Thorpe-Ingold effect in copper(II)-catalyzed formal hydroalkoxylation-hydroarylation reaction of alkynols with indoles

The use of Cu(OTf)₂ as a catalyst for tandem hydroalkoxylation-hydroarylation reaction of alkynes tethered with hydroxyl group is reported. The reaction proceeds at 60 °C or even at room temperature with 5 mol % catalyst loading and produces C-3-substituted indoles in good to high yields. The method was shown to be applicable to a broad range of indoles, containing electron-withdrawing and electron-donating substituents, and alkynol substrates bearing sterically demanding substituents in the tether. Interestingly, it was found that Thorpe-Ingold effect is operating for this cyclization reaction. Easy availability and low cost of Cu(OTf)₂ make this method attractive and amenable for large-scale synthesis compared to known literature methods.     

Pt(II)-catalyzed hydroarylation reaction of alkynes with pyrroles and furans

A Pt(II) catalyst showed a drastic effect on hydroarylation of alkynes with pyrroles and furans compared with Pd(OAc)₂ catalyst. The hydroarylation reactions proceeded smoothly under mild conditions to give double-hydroarylation products in good yields. Mono-adducts were formed only when the second hydroarylation was inhibited by steric hindrance of substrates or low reactivity of the mono-adducts.     

Gold(I)-catalyzed formation of 3-pyrazolines through cycloaddition of diaziridine to alkynes

This work reports the high-yield formation of pyrazoline derivatives mediated by gold(I) catalysts. The reaction utilizes a diaziridine, which has seen only limited usage in organic methodology. Mechanistic studies suggest a gold-mediated opening of the diazridine ring, alkyne insertion, and finally an intramolecular hydroamination to furnish the product.     

Rh(I)-catalyzed reaction of 2-(chloromethyl)phenylboronic acids and alkynes leading to indenes

The reaction of 2-(chloromethyl)phenylboronic acid (1) with alkynes in the presence of a Rh(I) complex gave indene derivatives in high yields. The regioselectivity depends on the steric nature of the substituent on the alkynes. A bulky group favors the alpha-position of indenes.     

Cationic Gold(I) Complexes: Highly Efficient Catalysts for the Addition of Alcohols to Alkynes

Gold complexes are almost unknown in homogeneous catalysis , and for a long time gold was even thought of as “catalytically dead”. This is clearly not the case for cationic phosphanegold(I ) complexes (see reaction below), which can catalyze the addition of alcohols to alkynes with turnover frequencies up to 1.5 s⁻¹ and total turnover numbers up to 10⁵! R=H, alkyl, Ph, CH₂OH.     

Formation of cinnoline derivatives by a gold(I)-catalyzed hydroarylation of N-propargyl-N′-arylhydrazines

A study concerning the gold(I)-catalyzed hydroarylation of N-propargyl-N′-arylhydrazinecarboxylic acid methyl esters is described. The use of the gold complex [XPhosAu(NCCH₃)SbF₆] as the catalyst in refluxing nitromethane allows the generally rapid and efficient synthesis of a range of functionalized 4-exo-methylene-1,2-dihydrocinnolines.     

Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes: a direct synthesis of trisubstituted furans

A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction of terminal alkynes with β-keto α-diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans is operationally simple and applicable to wide substrate scope. Moreover, this synthesis employs cheap Cu(MeCN)₄PF₆ as the catalyst and no additional ligand is needed. Similar reaction has also been applied to ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the synthesis of 2,3,5-trisubstituted N-methoxypyrroles with limited success.     

Gold(III) (C^N) complex-catalyzed synthesis of propargylamines via a three-component coupling reaction of aldehydes, amines and alkynes

Propargylamines are synthesized in high yields via a gold(III) (C^N) complex-catalyzed three-component coupling reaction of aldehydes, amines and alkynes in water at 40 °C. Excellent diastereoselectivities (up to 99:1) have been achieved when chiral prolinol derivatives are employed as the amine component. Notably, the [Au(C^N)Cl₂] complex (N^CH = 2-phenylpyridine) could be repeatedly used for 10 reaction cycles, leading to an overall turnover number of 812.     

Regiocontrolled gold(I)-catalyzed cyclization reactions of N-(3-iodoprop-2-ynyl)-N-tosylanilines

The gold(I)-catalyzed cyclization reactions of N-(3-Iodoprop-2-ynyl)-N-tosylaniline derivatives afford iodinated 1,2-dihydroquinoline derivatives. Two regioisomer products are obtained, one derived from direct cyclization and other involving concomitant 1,2-iodo migration. The ratio of these two products can be modulated by a proper ancillary ligand in the gold catalyst.     

Rh(I)-catalyzed carbonylative cyclization reactions of alkynes with 2-bromophenylboronic acids leading to indenones

The Rh-catalyzed reaction of alkynes with 2-bromophenylboronic acids involves carbonylative cyclization to give indenones. The key steps in the reaction involve the addition of an arylrhodium(I) species to an alkyne and the oxidative addition of C-Br bonds on the adjacent phenyl ring to give vinylrhodium(I) species II. The regioselectivity depends on both the electronic and the steric nature of the substituents on the alkynes. A bulky group and an electron-withdrawing group favor the -position of indenones. In the case of silyl- or ester-substituted alkynes, the regioselectivity is extremely high. The selectivity increases in the order SiMe3 > COOR > aryl > alkyl. The reaction of norbornene with 2-bromophenylboronic acids under 1 atm of CO gives the corresponding indanone derivative. The reaction of alkynes with 2-bromophenylboronic acids under nitrogen gives naphthalene derivatives, in which two molecules of alkynes are incorporated. A vinylrhodium complex similar to II can also be generated by a different route by employing 2-bromophenyl(trimethylsilyl)acetylene and arylboronic acids in the presence of Rh(I) complex as the catalyst, resulting in the formation of indenones. The reaction of 1-(2-bromophenyl)-hept-2-yn-1-one with PhB(OH)2 in the presence of Rh(I) complex also resulted in carbonylative cyclization to give an indan-1,3-dione derivative.     

Synthesis of bis(indolyl)alkanes by a site-selective gold-catalyzed addition of indoles to butynol derivatives

A new site-selective hydroarylation reaction of alkynes catalyzed by gold complexes and directed by an internal hydroxyl group has been developed. Thus, the treatment of 3-butyn-1-ol derivatives with indoles and a catalytic amount of an in situ formed cationic gold complex leads to the formation of bis(indolyl)alkane derivatives. Particularly interesting is the reaction with terminal alkynes as the double addition of the indol occurs at the terminal carbon of the triple bond. The reaction conditions are very mild and the final bis(indolyl)alkanes are obtained in high yields.     

Heterogeneous gold(I)-catalyzed three-component reaction of aldehydes,alkynes, and orthoformates toward propargyl ethers

Abstract

A novel and efficient heterogeneous gold(I)-catalyzed three-component reaction of aldehydes, alkynes, and orthoformates has been developed that proceeds smoothly in dichloroethane (DCE) at 83?°C in the presence of 5?mol% magnetic nanoparticles-anchored phosphine gold(I) complex (Fe₃O₄@SiO₂-P-AuOTf) and offers a general and practical approach for the preparation of a variety of propargyl ethers with good yields. This heterogeneous gold(I) catalyst can be facilely recovered by simply applying an external magnetic field and recycled at least eight times without any apparent decrease in the catalytic efficiency.     

Gold(I)-catalyzed unprecedented rearrangement reaction between 2-aminobenzaldehydes with propargyl amines: an expedient route to 3-aminoquinolines

Access to aminoquinolines: a gold(I)-catalyzed unprecedented rearrangement reaction between 2-aminobenzaldehydes with propargyl amine was studied. The study provided, for the first time, direct access to 3-aminoquinolines in one step starting from readily available starting materials. Elegantly designed experiments were employed to unravel the mechanism of this unprecedented rearrangement, which are corroborated by DFT calculations.     

Gold(I)-catalyzed cascade cyclization reaction: highly regio- and diastereoselective intermolecular addition of water and alcohols to epoxy alkynes

We have developed a novel access to ketal skeletons through a highly regio- and diastereoselective intermolecular addition of water and alcohols to alkynyl epoxides catalyzed by gold(I). This procedure involves a domino three-membered ring-opening, 6-exo-cycloisomerization, and subsequent intra- or intermolecular nucleophilic addition to a double-bond sequence.     

Cu(I)-catalyzed one-pot reactions of isatins,indoles, and amines toward unsymmetrically substituted 2-carbonylarylureas

A series of unsymmetrical arylureas was obtained by the one-pot method for reacting isatins with indoles incorporating primary amino moieties, a significant heterocyclic skeleton for diverse pharmaceutically active structures. The reaction proceeds through Cu(I)-catalyzed C2C3 bond of the ring-opening isatins and then expands the substrates in the optimum conditions. Furthermore, selected compounds 4b and 4k exhibit moderate to good anti-schistosomicidal activities.     

Copper (II)-catalyzed regio- and stereoselective addition of H/P(O)R2 to alkynes

Cu(acac)₂ is the new universal catalyst for β-E regio- and stereoselective syn-addition of the H–P(O)-bond of diphenylphosphine oxide, H-phosphinates, dialkylphosphites to various alkynes in the synthesis of P(O)-containing alkenes. Without additives and ligands Cu(II)-compounds showed better results than CuI or Ni(acac)₂. The catalytic system developed is tolerant to typical organic functional groups present in the alkynes and to the nature of different substituents in the H–P(O)-compounds.     

Copper(I)-catalyzed asymmetric alkene aziridination mediated by PhI(OAc)2: a facile one-pot procedure

A facile one-pot procedure for copper-catalyzed PhI(OAc)₂-mediated asymmetric alkene aziridination had been developed. Commercially available PhI(OAc)₂ and sulfonamides were used to generate the nitrene precursors (PhINR) in situ for olefin aziridination. This one-pot procedure had been optimized using 4-nitrobenzenesulfonamide as the nitrene source. With 5 mol % of the chiral copper catalyst, these conditions afforded 94% yield of the isolated product with 75% ee. We had also developed a simple and rapid method to monitor the rate of this one-pot aziridination.     

An efficient heterogeneous gold(I)-catalyzed intermolecular cycloaddition of 2-aminoaryl carbonyls and internal alkynes leading to polyfunctionalized quinolines

The first heterogeneous intermolecular cycloaddition of 2-aminoaryl carbonyls and internal alkynes was realized in DMF at 100?°C by using a triphenylphosphine-functionalized MCM-41-supported gold(I) complex [MCM-41-PPh₃-AuCl] and AgOTf as catalysts, yielding a variety of polyfunctionalized quinolines in good to excellent yields. This heterogeneous gold(I) complex could easily be prepared via a simple two-step procedure from commercially available reagents and recovered by filtration of the reaction mixture. The recovered catalyst could be reused at least seven times with almost consistent activity without addition of AgOTf as a cocatalyst.     

Rh(I)-catalyzed formal [6 + 2] cycloaddition of 4-allenals with alkynes or alkenes in a tether

Rh(I)-catalyzed formal [6 + 2] cycloaddition of allenal 6 having an alkyne or alkene in a tether proceeded smoothly, giving 5-8- and 6-8-fused bicyclic ketone derivatives 7 in good to excellent yields. It was also found that cyclization of enantiomerically enriched (S)-6a (94% ee) gave cyclic ketone derivative (S)-7a in high yield with reasonable chirality transfer (86% ee). This result indicates that this cyclization proceeds through stereoselective formation of rhodacycle H' followed by insertion of a multiple bond.     

Ti(NMe2)4-catalyzed Markovnikov hydroamination of alkynes in the presence of N-heterocyclic carbenes and LiN(SiMe3)2

Intermolecular hydroamination of alkynes catalyzed by Ti(NMe₂)₄ was much improved with N-heterocyclic carbenes and LiN(SiMe₃)₂, by which high Markovnikov selectivity was attained for the coupling of nearly all alkynes and amines.