Gold(I)-catalyzed stereoselective formation of functionalized 2,5-dihydrofurans

[reaction: see text] A study concerning the gold(I)-catalyzed rearrangement of butynediol monobenzoates into functionalized 2,5-dihydrofurans is described. The mild reaction conditions employed allow the efficient and rapid stereoselective synthesis of a variety of 2,5-dihydrofurans via a sequence of two gold(I)-catalyzed isomerization steps.     

A general synthetic route to differentially functionalized angularly and linearly fused [6-7-5] ring systems: a Rh(I)-catalyzed cyclocarbonylation reaction

Investigations of a Rh(I)-catalyzed cyclocarbonylation reaction reveal its general synthetic utility for accessing highly functionalized tricyclic [6-7-5] linear and angular ring systems from allene-ynes. Three types of allene-ynes were prepared and subjected to Rh(I)-catalyzed cyclocarbonylation conditions. For three series of allene-ynes, the [6-7-5] ring systems were afforded in varying yields depending on the substrate structure. One series of allene-ynes afforded the [6-6-5] ring system possessing an alpha-alkylidene cyclopentenone as a result of a selective reaction with the proximal double bond of the allene.     

Synthesis of the tetracyclic framework of the erythrina alkaloids using a [4 + 2]-cycloaddition/Rh(I)-catalyzed cascade of 2-imidofurans

Several 2-imido substituted furans were found to undergo a rapid intramolecular [4 + 2]-cycloaddition to deliver oxabicyclo adducts in good to excellent yields. By using a Rh(I)-catalyzed ring opening of the resulting oxabicyclic adduct, it was possible to prepare several highly functionalized tetrahydro-1H-indol-2(3H)-one derivatives which were then used to prepare several erythrina alkaloids. By taking advantage of the Rh(I)-catalyzed reaction, it was possible to convert tert-butyl 3-oxo-5-carbomethoxy-10-oxa-2-azatricyclo[5.2.1.0(1,5)]dec-8-ene-2-carboxylate into the ring opened boronate by reaction with phenylboronic acid. Treatment of the boronate with pinacol/acetic acid afforded the corresponding diol which was used in a successful synthesis of racemic 3-demethoxyerythratidinone. During the course of these studies, several novel rearrangement reactions were encountered while attempting to induce an acid-initiated Pictet Spengler cyclization of a key lactam intermediate. The IMDAF/Rh(I)-catalyzed ring opening cascade sequence was also applied to the total synthesis of (+/-)-erysotramidine as well as the lycorine type alkaloid (+/-)-epi-zephyranthine.     

Gold(I) catalyzed isomerization of 5-en-2-yn-1-yl acetates: an efficient access to acetoxy bicyclo[3.1.0]hexenes and 2-cycloalken-1-ones

The gold(I) catalyzed rearrangement of 5-en-2-yn-1-yl acetates into functionalized acetoxy bicyclo[3.1.0]hexenes is described. The mild reaction conditions employed allow the efficient and rapid synthesis of a variety of such bicyclic compounds via a sequence of two gold(I)-catalyzed isomerization steps. Acetoxy bicyclo[3.1.0]hexenes products can be further transformed to 2-cycloalkenones by simple methanolysis.     

Phosphoramidite gold(I)-catalyzed diastereo- and enantioselective synthesis of 3,4-substituted pyrrolidines

In this article the utility of phosphoramidite ligands in enantioselective Au(I) catalysis was explored in the development of highly diastereo- and enantioselective Au(I)-catalyzed cycloadditions of allenenes. A Au(I)-catalyzed synthesis of 3,4-disubstituted pyrrolidines and γ-lactams is described. This reaction proceeds through the enantioselective Au(I)-catalyzed cyclization of allenenes to form a carbocationic intermediate that is trapped by an exogenous nucleophile, resulting in the highly diastereoselective construction of three contiguous stereogenic centers. A computational study (DFT) was also performed to gain some insight into the underlying mechanisms of these cycloadditions. The utility of this new methodology was demonstrated through the formal synthesis of (-)-isocynometrine.     

Copper-catalyzed iminoiodane-mediated aminolactonization of olefins: application to the synthesis of 5,5-disubstituted butyrolactones

A copper(I)-catalyzed reaction of a variety of 4-aryl-pent-4-enoates with nosyliminoiodane generated in situ provides the corresponding 5-aryl-5-nosylamidomethylbutyrolactones. The reaction presumably proceeds via an aziridine intermediate, which could be isolated in one case.     

Copper(I)-catalyzed carboxylation of aryl- and alkenylboronic esters

The copper(I)-catalyzed carboxylation reaction of aryl- and alkenylboronic esters proceeded smoothly under CO(2) to give the corresponding carboxylic acid in good yield. This reaction showed wide generality with higher functional group tolerance compared to the corresponding Rh(I)-catalyzed reaction.     

Signal amplification and transduction by photo-activated catalysis

A simple flavin-based catalytic system is able to transform light into chemical output with amplified response utilizing a Cu(I)-catalyzed cycloaddition reaction.     

Conjugate Addition vs Heck Reaction: A Theoretical Study on Competitive Coupling Catalyzed by Isoelectronic Metal (Pd(II) and Rh(I))

Density functional theory studies have been carried out to investigate the mechanism of the Pd(II)(bpy)- and Rh(I)(bpy)-catalyzed conjugate additions and their competitive Heck reactions involving α,β-unsaturated carbonyl compounds. The critical steps of the mechanism are insertion and termination. The insertion step favors 1,2-addition of the vinyl-coordinated species to generate a stable C-bound enolate intermediate, which then may isomerize to either an oxa-π-allyl species or an O-bound enolate. The termination step involves a competition between β-hydride elimination, leading to a Heck reaction product, and protonolysis reaction that gives a conjugate addition product. These two pathways are competitive in the Pd(II)-catalyzed reaction, while a preference for protonolysis has been found in the Rh(I)-catalyzed reaction. The calculations are in good agreement with the experimental observations. The potential energy surface and the rate-determining step of the β-hydride elimination are similar for both Pd(II)- and Rh(I)-catalyzed processes. The rate-determining steps of the Pd(II)- and Rh(I)-catalyzed protonolysis are different. Introduction of an N- or P-ligand significantly stabilizes the protonolysis transition state via the O-bound enolate or oxa-π-allyl complex intermediate, resulting in a reduced free energy of activation. However, the barrier of the β-hydride elimination is less sensitive to ligands. For the Rh(I)-catalyzed reaction, protonolysis is calculated to be more favorable than the β-hydride elimination for all investigated N and P ligands due to the significant ligand stabilization to the protonolysis transition state. For the Pd(II)-catalyzed reaction, the complex with monodentate pyridine ligands prefers the Heck-type product through β-hydride elimination, while the complex with bidentate N and P ligands favors the protonolysis. The theoretical finding suggests the possibility to control the selectivity between the conjugate addition and the Heck reaction by using proper ligands.     

Research on Au(I)-catalyzed ene-yne cycloisomerization for construction of quassinoid scaffold

Compounds that undergo Au(I)-catalyzed cycloisomerizations affording tetracyclic products that can be converted into compounds with the skeleton of bruceantin are described. The Au(I)-catalyzed cycloisomerizations reported herein are hindered by a 1,3-diaxial interaction between the substituent and the methyl group in the transition state. The use of small substituents was found to increase the yield of the desired product, while the reaction of substrates with large substituents afford undesired constitutional isomers.     

1,3-Phenylene-based symmetrical bis(urea-1,2,3-triazole) hybrids: Synthesis,antimicrobial and in silico studies as 14α-sterol demethylase inhibitors

Research on Chemical Intermediates - A series of symmetrical bis(urea-1,2,3-triazole) hybrids (5a–5f, 6a–6f) were synthesized via Cu(I)-catalyzed click reaction followed by...     

Enantioselective syntheses of tremulenediol A and tremulenolide A

[reaction: see text] An enantioselective entry to the skeleton of the tremulane sesquiterpenes is described. The approach features a series of efficient transition metal-catalyzed reactions commencing with an enantioselective rhodium(II)-catalyzed intramolecular cyclopropanation followed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalyzed [5 + 2] cycloaddition. This strategy was applied to the first enantioselective syntheses of tremulenediol A and tremulenolide A.     

A Simple Efficient Click Synthesis of Novel Crown Ethers Containing 1,2,3-Triazole Moieties

Novel crown ether derivative containing 1,4-disubstituted-1,2,3-triazole moieties were synthesized. At the first step of the synthesis 4,13-diaza-18-crown-6 and 4-aminobenzo-15-crown-5 were converted into terminal alkynes, which were then subjected to copper(I)-catalyzed alkyne-azide coupling (CuAAC) in methylene chloride. This coupling reaction was performed according to the concept of click chemistry, using an Amberlyst A-21-supported copper(I) iodide catalyst.

     

Features and applications of [Rh(CO)(2)Cl](2)-catalyzed alkylations of unsymmetrical allylic substrates

A novel regio- and stereoselective [Rh(CO)2Cl]2-catalyzed allylic alkylation of unsymmetrical allylic carbonates was discovered. The regioselectivity of the reaction favors product ratios in which substitution occurs at the carbon bearing the leaving group. When an enantiomerically enriched carbonate (> or = 99% ee) was examined, the Rh(I)-catalyzed allylic alkylation proceeded stereoselectively to provide the alkylation product with retention of absolute stereochemistry (98% ee). To establish the scope of the [Rh(CO)2Cl]2-catalyzed allylic alkylation, a variety of carbon and heteroatom nucleophiles were examined and the results described. As an application of the Rh(I)-catalyzed allylic alkylation, a series of novel domino reactions have been developed that couple the unique regio- and stereoselective [Rh(CO)2Cl]2-catalyzed alkylation of allylic trifluoroacetates with an intramolecular Pauson-Khand annulation, a cycloisomerization, or a [5+2] cycloaddition. A unique aspect of the method described is the use of a single catalyst to effect sequential transformations in which the catalytic activity is moderated simply by controlling the reaction temperature. Implementation of such processes provides a rapid and efficient entry to a variety of bicyclic carbon skeletons from simple precursors.     

Selective enhancement effects of silver salts on the transition metal-catalyzed synthesis of gem-difluorinated heterocyclics using 2,2-difluorohomopropargyl amides

The addition of silver salts had an effect on the catalyst activity in the Pd(0)-catalyzed cyclization-coupling tandem reaction, as well as in the Rh(I)-catalyzed Pauson-Khand reaction. The cationic palladium complex generated from Pd(PPh₃)₄ (2.5 mol%) with AgSbF₆ (1.5 equiv.) activates the triple bond of 2,2-difluoropropargylic amides to give the 4,5-disubstituted 3,3-difluoro-γ-lactams, through a sequential 5-endo-dig cyclization and cross-coupling reaction. The γ-lactam was transformed into ring-opened monofluorovinylic compounds after silica-gel chromatography. Pauson-Khand reaction of fluorinated 1,7-enyne amides using catalytic amounts of [Rh(COD)₂]₂ (5 mol%) and AgOTf (20 mol%) gave the corresponding gem-difluorinated bicyclic lactam.     

Rhodium-catalyzed tandem conjugate addition-Mannich cyclization reaction: straightforward access to fully substituted tetrahydroquinolines

A new Rh(I)-catalyzed tandem conjugate addition-Mannich cyclization reaction of imine-substituted electron-deficient alkenes with arylboronic acids has been developed to afford 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines. This is the first example involving imine group as a secondary electrophile in Rh(I)-catalyzed tandem reactions.     

Selective gold(I)-catalyzed formation of tetracyclic indolines: a single transition structure and bifurcations lead to multiple products

Several alkynylindoles undergo gold(I)-catalyzed cyclization reactions to form a single isomer in each case. Density functional theory shows why this reaction is favored over the many possible regio- and stereoisomeric reaction pathways. This transformation involves a two-step no-intermediate mechanism with surface bifurcations leading to two or three products. Such bifurcations could explain reactivity in many gold(I)-catalyzed enyne cyclization reactions.     

Rh(I)-catalyzed intramolecular hydroacylation in ionic liquids

Rh(I)-catalyzed hydroacylation of 4-alkenal or 4,6-dienal using ionic liquids (ILs) as reaction media proceeded smoothly, giving cyclopentanone or cycloheptenone derivatives in good yields. It was found that the IL recovered after the reaction, which should contain the Rh(I) catalyst, could be recycled 5-10 times without the loss of catalytic activity and enantioselectivity (in the case of asymmetric hydroacylation).     

Au(I)-catalyzed cyclization of enynes bearing an olefinic cycle

Gold(I)-catalyzed cyclization of enynes containing an olefinic cycle has been studied. The introduction of an olefinic ring instead of a terminal alkene in enynes dramatically increased the yield of the reaction. Enynes having an olefinic cycle were prepared by a rhodium-catalyzed intermolecular [4 + 2] cycloaddition of diynes with butadiene. Consecutive rhodium-catalyzed Diels-Alder/gold(I)-catalyzed cycloisomerization reactions were integrated in a one-pot reaction.     

Aryl methyl sulfides as substrates for rhodium-catalyzed alkyne carbothiolation: arene functionalization with activating group recycling

A Rh(I)-catalyzed method for the efficient functionalization of arenes is reported. Aryl methyl sulfides are combined with terminal alkynes to deliver products of carbothiolation. The overall process results in reincorporation of the original arene functional group, a methyl sulfide, into the products as an alkenyl sulfide. The carbothiolation process can be combined with an initial Rh(I)-catalyzed alkene or alkyne hydroacylation reaction in three-component cascade sequences. The utility of the alkenyl sulfide products is also demonstrated in simple carbo- and heterocycle-forming processes. We also provide mechanistic evidence for the course of this new process.