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 (R₃In) and subsequent metal–halogen exchange. The coupling reactions usually gave good yields and have a high atom economy with substoichiometric amounts of R₃In. 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.

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.

1,1’-Binaphthalenes and heterocyclic analogues can be efficiently prepared by palladium-catalysed cross-coupling reactions between tri(1-naphthyl)indium reagents and 1-halonaphthalenes and haloisoquinolines. The reactions were usually carried out in THF at 80 °C with a slight excess of the indium reagent (40 mol-%) and a low catalyst loading (4 mol% Pd) to afford the cross-coupling products in good yields (45–99%). The method allows the synthesis of sterically hindered 2-substituted and 2,2’-disubstituted 1,1’-binaphthalenes and naphthylisoquinolines. In addition, the coupling reactions can be performed enantioselectively and the best enantiomeric excesses were obtained by using the chiral amino-phosphane ferrocenyl ligand (R,S)-PPFA.

Cross-coupling reaction of organogold(I) phosphanes with organic electrophiles in aqueous media has been investigated. Reactions between isolated aryl-, alkenyl-, or alkynylgold(I) phosphanes and aryl halides or triflates, alkenyl halides, and allyl acetates proceed under palladium catalysis conditions at room temperature or 80 °C in water with THF as a co-solvent. The coupling reactions give good yields and are highly versatile and chemoselective, allowing the presence of free amino or hydroxy groups in the electrophile. This methodology was applied to the preparation of substituted phenylalanine esters in a demonstration that gold(I) organometallics are suitable reagents for metal-catalyzed cross-coupling reactions under protic conditions.

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.

A novel rhodium-catalyzed allylic substitution reaction using indium organometallics is reported. Aryl- and heteroarylindium reagents reacted in THF at 80 °C with primary and secondary allyl halides and their derivatives under rhodium(I) catalysis to afford the α-substituted products in good yields and with high regio- and stereoselectivity. The reaction takes place with substoichiometric amounts of the triorganoindium reagents, which demonstrates the efficiency of the indium–rhodium transmetallation process in carbon–carbon bond-forming reactions.

The synthesis of unsymmetrical 2,5-disubstituted thiophenes by selective and sequential palladiumcatalyzed cross-coupling reactions of indium organometallics with 2,5-dibromothiophene is reported. Following an iterative coupling sequence, a-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.

A novel rhodium-catalyzed conjugate addition of indium reagents to electron deficient olefins is reported. The reaction takes place in THF/MeOH at 110 °C using arylindium dichlorides, a rhodium(I)-binap complex as catalyst, and α,β-unsaturated ketones and lactones in good yields (45–94%). The addition of MeOH is crucial for an efficient transformation and NMR studies seem to indicate that promotes the catalytic cycle leaving the indium organometallic unaltered. The use of chiral non-racemic ligands allows performing the reaction with moderate enantioselectivities.

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 C₂-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 regio- and stereoselectivity of the palladium-catalysed cross-coupling reactions of indium organometallics with stereodefined 1-haloalkenes and 1,1-dihaloalkenes have been studied. Triorganoindium reagents (R₃In; R = alkyl, alkenyl, aryl and alkynyl) can be stereospecifically coupled with stereodefined alkenyl iodides in good yields and short reaction times under palladium catalysis. Additionally, the palladium- catalysed cross-coupling reaction of R₃In (90 mol%) with 1,1-dibromo-1-alkenes gave dicoupling products in high yields. When the reaction was performed with 40 mol% of aryl-, vinyl- and alkynylindium derivatives, trans-selective monosubstitution products were obtained in moderate to good yields. These selective couplings were performed with [Pd₂dba₃]/P(2-furyl)₃ (1:1, 2 mol%) at 0 °C or, for 1,1-dibromo-1-alkenes with an aromatic group in the b-position, Pd(DPEPhos)Cl₂] (2 mol%) at room temperature as the catalytic system. The resulting (Z)-monobromoalkenes can be further functionalized by cross-coupling reaction with various R₃In (R = alkyl, aryl and alkynyl) in the presence of [Pd(tBu₃P)₂] as catalyst, at room temperature, to provide trisubstituted olefins in good yields.

A short enantioselective synthesis of barrenazines A and B is described. Barrenazines A and B are prepared following a common synthetic route in nine steps (19% overall yield) and eight steps (21% overall yield), respectively, from readily available 4-methoxy-3-(triisopropylsilyl)pyridine. The synthesis relies on a highly diastereoselective nucleophilic addition of a Grignard reagent to a chiral acylpyridinium salt, a radical azidation of a silyl enol ether and the assembly of the pyrazine ring by reductive dimerization of a functionalized 5-azidopiperidin-4-one.

Allenes have been efficiently prepared by the reaction of propargylic esters (benzoates, acetates, carbonates) with triorganoindium compounds (R₃In) under palladium catalysis, via an S_N2’ rearrangement. The reaction proceeds smoothly at room temperature with a variety of aryl-, alkenyl-, and alkynylindium reagents. The yields obtained are high and the regioselectivity is complete both in the case of terminal and nonterminal propargylic esters.

A practical and efficient stereoselective synthesis of the side chain of neomarinone is reported. The synthesis was achieved in six steps (41% overall yield) from 2-methyl-2-cyclohexenone. The key step is a novel stereoselective 1,4-conjugate addition/enolate alkylation by an epoxide-opening reaction.

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).

Triorganoindium reagents (R₃In) react with propargylic esters under palladium catalysis via an S_N2’ rearrangement to afford allenes in good yields and with high regioselectivity. The reaction proceeds smoothly at room temperature with a variety of R₃In (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.

The use of indium organometallics in multifold and sequential cross-coupling reactions is reported. Triorganoindium reagents (R₃In) react, under palladium catalysis, with oligohaloarenes affording the multiple cross-coupling products in a single operation. In the reaction, the three organic groups (alkyl, aryl, alkenyl or alkynyl) attached to indium are efficiently transferred to the electrophile, with only a slight excess of organometallic reagent. We demonstrate that indium organometallics are useful reagents for sequential cross-coupling reactions. This reaction illustrates the high chemoselectivity of R₃In.

Enantiomerically pure natural and unnatural α-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_N2 product regioselectively and in good yield. The reaction proceeds with net inversion of the stereochemical configuration.

The synthesis of vitamin D₃ active metabolites [24R,25-(OH)₂-D₃, 24S,25-(OH)₂-D₃ and 1α,24R,25-(OH)₃-D₃] and the first 24-aminovitamin D₃ derivatives [24S-benzoylamino-25-OH-D₃ and 24S-benzoylamino-1α,25-(OH)₂-D₃] are reported. The stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of a iodide to a dioxolanone or to a oxazolidinone. The vitamin D triene system was constructed using the Lythgoe approach. The synthetic route, which is both short (6 or 7 steps from starting iodide) and efficient (32–45% overall yield), constitutes a practical method for the preparation of 24-functionalized metabolites and analogues of vitamin D₃. 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 α,β-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to a methylenedioxolanone and to a methyleneoxazolidinone 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 γ,δ-dioxolanyl-α,β-unsaturated esters also proceeds with good yields (51–99%). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer gives high diastereoselectivity, while the reactions with the E isomer 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 α-and γ-hydroxy acids and α-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.

A novel palladium-catalyzed carbonylative cross-coupling reaction that employs triorganoindium compounds is described. The reaction proceeds under a carbon monoxide atmosphere with alkyl-, alkynyl-, and arylindium reagents to give good yields of unsymmetrical ketones with high atom economy. All three organic groups attached to the metal are efficiently transferred in this carbonylative coupling reaction.

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_N2’ product.

Functionalized benzo[c]phenanthrenes ([4]helicenes) and [5]helicenes were synthesised in five steps from tetrahydronaphthalenone and tetrahydrophenanthrenone compounds using a novel synthetic approach based on a Diels–Alder reaction between inner–outer ring 1,3-bis(trimethylsilyloxy)-1,3-dienes and benzyne or quinones.

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.

The diastereoselective ultrasonically induced zinc–copper 1,4-addition of alkyl iodides to chiral α,β-unsaturated systems in aqueous media is reported. The reaction of a methylenedioxolanone with a variety of alkyl iodides takes place in good yields and with high diastereomeric excess. The 1,4-addition to (Z)-and (E)-γ,δ-dioxolanyl-a,b-unsaturated esters also proceeds with good yields: the Z-isomer gives good diastereoselectivities while the reactions with the E-isomer are non-stereoselective.

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 1a,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 a iodide to Seebach’s dioxolanone, and the vitamin D triene system was constructed using the Lythgoe approach.

The synthesis, which is both short (seven steps from iodide) 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.

The synthesis of the first 24-aminovitamin D₃ derivatives is reported. A stereoselective convergent synthetic approach was employed to prepare 24(S)-benzoylamino-25-hydroxyvitamin D₃ and 24(S)-benzoylamino-1a,25-dihydroxyvitamin D₃ in six steps from iodide 2 in 34% and 42% overall yields, respectively. The key step in the synthesis is a novel diastereoselective ultrasonically induced conjugate addition, promoted by the zinc–copper couple, of iodide 2 to a methyleneoxazolidinone in aqueous media. The conjugate vitamin D triene system was constructed using the Lythgoe approach.

The novel metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles is described. Triorganoindium compounds (R3In) containing alkyl, vinyl, aryl, and alkynyl groups are efficiently prepared from the corresponding lithium or magnesium organometallics by reaction with indium trichloride. The cross-coupling reaction of R3In with aryl halides and pseudohalides, vinyl triflates, benzyl bromides, and acid chlorides proceeds under palladium catalysis in excellent yields and with high chemoselectivity. Indium organometallics also react with aryl chlorides as under nickel catalysis. In the cross-coupling reaction the triorganoindium compounds transfer, in a clear example of atom economy, all three of the organic groups attached to the metal, as shown by the necessity of using only 34 mol% of indium. The feasibility of using R3In in reactions with different electrophiles, along with the high yields and chemoselectivities obtained, reveals indium organometallics to be useful alternatives to other organometallics in cross-coupling reactions.

A Diels-Alder reaction of novel inner-outer-ring 1,3-silyloxydienes with a variety of dienophiles to afford highly functionalized polycyclic structures is reported. The inner-outer-ring 1,3-silyloxydienes containing five- to seven-membered carbocyclic and heterocyclic rings were prepared in a single reaction vessel from 2-acetylcyclocarbonyls in quantitative yields. The Diels-Alder reaction with 1,4-benzoquinone (BQ), dimethyl acetylenedicarboxylate (DMAD), and methyl vinyl ketone (MVK) proceeded smoothly at room temperature, affording functionalized polycyclic naphthols, phenols, and enones with high regioselectivity and good yields (39-75%). Moreover, these dienes also reacted in a hetero-Diels-Alder reaction with benzaldehyde (BA) and N-benzylideneaniline (NBA) in the presence of catalytic amounts of ZnCl₂, affording substituted polycyclic pyranones and pyridinones in good yields (40-93%). Overall, our synthetic strategy provides straightforward access to an interesting set of polycyclic structures useful for natural and nonnatural product synthesis.

The design and synthesis of vitamin D₃ dimers and 1a,25-dihydroxyvitamin D₃ (calcitriol) dimers are described. The dimers were designed with a view to doubly binding the vitamin D receptor (VDR) and inducing the receptor homodimerization. In the dimers the units are linked through the C-11 position in ring C by an alkyl side chain of six or 10 carbon atoms, far from the hydroxy groups responsible for the VDR binding. The linker is formed by olefin metathesis of an olefinic side chain at the C-11 position introduced by stereoselective cuprate addition. The synthesis, which is both short and convergent, uses the Wittig-Horner approach to construct the vitamin D triene system and allows the preparation of dimers with a linker of modulated length with the purpose of optimizing the vitamin D₃-VDR interaction.

A novel palladium-catalyzed cross-coupling reaction of organoindium compounds with vinyl and aryl triflates or iodides is described. The. reaction proceeds for alkyl-, vinyl-, alkynyl-, and arylindium compounds in excellent yields and high chemoselectivity without any excess of the organometallic. Remarkably, indium organometallics transfer efficiently the three organic groups attached to the metal.

A dimer comprising two 1a,25-dihydroxyvitamin D₃ units linked by an alkyl side chain at C-11 was synthesized with a view to the simultaneous binding of two vitamin D receptor (VDR) molecules and the consequent induction of VDR dimerization. The short, convergent synthesis uses a stereoselective cuprate addition to introduce the linking side chain and a key ruthenium olefin metathesis as the dimerization step.

In this paper we describe regioselective one-pot preparations of inner-outer-ring 
1,3-bis[trimethylsilyloxy]dienes and their Diels-Alder reactions with electron-deficient dienophiles. The dienes were prepared in quantitative yield, and the Diels-Alder reactions proceeded smoothly, regioselectively and with good yields, allowing efficient construction of highly functionalized polycyclic skeletons such as naphthofurans, benzofurans and various carbocycles present in natural and non-natural products.

A novel, efficient nickel-catalyzed 1,4-conjugate addition of triorganoindium compounds to ,-unsaturated systems is described. Best results were obtained using Ni(COD)2. The range of groups susceptible of addition was studied using aryl and primary and tertiary alkyl organoindium compounds prepared from commercially available organolithium compounds by transmetallation with InCl3. Addition to enones, esters and nitriles occurred in yields ranging from 50 to 89%.