Discovery of Organic Optoelectronic Materials Powered by Oxidative Ar-H/Ar-H Coupling.

Efficient and streamlined synthetic methods that facilitate the rapid build-up of structurally diverse π-conjugated systems are of paramount importance in the quest for organic optoelectronic materials. Among these methods, transition-metal-catalyzed oxidative Ar-H/Ar-H coupling reactions between two (hetero)arenes have emerged as a concise and effective approach for generating a wide array of bi(hetero)aryl and fused heteroaryl structures. This innovative approach bypasses challenges associated with substrate pre-activation processes, thereby allowing for the creation of frameworks that were previously beyond reach using conventional Ar-X/Ar-M coupling reactions. These inherent advantages have ushered in new design patterns for organic optoelectronic molecules that deviate from traditional methods. This ground-breaking approach enables the transcendence of the limitations of repetitive material structures, ultimately leading to the discovery of novel high-performance materials. In this Perspective, we provide an overview of recent advances in the development of organic optoelectronic materials through the utilization of transition-metal-catalyzed oxidative Ar-H/Ar-H coupling reactions. We introduce several notable synthetic strategies in this domain, covering both directed and non-directed oxidative Ar-H/Ar-H coupling strategies, dual chelation-assisted strategy and directed ortho-C-H arylation/cyclization strategy. Additionally, we shed light on the role of oxidative Ar-H/Ar-H coupling reactions in the advancement of high-performance organic optoelectronic materials. Finally, we discuss the current limitations of existing protocols and offer insights into the future prospects for this field.

Stereochemical Editing.

Stereochemical editing has recently risen to prominence, allowing the direct editing of organic molecules with stereocenter(s) to adjust their relative stereochemistry at a late-stage. Several seminal light-driven stereochemical editing reactions such as deracemization and epimerization have been successively developed. Recently, Wendlandt and co-workers reported a versatile photochemical epimerization of unactivated tertiary stereogenic centers to rapidly prepare the stereoisomers that were previously challenging to access.

Highly Selective Radical Relay 1,4-Oxyimination of Two Electronically Differentiated Olefins.

Radical addition reactions of olefins have emerged as an attractive tool for the rapid assembly of complex structures, and have plentiful applications in organic synthesis, however, such reactions are often limited to polymerization or 1,2-difunctionalization. Herein, we disclose an unprecedented radical relay 1,4-oxyimination of two electronically differentiated olefins with a class of bifunctional oxime carbonate reagents via an energy transfer strategy. The protocol is highly chemo- and regioselective, and three different chemical bonds (C-O, C-C, and C-N bonds) were formed in a single operation in an orchestrated manner. Notably, this reaction provides rapid access to a large variety of structurally diverse 1,4-oxyimination products, and the obtained products could be easily converted into valuable biologically relevant δ-hydroxyl-α-amino acids. With a combination of experimental and theoretical methods, the mechanism for this 1,4-oxyimination reaction has been investigated. Theoretical calculations reveal that a radical chain mechanism might operate in the reaction.

Rhodium-Catalyzed Dealkenylative Arylation of Alkenes with Arylboronic Compounds.

The C-C bond formation reaction represents a fundamental and important transformation in synthetic chemistry, and exploring new types of C-C bond formation reactions is recognized as appealing, yet challenging. Herein, we disclose the first example of rhodium-catalyzed dealkenylative arylation of alkenes with arylboronic compounds, thereby providing an unconventional access to bi(hetero)aryls with excellent chemoselectivity. In this method, C(aryl)-C(alkenyl) and C(alkenyl)-C(alkenyl) bonds in various alkenes and 1,3-dienes can be cleaved via a hydrometalation and followed by ß-carbon elimination pathway for Suzuki-Miyaura reactions. Furthermore, a series of novel organic fluorescent molecules with excellent photophysical properties has been efficiently constructed with this protocol.

C-H Activation Based Copper-Catalyzed One-Shot Synthesis of N,O-Bidentate Organic Difluoroboron Complexes.

Organic BF2 complexes exhibit characteristics such as large Stokes shift, high quantum yield, strong emission intensity, and robust chemical stability, thereby being extensively used in various applications. Herein, we disclose a novel copper-catalyzed cascade C-H activation/acyloxylation and difluoroboronation of 2-phenylpyridine derivatives, thus providing a straightforward and rapid gateway to a series of N,O-bidentate organic BF2 complexes with excellent photophysical properties. Mechanism studies demonstrate that AgBF4 services as BF2 source and oxidant for this elegant transformation. Most of these BF2 complexes have broad and intense absorption and emission bands, and display bright and intensive blue fluorescence as well as large Stokes shifts.

Syngas-Free Highly Regioselective Rhodium-Catalyzed Transfer Hydroformylation of Alkynes to α,ß-Unsaturated Aldehydes.

The hydroformylation of alkynes is a fundamental and important reaction in both academic research and industry. Conventional methods focus on the conversion of alkynes, CO, and H2 into α,ß-unsaturated aldehydes, but they often suffer from problems associated with operation, regioselectivity, and chemoselectivity. Herein, we disclose an operationally simple, mild, and syngas-free rhodium-catalyzed reaction for the hydroformylation of alkynes via formyl and hydride transfer from an alkyl aldehyde. This synthetic method uses inexpensive and easy-to-handle n-butyraldehyde to overcome the challenge posed by the use of syngas in traditional approaches and employs a commercially available catalyst and ligand to transform a broad range of internal alkynes, especially alkynyl-containing complex molecules, into versatile stereodefined α,ß-unsaturated aldehydes with excellent chemo-, regio-, and stereoselectivity.

Iridium-Catalyzed Annulation Reactions of Thiophenes with Carboxylic Acids: Direct Evidence for a Heck-type Pathway.

The functionalization of thiophenes is a fundamental and important reaction. Herein, we disclose iridium-catalyzed one-pot annulation reactions of (benzo)thiophenes with (hetero)aromatic or α,ß-unsaturated carboxylic acids, which afford thiophene-fused coumarin-type frameworks. Dearomatization reactions of 2-substituted thiophenes with α,ß-unsaturated carboxylic acids deliver various thiophene-containing spirocyclic products. The occurrence of two interconnected reactions provides direct evidence for a Heck-type pathway. The mechanistic scenario described herein is distinctly different from the SE Ar and concerted metalation-protodemetalation (CMD) pathways encountered in the well-described oxidative C-H/C-H cross-coupling reactions of thiophenes with other heteroarenes.

Rhodium/Copper Cocatalyzed Highly trans-Selective 1,2-Diheteroarylation of Alkynes with Azoles via C-H Addition/Oxidative Cross-Coupling: A Combined Experimental and Theoretical Study.

Transition metal-catalyzed addition of diaryl alkynes with arylating reagents for the synthesis of tetraarylethylenes generally encounters rigorous reaction conditions and relies on the use of prefunctionalized substrates such as organic halides or surrogates and organometallic reagents. In this work, we establish a highly trans-selective 1,2-diheteroarylation of alkynes with azoles via a rhodium/copper cocatalyzed C-H addition/oxidative coupling process. Moreover, the diheteroarylation developed herein could open a door for the synthesis of heteroarene-doped tetraarylethylenes, and the photoluminescence (PL) spectra in THF-water mixtures and solid powder verify that these tetra(hetero)arylethylenes are aggregation-induced emission (AIE) active, building a new AIE molecule library. With a combination of experimental and theoretical methods, the reaction mechanism for addition/oxidative cross-coupling of internal alkynes with azoles has been investigated. Theoretical calculations reveal that the metalation/deprotonation of azole could occur with either rhodium or copper species. When azolylrhodium is formed, an alkyne could insert into the Rh-C bond. Another azolyl group could then transfer to rhodium from azolylcopper compound. The subsequent intramolecular trans-nucleophilic addition generates the second C-C bond. Meanwhile, the putative pathway for the formation of the hydroheteroarylated byproduct has also been explained by theoretical calculations.

Cobalt-Catalyzed Oxidative C-H/C-H Cross-Coupling between Two Heteroarenes.

The first example of cobalt-catalyzed oxidative C-H/C-H cross-coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)2 ⋅4 H2 O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag2 CO3 oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C-H bond activation pathway that the well-described oxidative C-H/C-H cross-coupling reactions between two heteroarenes typically undergo.

Standardizing Substrate Selection: A Strategy toward Unbiased Evaluation of Reaction Generality.

With over 10,000 new reaction protocols arising every year, only a handful of these procedures transition from academia to application. A major reason for this gap stems from the lack of comprehensive knowledge about a reaction's scope, i.e., to which substrates the protocol can or cannot be applied. Even though chemists invest substantial effort to assess the scope of new protocols, the resulting scope tables involve significant biases, reducing their expressiveness. Herein we report a standardized substrate selection strategy designed to mitigate these biases and evaluate the applicability, as well as the limits, of any chemical reaction. Unsupervised learning is utilized to map the chemical space of industrially relevant molecules. Subsequently, potential substrate candidates are projected onto this universal map, enabling the selection of a structurally diverse set of substrates with optimal relevance and coverage. By testing our methodology on different chemical reactions, we were able to demonstrate its effectiveness in finding general reactivity trends by using a few highly representative examples. The developed methodology empowers chemists to showcase the unbiased applicability of novel methodologies, facilitating their practical applications. We hope that this work will trigger interdisciplinary discussions about biases in synthetic chemistry, leading to improved data quality.

Iron-catalyzed oxidative C-H/C-H cross-coupling: an efficient route to α-quaternary α-amino acid derivatives.

Fully loaded: A coordinating activation strategy has been developed to furnish α-quaternary α-amino acids through the iron(III)-catalyzed oxidative functionalization of α-C(sp(3) )H bonds of α-tertiary α-amino acid esters. The reaction exhibits a broad substrate scope for both α-amino acids and nucleophiles (Nu) as well as good functional-group tolerance (see scheme, DTBP=di-tert-butyl peroxide, DCE=1,2-dichloroethane).

Iron-Catalyzed para-Selective C-H Allylation of Aniline Derivatives.

Transition-metal-catalyzed directed C-H allylation of arenes offers an efficient and straightforward approach to construct value-added allylic arenes. However, these reactions are often performed with precious transition-metal catalysts and mainly limited to ortho-C-H allylation of arenes. Herein, we disclose a novel iron-catalyzed para-C-H allylation of aniline derivatives with allyl alcohols via a chelation-induced strategy, providing various allylic arenes in good yields with excellent regio- and chemoselectivity. A simple FeCl3·6H2O is employed as a catalyst, serving a dual role in the reaction: (1) coordination with N-arylpicolinamide to alter the electronic property of the aromatic ring and (2) reaction with allyl alcohol to form allyl-Fe species.

Metal-free photosensitized radical relay 1,4-carboimination across two distinct olefins.

Intermolecular carboamination of olefins offers a powerful platform for the rapid construction of structurally complex amines from abundant feedstocks. However, these reactions often require transition-metal catalysis, and are mainly limited to 1,2-carboamination. Herein, we report a novel radical relay 1,4-carboimination across two distinct olefins with alkyl carboxylic acid-derived bifunctional oxime esters via energy transfer catalysis. The reaction is highly chemo- and regioselective, and multiple C-C and C-N bonds were formed in a single orchestrated operation. This mild and metal-free method features a remarkably broad substrate scope with excellent tolerance of sensitive functional groups, therefore providing easy access to structurally diverse 1,4-carboiminated products. Moreover, the obtained imines could be easily converted into valuable biologically relevant free γ-amino acids.

Photochemical single-step synthesis of ß-amino acid derivatives from alkenes and (hetero)arenes.

ß-Amino acids are frequently found as important components in numerous biologically active molecules, drugs and natural products. In particular, they are broadly utilized in the construction of bioactive peptides and peptidomimetics, thanks to their increased metabolic stability. Despite the number of methodologies established for the preparation of ß-amino acid derivatives, the majority of these methods require metal-mediated multistep manipulations of prefunctionalized substrates. Here we disclose a metal-free, energy-transfer enabled highly regioselective intermolecular aminocarboxylation reaction for the single-step installation of both amine and ester functionalities into alkenes or (hetero)arenes. A bifunctional oxime oxalate ester was developed to simultaneously generate C-centred ester and N-centred iminyl radicals. This mild method features a remarkably broad substrate scope (up to 140 examples) and excellent tolerance of sensitive functional groups, and substrates that range from the simplest ethylene to complex (hetero)arenes can participate in the reaction, thus offering a general and practical access to ß-amino acid derivatives.

AIE-Active Difluoroboron Complexes with N,O-Bidentate Ligands: Rapid Construction by Copper-Catalyzed C-H Activation.

The development of organic materials with high solid-state luminescence efficiency is highly desirable because of their fundamental importance and applicability in optoelectronics. Herein, a rapid construction of novel BF2 complexes with N,O-bidentate ligands by using Cu(BF4 )2 •6H2 O as a catalyst and BF2 source is disclosed, which avoids the need for pre-composing the N,O-bidentate ligands and features a broad substrate scope and a high tolerance level for sensitive functional groups. Moreover, molecular oxygen is employed as the terminal oxidant in this transformation. A library of 36 compounds as a new class of BF2 complexes with remarkable photophysical properties is delivered in good to excellent yields, showing a substituent-dependency on the photophysical properties, derived from the π-π* character of the photoexcited state. In addition, aggregation-induced emission (AIE) is observed and quantified for the brightest exemplars. The excited state properties are fully investigated in solids and in THF/H2 O mixtures. Hence, a new series of photofunctional materials with variable photophysical properties is reported, with potential applications for sensing, bioimaging, and optoelectronics.

Rhodium-catalyzed oxidative C-H/C-H cross-coupling of aniline with heteroarene: N-nitroso group enabled mild conditions.

The development of transition metal-catalyzed oxidative C-H/C-H cross-coupling between two (hetero)arenes to forge aryl-heteroaryl motifs under mild conditions is an appealing yet challenging task. Herein, we disclose a rhodium-catalyzed oxidative C-H/C-H cross-coupling reaction of an N-nitrosoaniline with a heteroarene under mild conditions. The judicious choice of the N-nitroso group as a directing group enables heightened reactivity. The coupled products could be transformed expediently to (2-aminophenyl)heteroaryl skeletons.

Rhodium(III)-Catalyzed Oxidative Cross-Coupling of Unreactive C(sp3)-H Bonds with C(sp2)-H Bonds.

The development of the oxidative cross-coupling of unreactive C(sp3)-H bonds with (hetero)arene C(sp2)-H bonds is considerably appealing, yet conceptually and practically challenging. Here, we disclose the rhodium-catalyzed oxidative heteroarylation of unactivated C(sp3)-H bonds with heteroarene C(sp2)-H bonds. This method provides a step-economic route to ß-heteroarylated 2-ethylpyridine derivatives, which exhibits relatively broad substrate scope, high tolerance level of sensitive functional groups, and high selectivity. The protocol can also be extended to the coupling reaction between 8-methylquinoline derivatives and heteroarenes.

Copper- or Nickel-Enabled Oxidative Cross-Coupling of Unreactive C(sp3)-H Bonds with Azole C(sp2)-H Bonds: Rapid Access to ß-Azolyl Propanoic Acid Derivatives.

ß-Azolyl propanoic acid derivatives are frequently found in biologically active molecules and pharmaceuticals. Here, we report the oxidative heteroarylation of unactivated C(sp3)-H bonds with azole C(sp2)-H bonds via copper or nickel catalysis with the aid of removable bidentate auxiliary, which provides a rapid pathway to ß-azolyl propanoic acid derivatives. A variety of azoles such as oxazole, benzoxazole, thiazole, benzothiazoles, benzimidazole, purine, and even [1,2,4]triazolo[1,5-a]pyrimidine could be engaged in this protocol.