Electronic Profiling of N-Phosphine Oxide-Substituted Imidazolin-2-ylidenes (PoxIms) and Imidazolidin-2-ylidenes (SPoxIms).

A detailed electronic study of the N-phosphine oxide functionalized imidazolin-2-ylidenes (PoxIms) and imidazolidin-2-ylidenes (SPoxIms) has been performed experimentally using IR, 13C, and 77Se NMR spectroscopies. While the net donor/acceptor properties of the (S)PoxIms could not be differentiated via IR spectroscopy (TEP), NMR spectroscopic methods (HEP, Se) reveal that the (S)PoxIms are slightly weaker σ-donors but stronger π-acceptors compared to common NHCs. Moreover, backbone and substituent-effects could also be resolved by the latter, allowing for a ranking of their electronic properties. Finally, the donicities of these well-designed NHC ligands in their bidentate κ2-C,O modes were evaluated using HEP2 and compared to those of classical chelators.

Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum.

Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(µ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(µ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.

Room-Temperature Reversible Chemisorption of Carbon Monoxide on Nickel(0) Complexes.

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and long-term storage of gaseous molecules. The formation of covalent bonds between the metal centers in the adsorbents and the targeted gases affects the desorption efficiency, especially when the oxidation state of the metal is low. Herein, we report a pressure-responsive nickel(0)-based system that is able to reversibly chemisorb carbon monoxide (CO) at room temperature. The use of N-heterocyclic carbene ligands with hemi-labile N-phosphine oxide substituents facilitates both the adsorption and desorption of CO on nickel(0) via ligand substitution. Ionic liquids were used as the reaction medium to enhance the desorption rate and establish a reusable system. These results showcase a way for the sustainable chemisorption of CO using a zero-valent transition-metal complex.

Rotation-Triggered Transmetalation on a Heterobimetallic Cu/Al N-Phosphine-Oxide-Substituted Imidazolylidene Complex.

A novel strategy for the preparation of heterobimetallic N-heterocyclic carbene (NHC) complexes is demonstrated using N-phosphine-oxide-substituted imidazolylidenes (PoxIms). In these heterobimetallic Cu/Al complexes, the Cu and Al centers can be either completely separated or brought near each other via the rotation of the N-phosphinoyl group in the PoxIm ligands. Triggered by this rotation, transmetalation to exchange the Cu-OtBu and Al-C6F5 bonds occurs on in situ-generated Cu/Al PoxIm complexes, and the Cu-C6F5 and Al-OtBu bonds are formed in excellent yield. On the basis of the results of mechanistic studies, including the isolation/in situ observation of key complexes and theoretical calculations, a plausible reaction mechanism for an intramolecular transmetalation is proposed to proceed via an activation complex that includes the simultaneous coordination of the phosphinoyl oxygen atom to the Cu as well as the Al centers. Furthermore, the formation of carbon-carbon bonds between Al(C6F5)3 and allyl bromide mediated/catalyzed by Cu/Al PoxIm complexes is demonstrated. Upon the consecutive transfer of three C6F5 groups from a single molecule of Al(C6F5)3, allyl pentafluorobenzene derivatives were obtained. The present results demonstrate the role of phosphine oxide in the activation of organoaluminum reagents for the transmetalation between Cu(I) complexes bearing NHCs as well as the benefit of constructing an intramolecular system based on a heterobimetallic complex to achieve efficient transmetalation by programming the encounter of two organometallic fragments.

Enantioselective Synthesis of Polycyclic γ-Lactams with Multiple Chiral Carbon Centers via Ni(0)-Catalyzed Asymmetric Carbonylative Cycloadditions without Stirring.

γ-Lactam derivatives with multiple contiguous stereogenic carbon centers are ubiquitous in physiologically active compounds. The development of straightforward and reliable synthetic routes to such chiral structural motifs in a stereocontrolled manner should thus be of importance. Herein, we report a strategy to construct polycyclic γ-lactam derivatives that contain more than two contiguous stereogenic centers in an enantioselective as well as atom-economic manner. Moreover, we have achieved the first enantioselective synthesis of strigolactam derivative GR-24, a racemic variant of which is a potential seed germination stimulator and plant-growth regulator. A key of the procedure presented here is a nickel(0)/chiral phosphoramidite-catalyzed asymmetric [2+2+1] carbonylative cycloaddition between readily accessible ene-imines and carbon monoxide, which proceeded enantioselectively to furnish up to 90% ee (>99% ee after recrystallization). The results of mechanistic studies, including the isolation of a chiral heteronickelacycle, support that the enantioselectivity on the two contiguous carbon atoms of the γ-lactams is determined during the oxidative cyclization on nickel(0).

Axial Chirality around N-P Bonds Induced by Complexation between E(C6F5)3 (E = B, Al) and an N-Phosphine Oxide-Substituted Imidazolinylidene: A Key Intermediate in the Catalytic Phosphinoylation of CO2.

Complexation-induced axial chirality around an N-P bond occurs upon the predominant coordination of the N-phosphinoyl group in the N-phosphine oxide-substituted imidazolinylidene (SPoxIm) to B(C6F5)3. (Ra) and (Sa) atropisomers of (κ-O-SPoxIm)B(C6F5)3 were observed independently in the single-crystal lattice and the optimized gas-phase structure. Experimental and theoretical studies confirmed that this axial chirality arises from the restricted rotation around the N-P bond, caused by the steric repulsion between the C5-H atoms of the imidazolinylidene ring and the C6F5 rings on the B(C6F5)3 unit. Conversely, this axial chirality was not certainly observed via the complexation between SPoxIm and Al(C6F5)3. The carbene carbon atoms in (κ-O-SPoxIm)E(C6F5)3 (E = B, Al) remain sufficiently nucleophilic to react with CO2, and the phosphinoylation of CO2 with SPoxIm proceeds far more rapidly in the presence of a catalytic amount of Al(C6F5)3 than in the absence of Al(C6F5)3.

Main-Group-Catalyzed Reductive Alkylation of Multiply Substituted Amines with Aldehydes Using H2.

Given the growing demand for green and sustainable chemical processes, the catalytic reductive alkylation of amines with main-group catalysts of low toxicity and molecular hydrogen as the reductant would be an ideal method to functionalize amines. However, such a process remains challenging. Herein, a novel reductive alkylation system using H2 is presented, which proceeds via a tandem reaction that involves the B(2,6-Cl2C6H3)( p-HC6F4)2-catalyzed formation of an imine and the subsequent hydrogenation of this imine catalyzed by a frustrated Lewis pair (FLP). This reductive alkylation reaction generates H2O as the sole byproduct and directly functionalizes amines that bear a remarkably wide range of substituents including carboxyl, hydroxyl, additional amino, primary amide, and primary sulfonamide groups. The synthesis of isoindolinones and aminophthalic anhydrides has also been achieved by a one-pot process that consists of a combination of the present reductive alkylation with an intramolecular amidation and intramolecular dehydration reactions, respectively. The reaction showed a zeroth-order and a first-order dependence on the concentration of an imine intermediate and B(2,6-Cl2C6H3)( p-HC6F4)2, respectively. In addition, the reaction progress was significantly affected by the concentration of H2. These results suggest a possible mechanism in which the heterolysis of H2 is facilitated by the FLP comprising THF and B(2,6-Cl2C6H3)( p-HC6F4)2.

N-Phosphine Oxide-Substituted Imidazolylidenes (PoxIms): Multifunctional Multipurpose Carbenes.

This article discusses the concept of N-heterocyclic carbenes (NHCs) equipped with more than one functional moiety, which allows using these NHCs for multiple purposes. A pioneering example for such NHCs is N-phosphine oxide-substituted imidazolylidenes (PoxIms), and their synthesis and strategic use are highlighted. The utility of PoxIms by far exceeds the conventional use as multidentate ligands for metal complexes on account of the synergetic functions of the carbene and the N-phosphine oxide group(s).

Efficient Synthesis of Polycyclic γ-Lactams by Catalytic Carbonylation of Ene-Imines via Nickelacycle Intermediates.

The nickel(0)-catalyzed carbonylative cycloaddition of 1,5- and 1,6-ene-imines with carbon monoxide (CO) is reported. Key to this reaction is the efficient regeneration of the catalytically active nickel(0) species from nickel carbonyl complexes such as [Ni(CO)3 L]. A variety of tri- and tetracyclic γ-lactams were thus prepared in excellent yields with 100 % atom efficiency. Preliminary results on asymmetric derivatives promise potential in the synthesis of enantioenriched polycyclic γ-lactams.

Catalytic Transformation of Aldehydes with Nickel Complexes through η(2) Coordination and Oxidative Cyclization.

Chemists no longer doubt the importance of a methodology that could activate and utilize aldehydes in organic syntheses since many products prepared from them support our daily life. Tremendous effort has been devoted to the development of these methods using main-group elements and transition metals. Thus, many organic chemists have used an activator-(aldehyde oxygen) interaction, namely, η(1) coordination, whereby a Lewis or Brønsted acid activates an aldehyde. In the field of coordination chemistry, η(2) coordination of aldehydes to transition metals by coordination of a carbon-oxygen double bond has been well-studied; this activation mode, however, is rarely found in transition-metal catalysis. In view of the distinctive reactivity of an η(2)-aldehyde complex, unprecedented reactions via this intermediate are a distinct possibility. In this Account, we summarize our recent results dealing with nickel(0)-catalyzed transformations of aldehydes via η(2)-aldehyde nickel and oxanickelacycle intermediates. The combination of electron-rich nickel(0) and strong electron-donating N-heterocyclic carbene (NHC) ligands adequately form η(2)-aldehyde complexes in which the aldehyde is highly activated by back-bonding. With Ni(0)/NHC catalysts, processes involving intramolecular hydroacylation of alkenes and homo/cross-dimerization of aldehydes (the Tishchenko reaction) have been developed, and both proceed via the simultaneous η(2) coordination of aldehydes and other π components (alkenes or aldehydes). The results of the mechanistic studies are consistent with a reaction pathway that proceeds via an oxanickelacycle intermediate generated by the oxidative cyclization with a nickel(0) complex. In addition, we have used the η(2)-aldehyde nickel complex as an effective activator for an organosilane in order to generate a silicate reactant. These reactions show 100% atom efficiency, generate no wastes, and are conducted under mild conditions.

Strategic Utilization of Multifunctional Carbene for Direct Synthesis of Carboxylic-Phosphinic Mixed Anhydride from CO2.

Direct synthesis of carboxylic-phosphinic mixed anhydrides has been achieved by treating carbon dioxide with N-phosphine oxide-substituted imidazolylidenes (PoxIms) that contain both nucleophilic carbene and electrophilic phosphorus moieties. This novel mixed anhydride was efficiently derivatized into an ester, an amide, and an unsymmetrical ketone via transformation into its corresponding imidazolium salt followed by a dual substitution reaction. The presented work used well-designed multifunctional carbene reagents to establish a novel utility for carbon dioxide in organic synthesis.

Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles: Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process.

A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential activation of an aldehyde and a silane by nickel(0). This strategy was applied to a simultaneous generation of carbon- and silicon-stereogenic centers with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial mechanistic studies revealed the complete switching of an aryl-transfer process from an intermolecular (racemic synthesis in the presence of IPr) to an intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A plausible rationale for the switching of the aryl-transfer process is given by a preliminary DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an η(2)-arene:η(2)-aldehyde fashion would be a key to the intramolecular process, while the formation of the corresponding intermediate is not possible in the presence of IPr. Owing to the chemically labile nature of its C-Si and O-Si bonds, enantioenriched benzoxasiloles are utilized for the synthesis of chiral building blocks and antihistaminic and anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with no erosion of the enantiomeric excess.

Pentacoordinated carboxylate π-allyl nickel complexes as key intermediates for the Ni-catalyzed direct amination of allylic alcohols.

Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5-cyclooctadiene)2 ] and 1,1'-bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu4 NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu4 NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated η(3) -allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.

A Strategy to Control the Reactivation of Frustrated Lewis Pairs from Shelf-Stable Carbene Borane Complexes.

N-Phosphine oxide substituted imidazolylidenes (PoxIms) have been synthesized and fully characterized. These species can undergo significant changes to the spatial environment surrounding their carbene center through rotation of the phosphine oxide moiety. Either classical Lewis adducts (CLAs) or frustrated Lewis pairs (FLPs) are thus formed with B(C6 F5 )3 depending on the orientation of the phosphine oxide group. A strategy to reactivate FLPs from CLAs by exploiting molecular motions that are responsive to external stimuli has therefore been developed. The reactivation conditions were successfully controlled by tuning the strain in the PoxIm-B(C6 F5 )3 complexes so that reactivation only occurred above ambient temperature.

Nickel(0)-catalyzed [2 + 2 + 1] carbonylative cycloaddition of imines and alkynes or norbornene leading to γ-lactams.

The first nickel(0)-catalyzed [2 + 2 + 1] carbonylative cycloaddition reaction of imines and alkynes or norbornene has been achieved by employing phenyl formate as a CO source. With this method, a variety of N-benzenesulfonyl, -tosyl, and -phosphoryl-substituted γ-lactams can be prepared in good to high yields.

Highly efficient activation of organosilanes with η2-aldehyde nickel complexes: key for catalytic syntheses of aryl-, vinyl-, and alkynyl-benzoxasiloles.

An η(2)-aldehyde nickel complex was utilized as an effective activator for an organosilane in order to generate a hypervalent silicate reactant for the first time. This method was successfully applied to the highly efficient syntheses of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles from benzaldehydes with aryl-, vinyl-, and alkynylsilyl groups at the ortho position. Initial mechanistic studies revealed that an intermolecular aryl transfer process was involved in the reaction mechanism. The formation of an η(2)-aldehyde complex was directly confirmed by NMR.

Nickel-catalyzed synthesis of N-aryl-1,2-dihydropyridines by [2+2+2] cycloaddition of imines with alkynes through T-shaped 14-electron aza-nickelacycle key intermediates.

Despite there being a straightforward approach for the synthesis of 1,2-dihydropyridines, the transition-metal-catalyzed [2+2+2] cycloaddition reaction of imines with alkynes has been achieved only with imines containing an N-sulfonyl or -pyridyl group. Considering the importance of 1,2-dihydropyridines as useful intermediates in the preparation of a wide range of valuable organic molecules, it would be very worthwhile to provide novel strategies to expand the scope of imines. Herein we report a successful expansion of the scope of imines in nickel-catalyzed [2+2+2] cycloaddition reactions with alkynes. In the presence of a nickel(0)/PCy3 catalyst, a reaction with N-benzylidene-P,P-diphenylphosphinic amide was developed. Moreover, an application of N-aryl imines to the reaction was also achieved by adopting N-heterocyclic carbene ligands. The isolation of an (η(2)-N-aryl imine)nickel(0) complex containing a 14-electron nickel(0) center and a T-shaped 14-electron five-membered aza-nickelacycle is shown. These would be considered as key intermediates of the reaction. The structure of these complexes was unambiguously determined by NMR spectroscopy and X-ray analyses.

In-silico-assisted derivatization of triarylboranes for the catalytic reductive functionalization of aniline-derived amino acids and peptides with H2.

Cheminformatics-based machine learning (ML) has been employed to determine optimal reaction conditions, including catalyst structures, in the field of synthetic chemistry. However, such ML-focused strategies have remained largely unexplored in the context of catalytic molecular transformations using Lewis-acidic main-group elements, probably due to the absence of a candidate library and effective guidelines (parameters) for the prediction of the activity of main-group elements. Here, the construction of a triarylborane library and its application to an ML-assisted approach for the catalytic reductive alkylation of aniline-derived amino acids and C-terminal-protected peptides with aldehydes and H2 is reported. A combined theoretical and experimental approach identified the optimal borane, i.e., B(2,3,5,6-Cl4-C6H)(2,6-F2-3,5-(CF3)2-C6H)2, which exhibits remarkable functional-group compatibility toward aniline derivatives in the presence of 4-methyltetrahydropyran. The present catalytic system generates H2O as the sole byproduct.

Main group catalysis for H2 purification based on liquid organic hydrogen carriers.

Molecular hydrogen (H2) is one of the most important energy carriers. In the midterm future, a huge amount of H2 will be produced from a variety of hydrocarbon sources through conversion and removal of contaminants such as CO and CO2. However, bypassing these purification processes is desirable, given their energy consumption and environmental impact, which ultimately increases the cost of H2. Here, we demonstrate a strategy to separate H2 from a gaseous mixture of H2/CO/CO2/CH4 that can include an excess of CO and CO2 relative to H2 and simultaneously store it in N-heterocyclic compounds that act as liquid organic hydrogen carriers (LOHCs), which can be applied to produce H2 by subsequent dehydrogenation. Our results demonstrate that LOHCs can potentially be used for H2 purification from CO- and CO2-rich crude H2 in addition to their well-established use in H2 storage.