Transition Metal-Mimicking Relay Catalysis by a Low-Valent Phosphorus Compound.

Low-valent main group species have been evolving as powerful alternatives to transition metals over the years due to their advantages such as low toxicity and high abundance. However, the inability of main group elements to mimic the redox-switching property of transition metals often limits their role as catalysts. Here, we demonstrate the use of a low-valent phosphorus(I) compound as an efficient metal-free catalyst for the synthesis of biologically relevant γ-butyrolactones through dual activation under ambient reaction conditions. The highly nucleophilic phosphorus(I) center plays a key role in leading to this transformation. Extensive experimental and theoretical studies suggest that the phosphorus center exhibits facile switching between its reduced state [P(I)] and its oxidized state [P(III)] during this transformation, mimicking the behavior of transition metals.

Cross-Coupling Between Aryl Halides and Aryl Alkynes Catalyzed by an Odd Alternant Hydrocarbon.

Catalytic cross-coupling between aryl halides and alkynes is considered an extremely important organic transformation (popularly known as the Sonogashira coupling) and it requires a transition metal-based catalyst. Accomplishing such transformation without any transition metal-based catalyst in the absence of any external stimuli such as heat, photoexcitation or cathodic current is highly challenging. This work reports transition-metal-free cross-coupling between aryl halides and alkynes synthesizing a rich library of internal alkynes without any external stimuli. A chemically double-reduced phenalenyl (PLY)-based molecule with the super-reducing property was employed for single electron transfer to activate aryl halides generating reactive aryl radicals, which subsequently react with alkyne. This protocol covers not only various types of aryl, heteroaryl and polyaryl halides but also applies to a large variety of aromatic alkynes at room temperature. With a versatile substrate scope successfully tested on more than 75 entries, this radical-mediated pathway has been explained by several control experiments. All the key reactive intermediates have been characterized with spectroscopic evidence. Detailed DFT calculations have been instrumental in portraying the mechanistic pathway. Furthermore, we have successfully extended this transition-metal-free catalytic strategy for the first time towards solvent-free cross-coupling between solid aryl halide and alkyne substrates.

Highly Stable Self-Regenerating Organic Multi-Redox Systems derived from Bicyclic (Alkyl)(amino)carbenes (BICAACs).

An extended class of organic multi-redox systems was derived from bicyclic(alkyl)amino carbenes (BICAACs). The highly-conjugated system undergoes a total of 4 redox events spanning a 1.8 V redox range. These organic compounds exhibited four different stable redox states (dication, radical cation, neutral and radical anion), and all of them were characterized either by single crystal X-ray study and/or various spectroscopic studies. Three of the four redox states are stable to air and moisture. The availability of stable multiple redox states demonstrated promise towards their efficacy in the symmetric H-cell charge/discharge cycling. Among various redox states, the dication/neutral state works efficiently and continuously for 1500 cycles in 2e- charge/discharge process outside glovebox in commercially available DMF with minimum capacity loss (retaining nearly 90 % Coulombic efficiency). Surprisingly, the efficiency of the redox cycle was retained even if the system was exposed to air for 30 days when it slowly regenerated to the initial deep blue radical cation, and it exhibited another 100 charge/discharge cycles with a minimal capacity loss. Such a stable H-cell cycling ability is not well known among organic molecule-based systems.

Phenalenyl Radical: Smallest Polycyclic Odd Alternant Hydrocarbon Present in the Graphene Sheet.

Phenalenyl, a zigzag-edged odd alternant hydrocarbon unit can be found in the graphene nanosheet. Hückel molecular orbital calculations indicate the presence of a nonbonding molecular orbital (NBMO), which originates from the linear combination of atomic orbitals (LCAO) arising from 13 carbon atoms of the phenalenyl molecule. Three redox states (cationic, neutral radical, and anionic) of the phenalenyl-based molecules were attributed to the presence of this NBMO. The cationic state can undergo two consecutive reductions to result in neutral radical and anionic states, stepwise, respectively. The phenalenyl-based radicals were found as crucial building blocks and attracted the attention of various research fields such as organic synthesis, material science, computation, and device physics. From 2012 onward, a strategy was devised using the cationic state of phenalenyl-based molecules and in situ generated phenalenyl radicals, which created a new domain of catalysis. The in situ generated phenalenyl radicals were utilized for the single electron transfer (SET) process resulting in redox catalysis. This emerging range of applications rejuvenates the more than six decades-old phenalenyl chemistry. This review captures such developments ranging from fundamental understanding to multidirectional applications of phenalenyl-based radicals.

Metal-Ligand Cooperativity in MnI -Catalysed N-Formylation of Secondary Amides and Lactams Using CO2 at Room Temperature.

A MnI catalyst featuring redox-active tridentate phenalenyl (PLY) ligand has been used for catalytic N-formylation of secondary amides and lactams under 1 atm CO2 as a C1 source at room temperature for the first time. The protocol is applicable to a wide range of secondary amides including heterocycles, bio-active cinnamide derivatives and the diversification of therapeutic molecules. In-depth mechanistic investigations based on experimental outcomes and DFT calculations suggested an unconventional metal-ligand cooperation, where a ligand-centred radical plays a crucial role in initiating the reaction process.

Reduced-Phenalenyl-Based Molecule as a Super Electron Donor for Radical-Mediated C-N Coupling Catalysis at Room Temperature.

We demonstrate that an in situ generated di-reduced phenalenyl (PLY) species accumulates sufficiently high energy and acts as a super electron donor to generate aryl radicals from aryl halides to accomplish Buchwald-Hartwig-type C-N cross-coupling reactions at room temperature. This catalytic protocol does not require any external stimuli such as heat, light, or cathodic current. This protocol shows a wide variety of substrate scope covering different genres of aryl and heteroaryl halides with various aromatic as well as aliphatic amines and late-stage functionalization of the well-known natural products. The control experiments, along with extensive density functional theory (DFT) calculations, unveil that the aryl radical is generated by a single electron transfer from the di-reduced PLY to the aryl halide substrate. The aryl radical acts as an electrophile and binds with amine, leading to the chemically driven radical-mediated C-N cross-coupling under transition-metal-free conditions.

Benzimidazolylidene-Stabilized Borenium Ion for Catalytic Hydrogenation of N-Heterocycles.

Herein, we report the synthesis of a benzimidazolylidene-stabilized borane adduct and its borenium ion. This borenium ion was used as a metal-free catalyst for hydrogenating various substituted quinoline N-heterocycles under ambient conditions. Furthermore, this method was utilized to synthesize two drug molecules: galipinine and angustureine. A detailed DFT study was performed to understand this metal-free catalytic hydrogenation.

Mesoionic N-Heterocyclic Imines as Super Nucleophiles in Catalytic Couplings of Amides with CO2.

An extended class of stable mesoionic N-heterocyclic imines (mNHIs), containing a highly polarized exocyclic imine moiety, were synthesized. The calculated proton affinities (PA) and experimentally determined Tolman electronic parameters (TEPs) reveal that these synthesized mNHIs have the highest basicity and donor ability among NHIs reported so far. The superior nucleophilicity of newly designed mNHIs was utilized in devising a strategy to incorporate CO2 as a bridging unit under reductive conditions to couple inert primary amides. This strategy was further extended to hetero-couplings between amide and amine using CO2 . These hitherto unknown catalytic transformations were introduced in the diversification of various biologically active drug molecules under metal-free conditions. The underlying mechanism was explored by performing a series of control experiments, characterizing key intermediates using spectroscopic and crystallographic techniques.

An NHC-Stabilised Phosphinidene for Catalytic Formylation: A DFT-Guided Approach.

In recent years, the applications of low-valent main group compounds have gained momentum in the field of catalysis. Owing to the accessibility of two lone pairs of electrons, NHC-stabilised phosphinidenes have been found to be excellent Lewis bases; however, they cannot yet be used as catalysts. Herein, an NHC-stabilised phosphinidene, 1,3-dimethyl-2-(phenylphosphanylidene)-2,3-dihydro-1H imidazole (1), for the activation of CO2 is reported.A closer inspection of the CO2 activation process by DFT calculations along with intrinsic bond orbital analysis shows that phosphinidene is associated with phenylsilane through a noncovalent π-π interaction between two phenyl rings which activates the Si-H bond facilitating hydride transfer to the CO2 molecule. Detailed DFT studies along with spectroscopic experiments were combined to understand the mechanism of CO2 activation and its catalytic reductive functionalisation leading to the formylation of a range of chemically inert primary amides under mild reaction conditions.

Reduced Phenalenyl in Catalytic Dehalogenative Deuteration and Hydrodehalogenation of Aryl Halides.

Dehalogenative deuteration reactions are generally performed through metal-mediated processes. This report demonstrates a mild protocol for hydrodehalogenation and dehalogenative deuteration of aryl/heteroaryl halides (39 examples) using a reduced odd alternant hydrocarbon phenalenyl under transition metal-free conditions and has been employed successfully for the incorporation of deuterium in various biologically active compounds. The combined approach of experimental and theoretical studies revealed a single electron transfer-based mechanism.

A Bottleable Imidazole-Based Radical as a Single Electron Transfer Reagent.

Reduction of 1,3-bis(2,6-diisopropylphenyl)-2,4-diphenyl-1H-imidazol-3-ium chloride (1) resulted in the formation of the first structurally characterized imidazole-based radical 2. 2 was established as a single electron transfer reagent by treating it with an acceptor molecule tetracyanoethylene. Moreover, radical 2 was utilized as an organic electron donor in a number of organic transformations such as in activation of an aryl-halide bond, alkene hydrosilylation, and in catalytic reduction of CO2 to methoxyborane, all under ambient temperature and pressure.

Stable abnormal N-heterocyclic carbenes and their applications.

Although N-heterocyclic carbenes (NHCs) have been known as ligands for organometallic complexes since the 1960s, these carbenes did not attract considerable attention until Arduengo et al. reported the isolation of a metal-free imidazol-2-ylidene in 1991. In 2001 Crabtree et al. reported a few complexes featuring an NHC isomer, namely an imidazol-5-ylidene, also termed abnormal NHC (aNHCs). In 2009, it was shown that providing to protect the C-2 position of an imidazolium salt, the deprotonation occurred at the C-5 position, affording imidazol-5-ylidenes that could be isolated. Over the last ten years, stable aNHCs have been used for designing a range of catalysts employing Pd(ii), Cu(i), Ni(ii), Fe(0), Zn(ii), Ag(i), and Au(i/iii) metal based precursors. These catalysts were utilized for different organic transformations such as the Suzuki-Miyaura cross-coupling reaction, C-H bond activation, dehydrogenative coupling, Huisgen 1,3-dipolar cycloaddition (click reaction), hydroheteroarylation, hydrosilylation reaction and migratory insertion of carbenes. Main-group metal complexes were also synthesized, including K(i), Al(iii), Zn(ii), Sn(ii), Ge(ii), and Si(ii/iv). Among them, K(i), Al(iii), and Zn(ii) complexes were used for the polymerization of caprolactone and rac-lactide at room temperature. In addition, based on the superior nucleophilicity of aNHCs, relative to that of their nNHCs isomers, they were used for small molecules activation, such as carbon dioxide (CO2), nitrous oxide (N2O), tetrahydrofuran (THF), tetrahydrothiophene and 9-borabicyclo[3.3.1]nonane (9BBN). aNHCs have also been shown to be efficient metal-free catalysts for ring opening polymerization of different cyclic esters at room temperature; they are among the most active metal-free catalysts for ε-caprolactone polymerization. Recently, aNHCs successfully accomplished the metal-free catalytic formylation of amides using CO2 and the catalytic reduction of carbon dioxide, including atmospheric CO2, into methanol, under ambient conditions. Although other transition metal complexes featuring aNHCs as ligand have been prepared and used in catalysis, this review article summarize the results obtained with the isolated aNHCs.

Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides.

A series of boron-containing lipids were prepared by reactions of cyclic oxonium derivatives of polyhedron boranes and metallacarboranes (closo-dodecaborate anion, cobalt and iron bis(dicarbollides)) with amine and carboxylic acids which are derived from cholesterol. Stable liposomal formulations, on the basis of synthesized boron-containing lipids, hydrogenated soybean l-α-phosphatidylcholine and (HSPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) as excipients, were prepared and then characterized by dynamic light scattering (DLS) that revealed the formation of particles to be smaller than 200 nm in diameter. The resulting liposomal formulations showed moderate to excellent loading and entrapment efficiency, thus justifying the design of the compounds to fit in the lipid bilayer and ensuring ease of in vivo use for future application. The liposomal formulations based on cobalt and iron bis(dicarbollide)-based lipids were found to be nontoxic against both human breast normal epithelial cells MCF-10A and human breast cancer cells MCF-7.

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors.

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.

Transition-Metal-Free Catalytic Carboalkoxylation of Styrenes at Room Temperature.

Herein, we describe the first transition-metal-free catalytic carboalkoxylation of styrenes with aryl diazonium salts by Meerwein addition in the presence of a phenalenyl ligand at room temperature without requiring any light stimulation. This three-component reaction allows facile difunctionalization of styrene derivatives with various alcohols (such as 1, 2, and 3°) as the source of alkoxy group during this transformation. The key intermediates and the transition states involved in this reaction path were unraveled by a series of control experiments coupled with density functional theory calculations. The full mechanistic investigation provides an understanding of the selectivity toward carboalkoxylation (Meerwein arylation addition elimination) in the presence of various alcohols over the simple arylation to multiple bond (Meerwein arylation-elimination) reaction.

Phenalenyl Based Aluminum Compound for Catalytic C-H Arylation of Arene and Heteroarenes at Room Temperature.

Main group metal based catalysis has been considered to be a cost-effective alternative way to the transition metal based catalysis, due to the high abundance of main group metals in the Earth's crust. Among the main group metals, aluminum is the most abundant (7-8%) in the Earth's crust, making the development of aluminum based catalysts very attractive. So far, aluminum based compounds have been popularly used as Lewis acids in a variety of organic reactions, but chemical transformation demanding a redox based process has never utilized an Al(III) complex as a catalyst. Herein, we tuned the redox noninnocence behavior of a phenalenyl ligand by coupling with Al(III) ion, which subsequently can store the electron upon reduction with K to carry out direct C-H arylation of heteroarenes/mesitylene at ambient temperature. A mechanistic investigation revealed that a three-electron reduced phenalenyl based triradical aluminum(III) complex plays the key role in such catalysis. The electronic structure of the catalytically active triradical species has been probed using EPR spectroscopy, magnetic susceptibility measurements, and electronic structure calculations using a DFT method.

Catalytic Reduction of Nitriles by Polymethylhydrosiloxane Using a Phenalenyl-Based Iron(III) Complex.

The reduction of nitriles to primary amines using an inexpensive silane such as polymethylhydrosiloxane (PMHS) is an industrially important reaction. Herein we report the synthesis of an earth-abundant Fe(III) complex bearing a phenalenyl-based ligand that was characterized by mass spectroscopy, elemental analysis, cyclic voltammetry, and single-crystal X-ray diffraction. The complex showed excellent catalytic activity toward reduction of aromatic, heteroaromatic, aliphatic, and sterically crowded nitriles to produce primary amines using polymethylhydrosiloxane (PMHS).

Interface-engineered templates for molecular spin memory devices.

The use of molecular spin state as a quantum of information for storage, sensing and computing has generated considerable interest in the context of next-generation data storage and communication devices, opening avenues for developing multifunctional molecular spintronics. Such ideas have been researched extensively, using single-molecule magnets and molecules with a metal ion or nitrogen vacancy as localized spin-carrying centres for storage and for realizing logic operations. However, the electronic coupling between the spin centres of these molecules is rather weak, which makes construction of quantum memory registers a challenging task. In this regard, delocalized carbon-based radical species with unpaired spin, such as phenalenyl, have shown promise. These phenalenyl moieties, which can be regarded as graphene fragments, are formed by the fusion of three benzene rings and belong to the class of open-shell systems. The spin structure of these molecules responds to external stimuli (such as light, and electric and magnetic fields), which provides novel schemes for performing spin memory and logic operations. Here we construct a molecular device using such molecules as templates to engineer interfacial spin transfer resulting from hybridization and magnetic exchange interaction with the surface of a ferromagnet; the device shows an unexpected interfacial magnetoresistance of more than 20 per cent near room temperature. Moreover, we successfully demonstrate the formation of a nanoscale magnetic molecule with a well-defined magnetic hysteresis on ferromagnetic surfaces. Owing to strong magnetic coupling with the ferromagnet, such independent switching of an adsorbed magnetic molecule has been unsuccessful with single-molecule magnets. Our findings suggest the use of chemically amenable phenalenyl-based molecules as a viable and scalable platform for building molecular-scale quantum spin memory and processors for technological development.

Integrating Organic Lewis Acid and Redox Catalysis: The Phenalenyl Cation in Dual Role.

In recent years, merging different types of catalysis in a single pot has drawn considerable attention and these catalytic processes have mainly relied upon metals. However, development of a completely metal free approach integrating organic redox and organic Lewis acidic property into a single system has been missing in the current literature. This study establishes that a redox active phenalenyl cation can activate one of the substrates by single electron transfer process while the same can activate the other substrate by a donor-acceptor type interaction using its Lewis acidity. This approach has successfully achieved light and metal-free catalytic C-H functionalization of unactivated arenes at ambient temperature (39 entries, including core moiety of a top-selling molecule boscalid), an economically attractive alternative to the rare metal-based multicatalysts process. A tandem approach involving trapping of reaction intermediates, spectroscopy along with density functional theory calculations unravels the dual role of phenalenyl cation.

Exploring Closed-Shell Cationic Phenalenyl: From Catalysis to Spin Electronics.

The odd alternant hydrocarbon phenalenyl (PLY) can exist in three different forms, a closed-shell cation, an open-shell radical, and a closed-shell anion, using its nonbonding molecular orbital (NBMO). The chemistry of PLY-based molecules began more than five decades ago, and so far, the progress has mainly involved the open-shell neutral radical state. Over the last two decades, we have witnessed the evolution of a range of PLY-based radicals generating an array of multifunctional materials. However, it has been admitted that the practical applications of PLY radicals are greatly challenged by the low stability of the open-shell (radical) state. Recently, we took a different route to establish the utility of these PLY molecules using the closed-shell cationic state. In such a design, the closed-shell unit of PLY can readily accept free electrons, stabilizing in its NBMO upon generation of the open-shell state of the molecule. Thus, one can synthetically avoid the unstable open-shell state but still take advantage of this state by in situ generating the radical through external electron transfer or spin injection into the empty NBMO. It is worth noting that such approaches using closed-shell phenalenyl have been missing in the literature. This Account focuses on our recent developments using the closed-shell cationic state of the PLY molecule and its application in broad multidisciplinary areas spanning from catalysis to spin electronics. We describe how this concept has been utilized to develop a variety of homogeneous catalysts. For example, this concept was used in designing an iron(III) PLY-based electrocatalyst for a single-compartment H2O2 fuel cell, which delivered the best electrocatalytic activity among previously reported iron complexes, organometallic catalysts for various homogeneous organic transformations (hydroamination and polymerization), an organic Lewis acid catalyst for the ring opening of epoxides, and transition-metal-free C-H functionalization catalysts. Moreover, this concept of using the empty NBMO present in the closed-shell cationic state of the PLY moiety to capture electron(s) was further extended to an entirely different area of spin electronics to design a PLY-based spin-memory device, which worked by a spin-filtration mechanism using an organozinc compound based on a PLY backbone deposited over a ferromagnetic substrate. In this Account, we summarize our recent efforts to understand how this unexplored closed-shell state of the phenalenyl molecule, which has been known for over five decades, can be utilized in devising an array of materials that not only are important from an organometallic chemistry or organic chemistry point of view but also provide new understanding for device physics.