photocatalytic efficiency and adapt them for the preparation of reusable photocatalytic systems. Nine [Ru(phen)(bpy)2]2+-type complexes (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline) (Ru-Pcat) bearing the P(O)(OEt)2 substituent attached to the phen core directly or through a 1,4-phenylene linker were synthesized and characterized by spectroscopic and electrochemical techniques. The coordination mode of phen ligands was confirmed by single crystal X-ray analysis. The (spectro)electrochemical data show that the first electron transfer in Ru-Pcat takes place on the phen ligand. The emission maxima and quantum yields are strongly affected by the substitution pattern, reaching the far-red region (697 nm) for Ru-3,8P2. The singlet oxygen quantum yields of Ru-Pcat were evaluated using the chemical trapping method. Finally, the photocatalytic performance of Ru-Pcat in the oxidation of sulfides with molecular oxygen was investigated. Both dialkyl and alkyl aryl sulfides were quantitatively transformed into sulfoxides under irradiation with a blue LED in the acetonitrile-water mixture (10 : 1) using a low loading of 0.005-0.05 mol% Ru(II) photocatalysts. To rationalize the effect of phosphonate substituents on the photocatalytic efficiency, comparative kinetic studies of (1) 4-nitrothioanisole oxidation proceeding predominantly via the electron transfer pathway and (2) oxidation of dibutyl sulfide wherein singlet oxygen serves as an oxidant have been performed. It was demonstrated that complexes with the P(O)(OEt)2 substituent at positions 4 and 7 outperform the benchmark photocatalyst Ru-(bpy)3 and the parent complex Ru-phen in the reactions proceeding through electron transfer (reductive quenching photocatalytic cycle). The TON in the oxidation of 4-methoxythioanisole was found to be as high as 1 000 000 that is, to our knowledge, the highest among previously reported photocatalysts. In contrast, upon separating the P(O)(OEt)2 group and the phen core with the 1,4-phenylene linker, singlet oxygen quantum yields significantly increase that favors reactions proceeding through energy transfer (the oxidation of dibutyl sulfide in our case). Thus, both series of Ru(II) complexes prepared in this work are promising for the improvement of known photocatalytic reactions and the development of new transformations.

Annulation-Triggered Denitrogenative Transformations of 2-(5-Iodo-1,2,3-triazolyl)benzoic Acids.

The ability of [1,2,3]triazolobenzoxazinones to act as a source of "hidden" diazo group was discovered. These diazo precursors can be easily prepared by the intramolecular cyclization of 2-(5-iodo-1,2,3-triazolyl)benzoic acids. The Cu-catalyzed capture of the hidden diazo group allows for further functionalization through the denitrogenative pathway. The transformations proceed via the formation of either diazoimine or diazoamide intermediates. Novel routes to various anthranilamides as well as thiolated benzoxazinones were developed using the one-pot cyclization/diazo capture procedure.

Synthesis of α-Aryldiazophosphonates via a Diazo Transfer Reaction.

The simple synthetic procedure for preparation of α-aryl-α-diazophosphonates via a diazo transfer reaction is proposed. Benzylphosphonates reacted with tosyl azide (TsN3) in the presence of potassium tert-butoxide (KOtBu) to afford diazophosphonates in a yield up to 79%. The proposed method is general. The reaction uses easily available starting materials, tolerates various functional groups, and may be applied for multi-gram scale synthesis.

Mono- and Diamination of 4,6-Dichloropyrimidine, 2,6-Dichloropyrazine and 1,3-Dichloroisoquinoline with Adamantane-Containing Amines.

N-heteroaryl substituted adamantane-containing amines are of substantial interest for their perspective antiviral and psychotherapeutic activities. Chlorine atom at alpha-position of N-heterocycles has been substituted by the amino group using convenient nucleophilic substitution reactions with a series of adamantylalkylamines. The prototropic equilibrium in these compounds was studied using NMR spectroscopy. The introduction of the second amino substituent in 4-amino-6-chloropyrimidine, 2-amino-chloropyrazine, and 1-amino-3-chloroisoquinoline was achieved using Pd(0) catalysis.

Domino Construction of Benzoxazole-Derived Sulfonamides via Metal-Free Denitrogenation of 5-Iodo-1,2,3-triazoles in the Presence of SO2 and Amines.

A straightforward domino approach to assemble benzoxazole-derived sulfonamides has been developed. The method is based on annulation-induced in situ generation of diazo compounds from readily available 2-(5-iodo-1,2,3-triazolyl)phenols, followed by metal-free denitrogenative transformation upon the action of 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) and amines. The protocol is operationally simple and features a broad substrate scope, furnishing a library of target compounds in generally good yields.

Chemodivergent reactions.

An important strategy for the efficient generation of diversity in molecular structures is the utilization of common starting materials in chemodivergent transformations. The most studied solutions for switching the chemoselectivity rely on the catalyst, ligand, additive, solvent, temperature, time, pressure, pH and even small modifications in the substrate. In this review article several processes have been selected such as inter- and intramolecular cyclizations, including carba-, oxa-, thia- and oxazacyclizations promoted mainly by Brønsted or Lewis acids, transition metals and organocatalysts, as well as radical reactions. Catalyst-controlled intra- and intermolecular cyclizations are mainly described to give five- and six-membered rings. Cycloaddition reactions involving (2+2), (3+2), (3+3), (4+1), (4+2), (5+2), (6+2) and (7+2) processes are useful reactions for the synthesis of cyclic systems using organocatalysts, metal catalysts and Lewis acid-controlled processes. Addition reactions mainly of carba- and heteronucleophiles to unsaturated conjugated substrates can give different adducts via metal catalyst-, Lewis acid- and solvent-dependent processes. Carbonylation reactions of amines and phenols are carried out via ligand-controlled transition metal-catalyzed multicomponent processes. Ring-opening reactions starting mainly from cyclopropanols, cyclopropenols and epoxides or aziridines are applied to the synthesis of acyclic versus cyclic products under catalyst-control mainly by Lewis acids. Chemodivergent reduction reactions are performed using dissolving metals, sodium borohydride or hydrogen transfer conditions under solvent control. Oxidation reactions include molecular oxygen under solvent control or using different dioxiranes, as well as chemodivergent palladium catalyzed cross-coupling reactions using boronic acids are applied to aromatic and allenic compounds. Other chemodivergent reactions such as alkylations and allylations under transition metal catalysis, dimerization of acetylenes, bromination of benzylic substrates, and A3-couplings are performed via catalyst- or reaction condition-dependent processes.

Synthesis and Evaluation of the (S)-BINAM Derivatives as Fluorescent Enantioselective Detectors.

Pd(0)-catalyzed amination was employed for the synthesis of a new family of (S)-1,1'-bianaphthalene-2,2'-diamine derivatives possessing additional chiral and fluorophore substituents. The compounds thus obtained were tested as potential detectors of seven amino alcohols, and some of them were found to be able to recognize individual enantiomers of certain amino alcohols by specific changes of their emission spectra in the presence of these analytes. A pronounced dependence of the detecting abilities on the nature of the substituents in the (S)-BINAM derivatives was observed.

Assembly of Thiosubstituted Benzoxazoles via Copper-Catalyzed Coupling of Thiols with 5-Iodotriazoles Serving as Diazo Surrogates.

An efficient cascade approach to thiosubstituted benzoxazoles has been developed. The transformation starts with in situ generation of a diazo compound via annulation-triggered electrocyclic opening of the 1,2,3-triazole ring. The subsequent Cu-catalyzed trapping of diazo intermediates by various thiols affords the desired heterocycles in generally good yields of up to 91%. The protocol features very good functional group tolerance and is applicable to substrates with different electronic properties.

Selective Metal-Controlled Synthesis of Trifluoromethylated (Indolin-2-ylidene)methyl- and Quinolin-3-ylphosphonates.

Metal-catalyzed (Cu, Ag, Au) reactions of alkynylphosphonates with 1-(2-aminophenyl)-2,2,2-trifluoroethan-1-ones were developed. Terminal alkyne diethyl ethynylphosphonate reacted with ketones to give different products depending on the catalyst used. With a CuI/PPh3 catalytic system, the formation of CF3-containing indoline derivatives was observed with good yields. The use of AgSbF6 as a catalyst led to quinoline derivatives in high yields. The less reactive 2-substituted ethynylphosphonates required gold complexes as catalysts to provide the corresponding 2-aryl(alkyl) substituted 4-(trifluoromethyl)quinolin-3-ylphosphonates with good yields.

A Route to Triazole-Fused Sultams via Metal-Free Base-Mediated Cyclization of Sulfonamide-Tethered 5-Iodotriazoles.

An efficient direct approach to triazole-fused sultams has been developed. The key step of the proposed strategy is base-mediated cyclization of sulfonamide-tethered 5-iodo-1,2,3-triazoles which are readily available via an improved protocol for Cu-catalyzed 1,3-dipolar cycloaddition. The annulation of the sultam fragment to the triazole ring proceeds smoothly under transition-metal-free conditions in the presence of Cs2CO3 in dioxane at 100 °C and affords fused heterocycles in high yields up to 99%. The favorability of an SNAr-like mechanism for the cyclization was supported by DFT calculations. The applicability of the developed procedure to modification of natural compounds was demonstrated by preparation of a deoxycholic acid derivative.

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives.

Colchicine, the main alkaloid of Colchicum autumnale, is one of the most famous natural molecules. Although colchicine belongs to the oldest drugs (in use since 1500 BC), its pharmacological potential as a lead structure is not yet fully exploited. This review is devoted to the synthesis and structure-activity relationships (SAR) of colchicine alkaloids and their analogues with modified A, B, and C rings, as well as hybrid compounds derived from colchicinoids including prodrugs, conjugates, and delivery systems. The systematization of a vast amount of information presented to date will create a paradigm for future studies of colchicinoids for neoplastic and various other diseases.