Dual Catalytic Approach Research Articles

Demonstrating Synergistic Activity of Magnetic Iron Oxide Nano Photocatalyst for C-H Activation in Heterogeneous Phase.

This report describes a dual catalytic approach for the versatile C‒H arylation of arenes under photo-excitation at room temperature. The cooperative catalysis utilizes iron oxide magnetic nanoparticles (which mostly contain Fe3O4 along with some γ-Fe2O3) as the potential photocatalyst, which merges with the Pd-catalyzed C‒H activation cycle for the reductive generation of aryl radical from aryl diazonium salt, revealing its photocatalytic activities. The method is applicable to a wide range of aryl coupling partners and different directing groups, demonstrating excellent productivity, nice co-operativity and recyclability. Adequate control experiments and mechanistic studies assisted in establishing the radical-based mechanism for the C‒H arylation occurring in the heterogeneous phase.

Site‐selective Photoredox‐Catalyzed Late‐stage Benzylic Hydrogen Isotope Exchange

A highly regioselective visible light photoredox‐catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst in combination with a thiol‐based hydrogen atom transfer catalyst, while the use of D2O as an isotope source ensures operational simplicity and cost‐effectiveness. High reactivity has been achieved for electron‐rich benzylic positions. Moreover, targeted radical formation enables unprecedented selective HIE on intramolecular competing benzylic and alpha to heteroatom positions with moderate to excellent deuterium incorporation. The utility of the reaction was demonstrated on the late‐stage HIE of several natural compounds and drug derivatives. Experimental studies and density functional theory (DFT) calculations suggested a single electron transfer (SET) mechanism followed by deprotonation to generate the benzylic radical, and revealed the importance of halogenated solvents or additives. Upon a weak complexation of the halogenated species to the substrate, an oxidation potential lowering effect is induced, as well as a stabilization of the radical‐cation species through spin delocalization.

Site-selective Photoredox-Catalyzed Late-stage Benzylic Hydrogen Isotope Exchange.

A highly regioselective visible light photoredox-catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst in combination with a thiol-based hydrogen atom transfer catalyst, while the use of D2O as an isotope source ensures operational simplicity and cost-effectiveness. High reactivity has been achieved for electron-rich benzylic positions. Moreover, targeted radical formation enables unprecedented selective HIE on intramolecular competing benzylic and alpha to heteroatom positions with moderate to excellent deuterium incorporation. The utility of the reaction was demonstrated on the late-stage HIE of several natural compounds and drug derivatives. Experimental studies and density functional theory (DFT) calculations suggested a single electron transfer (SET) mechanism followed by deprotonation to generate the benzylic radical, and revealed the importance of halogenated solvents or additives. Upon a weak complexation of the halogenated species to the substrate, an oxidation potential lowering effect is induced, as well as a stabilization of the radical-cation species through spin delocalization.

Pd/Cu Dual Catalysis for the Oxidative Dearomatization of PyrroleDerivatives: Mechanistic Insights and Biological Studies

AbstractHerein we report dearomatization of pyrrole ring followed by rearomatization of cyclohexyl ring to obtain isoindolinone scaffold by a Pd/Cu dual catalysis approach in an atom economic way with moderate to high yield. The expected Pd/Cu catalyzed dual C(sp2)‐H activation via normal catalytic cycle can be override by unusual oxidative dearomatization reaction which has been established by DFT calculation. The biological importance of isoindolinone scaffold insists us to successfully investigate in vitro antileishmanial activity of L.Donovani.

Photoredox dual catalysis using stimulus-responsive fluoresceins for colorimetric detection of Hg(II) ions

We demonstrate photoredox dual catalysis using fluorescein derivatives and apply it to polymerization-based signal amplification (PBA) under the irradiation of visible light. The mechanism of the photoredox dual catalysis is elucidated using electron paramagnetic resonance (EPR) and UV–Vis spectroscopies. We applied the photoredox dual catalysis to amplify and readout the signal of Hg(II) ions with the unaided eye through photoinitiated free-radical polymerization. Although PBA offers a reliable and rapid colorimetric method for analyte detection, its sensitivity remains a challenge compared with fluorescence detection. To address this issue, we designed a dual system involving activatable fluoresceins that selectively react to external stimuli, followed by their action as photoredox catalysts/initiators. As a proof-of-concept, we employed fluorescin (rFL) and eosin hydrazide (EYHZ) as light- and Hg(II) ion-responsive probes, respectively. This dual system selectively initiated the polymerization of poly(ethylene glycol) diacrylate (PEGDA) in the presence of Hg(II) ions under visible light. Remarkably, this photoredox dual catalysis approach allowed the unaided eye to detect of Hg(II) ions as low as 90 nM in aqueous solution, demonstrating its potential for sensitive and versatile sensing applications.

A Bimolecular Homolytic Substitution-Enabled Platform for Multicomponent Cross-Coupling of Unactivated Alkenes.

The construction of C(sp3)-C(sp3) bonds remains one of the most difficult challenges in cross-coupling chemistry. Here, we report a photoredox/nickel dual catalytic approach that enables the simultaneous formation of two C(sp3)-C(sp3) linkages via trimolecular cross-coupling of alkenes with alkyl halides and hypervalent iodine-based reagents. The reaction harnesses a bimolecular homolytic substitution (SH2) mechanism and chemoselective halogen-atom transfer (XAT) to orchestrate the regioselective addition of electrophilic and nucleophilic alkyl radicals across unactivated alkenes without the need for a directing auxiliary. Utility is highlighted through late-stage (fluoro)alkylation and (trideutero)methylation of C═C bonds bearing different substitution patterns, offering straightforward access to drug-like molecules comprising sp3-hybridized carbon scaffolds.

Green light-mediated dual eosin Y/PdII-catalyzed C(sp2)-H arylation of N-H unprotected 2-arylquinazolinones.

We report herein an eosin Y/Pd(II) dual catalytic approach for regio- and chemoselective C(sp2)-H monoarylation of N-H unprotected 2-phenyl quinazolinone derivatives under green light irradiation with no necessity for any base/additive/external oxidant. The free N-H moiety was post-modified for quinazolinone scaffold diversification and C-H annulation.

Room temperature C-O bond cleavage of vinyl cyclic synthons via a metallaphotoredox approach.

Herein, we report visible-light induced C-O bond cleavage of vinyl-appended cyclic synthons via a Co(II)-photoredox dual catalytic approach operating at room temperature. This methodology exhibits a broad scope and is capable of accessing linear as well as branched allyl arenes simply by tuning the ring size of the cyclic motifs, in a mild and environmentally friendly protocol. Mechanistic studies unveil an interesting aspect of the reaction pathway involving a challenging homolytic cleavage of the Co(III)-O bond, 1,5-HAT of an unstable Co(II)-organometallic intermediate, and the key roles of O2 and the photocatalyst. The successful removal of the directing group further adds an important dimension to the methodology.

Merging decatungstate photocatalysis and copper‐catalyzed azide‐alkyne cycloaddition reaction for the formation of 1,2,3‐triazoles in water†

Merging photoredox and catalysis by transition metals, coined as metallaphotoredox catalysis, proved to be an excellent new platform for the development of new synthetic strategies for the formation of carbon–carbon and carbon‐heteroatom bonds. Herein, we report a dual catalytic system that has been successfully developed for the azide‐alkyne ligation process to yield 1,4‐disubstituted‐1,2,3‐triazoles. It consists of merging the decatungstate anion [W10O32]4−‐photocatalyzed hydrogen atom transfer from ethanol as a source of hydrogen atom abstraction to produce the one‐electron‐reduced form H+[W10O32]5−, which reduces Cu(II) precursor into Cu(I) starting then the copper‐catalyzed azide‐alkyne cycloaddition reaction (CuAAC). The resulting bifunctional H+[W10O32]5−/Cu catalytic system operates efficiently in an environmentally benign water–ethanol solvent mixture as reaction medium, resulting in the regioselective formation of 1,4‐disubstituted‐1,2,3‐triazole derivatives, with high yields up to 99% and large substrate application scope under mild conditions. This dual catalytic approach has proven to function under sunlight exposition too with recovery and reuse of the catalytic system for several times.

Photocatalytic Aerobic Cyclization of N-Propargylamides Enabled by Selenium-π-Acid Catalysis.

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.

Asymmetric Addition of Allylsilanes to Aldehydes: A Cr/Photoredox Dual Catalytic Approach Complementing the Hosomi–Sakurai Reaction

The allylation of aldehydes is a fundamental transformation in synthetic organic chemistry. Among the multitude of available reagents, allylsilanes especially have been established as a preferred allyl source. As initially reported by Hosomi and Sakurai, these non-toxic and highly stable reagents add to carbonyls via an open transition state upon Lewis acid activation. Herein, we report a general strategy to access a variety of valuable homoallylic alcohols in opposite chemo- and diastereoselectivity to the established Hosomi–Sakurai conditions by switching to photocatalytic activation in combination with a closed transition state (chromium catalysis). Moreover, this dual catalytic approach displays a straightforward way to introduce excellent levels of enantioselectivity and its mild conditions allow for a broad substrate scope including chiral boron-substituted products as a highlight. To emphasize the synthetic utility, our method was applied as the key step in the synthesis of a bioactive compound and in the late-stage functionalization of steroid derivatives. Detailed mechanistic studies and DFT calculations hint toward an unprecedented photo-initiated chain being operative.

Photocatalytic Direct Decarboxylation of Carboxylic Acids to Derivatize or Degrade Polymers.

Visible light-mediated direct decarboxylation of carboxylic acids with an acridine photocatalyst is a convenient and powerful method to generate carbon-centered radicals in polymer chains. Advantageously, this process proceeds under mild conditions, without preactivation of the acid groups. We utilize decarboxylation in the presence of a hydrogen atom donor to form statistical acrylate-ethylene and acrylate-propylene copolymers, which are challenging to obtain by direct polymerization. We additionally show that decarboxylation of methacrylic acid units within polymethacrylates can trigger degradation of the polymer backbones. Moreover, a dual catalytic approach, which combines the function of an acridine photocatalyst with that of a cobaloxime catalyst, is leveraged to furnish unique copolymers with pendent alkenes. Our work indicates that direct decarboxylation is a versatile technique for the synthesis of functional materials with tailored compositions and properties.

Photocatalytic Direct Decarboxylation of Carboxylic Acids to Derivatize or Degrade Polymers

AbstractVisible light‐mediated direct decarboxylation of carboxylic acids with an acridine photocatalyst is a convenient and powerful method to generate carbon‐centered radicals in polymer chains. Advantageously, this process proceeds under mild conditions, without preactivation of the acid groups. We utilize decarboxylation in the presence of a hydrogen atom donor to form statistical acrylate‐ethylene and acrylate‐propylene copolymers, which are challenging to obtain by direct polymerization. We additionally show that decarboxylation of methacrylic acid units within polymethacrylates can trigger degradation of the polymer backbones. Moreover, a dual catalytic approach, which combines the function of an acridine photocatalyst with that of a cobaloxime catalyst, is leveraged to furnish unique copolymers with pendent alkenes. Our work indicates that direct decarboxylation is a versatile technique for the synthesis of functional materials with tailored compositions and properties.

Enantioselective Photochemical Reactions Enabled by Triplet Energy Transfer.

For molecules with a singlet ground state, the population of triplet states is mainly possible (a) by direct excitation and subsequent intersystem crossing or (b) by energy transfer from an appropriate sensitizer. The latter scenario enables a catalytic photochemical reaction in which the sensitizer adopts the role of a catalyst undergoing several cycles of photon absorption and subsequent energy transfer to the substrate. If the product molecule of a triplet-sensitized process is chiral, this process can proceed enantioselectively upon judicious choice of a chiral triplet sensitizer. An enantioselective reaction can also occur in a dual catalytic approach in which, apart from an achiral sensitizer, a second chiral catalyst activates the substrate toward sensitization. Although the idea of enantioselective photochemical reactions via triplet intermediates has been pursued for more than 50 years, notable selectivities exceeding 90% enantiomeric excess (ee) have only been realized in the past decade. This review attempts to provide a comprehensive survey on the various photochemical reactions which were rendered enantioselective by triplet sensitization.

Chiral Primary Amine/Ketone Cooperative Catalysis for Asymmetric α-Hydroxylation with Hydrogen Peroxide.

Carbonyls and amines are yin and yang in organocatalysis as they mutually activate and transform each other. These intrinsically reacting partners tend to condense with each other, thus depleting their individual activity when used together as cocatalysts. Though widely established in many prominent catalytic strategies, aminocatalysis and carbonyl catalysis do not coexist well, and, as such, a cooperative amine/carbonyl dual catalysis remains essentially unknown. Here we report a cooperative primary amine and ketone dual catalytic approach for the asymmetric α-hydroxylation of β-ketocarbonyls with H2O2. Besides participating in the typical enamine catalytic cycle, the chiral primary amine catalyst was found to work cooperatively with a ketone catalyst to activate H2O2 via an oxaziridine intermediate derived from an in-situ-generated ketimine. Ultimately, this enamine-oxaziridine coupling facilitated the highly controlled α-hydroxylation of several β-ketocarbonyls in excellent yield and enantioselectivity. Notably, late-stage hydroxylation for peptidyl amide or chiral esters can also be achieved with high stereoselectivity. In addition to its operational simplicity and mild conditions, this cooperative amine/ketone catalytic approach also provides a new strategy for the catalytic activation of H2O2 and expands the domain of typical amine and carbonyl catalysis to include this challenging transformation.

C-H bond functionalization by dual catalysis: merging of high-valent cobalt and photoredox catalysis.

The merger of transition metal catalysis and photocatalysis has emerged as a versatile platform that opened the gateway to diverse low-energy pathways for several synthetic transformations. However, amidst the first-row transition metals, directed C-H bond functionalization mediated by high-valent cobalt catalysis has advanced with rising momentum owing to its unique reactivity and the ability to participate in both one- and two-electron transfer reactions. However, the use of expensive, privileged Cp* ligands or use of stoichiometric silver(I) or manganese(III) is unavoidable. Despite significant advances in their respective fields, the combination of these two "green" approaches to further the vested interest of the scientific research community towards the development of ecofriendly and sustainable protocols is noticeably limited. Thus, the methodology based on high-cobalt-photoredox dual-catalytic strategy has high dormant potential and is worthy to explore. Herein, we highlight the recent advances in the high-valent cobalt-catalyzed sustainable catalytic approach by harnessing light energy for oxidative C-H bond functionalization. With this, we hope to inspire the development of unexplored cobalt-photoredox-catalyzed reactions with improved efficiency and selectivity.

Investigation of β-alkynol inhibition mechanism and Ru/Pt dual catalysis in Karstedt catalyzed hydrosilylation cure systems

β-Alkynol inhibitors play an important role in Karstedt catalyzed hydrosilylation cure silicone chemistry by providing a long working time at low temperatures, while allowing for rapid cure at elevated temperatures. Using 13C-labeled 1-ethynyl-1-cyclohexanol (13C-1) as a representative of the β-alkynol inhibitor, it was possible to monitor the change in this component in an actual silicone composition by 1H and 13C NMR during cure. The data showed that 13C-1 was selectively consumed by Pt-catalyzed hydrosilylation with the Si—H siloxane in the formulation in spite of the presence of large excess of vinyl groups from the vinyl polysiloxane component. The reaction rate was highly dependent on the Si—H siloxane used, the reaction temperature and presence of the tertiary -OH group in 13C-1. These results suggest that the high selectivity of the terminal alkyne over vinyl for hydrosilylation and the temperature dependent reaction kinetics are keys to understanding the inhibition mechanism for β-alkynols. These studies also inspired a Ru/Pt dual catalyst approach to lower the cure temperature of the silicone composition while maintaining a suitable working time. This approach is based on the hypothesis that the Ru co-catalyst can selectively catalyze the hydrosilylation of the β-alkynol in a temperature dependent manner, and its consumption would subsequently release the Pt-catalyst to rapidly cure the composition. Evaluation of a range of Ru-complexes led to the identification the complex [Cp*Ru(MeCN)3]+OTf- and its dodecanenitrile derivatives as a prototype from which the effectiveness of the dual catalysis approach was validated in a silicone release coating application with a cure temperature of 85oC and cure time of 4 seconds.

Dual Catalytic Ring-Opening Polymerization of Ethylene Carbonate for the Preparation of Degradable PEG.

A dual catalytic setup, consisting of a range of different Lewis bases (including N-heterocyclic olefins, phosphazenes and nitrogen bases) and simple Lewis acids (such as LiCl, MgF2, BEt3), was employed to prepare poly(ether carbonate)s from five-membered, cyclic ethylene carbonate (EC). Polymerizations were conducted under microwave irradiation at T = 160-200 °C with low catalyst loading (0.4-0.005 mol % regarding organobases) in the bulk, enabling access to molar masses of up to 10 000 g/mol. A combination of kinetic investigation, GPC, MALDI-ToF MS, and NMR analysis underlines that the polymerization can be highly effective (TON up to >17 000) but side reactions still occur, resulting in a moderately controlled process. In contrast to traditional procedures, where increased ether contents can typically only be realized by higher temperatures and longer reaction times (at the cost of much reduced molar masses), the dual catalytic approach reveals the choice of the Lewis acid as a more effective tuning parameter for this property. Thus, while carbonate contents of up to 30% are possible, application of LiCl as cocatalyst provides a polymer with high ether content (90-99%, Mn = 800-10 000 g/mol), a finding that also seems to apply for other lithium salts. Thus, using this operationally simple setup and EC as a cheap feedstock, a copolymer which is essentially a degradable poly(ethylene glycol) can be prepared in a one-pot, one-step approach. Notably, the obtained low-carbonate content allows for the preparation of semicrystalline poly(ether carbonate), further underlining the "PEG-likeness" of the material.

Enantioselective Synthesis of N-Benzylic Heterocycles: A Nickel and Photoredox Dual Catalysis Approach.

Reported herein is a dual nickel- and photoredox-catalyzed modular approach for the preparation of enantioenriched N-benzylic heterocycles. α-Heterocyclic carboxylic acids, easily obtainable from common commercial material, are reported as suitable substrates for a decarboxylative strategy in conjunction with a chiral pyridine-oxazoline (PyOx) ligand, providing quick access to enantioenriched drug-like products. The presence of a directing group on the heterocyclic moiety is shown to be beneficial, affording improved stereoselectivity in a number of cases.

On-DNA Decarboxylative Arylation: Merging Photoredox with Nickel Catalysis in Water.

A new catalytic manifold that merges photoredox with nickel catalysis in aqueous solution is presented. Specifically, the combination of a highly active, yet air-stable, nickel precatalyst with a new electron-deficient pyridyl carboxamidine ligand was key to the development of a water-compatible nickel catalysis platform, which is a crucial requirement for the preparation of DNA-encoded libraries (DELs). Together with an iridium-based photocatalyst and a powerful light source, this dual catalysis approach enabled the efficient decarboxylative arylation of α-amino acids with DNA-tagged aryl halides. This C(sp2)-C(sp3) coupling tolerates a wide variety of functional groups on both the amino acid and the aryl halide substrates. Due to the mild and DNA-compatible reaction conditions, the presented transformation holds great potential for the construction of DELs. This was further evidenced by showing that well plate-compatible LED arrays can serve as competent light sources to facilitate parallel synthesis. Lastly, we demonstrate that this procedure can serve as a blueprint toward the adaptation of other established nickel metallaphotoredox transformations to the idiosyncratic requirements of a DEL.