Triarylbismuth Reagents Research Articles

High efficient copper-promoted N-arylation of secondary and primary amines with triarylbismuth reagents under mild conditions

Triarylbismuths were found to be highly efficient arylating reagents for copper-promoted N-arylation of secondary and some heteroaryl and aliphatic primary amines with over 49 examples. A variety of sterically diverse tertiary and secondary amines could be obtained in good to excellent yields with good functional group compatibility. The operational simplicity, mild reaction conditions as well as the option for efficient gram-scale preparation, makes the process much more practical.

On the Copper-Promoted Backbone Arylation of Histidine-Containing Peptides Using Triarylbismuthines

AbstractWe report herein our detailed investigation on the histidine-directed backbone arylation of histidine-containing peptides using triarylbismuth reagents. The reaction proceeds on the backbone NH of the amino acid that precedes the histidine, the so-called n–1 position. The protocol is applicable to dipeptides where the histidine is located at the C-terminus and to tripeptides where the histidine occupies the central position. The transformation is promoted by copper(II) acetate in the presence of phenanthroline (Phen) and diisopropylethylamine in dichloromethane at 50 °C under oxygen. An excellent scope was observed for the triarylbismuthines. In all cases, the imidazole ring of the histidine is protected with a trityl group to prevent the arylation of the side chain. An ATCUN-like model is proposed to explain the observed results.

Pd-Catalyzed cross-coupling synthesis of 4-aryl-3-formylcoumarins.

The threefold cross-coupling of triarylbismuth reagents with 4-chloro-3-formylcoumarins furnished the corresponding 4-aryl-3-formylcoumarins in a chemoselective manner with high yields under Pd-catalyzed conditions. This method was successfully applied to electronically different triarylbismuth reagents and 4-chloro-3-formylcoumarins preserving the 3-formyl group in the coumarin scaffold.

Chemo‐selective Synthesis of 4‐Chloro‐3‐(arylethynyl)coumarins and their Synthetic Transformations

AbstractA study describing the chemoselective reactivity of 4‐chloro‐3‐(2,2‐dibromovinyl)‐2H‐chromen‐2‐ones with triarylbismuth reagents in the synthesis of 4‐chloro‐3‐(arylethynyl)coumarins under Pd‐catalyzed conditions is presented. A viable Pd‐catalyzed protocol for the chemoselective cross‐coupling reactivity of the 3‐gem‐dibromide in comparison to the 4‐chloro substituent in coumarin substrates is developed. The synthetic scope of 4‐chloro‐3‐(arylethynyl)coumarins with reactive 4‐chloro substituent was further demonstrated in the synthesis of 2‐(arylethynyl)benzofurans, 4‐(N‐heteroaryl)‐3‐(arylethynyl)coumarins, and 4‐methoxy‐3‐(p‐tolylethynyl)coumarin under different reaction conditions.

Copper-Promoted N-Arylation of the Imidazole Side Chain of Protected Histidine by Using Triarylbismuth Reagents.

The N-arylation of the side chain of histidine by using triarylbismuthines is reported. The reaction is promoted by copper(II) acetate in dichloromethane at 40 °C under oxygen in the presence of diisopropylethylamine and 1,10-phenanthroline and allows the transfer of aryl groups with substituents at any position of the aromatic ring. The reaction shows excellent functional group tolerance and is applicable to dipeptides where the histidine is located at the N terminus. A histidine-guided backbone N-H arylation was observed in dipeptides where the histidine occupies the C terminus.

Pd‐Catalyzed Domino Cross‐Coupling: Synthesis of Functionalized 4‐(Arylethynyl)Coumarins

AbstractA Pd‐catalyzed domino cross‐coupling methodology was developed to synthesize various 4‐(arylethynyl)coumarin derivatives involving 4‐(gem‐dibromovinyl)coumarins and triarylbismuths as threefold aryl donor reagents. In these reactions, 4‐(gem‐dibromovinyl)coumarin derivatives have been cross‐coupled with sub‐stoichiometric amounts of triarylbismuth reagents. This study involving mono‐, chemoselective and bis‐couplings have been demonstrated with versatile reactivity under the established Pd‐catalyzed domino coupling conditions affording good to high product yields.

Copper‐Promoted O‐Arylation of the Phenol Side Chain of Tyrosine Using Triarylbismuthines

A general method for the O‐arylation of the side chain of tyrosine using triarylbismuth reagents is reported. The reaction is mediated by copper diacetate, operates at 50 °C under oxygen in dichloromethane in the presence of pyridine, shows excellent functional group compatibility, and retains the integrity of the stereogenic center. The protocol was used to arylate the tyrosine residue of dipeptides and tripeptides.

Copper‐Promoted N‐Arylation of the Indole Side Chain of Tryptophan Using Triarylbismuthines

A simple protocol for the regioselective N‐arylation of the indole side chain of tryptophan using triarylbismuth reagents as the arylating agent is reported. The reaction is catalyzed by copper(II) acetate, and operates in the presence of triethylamine or pyridine under air at 50 °C. This reaction allows the transfer of aryl groups bearing electron neutral, donating or withdrawing substituents at any position of the ring, shows high functional group tolerance, and retains the integrity of the stereogenic center. The protocol was utilized to N‐arylate tryptophan‐containing di‐ and tripeptides.

Rapid Bis‐Coupling Reactivity with Triarylbismuth Reagents: Synthesis of Structurally Diverse Scaffolds and Step‐economic Convergent Synthesis of Quebecol

The cross‐coupling study of gem‐dibromoesters with triarylbismuths as threefold arylating reagents was investigated under palladium‐catalyzed conditions. This study using triarylbismuth reagents explored the cross‐coupling reactivity with various functionalized gem‐dibromoesters. It furnished a variety of multi‐functional trisubstituted acrylates embedded with aryl, alkene and alkyne scaffolds in high yields. The present study in turn, provided easy access to various triarylated acrylates and functionalized 1,3‐dienyl and 1,3‐enyne esters. Further, the established method applied in the step‐economic and convergent synthesis of quebecol natural product in good yield.

Pd-catalyzed atom-efficient cross-coupling of triarylbismuth reagents with protecting group-free iodophenylmethanols: Synthesis of biarylmethanols

An atom-efficient procedure for the synthesis of functionalized biarylmethanols via the Pd-catalyzed cross-coupling reactions of differently functionalized iodophenylmethanols and triarylbismuth reagents is described. This protecting group-free direct couplings of 2-, 3- or 4-iodophenylmethanols with triarylbismuth reagents afforded biarylmethanols in good to high yields.

Pd-catalyzed protecting-group-free cross-couplings of iodophenols with atom-economic triarylbismuth reagents

An efficient protocol for the protecting-group-free synthesis of unsymmetrical hydroxybiaryls via the Pd-catalyzed cross-couplings of unprotected iodophenols with triarylbismuth reagents is described. The presented protocols exhibits good to high yields of hydroxybiaryls.

Atom-efficient Pd-catalyzed cross-couplings of chloroarenes with triarylbismuth reagents

Various Pd-catalyzed protocols have been developed for the atom-efficient cross-coupling of chloroarenes with triarylbismuth reagents. Using the developed protocols, an efficient synthesis of unsymmetrical biaryls in good to excellent yields was achieved by employing electron-deficient chloroarenes and a range of triarylbismuth reagents.

Cross-coupling reactivity of 1,1-dichloroalkenes under palladium catalysis: domino synthesis of diarylalkynes

An efficient synthesis of diarylalkynes was achieved from the domino cross-coupling reaction of 1,1-dichloroalkenes with triarylbismuth reagents under palladium-catalyzed conditions.

Base free palladium-Ag2O catalyzed decarboxylative cross-coupling of alkynyl carboxylic acids with triarylbismuth reagents

We have developed a novel base free methodology for the decarboxylative cross-coupling reaction of alkynyl carboxylic acids with triarylbismuth reagents. The decarboxylative cross-coupling reaction proceeds using the homogeneous Pd(OAc)2-Ag2O catalytic system at room temperature with short reaction time. Triarylbismuth reagents are particularly attractive due to their air and moisture stability, high functional group tolerance and threefold arylating property. This methodology is particularly useful for the synthesis of unsymmetrical substituted alkynes.

Functional group manoeuvring for tuning stability and reactivity: synthesis of cicerfuran, moracins (D, E, M) and chromene-fused benzofuran-based natural products.

The protecting group manoeuvring as a strategy was applied for tuning the stability and reactivity of 4-(2,2-dibromovinyl)benzene-1,3-diol (12a) and 6-(2,2-dibromovinyl)-2,2-dimethylchroman-7-ol (22) in the domino synthesis of benzofuran-based natural products (1-8). The functional group demands and their impact on the reactivity driven by electronic effects were successfully managed by varying the protecting groups with substituted gem-dibromovinylphenols in domino couplings and triarylbismuth reagents under palladium-catalyzed conditions. This approach paved the way for the synthesis of moracin M (1) and cicerfuran (2), and the first time synthesis of moracin D (3) and moracin E (4) along with chromene-fused benzofuran-based natural products (5-8) in overall good yields.

Atom economic palladium catalyzed novel approach for arylation of benzothiazole and benzoxazole with triarylbismuth reagents via C[sbnd]H activation

We have developed a novel method for the direct CH functionalization of benzothiazole and benzoxazole using triarylbismuth reagents. The arylation proceeds using the homogeneous catalytic system PdCl2, Cu(OAc)2 and PPh3 ligand. Triarylbismuthines, which act as threefold arylating reagents, have low toxicity, are green and ecofriendly. These methodologies are particularly useful to prepare arylated benzothiazoles and benzoxazoles.

Preparation of 3-O-aryl chloramphenicol derivatives via chemoselective copper-catalyzed O-arylation of (1R,2R)-(−)-N-BOC-2-amino-1-(4-nitrophenyl)-1,3-propanediol using triarylbismuthines

A copper-catalyzed protocol for the chemoselective arylation of (1R,2R)-(−)-N-BOC-2-amino-1-(4-nitrophenyl)-1,3-propanediol using triarylbismuth reagents is reported. The reaction operates under simple and mild conditions, shows good functional group tolerance and allows the installation of ortho-, meta-, and para-substituted aryl groups in moderate to good yields. These arylated products are then transformed in two steps into their corresponding N-dichloroacetamide derivatives. This sequence provides an expedient access to 3-O-aryl chloramphenicol derivatives.

Synthesis of Highly Functionalized Triarylbismuthines by Functional Group Manipulation and Use in Palladium- and Copper-Catalyzed Arylation Reactions.

Organobismuthines are an attractive class of organometallic reagents that can be accessed from inexpensive and nontoxic bismuth salts. Triarylbismuthines are particularly interesting due to their air and moisture stability and high functional group tolerance. We report herein a detailed study on the preparation of highly functionalized triarylbismuth reagents by triple functional group manipulation and their use in palladium- and copper-catalyzed C-, N-, and O-arylation reactions.

Rapid Access to Benzofuran‐Based Natural Products through a Concise Synthetic Strategy

AbstractA concise strategy is described for the synthesis of ailanthoidol (1), egonol (2), homoegonol (3), demethoxyegonol (4), demethoxyhomoegonol (5), and stemofuran A (6). This approach involves a Pd‐catalysed domino cyclization/coupling process using triarylbismuth reagents for the generation of the benzofuran core. Subsequent structural modifications then give the final targets. The high yielding synthesis of the recently isolated natural products egonol‐9(Z)‐12(Z)‐linoleate (2a), 7‐demethoxyegonol‐9(Z)‐12(Z)‐linoleate (4a), and 7‐demethoxy‐egonol‐9(Z)‐oleate (4b) are also reported.

Rapid Access to Triarylated Cyclotriveratrylenes from Threefold Couplings of CTV‐I3 with Triarylbismuth Reagents

AbstractA series of C3‐symmetric triiodocyclotriveratrylene (CTV‐I3) derivatives have been successfully arylated to afford the corresponding triarylcyclotriveratrylene derivatives in high yields by using triarylbismuth compounds as threefold coupling reagents under palladium‐catalyzed conditions. This functionalization is valuable in the context of the development of new synthetic and coupling studies to rapidly access cyclotriveratrylene molecular skeletons with rigid and deeper cavities.