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In this study, a series of BODIPY dyes were synthesized, containing various substituents at meso position. Further functionalization of the BODIPY framework at C2 and C2-C6 position(s) by palladium-catalysed cross-coupling reactions using organoindium reagents (R 3 In) was efficiently assessed, starting from C2(6)-halogenated BODIPYs, and their optical properties were measured. The cytotoxicity of BODIPY dyes on SH-SY5Y neuronal cells by MTT assay showed that those compounds bearing thien-2-yl and benzonitrile moieties at meso position, exhibited great efficiency in maintaining cell viability under all tested conditions (up to 50 µM for 24 h and 48 h). Furthermore, nanoliposomal encapsulation of a hydrophobic BODIPY, incorporating bis(trifluoromethyl)phenyl substituents at C2 and C6 positions, through the lipid-extrusion method was addressed. The liposomes exhibited spherical shape as observed in cryo-TEM image, with average particle size of 120 nm (average PdI 0.05) and Zeta potential 54.69 mV by DLS measurements. Simple incubation of gliobastoma U-87 cells with prepared liposomes led to efficient internalization, and visualization of brightness BODIPY in cytoplasm using fluorescence confocal microscopy, demonstrating encapsulation enhance biocompatibility of the hydrophobic BODIPY as preliminary approximation for further biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pyrroles, privileged structural motifs in drug and material science, have been synthesized by indium(III)-catalyzed intramolecular cyclization of homopropargyl azides. This methodology exhibits a broad substrate scope, providing substituted pyrroles and bispyrroles in good yields. Furthermore, an atom-economical sequential method for the synthesis of benzo[ g ]indoles has been discovered from azido-diynes using InCl 3 as catalyst. The method involves two successive intramolecular indium-catalyzed 5 -endo-dig alkyne hydroamination and a hydroarylation reactions with 6 -endo-dig regioselectivity.

A new atom-economical synthesis of β-alkenyl-substituted BODIPYs via indium(III)-catalyzed intermolecular alkyne hydroarylation with meso -substituted BODIPYs is described. While catalysis with InI 3 allows the double β-functionalization of BODIPY, resulting in regioselectively branched β,β'-disubstituted alkenyl BODIPYs, catalytic InCl 3 enables the formation of linear β-substituted alkenyl BODIPYs. Subsequent In(III)-catalyzed intermolecular alkyne hydroarylation allows the synthesis of unsymmetrical push - pull BODIPY derivatives. Therefore, indium catalysis offers complementary regioselectivity in good chemical yields and functional group tolerance. The resulting BODIPY dyes displayed bathochromically shifted absorption and emission according to the electron-nature of the substituents in the alkenyl moiety with high molar extinction coefficients (ε up to 88,200 M -1 cm -1 ) and quantum yields (0.14-0.96).

A microwave-assisted one-pot synthesis of BODIPY dyes from pyrroles and acyl chlorides is reported. This protocol features short reaction times, low temperatures, minimum amount of solvent, scalability, versatility, and good yields of the products. These simple, efficient and sustainable conditions can be also applied to the synthesis of derivatives such as BOPHY, BOAHY and BOPAHY.

The indium(III)-catalyzed cascade cycloisomerization reaction of 1,5-enynes with pendant aryl nucleophiles is reported. The reaction proceeds in cascade under mild reaction conditions, using InI 3 (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene ( E and Z isomers) and with terminal and internal alkynes. Using 1-bromo-1,5-enynes, a one-pot sequential indium-catalyzed cycloisomerization and palladium-catalyzed cross-coupling with triorganoindium reagents were developed. The double cyclization is stereospecific and operates via a biomimetic cascade cation-olefin through 1,5-enyne cyclization ( 6-endo - dig ) and subsequent C-C hydroarylation or C-O phenoxycyclization. Density functional theory (DFT) computational studies on 1,5-enynyl aryl ethers support a two-step mechanism where the first stereoselective 1,5-enyne cyclization produces a nonclassical carbocation intermediate that evolves to the tricyclic reaction product through a S E Ar mechanism. Using this approach, a variety of tricyclic heterocycles such as benzo[ b ]chromenes, phenanthridines, xanthenes, and spiroheterocyclic compounds are efficiently synthesized with high atom economy.

Cross-coupling reactions stand among the most important reactions in chemistry [...].

Triorganoindium reagents (R 3 In) react with tetrahydroisoquinolines (THIQs) in the presence of Ph 3 CBF 4 as an oxidant to afford 1-substituted THIQs. The reaction proceeds in good yields at rt using 50 mol % R 3 In with a variety of organic groups. 1 H NMR studies show the generation of an iminium ion intermediate, supporting a two-step mechanism based on THIQ oxidation and R 3 In nucleophilic addition. This reaction was applied to the synthesis of the alkaloid nuciferine in three steps.

A series of donor-acceptor-acceptor (D-A-A) and donor-acceptor-donor (D-A-D) systems based on a pyrimidine π-spacer with various substituents at the C-2 position has been successfully prepared. The synthesis involved site-selective palladium cross-coupling reactions of chloropyrimidines with triorganoindium reagents and proceed in good yields and with atom economy. 4-( N , N -Diphenylamino)phenyl was chosen as the donor group and thien-2-yl dicyanovinylene as the acceptor one. The optical, vibrational, electrochemical, and density functional theory (DFT) calculations of these molecular systems were analyzed, and experimental values show the important role of the substituents at the C-2 position of the pyrimidine with stronger electron accepting ability, absorption in a wide range of UV/vis, acceptable fluorescence lifetime, and effective intramolecular charge transfer (ICT) properties. The ICT was observed in both series by the bathochromic shift on increasing the polarity of the solvent. In addition, DFT calculations found lower lowest unoccupied molecular orbitals of D-A-A molecules that suggest good electron ejection and transportation, being good properties for their application in various organic optoelectronic devices.

This review focuses on the utilization of indium(iii) as π-acid for the activation of C-C unsaturated bonds in organic synthesis. In addition to its well-known σ-coordination with carbonyl derivatives, indium(iii) undergoes efficient π-coordination with unsaturated systems to trigger nucleophilic addition. Accordingly, indium(iii) halides and salts (InX3, X = Cl, Br, I, OTf, ONf, NTf2) have been reported as useful catalysts for a broad range of carbon-carbon and carbon-heteroatom bond formation reactions, including hydrofunctionalization (hydroarylation, hydroamination, hydroalkoxylation, and hydrothiolation), enyne cycloisomerization, and related reactions. In these reactions the counterion has a significant effect on the catalytic activity, and the development of novel In(iii) complexes and the generation of highly electrophilic cationic indium(iii) species has increased its synthetic applications as a π-acid catalyst.

Indium(III) halides catalyze the hydroalkoxylation reaction of ortho-alkynylphenols to afford benzo[ b]furans in good yields. The reaction proceeds with 5- endo- dig regioselectivity with a variety of phenols functionalized at the arene and alkyne moieties in high yields using InI 3 (5 mol %) in DCE. Experimental and computational studies support a mechanism based on the indium(III) π-Lewis acid activation of the alkyne followed by nucleophilic addition of the phenol and final protodemetalation to afford the corresponding benzo[ b]furan. DFT calculations suggest that dimer In 2 I 6 is the catalytic species through a novel double coordination with the alkyne and the hydroxyl group.

The activation of C⁻H bonds through catalytic reactions using transition metals is an important challenge in organic chemistry in which the intermediates are related to those produced in the classical cross-coupling reactions. As part of our research program devoted to the development of metal-catalyzed reactions using indium organometallics, a protocol for the C⁻H activation and C⁻C coupling of 2-arylpyridines with triorganoindium reagents under Rh(I) catalysis is reported. Under the optimized conditions, we found that Me₃In and Ar₃In reagents reacted with 2-arylpyridines and related compounds in the presence of Rh(PPh₃)₃Cl, in PhCl/THF (9:1), at 120 °C for 48 h, to afford the ortho -coupling products in moderate to good yields. The nitrogen atom in the pyridine ring acts as a directing group to assist the functionalization at the ortho position of the aryl group forming a new C⁻C bond at this position.

Bench-stable solid triorganoindium compounds have been prepared by coordination with 4-(dimethylamino)pyridine (DMAP). The solid R 3 In(DMAP) complexes are obtained from the corresponding solution of R 3 In in quantitative yield and can be stored for up to several weeks. These reagents show excellent reactivity in palladium-catalyzed cross-coupling reactions with organic electrophiles.

A transition-metal-free coupling of triorganoindium reagents with benzopyranyl acetals mediated by a Lewis acid has been developed. The reaction of R3In with chromene and isochroman acetals in the presence of BF3·OEt2 afforded 2-substituted chromenes and 1-substituted isochromans, respectively, in good yields. The reactions proceed with a variety of triorganoindium reagents (aryl, heteroaryl, alkynyl, alkenyl, alkyl) using only 50 mol % of the organometallic, thus demonstrating the efficiency of these species. Preliminary mechanistic studies indicate the formation of an oxocarbenium ion intermediate in the presence of the Lewis acid.

Indium(III) halides catalyze efficiently the intramolecular hydroarylation (IMHA) of aryl propargyl ethers. The reaction proceeds regioselectively with terminal and internal alkynes bearing electron-rich and electron-deficient substituents in the benzenes and alkynes affording only the 6-endo dig cyclization product. Additionally, a sequential indium-catalyzed IMHA and palladium-catalyzed Sonogashira coupling can be performed in one reaction vessel. Experiments with deuterium support a mechanism through electrophilic aromatic substitution.

The synthesis and photochemical study of novel nonsymmetrical 1,2-dithienylethenes (DTEs) with a maleimide bridge have been carried out. The synthetic approach to the DTEs was based on successive selective palladium-catalyzed cross-coupling reactions of 5-susbtituted-2-methyl-3-thiophenyl indium reagents with 3,4-dichloromaleimides. The required organoindium reagents were prepared from 2-methyl-3,5-dibromothiophene by a selective (C-5) coupling reaction with triorganoindium compounds (R3 In) and subsequent metal-halogen exchange. The coupling reactions usually gave good yields and have a high atom economy with substoichiometric amounts of R3 In. The results of photochemical studies show that these novel dithienylmaleimides undergo a photocyclization reaction upon irradiation in the UV region and a photocycloreversion after excitation in the visible region, thus they can be used as photochemical switches. ON-OFF operations can be repeated in successive cycles without appreciable loss of effectiveness in the process., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Triorganoindium reagents (R3In, R = aryl, heteroaryl, alkynyl) react selectively under palladium catalysis with N-benzyl-2,4,5-triiodoimidazole to afford the C-2 monocoupling products. The reaction proceeds efficiently for a variety of aryl- and heteroarylindium reagents with the transfer of all three organic groups attached to the metal. The coupling products can be used in a subsequent two-fold cross-coupling to give trisubstituted imidazoles in good yields. This approach was employed to synthesize neurodazine and analogues in good yields.

4,6-Disubstituted-2-(4-morpholinyl)pyrimidines, an important class of bioactive compounds, have been synthesized from 4,6-dichloro-2-(4-morpholinyl)pyrimidine by selective and sequential palladium-catalyzed cross-coupling reactions using triorganoindium reagents. This methodology, being efficient and versatile, allowed the synthesis of a variety of non-symmetrical pyrimidines functionalized at C-4 and C-6 positions.

The synthesis of unsymmetrical 2,5-disubstituted thiophenes by selective and sequential palladium-catalyzed cross-coupling reactions of indium organometallics with 2,5-dibromothiophene is reported. Following an iterative coupling sequence, α-oligothiophenes were synthesized in good yields and with high atom economy.

Aryl and alkenylgold(I) phosphanes react regioselectively with allylic electrophiles such as cinnamyl and geranyl halides (bromide, chloride and acetates) under palladium catalysis in THF at 80 °C to afford the α-substitution product with moderate to high yields. When the reaction is performed with a chiral enantiopure secondary acetate, the α-substituted cross-coupling product is obtained with complete inversion of the stereochemistry.

The palladium-catalyzed cross-coupling reaction of organogold(I) reagents (alkyl, alkenyl, aryl, and alkynyl) with organic electrophiles, such as aryl and alkenyl halides, aryl triflates, benzyl bromide, and benzoyl chloride is reported. The reaction takes place, under palladium catalysis, at room temperature with short reaction times to give the corresponding cross-coupling products in high yields.

Fumaquinone, a novel prenylated naphthoquinone antibiotic, was synthetized from ethyl acetoacetate in three steps (58% overall yield). The key step of the synthesis is the construction of the naphthoquinone skeleton by a regioselective Diels-Alder reaction between a 2-alkyl 1,3-bis(trimethylsilyloxy)-1,3-diene derivative and a bromoquinone. This short and versatile approach confirms the structure of fumaquinone and allows the synthesis of derivatives at the C-6 position.

A versatile enantioselective total synthesis of barrenazines A and B has been accomplished from 1,4-butanediol. The key steps of the synthesis are a sequential allylboration/ring-closing metathesis for the construction of the tetrahydropyridine ring and the preparation of a functionalized 4-azidopiperidin-5-one through a stereoselective epoxidation and regioselective ring-opening reaction. The C(2)-symmetrical pyrazine skeleton of barrenazines was prepared by dimerization of the azidopiperidinone, and the carbon side chain was completed by copper-catalyzed reactions using Grignard reagents.

Unsymmetrical 3,4-disubstituted maleimides have been synthesized by palladium-catalyzed cross-coupling reactions of indium organometallics with 3,4-dihalomaleimides. The synthesis was performed by stepwise or sequential one-pot palladium-catalyzed cross-coupling reactions with various triorganoindium reagents. This method was used to prepare a wide variety of alkyl, aryl, heteroaryl, and alkynyl 3,4-disubstituted maleimides in good yields and with high selectivity and atom economy.

The first total synthesis of (+)-neomarinone has been achieved by following a concise and convergent route using methyl (R)-lactate and (R)-3-methylcyclohexanone as chiral building blocks. Key steps of the synthesis are the stereocontrolled formation of the two quaternary stereocenters by diastereoselective 1,4-conjugate addition and enolate alkylation reactions, and the construction of the furanonaphthoquinone skeleton by regioselective Diels-Alder reaction between a 1,3-bis(trimethylsilyloxy)-1,3-diene and a bromoquinone. The synthesis proves the relative and absolute stereochemistry of natural neomarinone.

The palladium-catalyzed cross-coupling reaction of triorganoindium reagents (R3In) with 5-bromo-2-chloropyrimidine proceeds chemoselectively, in good yields, to give 5-substituted-2-chloropyrimidines or 2,5-disubstituted pyrimidines using 40 or 100 mol % of R3In, respectively. Sequential cross-couplings are also performed, in one pot, using two different R3In. This method was used to achieve the first synthesis of the alkaloid hyrtinadine A. The key step was a two-fold cross-coupling reaction between a tri(3-indolyl)indium reagent and 5-bromo-2-chloropyrimidine.

The first enantioselective sp-sp3 cross-coupling reaction between alkynyl organometals and racemic benzyl bromides is reported. The coupling is performed at room temperature by using NiBr2diglyme and (S)-(iPr)-Pybox as the catalytic system and trialkynylindium reagents as nucleophiles. The reaction is stereoconvergent, both enantiomers of the racemic benzyl bromide are converted into one enantiomer of the product, and stereospecific. The reaction takes place efficiently in good yields and with high atom economy, as the triorganoindium reagents transfer the three organic groups attached to indium (only 40 mol % of R3In is used).

Six new calcitriol analogues, conformationally restricted at their side chain by the introduction of both a cyclopropane ring at C17-C20 and a double or triple bond at C22, were synthesized using the Wittig-Horner approach to construct the triene system. The six CD-ring and side-chain bearing fragments were prepared from ketone 14 by a divergent route to generate both series of epimers at C20, followed by stereoselective cyclopropanation. The (E)-alkenyl side chain was synthesized by means of a Wittig reaction. The alkynyl side chain was prepared by Corey-Fuchs homologation, followed by alkylation. The (Z)-alkenyl side chain was prepared from the previous alkyne by partial hydrogenation. The 20-epi analogues bind more strongly to VDR than the corresponding analogues with the C20 natural stereochemistry. These results can be reasoned by conformational analysis and hydrophobic interactions with the VDR ligand-binding domain.

A range of biaryl compounds (aryl-aryl, aryl-heteroaryl, and heteroaryl-heteroaryl) can be efficiently prepared by a palladium-catalyzed cross-coupling reaction between ortho-substituted triarylindium reagents and aryl halides. The triarylindium reagents are prepared by directed ortho-lithiation and transmetallation to indium from the corresponding benzene derivatives using various directed metallation groups (DMGs). The reaction proceeds smoothly in high yields and short reaction times with high atom economy (the three aryl groups attached to indium are efficiently transferred).

[reaction: see text] Triorganoindium reagents (R(3)In) react with propargylic esters under palladium catalysis via an S(N)2' rearrangement to afford allenes in good yields and with high regioselectivity. The reaction proceeds smoothly at room temperature with a variety of R(3)In (aryl, alkenyl, alkynyl, and methyl). When chiral, nonracemic propargylic esters are employed, the reaction takes place with high anti-stereoselectivity providing allenes with high enantiomeric excess.

Enantiomerically pure natural and unnatural alpha-amino acids have been synthesized from a chiral methyleneoxazolidinone by means of a highly diastereoselective 1,4-conjugate addition of alkyl iodides in aqueous media. The zinc-copper conjugate addition reaction exhibits high chemoselectivity, with the possibility of using functionalized iodides, to afford a single diastereomer in short reaction times and with good yields.

The palladium(0)-catalyzed cross-coupling reaction of allylic halides and acetates with indium organometallics is reported. In this synthetic transformation, triorganoindium compounds and tetraorganoindates (aryl, alkenyl, and methyl) react with cinnamyl and geranyl halides and acetates to afford the S(N)2 product regioselectively and in good yield. The reaction proceeds with net inversion of the stereochemical configuration.

The synthesis of vitamin D(3) active metabolites [24R,25-(OH)(2)-D(3), 24S,25-(OH)(2)-D(3) and 1alpha,24R,25-(OH)(3)-D(3)] and the first 24-aminovitamin D(3) derivatives [24S-benzoylamino-25-OH-D(3) and 24S-benzoylamino-1alpha,25-(OH)(2)-D(3)] are reported. The stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of iodide 8 to dioxolanone 6 or oxazolidinone 7. The vitamin D triene system was constructed using the Lythgoe approach. The synthetic route, which is both short (6 or 7 steps from iodide 8) and efficient (32-45% overall yield), constitutes a practical method for the preparation of 24-functionalized metabolites and analogues of vitamin D(3). The ultrasonically induced conjugate addition in the key step provides a novel example of a highly stereoselective reaction promoted by the zinc-copper couple in aqueous media.

The stereoselectivity of the ultrasonically induced zinc--copper conjugate addition of iodides to chiral alpha,beta-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to methylenedioxolanone 1 and methyleneoxazolidinone 2 to afford the 1,4-addition products in good yields (38-95 %) and with high diastereomeric excess (44-90 % de). The 1,4-addition to chiral gamma,delta-dioxolanyl-alpha,beta-unsaturated esters 3-5 also proceeds with good yields (51-99 %). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer 3 gives high diastereoselectivity, while the reactions with the E isomer 4 are nonstereoselective. The reaction proceeds with excellent chemoselectivity and allows the use of iodides bearing ester, hydroxy, and amino groups. Since the 1,4-addition products can be readily hydrolyzed, this methodology constitutes a novel entry for the enantioselective synthesis of alpha- and gamma-hydroxy acids and alpha-amino acids in aqueous media. The results obtained support the radical mechanism proposed by Luche, and represent one of the few examples of a radical stereoselective conjugate addition in aqueous medium.

The first nucleophilic allylic substitution reactions of triorganoindium compounds with allylic halides and phosphates are reported. The reactions of trialkyl- and triarylindium reagents with cinnamyl and geranyl halides and phosphates, with the aid of copper catalysis [Cu(OTf)(2)/P(OEt)(3)], are described. In general, the reaction proceeds efficiently to give good yields and regioselectively to afford the S(N)2' product.

Multifold and sequential palladium-catalyzed cross-coupling reactions can be performed between triorganoindium compounds and oligohaloarenes using only a small excess of the organometallic reagent, low catalyst charge loading and short reaction times.

A novel convergent synthetic approach to new analogues of calcitriol modified at the C-18 position is reported. The key step in the synthesis is the 20-hydroxyl-directed photochemical iodination of the 18-methyl group in the presence of (diacetoxyiodo)benzene. Using this methodology, two new analogues of calcitriol were prepared: the first contains a hydroxylated alkyl side chain attached at C-18 with the natural side chain replaced by an isopropylidene group; the second is a conformationally locked analogue due to an extra oxacycle between the C-18 and C-20 positions.

Vitamin D3 active metabolites 24R,25-(OH)2-D3, 24S,25-(OH)2-D3, and 1 alpha, 24R,25-(OH)3-D3 were synthesized by a convergent and stereoselective approach. In the synthetic route, the stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of iodide 6 to Seebach's dioxolanone 5, and the vitamin D triene system was constructed using the Lythgoe approach. The synthesis, which is both short (seven steps from iodide 6) and efficient (32-40% overall yield), allows the preparation of large quantities of the metabolites and provides a novel example of a highly stereoselective reaction promoted by the zinc-copper couple in aqueous media.