Sp Coupling Research Articles

Cu(I)/N,N-Imine Ligand Catalyzed C(sp3)-C(sp) Coupling of Alkyl Bromides with Alkynes: Scope and Mechanistic Investigation.

We have developed an efficient Cu/N,N-bidentate imine ligand catalytic system for C(sp3)-C(sp) coupling to obtain internal alkynes, di/trisubstituted allenes and strained bridged cyclic lactams in moderate to excellent yields from readily available alkyl(benzyl) bromides in one-pot transformation. Density Functional Theory (DFT) assisted mechanistic study along with control experiments support the involvement of bialkynylated copper species which undergo single electron transfer (SET) with alkyl halides to generate radical intermediate in the reaction. The N,N-bidentate imine ligand plays a vital role in stabilization of intermediate copper complex and facilitates the product formation.

Selective Synthesis of 5‐Alkynyl Trisubstituted 1,2,3‐triazoles from Azides and Alkynes via Photoexcited Copper(I)acetylides

AbstractVisible‐light‐initiated copper(I) catalyzed selective synthesis of 5‐alkynyl trisubstituted 1,2,3‐triazoles from azides and alkynes is reported. The reaction proceeded via photoexcited copper(I)acetylides with azides to in‐situ formation of cuprate‐triazole followed by oxidative C−C(sp) coupling with another alkynes. The UV‐Visible spectrum shows that in‐situ photoexcited copper(I)acetylides (λabs=425–485 nm) is most probably the key light absorbing species responsible for CuAAC reactions.

Visible-Light-Mediated Deoxyalkynylation of Activated Tertiary Alcohols.

In this paper, visible-light-induced deoxyalkynylation of activated tertiary alcohols has been successfully performed under mild reaction conditions with ethynylbenziodoxole as the readily available alkynylation reagent. The desired C(sp3)-C(sp) coupling can smoothly occur with 4-CzIPN as a photocatalyst, affording a wide range of valuable alkynylation products bearing quaternary carbon centers in 37-84% yields.

Nickel-Catalyzed Sonogashira Coupling Reactions of Nonactivated Alkyl Chlorides under Mild Conditions

The two nickel chlorides 1 and 2 with [P,S] and [P,Se] bidentate ligands, respectively, were synthesized and used as catalysts for Sonogashira coupling reaction. Both 1 and 2 are efficient catalysts for Sonogashira C(sp3)–C(sp) coupling reactions. Complex 1 has better catalytic activity than complex 2. In a combination of 1 mol % catalyst loading of 1 and CuI/Cs2CO3/DMSO at 25 °C for the coupling reactions of alkyl iodides with terminal alkynes, the corresponding coupling products were obtained in moderate to excellent yields. This catalytic system is also suitable for alkyl bromides at 40 °C. It must be pointed out that with NaI as an additive complex 1 could effectively catalyze the C(sp3)–C(sp) coupling of nonactivated alkyl chlorides with alkynes under mild conditions (50 °C) with low catalyst loading (1 mol %). Complex 1 is easy to synthesize and has efficient catalytic activity, especially for alkyl chlorides, under mild conditions.

Double perovskite Ba2BiTaO6 as a promising p-type transparent conductive oxide: A first-principles defect study

The realization of p-type transparent conductive oxides (TCOs) is a long-standing difficulty because of their generally large hole effective mass and low doping limit ascribed to the strong electronegativity of oxygen. By introducing a Bi atom with a lone-pair s orbital on the B site, double perovskite Ba2BiTaO6 could exhibit a dispersive upper valence band and a small hole effective mass due to the strong sp antibonding coupling. In contrast to n-type TCOs, i.e., ZnO and In2O3, first-principles studies on the intrinsic defects of Ba2BiTaO6 show that it is able to exhibit a good p-type property or stay intrinsic instead of being n-type by tuning the chemical potentials and its dominated defects (VBa, VBi, BaBi, and BiTa) are shallow acceptors, indicating that Ba2BiTaO6 is able to be a promising p-type TCO. This work shows that perovskites could be a class of potential p-type TCOs by introducing strong sp coupling with lone-pair-s-orbital elements.

Access to Divergent Fluorinated Enynes and Arenes via Palladium-Catalyzed Ring-Opening Alkynylation of gem-Difluorinated Cyclopropanes.

Herein, we describe a palladium-catalyzed alkynylation of gem-difluorinated cyclopropanes via C-C bond activation/C-F bond cleavage, followed by C-C(sp) coupling. The new approach proceeds with broad substrate scope under mild reaction conditions, whereas both 1,1-disubstituted and complex-molecule-modified gem-difluorinated cyclopropanes react smoothly with high stereoselectivity. The developed method provides efficient and convenient ways access to diversity of important fluorinated enynes and arenes by slightly modification of the reaction conditions.

The Fascinating Chemistry of α-Haloamides.

The aim of this review is to highlight the rich chemistry of α‐haloamides originally mainly used to discover new C−N, C−O and C−S bond forming reactions, and later widely employed in C−C cross‐coupling reactions with C(sp3), C(sp2) and C(sp) coupling partners. Radical‐mediated transformations of α‐haloamides bearing a suitable located unsaturated bond has proven to be a straightforward alternative to access diverse cyclic compounds by means of either radical initiators, transition metal redox catalysis or visible light photoredox catalysis. On the other hand, cycloadditions with α‐halohydroxamate‐based azaoxyallyl cations have garnered significant attention. Moreover, in view of the important role in life and materials science of difluoroalkylated compounds, a wide range of catalysts has been developed for the efficient incorporation of difluoroacetamido moieties into activated as well as unactivated substrates.

Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)\u2212H bonds with alkynes

Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp3)—C(sp) coupling of unactivated C(sp3)−H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp3)—H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-based N,N,P-ligand catalyst for asymmetric oxidative cross-coupling of unactivated C(sp3)—H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use of N-fluoroamide as a mild oxidant is essential to site-selectively generate alkyl radical species while efficiently avoiding Glaser homocoupling. This reaction accommodates a range of (hetero)aryl and alkyl alkynes; (hetero)benzylic and propargylic C(sp3)−H bonds are all applicable. This process allows expedient access to chiral alkynyl amides/aldehydes. More importantly, it also provides a versatile tool for the construction of chiral C(sp3)—C(sp), C(sp3)—C(sp2), and C(sp3)—C(sp3) bonds when allied with follow-up transformations.

Photosensitized oxidative addition to gold(I) enables alkynylative cyclization of o-alkylnylphenols with iodoalkynes.

The well-established oxidative addition-reductive elimination pathway is the most followed one in transition metal-catalysed cross-coupling reactions. While readily occurring with a series of transition metals, gold(I) complexes have shown some reluctance to undergo oxidative addition unless special sets of ligands on gold(I), reagents or reaction conditions are used. Here we show that under visible-light irradiation, an iridium photocatalyst triggers-via triplet sensitization-the oxidative addition of an alkynyl iodide onto a vinylgold(I) intermediate to deliver C(sp)2-C(sp) coupling products after reductive elimination. Mechanistic and modelling studies support that an energy-transfer event takes place, rather than a redox pathway. This particular mode of activation in gold homogenous catalysis was applied in several dual catalytic processes. Alkynylbenzofuran derivatives were obtained from o-alkynylphenols and iodoalkynes in the presence of catalytic gold(I) and iridium(III) complexes under blue light-emitting diode irradiation.

Gold-Catalyzed C(sp2 )-C(sp) Coupling by Alkynylation through Oxidative Addition of Bromoalkynes.

A gold(I)-catalyzed cascade cyclization-alkynylation of allenoates using alkynyl bromide to generate β-alkynyl-γ-butenolides was investigated. Whereas alkynyl iodides afforded significant amounts of the homo-coupling of two lactone units, alkynyl bromides led to a selective reaction, and a broad functional group tolerance was observed. Under the optimized reaction conditions, it was possible to directly synthesize a large range of β-alkynyl-γ-butenolides in moderate to good yields without the need for any external oxidant.

A convenient route to 1,3-diynes using ligand-free Cadiot-Chodkiewicz coupling reaction at room temperature under aerobic conditions

In this study, we report a copper-catalyzed ligand-free Cadiot-Chodkiewicz coupling reaction. No additives or ligands are required for this Cu-catalyzed C(sp)-C(sp) coupling reaction of terminal alkynes with alkynyl halides. The low cost of copper catalyst, excellent yield of the products, suppression of side-products and mild reaction conditions are the major advantages of this protocol.

A walk around the application of nanocatalysts for cross-dehydrogenative coupling of C-H bonds.

Cross-dehydrogenative coupling reactions between two unmodified C–H bonds are one of the most attractive and fundamental strategies for the construction of C–C bonds. As these reactions avoid pre-functionalization and de-functionalization of the substrates, they are cleaner, safer, and faster than traditional cross-coupling reactions. After the introduction of the modern area of cross-dehydrogenative coupling in 2003, many efforts have been devoted to the development of more efficient and selective catalytic systems for these appealing reactions. Among the different types of catalytic systems that have been investigated, nanostructured metal catalysts are highly attractive in view of their high catalytic performance, easy separability and good reusability. The purpose of this review is to focus on the application of nanocatalysts for cross-dehydrogenative coupling of C–H bonds with particular emphasis on the mechanistic aspects of the reactions. Specifically, we have structured this review based on the type of C–C bonds. Thus, the review is divided into six major sections: (i) C(sp3)–C(sp3) coupling; (ii) C(sp3)–C(sp2) coupling; (iii) C(sp3)–C(sp) coupling; (iv) C(sp2)–C(sp2) coupling; (v) C(sp2)–C(sp) coupling; and (vi) C(sp)–C(sp) coupling.

Visible light promoted coupling of alkynyl bromides and Hantzsch esters for the synthesis of internal alkynes.

A metal-free visible light promoted C(sp3)-C(sp) coupling reaction of alkynyl bromides and Hantzsch esters was developed, giving internal alkynes with primary, secondary, tertiary alkyl or other functional groups in good to high yields.

Metal-catalyzed synthesis of five-membered ring N-heterocycles. A recent update

The review deals with the metal-catalyzed synthetic methods used for the construction of 5-membered nitrogen-containing aromatic and nonaromatic heterocycles with one to three nitrogen atoms, published in the years 2008–2017. The methodology is based on the metalcatalyzed activation of the alkyl C(sp3)–H, alkenyl C(sp2)–H, and terminal alkyne C(sp)–H bonds of appropriate precursors in order to perform intermolecular and intramolecular reactions. These bond forming reactions include C(sp3)–C(sp2), C(sp2)–C(sp2), and C(sp2)–C(sp) coupling, hydroamination at C(sp2)–H and C(sp)–H bonds, and oxidative amination of alkyl C(sp3)–H, alkenyl and arene C(sp2)–H, and terminal alkyne C(sp)–H bonds. Two further bond forming methods are intramolecular nitrenoid–arene C(sp2) coupling and cycloaddition reactions. Transition metals are systematically used in these synthetic methods, and only in a few cases Lewis acids are used as catalysts. In general, the metal-catalyzed cyclizations leading to five-membered heterocycles are very efficient and particularly useful in the synthesis of natural and unnatural biologically active products.

Metallaphotoredox-catalysed sp(3)-sp(3) cross-coupling of carboxylic acids with alkyl halides.

In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp(3)-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp(2)-hybridized species, the development of methods for sp(3)-sp(3) bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp(3)-sp(3) bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp(3)-sp(3) coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp(3)-sp(3) bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for many primary and secondary carboxylic acids. The merit of this coupling strategy is illustrated by the synthesis of the pharmaceutical tirofiban in four steps from commercially available starting materials.

Exploiting the Bis-Nucleophilicity of α-Aminoboronates: Copper-Catalyzed, Intramolecular Aminoalkylations of Bromobenzoyl Chlorides.

α-Aminoboronate salts are interesting examples of heteroatomic species containing adjacent nucleophilic centers. We have developed an acylation/arylation reaction using 2-bromobenzoyl chlorides as bis-electrophiles that harnesses the nucleophilicity of both positions, leading to isoindolinones. The reactions proceed under mild conditions via an intramolecular, Cu-catalyzed sp(3)-sp(2) coupling, giving products in up to 95% yield. These conditions enable arylation of α,α-disubstituted aminoboronates, which are difficult to accomplish using methods based on less abundant and more expensive transition metals.

Palladium catalyzed regioselective B-C(sp) coupling via direct cage B-H activation: synthesis of B(4)-alkynylated o-carboranes.

Pd-catalyzed carboxylic acid guided regioselective alkynylation of cage B(4)-H bonds in o-carboranes has been achieved for the first time using two different catalytic systems. In the presence of 5 mol% Pd(OAc)2 and 3 equiv. of AgOAc, the reaction of 1-COOH-2-R1-C2B10H10 with R3SiC[triple bond, length as m-dash]CBr in ClCH2CH2Cl gives 4-(R3SiC[triple bond, length as m-dash]C)-2-R1-o-C2B10H10 in moderate to high yields. This reaction is compatible with alkynes possessing sterically bulky silyl groups such as iPr3Si or t BuMe2Si. Meanwhile, another catalytic system of Pd(OAc)2/AgOAc/K2HPO4 can catalyze the direct B(4)-alkynylation of 1-COOH-2-R1-C2B10H10 with terminal alkynes R2C[triple bond, length as m-dash]CH in moderate to high yields. The latter has a broader substrate scope from bulky silyl to aromatic to carboranyl substituents. Desilylation of the resultant products affords carboranyl acetylene 4-(HC[triple bond, length as m-dash]C)-2-R1-o-C2B10H10 which can undergo further transformations such as Sonogashira coupling, dimerization and click reactions. It is suggested that the above two catalytic systems may proceed via Pd(ii)-Pd(iv)-Pd(ii) and Pd(ii)-Pd(0)-Pd(ii) catalytic cycles, respectively. In addition, the silver salt is found to promote the decarboxylation reaction and thereby controls the mono-selectivity.

ChemInform Abstract: The Facile Construction of the Phthalazin‐1(2H)‐one Scaffold via Copper‐Mediated C—H(sp2)/C—H(sp) Coupling under Mild Conditions.

AbstractThe reactions of benzamides [e.g. (I)] and terminal alkynes [e.g. (II)] give isoindolinones [e.g. (III)] via a Cu‐mediated cascade coupling and intramolecular annulation.

Stereospecific Pd-Catalyzed Intermolecular C(sp(3))-C(sp) Cross-Coupling of Diarylmethyl Carbonates and Terminal Alkynes Under Base-Free Conditions.

A palladium-catalyzed intermolecular decarboxylative C(sp(3))-C(sp) coupling of diarylmethyl carbonates and terminal alkynes has been developed. The reaction proceeds smoothly under external base-free conditions to deliver the corresponding alkynylated diarylmethanes with the liberation of CO2 and MeOH as the sole byproducts. Moreover, enantioenriched diarylmethyl carbonates are stereospecifically converted to optically active cross-coupling products with inversion of configuration. Thus, the stereospecific palladium catalysis can provide new and unique access to the alkynylated chiral tertiary stereocenters, which are relatively difficult to construct by conventional methods.

Interactions between excitation and extraction modes in an organic-based plasmon-emitting diode

This study demonstrates the feasibility of enhancing an organic-based plasmon-emitting diode on the directional light beaming efficiency by near-field surface plasmon polaritons (SPPs) in both metal grating and polymer grating nanostructures. The interaction between organic/metal and PR/metal interfaces to cause SPPs can facilitate specific directional emission. Directional emission properties give rise to a spectral band-gap response enhancement. Our results also verify that efficient surface plasmon grating coupled emissions (SPGCEs) can improve directionality under index-mediated tuning. Experimental results indicate SP decoupling emission in the visible light. The subsequent emission intensity can increase by up to 3.5 times. Moreover, a narrow FWHM of approximately 60nm in a defined direction is achieved, and an SP coupling rate is approximately 80% on the metal grating structure. The proposed method is highly promising for use as an active plasmonic emitter and discoloration biosensors with enhanced SPPs resonance energy, owing to interactions with the organic/metal nanostructure.