Alkynyl Substrates Research Articles

Harnessing the Potential of Electron Donor-Acceptor Complexes and N-Centered Radicals: Expanding the Frontiers of Isoquinoline Derivative Synthesis.

Research on synthesizing nitrogen-containing heterocyclic scaffolds is important because these structures are commonly found in Nature, such as in the alkaloids' family. In our study, we propose a new method to synthesize the isoquinoline core using an electron donor-acceptor (EDA) complex strategy. Our mechanistic investigations have confirmed that our synthesis process operates through an EDA mechanism, which is not extensively discussed in the literature, particularly regarding its applications on alkynyl substrates. This EDA strategy has proven to be a simple and straightforward way to produce isoquinoline scaffolds and their derivatives without the need for metal catalysts.

Mechanistic Insights into Multisilver-Mediated Synergistic Activation of Terminal Alkynes.

Synergistic effect extensively exists in multimetal-involved catalytic or mediated processes of group 11 metals due to their remarkable metallophilic interactions. Herein, we present a multiple synergism model for alkynyl substrates and conduct theoretical investigations on various multimetallic bonding modes and the corresponding synergistic activations. We computationally screen nine alkynyl multisilver coordination modes and sequence their reactivity shown in an intramolecular nucleophilic addition reaction by the trend of active μ4-η1η1η2η2 and μ3-η1η1η2 to the relatively inert μ2-η1η2. The transition-state (TS) stabilization of the high-nuclearity mode mainly comes from the significant negative interaction energies between Agn and the substrate based on the distortion/interaction analysis. Energy decomposition analysis-natural orbitals for chemical valence (EDA-NOCV) analysis further reveals the charge-accepting reservoir effect of the polysilver moiety and the orbital match between the alkynyl group and specific spatial arrangement of silver atoms to account for this efficient activation. In addition, tests on different ligands coordinated to silver atoms show a correlation of the ligand conformation adjustability with the reactivity of the alkynyl unit, and the accommodable η2 activation unit embodies a lower deformation energy than the other homonuclear synergistic modes. Privileged multiple synergistic models have been further evidenced based on on-bench experiments by isolating trisilver and tetrasilver alkynyl complexes. This study not only systematically evaluates the multimetallic synergism of different coordination modes in alkyne activation but also provides a guidance for the future design of multimetallic catalysts.

Diorganyl Dichalcogenides and Copper/Iron Salts: Versatile Cyclization System To Achieve Carbo- and Heterocycles from Alkynes

AbstractOrganochalcogen-containing cyclic molecules have shown several promising pharmacological properties. Consequently, different strategies have been developed for their synthesis in the past few years. Particularly due to the low cost and environmental aspects, copper- and iron-promoted cyclization reactions of alkynyl substrates have been broadly and efficiently applied for this purpose. This short review presents an overview of the most recent advances in the synthesis of organochalcogen-containing carbo- and heterocycles by reacting diorganyl disulfides, diselenides, and ditellurides with alkyne derivatives in the presence of copper and iron salts to promote cyclization reactions.1 Introduction2 Synthesis of Carbo- and Heterocycles via Reactions of Alkynes with Diorganyl Dichalcogenides and Copper Salts3 Synthesis of Carbo- and Heterocycles via Reactions of Alkynes with Diorganyl Dichalcogenides and Iron Salts4 Conclusions

Mild, Modular, and Convergent Synthesis of Helical Naphtho[2,1-c]chromenes via a Multistep Cyclization/Aromatization Cascade Sequence.

Tetracyclic 6H-naphtho[2,1-c]chromenes are expeditiously synthesized through a BF3·OEt2-mediated, three-step cascade reaction, creating new central pyran and aromatic rings. The cascade involves the addition of phenol-derived alkynyl substrates to BF3-activated aldehydes followed by alkyne-Prins cyclization, Friedel-Crafts reaction, and final elimination. Aliphatic and electron-deficient aromatic aldehydes afford the products in 50-74% isolated yields, but benzaldehyde and tolualdehyde resulted in lower yields. X-ray analysis of a p-bromophenyl derivative (5aA) shows the two aromatic moieties are twisted by 28° to create a helical backbone.

Tris(2,4,6-trifluorophenyl)borane: An Efficient Hydroboration Catalyst.

The metal‐free catalyst tris(2,4,6‐trifluorophenyl)borane has demonstrated its extensive applications in the 1,2‐hydroboration of numerous unsaturated reagents, namely alkynes, aldehydes and imines, consisting of a wide array of electron‐withdrawing and donating functionalities. A range of over 50 borylated products are reported, with many reactions proceeding with low catalyst loading under ambient conditions. These pinacol boronate esters, in the case of aldehydes and imines, can be readily hydrolyzed to leave the respective alcohol and amine, whereas alkynyl substrates result in vinyl boranes. This is of great synthetic use to the organic chemist.

Synthesis of Cyclic Carbonates from Alkenyl and Alkynyl Substrates

AbstractAs an extensively used chemical product, cyclic carbonate was generally synthesized by transesterification, or the cycloaddition of epoxides, diols with CO2. To reduce the production costs and expand the raw materials, alkenyl and alkynyl substrates have caused much attention in the synthesis of cyclic carbonates, such as olefins, allyl alcohols and propargylic alcohols. Based on the alkenyl substrate, the synthetic process involves a continuous reaction of oxidative carboxylation, with epoxide or halohydrin as an intermediate usually. Therefore, peroxides and nucleophiles (halogens or organic bases) are often necessary in the conversion. Using propargylic alcohols to produce α‐alkylidene cyclic carbonates, noble metal catalysts play crucial roles in alkynyl activation, and organic bases are considered to assist the intramolecular and intermolecular proton transfer and combine CO2 molecular. As the carboxyl sources in products, inorganic carbonates and organic carboxylic acids also have some applications instead of CO2. In this review, we summarized the synthetic routes of cyclic carbonates from alkenyl and alkynyl substrates in the aspect of catalyst, mechanism and the development tendency.

ChemInform Abstract: Late Stage Trifluoromethylthiolation Strategies for Organic Compounds

AbstractReview: [117 refs.

Hydroformylation of 2‐Alkynylanilines: Toward an Alternative Methodology for the Synthesis of 3‐Substituted Indoles

AbstractA potentially viable route for the synthesis of 3‐substituted indoles is presented herein. The methodology is based on a regioselective Rh‐catalysed hydroformylation of prepared 2‐alkyn‐1‐ylanilines. The requisite 2‐alkynylaniline substrates were prepared in high yields (>85 %) using the Pd‐catalysed Sonogashira reaction. A catalyst complex that comprises RhI(CO)(PPh3)3 and 1,2‐bis(diphenylphosphino)ethane as the ligand allowed the quantitative conversions of the alkynyl substrates with selectivities >75 % for the desired 3‐substituted indoles.

ChemInform Abstract: Microwave Assisted Tandem Heck—Sonogashira Reactions of N,N‐Di‐Boc‐Protected 6‐Amino‐5‐iodo‐2‐methyl Pyrimidin‐4‐ol in an Efficient Approach to Functionalized Pyrido[2,3‐d]pyrimidines.

A microwave assisted tandem Heck-Sonogashira cross-coupling reaction between 6-N,N-di-Boc-amino-5-iodo-2-methyl pyrimidin-4-ol and various aryl alkynyl substrates has been developed. This process generates novel 5-enynyl substituted pyrimidines, which can be transformed to novel functionalized pyrido[2,3-d]pyrimidines by way of a silver catalyzed cyclization reaction.

Microwave assisted tandem Heck-Sonogashira reactions of N,N-di-Boc-protected 6-amino-5-iodo-2-methyl pyrimidin-4-ol in an efficient approach to functionalized pyrido[2,3-d]pyrimidines.

A microwave assisted tandem Heck-Sonogashira cross-coupling reaction between 6-N,N-di-Boc-amino-5-iodo-2-methyl pyrimidin-4-ol and various aryl alkynyl substrates has been developed. This process generates novel 5-enynyl substituted pyrimidines, which can be transformed to novel functionalized pyrido[2,3-d]pyrimidines by way of a silver catalyzed cyclization reaction.

Gold-catalysed Homocoupling of Alkynes

The homocoupling reaction of alkynes was carried out in the presence of 10 mol% AuCl3 using I2 as oxidant to generate 1,3-diynes products in high yield. The method is simple, safe and efficient. Both aryl and alkyl substituted alkynyl substrates reacted smoothly. AuClPPh3 also showed comparable catalytic activity to this transformation under a nitrogen atmosphere.

ChemInform Abstract: Tf2O‐Catalyzed Friedel—Crafts Alkylation to Synthesize Dibenzo[a,d]cycloheptene Cores and Application in the Total Synthesis of Diptoindonesin D, Pauciflorial F, and (.+‐.)‐Ampelopsin B.

AbstractA general protocol is developed to cyclize alkynyl substrates such as (I) to dibenzo[a,d]cycloheptenes using Tf2O as the catalyst.

ChemInform Abstract: Asymmetric Synthesis of Allenyl Oxindoles and Spirooxindoles by a Catalytic Enantioselective Saucy—Marbet Claisen Rearrangement.

AbstractThe rearrangement of alkynyl substrates allows the synthesis of allenyl oxindoles having a quarternary stereocenters.

Asymmetric Synthesis of Allenyl Oxindoles and Spirooxindoles by a Catalytic Enantioselective Saucy–Marbet Claisen Rearrangement

Asymmetric Synthesis of Allenyl Oxindoles and Spirooxindoles by a Catalytic Enantioselective Saucy–Marbet Claisen Rearrangement

ChemInform Abstract: Enantioselective and Regioselective Organocatalytic Conjugate Addition of Malonates to Nitroenynes.

The first catalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroenynes catalyzed by cinchona alkaloid-based thiourea organocatalysts has been developed. The 1,4-addition adducts were obtained solely, in moderate to good yields (up to 93 %) with good enantioselectivities (up to 99 % ee). This protocol affords a conceptually different entry to the precursors of pharmaceutically important chiral β-alkynyl acid derivatives and synthetically useful chiral nitroalkynes. Notably, the protocol worked well with both aryl- and alkyl-substituted alkynyl substrates.

Enantioselective and Regioselective Organocatalytic Conjugate Addition of Malonates to Nitroenynes

The first catalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroenynes catalyzed by cinchona alkaloid-based thiourea organocatalysts has been developed. The 1,4-addition adducts were obtained solely, in moderate to good yields (up to 93%) with good enantioselectivities (up to 99% ee). This protocol affords a conceptually different entry to the precursors of pharmaceutically important chiral β-alkynyl acid derivatives and synthetically useful chiral nitroalkynes. Notably, the protocol worked well with both aryl- and alkyl-substituted alkynyl substrates.

Asymmetric synthesis of bicyclic amidines via rhodium-catalyzed [2+2+2] cycloaddition of carbodiimides.

A highly enantioselective rhodium-catalyzed [2+2+2] cycloaddition of terminal alkynes and alkenyl carbodiimides has been developed. This reaction demonstrates the feasibility of olefin insertion into carbodiimide-derived metalacycles and provides a new class of chiral bicyclic amidines as the major products. An isonitrile migration process responsible for the formation of the minor cycloadduct can be observed and is highly sensitive to the electronics of alkynyl substrates.