Indium(III)-Catalyzed Synthesis of Pyrroles and Benzo[]indoles by Intramolecular Cyclization of Homopropargyl Azides.

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[]indoles has been discovered from azido-diynes using InCl as catalyst.

Synthesis and Photophysical Properties of β-Alkenyl-Substituted BODIPY Dyes by Indium(III)-Catalyzed Intermolecular Alkyne Hydroarylation.

A new atom-economical synthesis of β-alkenyl-substituted BODIPYs via indium(III)-catalyzed intermolecular alkyne hydroarylation with -substituted BODIPYs is described. While catalysis with InI allows the double β-functionalization of BODIPY, resulting in regioselectively branched β,β'-disubstituted alkenyl BODIPYs, catalytic InCl enables the formation of linear β-substituted alkenyl BODIPYs. Subsequent In(III)-catalyzed intermolecular alkyne hydroarylation allows the synthesis of unsymmetrical - BODIPY derivatives.

Microwave-assisted direct synthesis of BODIPY dyes and derivatives.

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.

Indium(III)-Catalyzed Stereoselective Synthesis of Tricyclic Frameworks by Cascade Cycloisomerization Reactions of Aryl 1,5-Enynes.

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 (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene ( 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.

Advances in Cross-Coupling Reactions.

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

Transition-Metal-Free Oxidative Cross-Coupling of Triorganoindium Reagents with Tetrahydroisoquinolines.

Triorganoindium reagents (RIn) react with tetrahydroisoquinolines (THIQs) in the presence of PhCBF as an oxidant to afford 1-substituted THIQs. The reaction proceeds in good yields at rt using 50 mol % RIn with a variety of organic groups. H NMR studies show the generation of an iminium ion intermediate, supporting a two-step mechanism based on THIQ oxidation and RIn nucleophilic addition.

Synthesis of D-A-A and D-A-D Pyrimidine π-Systems Using Triorganoindium Reagents: Optical, Vibrational, and Electrochemical Studies.

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-(,-Diphenylamino)phenyl was chosen as the donor group and thien-2-yl dicyanovinylene as the acceptor one.

Indium(iii) as π-acid catalyst for the electrophilic activation of carbon-carbon unsaturated systems.

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.

Triorganoindium Reagents in Rh-Catalyzed C⁻H Activation/C⁻C Cross-Coupling Reactions of 2-Arylpyridines.

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 -coupling products in moderate to good yields.

Indium(III)-Catalyzed Synthesis of Benzo[ b]furans by Intramolecular Hydroalkoxylation of ortho-Alkynylphenols: Scope and Mechanistic Insights.

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 (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.

Synthesis of bench-stable solid triorganoindium reagents and reactivity in palladium-catalyzed cross-coupling reactions.

Bench-stable solid triorganoindium compounds have been prepared by coordination with 4-(dimethylamino)pyridine (DMAP). The solid RIn(DMAP) complexes are obtained from the corresponding solution of RIn 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.

Transition-Metal-Free Cross-Coupling of Indium Organometallics with Chromene and Isochroman Acetals Mediated by BF3·OEt2.

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.

Indium-catalyzed intramolecular hydroarylation of aryl propargyl ethers.

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.

Nonsymmetrical 3,4-dithienylmaleimides by cross-coupling reactions with indium organometallics: synthesis and photochemical studies.

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.

Triorganoindium reagents in selective palladium-catalyzed cross-coupling with iodoimidazoles: synthesis of neurodazine.

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.

Synthesis of 4,6-disubstituted 2-(4-morpholinyl)pyrimidines by cross-coupling reactions using triorganoindium compounds.

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.

Synthesis of functionalized thiophenes and oligothiophenes by selective and iterative cross-coupling reactions using indium organometallics.

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.

Palladium-catalyzed cross-coupling reactions of organogold(I) phosphanes with allylic electrophiles.

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.

A versatile synthesis of fumaquinone.

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.

Palladium-catalyzed cross-coupling reactions of organogold(I) reagents with organic electrophiles.

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.

A versatile enantioselective synthesis of barrenazines.

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.

Synthesis of 3,4-disubstituted maleimides by selective cross-coupling reactions using indium organometallics.

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.

Total synthesis of (+)-neomarinone.

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.

Cross-coupling reactions of indium organometallics with 2,5-dihalopyrimidines: synthesis of hyrtinadine A.

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.

Enantioselective nickel-catalyzed cross-coupling reactions of trialkynylindium reagents with racemic secondary benzyl bromides.

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.