Unravelling a bench-stable zinc-amide compound as highly active multitasking catalyst for radical-mediated selective alk(en)ylation of unactivated carbocycles under mild conditions.

The direct functionalization of unactivated organic moieties via C-C bond formation has long fascinated synthetic chemists. Although base-metal systems are steadily emerging in this area, achieving multitasking activity in a single catalyst to execute several such functionalizations under mild conditions is challenging. To address this, we herein report an effective protocol for the selective C-alk(en)ylation of indene/fluorene with alcohol as a green alkylating agent employing a naturally abundant and eco-friendly zinc-derived compound, for the first time. Notably, this study unveils the unique potential of a bench-stable Zn compound bearing an amidated imidazolium salt towards C-C bond-forming reactions utilizing an array of alcohols, ranging from aliphatic to aromatic and, attractively, even secondary alcohols. Moreover, this readily scalable protocol, which proceeds via an underdeveloped radical-mediated borrowing hydrogen protocol (an aldehyde is generated from an alcohol, and subsequent condensation with indene/fluorene provides the corresponding alkenylated products) established based on a range of control experiments, works effortlessly under mild conditions using a low catalyst loading. Notably, this approach affords remarkable selectivity towards alkylated or alkenylated products with a high level of functional group tolerance and chemoselectivity. Crucially, the catalytic activity of these Zn compounds can be attributed to their hydrogen atom transfer (HAT) capability, while their selectivity towards different products can be understood in terms of employed reaction conditions. Lastly, the synthetic utility of obtained products was showcased by their late-stage functionalization to access unsymmetrical 9,9-disubstituted fluorenes, which are potentially useful for various optoelectronic applications.

Amine-functionalized bifunctional CoIII-NHC complexes: highly effective phosphine-free catalysts for the α-alkylation of nitriles.

Newly developed amine functionalized NHC-supported CoIII-complexes have been identified as highly effective bifunctional catalysts for the α-alkylation of nitriles using a plethora of alcohols, ranging from aliphatic to aromatic and intriguingly, also secondary ones. Comparison of their activities with the non-bifunctional analogues uncovered their extremely high activities although possessing the high-valent CoIII-center due to metal-ligand cooperativity, which has been established by an array of control experiments.

(Benz)imidazo[1,2-a]quinolinium Salts: Access via Unprecedented Regiospecific non-AAIPEX Strategy and Study of Their Tunable Properties.

An unprecedented non-AAIPEX protocol has been developed to access diverse monosubstituted cationic polycyclic heteroaromatic compounds (cPHACs) from the readily available azolium salts and phenacyl bromides via Ru(II)-catalyzed tandem annulation cum aromatization. This atom-economic protocol executes a range of intermediate steps e. g. double C-H activation, nucleophilic addition, annulation, and dehydration cum aromatization in one-pot manner under the generation of H2O as the sole byproduct. Moreover, the systematic tunability of photo-physical and electrochemical properties of these new class of cPHACs can be authenticated from the DFT calculated frontier molecular orbital energies that might be beneficial for their potential applications in optoelectronics and DNA intercalation.

Heteroditopic NHC Ligand Supported Manganese(I) Complexes: Synthesis, Characterization, and Activity as Non-bifunctional Phosphine-Free Catalyst for the α-Alkylation of Nitriles.

In the present work, several manganese(I) complexes of chelating heteroditopic ligands Mn1-3, featuring ImNHC (imidazol-2-ylidene) connected to a 1,2,3-triazole-N or tzNHC (1,2,3-triazol-5-ylidene) donors via a methylene spacer, with possible modifications at the triazole backbone have been synthesized and completely characterized. Notably, the CO stretching frequencies, electrochemical analysis, and frontier orbital analysis certainly suggest that the chelating ImNHC-tzNHC ligands have stronger donation capabilities than the related ImNHC-Ntz ligand in the synthesized complexes. Moreover, these well-defined phosphine-free Mn(I)-NHC complexes have been found to be effective non-bifunctional catalysts for the α-alkylation of nitriles using alcohols and importantly, the catalyst Mn1 containing ImNHC connected to a weaker triazole-N donor displayed higher activity compared to Mn2/Mn3 containing an unsymmetrical bis-carbene donors (ImNHC and tzNHC). A wide range of aryl nitriles were coupled with diverse (hetero)aromatic as well as aliphatic alcohols to get the corresponding products in good to excellent yields (32 examples, up to 95 % yield). The detailed mechanistic studies including deuterium labelling experiments reveal that the reaction follows a Borrowing Hydrogen pathway.

Heterobimetallic Complexes Bridged by an Unsymmetrical Bis(NHC) Ligand: Study of Enhanced Catalytic Activity in Tandem Transformations and Understanding of Cooperativity between the Metal Centers.

The bis(azolium) salt [L1-H2 ]Br2 was found to serve as a suitable platform for accessing the heterobimetallic IrIII -M (M=PdII /AuI ) and PdII -IrIII complexes. Initially, selective mono-metalation of [L1-H2 ]Br2 yielded an orthometalated IrIII - or non-orthometalated PdII -complex. Sequential metalation of the mono-IrIII complex resulted in the formation of heterobimetallic IrIII -PdII /AuI complexes. Similarly, a distinct heterobimetallic PdII -IrIII complex was synthesized starting from the mono-PdII complex. Further, the corresponding homobimetallic IrIII -IrIII and PdII -PdII complexes were directly obtained from [L1-H2 ]Br2 . Additionally, monometallic PdII and IrIII analogues were synthesized from [L2-H]Br and [L3-H]Br, respectively. The heterobimetallic IrIII -PdII and PdII -IrIII complexes were then evaluated as catalysts in various one-pot tandem catalytic reactions in which they demonstrated superior activity than the mixtures of both their corresponding homobimetallic IrIII -IrIII /PdII -PdII and monometallic IrIII /PdII counterparts, under the constant concentrations of metal centers. Moreover, while comparing complexes IrIII -PdII and PdII -IrIII , the former exhibits higher activity in all the studied reactions. All these findings suggest the presence of some form of cooperativity between the two metal centers (Ir and Pd) connected by a single ligand framework in IrIII -PdII and PdII -IrIII complex, with IrIII -PdII displaying better cooperativity that has been validated by electrochemical, NMR, and DFT studies.

'Click'-Derived 1,2,3-Triazolium Salts Featuring a 4-Halo-phenyl Group: Precursors for Heterobimetallic Complexes.

The 'click'-derived 1,2,3-triazolium salts [L1/L2-H]I (1-(4-iodo/bromo-phenyl)-1H-1,2,3-triazolium salt) featuring two distinct coordination sites, one via oxidative addition and other via classical deprotonation cum metalation, were designed and explored towards the synthesis of various mono- and bimetallic complexes. Accordingly, a series of well-characterized 1,2,3-triazol-5-ylidene coordinated cyclometalated transition metal complexes (1-3) were obtained. However, these complexes were found to be ineffective in accessing the desired heterobimetallic complexes. Nevertheless, same ligand systems readily underwent oxidative addition with Pd0 metal precursors, to give the PdII complexes 4/5, and the considerable change and reversal in chemical shift values of the triazole C4/C5-backbone protons (C4-H being downfield shifted than that of C5-H) of these oxidatively added PdII complexes were detected. The PdII complex 5 with chelating DPPE was finally successfully applied for the synthesis of the heterobimetallic PdII -RuII complex 6 and 2D NMR analyses, as well as DFT calculations supported the formation of the rare C4/C5-unprotected 1,2,3-triazol-4-ylidene coordinated RuII -complex.

Base-catalyzed Effective C2-Amidation of Azolium Salts Using Isocyanates under Mild Conditions.

An unprecedented base-catalyzed hydroarylation of isocyanates with azolium salts was developed, which follows a simple reaction pathway and provided facile access to diverse C2-amidated azolium salts under mild conditions. Importantly, this methodology can also be applied for the successive C2-amidation of a bisimidazolium salt with two different isocyanates to provide the corresponding unsymmetrically substituted bisamide derivatives. Notably, the obtained amidated salts can also serve as a prominent carbene surrogate for the synthesis of metal-NHC complexes.

N-Heterocyclic Carbene-Supported Nickel-Catalyzed Selective (Un)Symmetrical N-Alkylation of Aromatic Diamines with Alcohols.

The "borrowing hydrogen" (BH) approach for the N-alkylation of phenylenediamines using alcohols as coupling partners is highly challenging due to the selectivity issue of the generated products. Furthermore, the development of base-metal systems that can potentially substitute precious metals with competitive activity is a major challenge in BH catalysis. We present herein an efficient protocol for the N,N'-di-alkylation of aromatic diamines using an in situ-generated Ni-NHC complex from NiCl2 and the ligand L1, which gave access to a wide range of N,N'-di-alkylated orthophenylene diamines (rather than the generally observed benzimidazole derivatives), meta- and para-phenylene diamines along with 2,6-diamino pyridine derivatives in good to excellent yields. Moreover, the catalyst system was also successful in the derivatization of a clinically important drug molecule, Dapsone. Notably, the present protocol could be applied effectively to synthesize unsymmetrically substituted N,N'-di-alkylated diamines via sequential alkylation and is the first report in the base-metal system to the best of our knowledge. Diverse control experiments including the deuterium incorporation studies suggest that the present protocol proceeds via a BH sequence.

Towards new coordination modes of 1,2,3-triazolylidene: controlled by the nature of the 1st metalation in a heteroditopic bis-NHC ligand.

An unusual effect of the nature of the first metal coordination of a heteroditopic N-heterocyclic carbene ligand (L2) towards the coordination behavior of 1,2,3-tzNHC is explored. The first metal coordination at the ImNHC site (complexes 3 and 4) was noted to substantially influence the electronics of the 1,2,3-triazolium moiety leading to an unprecedented chemistry of this MIC donor. Along this line, the RhIII/IrIII-orthometalation in complexes 4 makes the triazolium C4-H more downfield shifted than C5-H, whereas a reverse trend, although to a lesser extent, is observed in the case of the non-chelated PdII-coordination. This difference in behavior assisted us to achieve the selective activation of triazole C4/C5 positions, not observed before, as supported by the isolation of the homo- and hetero-bimetallic complexes, 5, 6 and 7-9via C5- and C4-metalation, respectively. Furthermore, the %V bur calculations eliminate any considerable steric influence and the DFT studies strongly support the selectivity observed during bimetalation.

Silver-Catalyzed One-Pot Three-Component Synthesis of α-Aminonitriles and Biologically Relevant α-Amino-phosphonates.

A simple silver salt (AgSbF6 )-catalyzed aminophosphonylation and Strecker reaction have been developed and successfully applied to a wide range of substrates (>55 substrates). This solvent-, ligand-, and base-free one-pot three-component protocol operates effectively at room temperature to provide diversified α-aminophosphonates and α-aminonitriles, which gave access to the respective α-amino amides. Importantly, the present catalyst system is also capable to produce the rarely reported and biologically relevant aminophosphonates (having anti-leishmanial activity). Further, mechanistic studies reveal that the present phosphonylation protocol follows a radical pathway.

Self-Assembly of a Bis-NHC Ligand and Coinage Metal Ions: Unprecedented Metal-Driven Chemistry between the Tri- and Tetranuclear Species.

The discrete multinuclear AgI -NHC complexes [Agn (1)n )](X)n ; (n=3 or 4, X=BF4 , PF6 ), synthesized from a bis-NHC ligand 1 and AgI ions via multiligand self-assembly, were observed to be in equilibrium between two forms (tri- and tetranuclear) in solution on the NMR timescale, which is unprecedented in CNHC -donor based chemistry. The existence of both the species was confirmed by various studies such as NMR (1 H, VT, 2D-DOSY) and ESI-MS analysis along with concentration studies. Importantly, replacing AgI with other coinage metals (AuI and CuI ) was found to alter the phenomenon entirely: a slow exchange from the tetra- to trinuclear species was noticed for the AuI complexes (4 a, b), whereas no such process was detected in case of the CuI complexes (5 a, b).

Simple silver(I)-salt catalyzed selective hydroboration of isocyanates, pyridines, and quinolines.

AgSbF6 has been established as an effective catalyst for the hydroboration of structurally and electronically diverse isocyanates under ligand- and solvent-free conditions which selectively yielded either N-boryl formamides or N-boryl methylamines under different conditions. Further, various N-heterocycles can be selectively hydroborated using this simple catalytic system; pyridine derivatives undergo preferential 1,4 hydroboration whereas the formation of tetrahydroquinoline (after hydrolysis) via complete heterocycle hydrogenation was observed for quinolines.

RuII-Complexes of heteroditopic chelating NHC ligands: effective catalysts for the ß-alkylation of secondary alcohols and the synthesis of 2-alkylaminoquinoline derivatives following the dehydrogenative protocol.

RuII-Complexes of chelating heteroditopic N-heterocyclic carbene ligands featuring imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) donors connected via a CH2 spacer, 1a-c, were found to be very effective catalysts for the cross-coupling of secondary and primary alcohols with the elimination of H2O. Diverse ß-alkylated secondary alcohols were thus obtained by following this method in excellent yields of up to 95% by employing a very low catalyst (1a) loading of 0.01-0.001 mol% along with the inexpensive base KOH. Mechanistically, the present protocol follows the borrowing hydrogen strategy which was established by various control experiments including deuterium labelling experiments and importantly, 1H NMR and ESI-MS analyses validated the participation of a Ru-H species in the catalytic cycle. Remarkably, the present system displayed the highest Ru-based TON of 396 000 for the ß-benzylation of 1-phenylethanol with a catalyst loading of 1 ppm (0.0001 mol%). Additionally, diverse 2-alkylaminoquinoline derivatives were synthesized in a one-pot manner from 2-aminobenzyl alcohol, 2-arylacetonitrile, and various primary alcohols.

Recent Advances in the Syntheses and Catalytic Applications of Homonuclear Ru-, Rh-, and Ir-Complexes of CNHC

In the past few decades, chemistry of cyclometalated species has gained momentum with increased applications in several areas of scientific developments. Cyclometalation reactions result in the formation of stable metallacycles through the generation of metal-carbon covalent bonds by activating the unreactive Csp2 -H or Csp3 -H bonds. The extra stability gained by the formation of metallacycles enhances their applicability scopes especially in the area of homogeneous catalysis. In the recent research development in this area, NHC ligands (strong σ-donor and generally, weak π-acceptor) have been found to be one of the most suitable candidates for the intramolecular C-H activation process which leads to the cyclometalated species. The growth in the area of cyclometalation chemistry that started in the late 20th century is still continuing and in the past few decades, various examples of NHC derived transition metal-based cyclometalated complexes came into the picture. As covering all the reported literatures in this area (includes mainly late transition metals) will exceed the limits of minireview, we restricted ourselves to the recent (2015 - May 2021) examples of the most common Ru-, Rh-, and Ir-based CNHC ^C cyclometalated complexes and their applications in various homogeneous catalytic conversions such as transfer hydrogenation, amidation, oxidation of alcohols, annulations, and so forth.

[(PPh3)2NiCl2]-Catalyzed C-N Bond Formation Reaction via Borrowing Hydrogen Strategy: Access to Diverse Secondary Amines and Quinolines.

Commercially available [(PPh3)2NiCl2] was found to be an efficient catalyst for the mono-N-alkylation of (hetero)aromatic amines, employing alcohols to deliver diverse secondary amines, including the drug intermediates chloropyramine (5b) and mepyramine (5c), in excellent yields (up to 97%) via the borrowing hydrogen strategy. This method shows a superior activity (TON up to 10000) with a broad substrate scope at a low catalyst loading of 1 mol % and a short reaction time. Further, this strategy is also successful in accessing various quinoline derivatives following the acceptorless dehydrogenation pathway.

Silver-Catalyzed Hydroboration of C-X (X = C, O, N) Multiple Bonds.

AgSbF6 was developed as an effective catalyst for the hydroboration of various unsaturated functionalities (nitriles, alkenes, and aldehydes). This atom-economic chemoselective protocol works effectively under low catalyst loading, base- and solvent-free moderate conditions. Importantly, this process shows excellent functional group tolerance and compatibility with structurally and electronically diverse substrates (>50 examples). Mechanistic investigations revealed that the reaction proceeds via a radical pathway. Further, the obtained N,N-diborylamines were showcased to be useful precursors for amide synthesis.

Self-Assembly of Benzimidazole-Derived Tris-NHC Ligands and AgI -Ions to Hexanuclear Organometallic Cages and Their Unusual Transmetalation Chemistry.

Multi-ligand self-assembly to attain the AgI -N-heterocyclic carbene (NHC)-built hexanuclear organometallic cages of composition [Ag6 (3 a,b)4 ](PF6 )6 from the reaction of benzimidazole-derived tris(azolium) salts [H3 -3 a,b](PF6 )3 with Ag2 O was achieved. The molecular structures of the cages were established by X-ray diffraction studies along with NMR and MS analyses. The existence of a single assembly in solution was supported by diffusion-ordered spectroscopy (DOSY) 1 H NMR spectra. Further, transmetalation reactions of these self-assembled complexes, [Ag6 (3 a,b)4 ](PF6 )6 , with CuI /AuI -ions provided various coinage metal-NHC complexes having diverse molecular compositions, which included the first example of a hexanuclear CuI -dodecacarbene complex, [Cu6 (3 b)4 ](PF6 )6 .

Transition metal complexes of a bis(carbene) ligand featuring 1,2,4-triazolin-5-ylidene donors: structural diversity and catalytic applications.

Dialkylation of the 1,3-bis(1,2,4-triazol-1-yl)benzene with ethyl bromide results in the formation of [L-H2]Br2 which, upon salt metathesis with NH4PF6, readily yields the bis(triazolium) salt [L-H2](PF6)2 with non-coordinating counterions. [L-H2](PF6)2 and Ag2O react in a 1 : 1 ratio to yield a binuclear AgI-tetracarbene complex of the composition [(L)2Ag2](PF6)2 which undergoes a facile transmetalation reaction with [Cu(SMe2)Br] to deliver the corresponding CuI-NHC complex [(L)2Cu2](PF6)2. In contrast, the [L-H2]Br2 reacts with [Ir(Cp*)Cl2]2 to generate a doubly C-H activated IrIII-NHC complex 5. Similarly, the triazolinylidene donor supported diorthometalated RuII-complex 6 is also obtained. Complexes 5 and 6 represent the first examples of a stable diorthometalated binuclear IrIII/RuII-complex supported by 1,2,4-triazolin-5-ylidene donors. The synthesized IrIII-NHC complex 5 is found to be more effective than its RuII-analogue (6) for the reduction of a range of alkenes/alkynes via the transfer hydrogenation strategy. Conversely, RuII-complex 6 is identified as an efficient catalyst (0.01 mol% loading) for the ß-alkylation of a wide range of secondary alcohols using primary alcohols as alkylating partners via a borrowing hydrogen strategy.

Catalyst- and solvent-free efficient access to N-alkylated amines via reductive amination using HBpin.

A sustainable approach which works under catalyst- and solvent-free conditions for the synthesis of structurally diverse secondary amines has been uncovered. This one-pot protocol works efficiently at room temperature and is compatible with a wide range of sterically and electronically diverse aldehydes and primary amines. Notably, this simple process offers scalability, excellent functional group tolerance, chemoselectivity, and is also effective at the synthesis of biologically relevant molecules.

Ruthenium(II) Complexes of Heteroditopic N-Heterocyclic Carbene Ligands: Efficient Catalysts for C-N Bond Formation via a Hydrogen-Borrowing Strategy under Solvent-Free Conditions.

Both imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) have evolved to be elite groups of N-heterocyclic carbene (NHC) ligands for homogeneous catalysis. To develop efficient ruthenium(II)-based catalysts incorporating these ligands for C-N bond-forming reactions via hydrogen-borrowing methodology, we utilized chelating ligands integrated with ImNHC and mesoionic tzNHC donors connected via a CH2 spacer with a diverse triazole backbone. The synthesized ruthenium(II) complexes 3 are found to be highly efficient for C-N bond formation across a wide range of primary amine and alcohol substrates under solvent-free conditions, and among all of the complexes studied here, catalyst 3a with a mesityl substituent displayed maximum activity. To our delight, catalyst 3a is also effective for the selective mono-N-methylation of various anilines utilizing methanol as a coupling partner, known to be relatively more difficult than other alcohols. Furthermore, complex 3a also delivers various substituted quinolines successfully via the reaction of 2-aminobenzyl alcohol with several secondary alcohols. Importantly, catalyst 3a exhibited the highest activity among the reported ruthenium(II) complexes for both the N-benzylation of aniline [achieving a turnover number (TON) of 50000] and the realization of quinoline 8a by reacting 2-aminobenzyl alcohol with 2-phenylethanol (attaining a TON of 30000).