Phenalenyl-Based Photocatalyst for Bioinspired Oxidative Dehydrogenation of N-Heterocycles and Benzyl Alcohols.

The environmental benefits of molecular oxygen as the oxidizing agent in oxidation reactions that synthesize fine chemicals cannot be overstated. Increased interest in developing robust photocatalysts is stimulated by the fact that the current photocatalytic transformation boom has made previously inaccessible synthetic approaches possible. Motivated by enzymatic catalysis, employing a reusable phenalenyl-based photocatalyst, we have successfully developed oxidative dehydrogenation utilizing molecular oxygen as a greener oxidant. Under photoinduced oxidative dehydrogenation conditions, different types of saturated N-heterocycles and alcohols were successfully dehydrogenated. The versatility of this bioinspired protocol is demonstrated by the fact that a wide variety of N-heteroaromatics, such as quinoline, carbazole, quinoxaline, acridine, and indole derivatives, as well as aldehydes and ketones, were successfully synthesized. Detailed mechanistic studies validate the proposed mechanism. Fluorescence lifetime and CV experiments revealed the crucial role of water on the efficiency of the reaction. The present protocol also provides chemoselectivity and scalability, leading to superior results and allowing for the functionalization of bioactive molecules at a late stage in a sustainable manner.

Transforming Non-innocent Phenalenyl to a Potent Photoreductant: Captivating Reductive Functionalization of Aryl Halides through Visible-Light-Induced Electron Transfer Processes.

Herein, we have established a phenalenyl-based molecular scaffold which serves as a potent photoreductant utilizing the empty NBMO in the presence of a base to form a radical anion which, upon photoexcitation, behaves as a stronger reductant and accomplishes the cleavage of strong C-X (X = Cl, Br, I) bonds under milder reaction conditions. The base was found to be involved in a dual role of electron and hydrogen atom donor. Further, the aryl radical formed by the homolysis of C-X bonds in this technique was captured for the Csp2-Csp2 coupling with unactivated arenes. The photoreductant potency of the phenalenyl-based catalytic system was further extended to C-P as well as C-B bond formation reactions. EPR and lifetime studies reveal the formation of a persistent radical having a sufficient lifetime to take part in the reaction by the PET mechanism. Different spectroscopic techniques combined with DFT calculations were utilized for the characterization of active catalytic species and for the elucidation of plausible mechanistic pathways. This not only is the initial report of the application of phenalenyl as a photoreductant but also provides a completely metal-free (alkali and transition metal) approach for the challenging reductive functionalization of aryl halides at room temperature.

Radical-Based C-C Bond-Forming Processes Enabled by the Photoexcitation of 4-Alkyl-1,4-dihydropyridines.

We report herein that 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) can directly reach an electronically excited state upon light absorption and trigger the generation of C(sp3 )-centered radicals without the need for an external photocatalyst. Selective excitation with a violet-light-emitting diode turns alkyl-DHPs into strong reducing agents that can activate reagents through single-electron transfer manifolds while undergoing homolytic cleavage to generate radicals. We used this photochemical dual-reactivity profile to trigger radical-based carbon-carbon bond-forming processes, including nickel-catalyzed cross-coupling reactions.

Chemoselective reduction of the carbonyl functionality through hydrosilylation: integrating click catalysis with hydrosilylation in one pot.

Herein we report the chemoselective reduction of the carbonyl functionality via hydrosilylation using a copper(I) catalyst bearing the abnormal N-heterocyclic carbene 1 with low (0.25 mol %) catalyst loading at ambient temperature in excellent yield within a very short reaction time. The hydrosilylation reaction of α,ß-unsaturated carbonyl compounds takes place selectively toward 1,2-addition (C═O) to yield the corresponding allyl alcohols in good yields. Moreover, when two reducible functional groups such as imine and ketone groups are present in the same molecule, this catalyst selectively reduces the ketone functionality. Further, 1 was used in a consecutive fashion by combining the Huisgen cycloaddition and hydrosilylation reactions in one pot, yielding a range of functionalized triazole substituted alcohols in excellent yields.

Introducing Phenalenyl-Based Organic Lewis Acid as a Photocatalyst to Facilitate Oxidative Azolation of Unactivated Arenes.

By revealing the robust photooxidant properties of phenalenyl-based organic Lewis acid, we have introduced this moiety as an effective organophotocatalyst for the oxidative azolation of unactivated and feedstock arenes. In addition to its tolerance for various functional groups and scalability, this photocatalyst was shown to be promising for the defluorinative azolation of fluoroarenes.

Photoinduced Cerium-Mediated Decarboxylative Alkylation Cascade Cyclization of N-arylacrylamides and N-acryl-2-aryl benzimidazoles.

A mild and versatile cerium-mediated decarboxylative strategy for sequential alkylation/cyclization was developed for the synthesis of quaternary oxindoles and benzimidazo[2,1-a]isoquinolin-6(5H)-ones via photoinduced-LMCT. This operationally simple procedure relies on inexpensive and feedstock carboxylic acids as alkyl radical surrogates and aerial molecular oxygen as the terminal oxidant. This mild and atom economical protocol showed viability with a wide range of alkyl carboxylic acids (1° to 3° acids) as coupling partners and also allows the late-stage modification of pharmaceutically-important acids. Mechanistic studies revealed the reaction to follow radical pathway, while the decarboxylative event was studied by in situ FTIR.

Electricity Induced Rhodium-Catalyzed Oxidative C-H/N-H Annulation of Alkynes with Arylhydrophthalazinediones.

The development of stoichiometric oxidant-free regioselective annulation protocol is a challenging aspect in organic synthesis. Herein, we disclose electricity as a greener oxidant for the C-H/N-H annulation to construct cinnolines using rhodium(III) catalyst under mild conditions. A detailed mechanistic investigation revealed the possibility of both Rh(III/I) and Rh(III/IV) catalytic cycles for the formation of annulated product. Exclusive regioselectivity, diverse substrate scope, and commercially available cheap graphite electrodes are key features of this protocol.

Photoinduced ligand to metal charge transfer enabling cerium mediated decarboxylative alkylation of quinoxalin-2(1H)-ones.

Here, we report the cerium-mediated decarboxylative alkylation of quinoxalin-2(1H)-ones utilizing feedstock carboxylic acids as a radical precursor via photoinduced-LMCT. This operationally simple protocol overcomes the limitation of the direct use of carboxylic acids to access alkyl radicals. Spectroscopic investigations reveal the photoinduced LMCT and CO2 evolving events. We have utilized a broad range of alkyl carboxylic acids (1° to 3° acids), amino acids and pharmaceutically-important acids as a coupling partner to synthesise the desired alkylated heterocyclic product in good to excellent yields.

Exploring Eosin Y as a bimodular catalyst: organophotoacid mediated Minisci-type acylation of N-heteroarenes.

Here we report Eosin Y as a bimodular catalyst for Minisci-type acylation reactions. The formation of organic exciplexes between photoexcited Eosin Y and N-heteroarenes was found to be a stabilizing factor for photoacid catalysis under optimized conditions. Spectroscopic investigations such as steady state fluorescence quenching and dynamic lifetime quenching experiments were employed to better understand the role of Eosin Y as both a photoredox catalyst and a photoacid. Feedstock aldehydes were employed as acyl radical precursors for engaging in C-C bond formation reactions with a variety of nitrogen containing heterocycles.

Nonsolvent application of ionic liquids: organo-catalysis by 1-alkyl-3-methylimidazolium cation based room-temperature ionic liquids for chemoselective N-tert-butyloxycarbonylation of amines and the influence of the C-2 hydrogen on catalytic efficiency.

1-Alkyl-3-methylimidazolium cation based ionic liquids efficiently catalyze N-tert-butyloxycarbonylation of amines with excellent chemoselectivity. The catalytic role of the ionic liquid is envisaged as "electrophilic activation" of di-tert-butyl dicarbonate (Boc(2)O) through bifurcated hydrogen bond formation with the C-2 hydrogen of the 1-alkyl-3-methylimidazolium cation and has been supported by a downfield shift of the imidazolium C-2 hydrogen of 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][NTf(2)]) from δ 8.39 to 8.66 in the presence of Boc(2)O in the (1)H NMR and a drastic reduction of the catalytic efficiency with 1-butyl-2,3-dimethylimidazolium ionic liquids that are devoid of the C-2 hydrogen. The differential time required for reaction with aromatic and aliphatic amines has offered means for selective N-t-Boc formation during inter and intramolecular competitions. Preferential N-t-Boc formation with secondary aliphatic amine has been achieved in the presence of primary aliphatic amine. Comparison of the catalytic efficiency for N-t-Boc formation with a common substrate revealed that [bmim][NTf(2)] is superior to the reported Lewis acid catalysts.

Electrifying Sustainability on Transition Metal-Free Modes: An Eco-Friendly Approach for the Formation of C-N Bonds.

Embracing sustainable green methodologies and techniques in chemical transformations has always been in the limelight to the synthetic community. Electrosynthesis has emerged as a powerful, sustainable synthetic tool for molecular synthesis exploiting inexpensive electricity in place of sacrificial chemical oxidizing/reducing reagents. Herein, recent advances in the incorporation of transition metal-free redox mediators in electrosynthesis for the construction of C-N bonds are outlined. Furthermore, conjugation of this strategy with flow catalysis allows easy scale up of the synthesis of molecular assembly. This comprehensive Review provides an overview of metal-free mediated electro-construction of C-N bonds, focusing on the reaction mechanisms involved and its synthetic applications.

On catalysis by ionic liquids.

A molecular level mechanism of catalysis by an ionic liquid (IL) is proposed as an "electrophile nucleophile dual activation" through a "relay of cooperative hydrogen bonds and charge-charge interactions". Spectroscopic ((1)H NMR and IR) studies were used to probe the involvement of the C-2 hydrogen and the AcO(-) anion of [bmim][OAc] in the catalysis for O-t-Boc formation. Ion fishing by MALDI-TOF-TOF MS and MS-MS established the hydrogen bonded clusters.

Zirconocene catalyzed diastereoselective carbometalation of cyclobutenes.

The regio- and diastereoselective zirconocene-catalyzed carbomagnesiation of cyclobutenes is herein reported to afford configurationally stable cyclobutylmagnesium species that could subsequently react with a large variety of electrophiles to give polysubstituted cyclobutane species as a single diastereoisomer.

Diastereodivergent combined carbometalation/zinc homologation/C-C fragmentation reaction as an efficient tool to prepare acyclic allylic quaternary carbon stereocenters.

A new strategy has been developed to construct enantiomerically enriched acyclic allylic quaternary carbon stereocenters in a single-pot operation through a combined carbometalation/zinc homologation/fragmentation sequence. Proper tuning of the reaction conditions enables the synthesis of the two enantiomers starting from a single enantiomer of the starting material.

One-pot consecutive catalysis by integrating organometallic catalysis with organocatalysis.

The present study integrates two types of catalysis, namely, organometallic catalysis and organocatalysis in one reaction pot. In this process, the product of the first catalytic cycle acts as catalytic component for next catalytic cycle. The abnormal N-heterocyclic carbene-copper-based organometallic catalyst acts as an efficient catalyst for a click reaction to provide triazole, which, in turn, acts as an efficient organocatalyst for different organic transformations, for example, aza-Michael addition and multicomponent reactions, in a consecutive fashion in the same reaction pot.

Synergistic dual activation catalysis by palladium nanoparticles for epoxide ring opening with phenols.

Synergistic dual activation catalysis has been devised for epoxide phenolysis wherein palladium nanoparticles induce electrophilic activation via coordination with the epoxide oxygen followed by nucleophilic activation through anion-π interaction with the aromatic ring of the phenol, and water (reaction medium) also renders assistance through 'epoxide-phenol' dual activation.

Ionic liquid catalysed reaction of thiols with α,ß-unsaturated carbonyl compounds--remarkable influence of the C-2 hydrogen and the anion.

Hydrogen bond induced reactivity and selectivity control in the 1-butyl-3-methylimidazolium based ionic liquid catalysed reaction of thiols with α,ß-unsaturated carbonyl compounds is reported with remarkable influence of the anion and the C-2 hydrogen in catalytic activity and reversal of selectivity.

Surfactant mediated oxygen reuptake in water for green aerobic oxidation: mass-spectrometric determination of discrete intermediates to correlate oxygen uptake with oxidation efficiency.

A novel strategy of catalytic green aerobic oxidation by surfactant-mediated oxygen reuptake in water offers a new dimension to the applications of surfactants to look beyond as solubility aids and a conceptual advancement in understanding the role of surfactants in aquatic organic reactions through mass spectrometry guided identification of discrete intermediates.

Supramolecular assemblies in ionic liquid catalysis for aza-Michael reaction.

Supramolecular assemblies formed by a relay of cooperative hydrogen bonds and charge-charge interactions have been identified/characterized by (+ve) ESI and MALDI-TOF-TOF MS and MS-MS studies during the aza-Michael reaction of amines with alpha,beta-unsaturated carbonyl compounds in the presence of ionic liquids (ILs) digging out the role of catalysis by ILs, forming the basis of rational design/selection as organocatalysts, and offering a diagnostic model to predict/rationalize the selectivity of the aza-Michael reaction in a competitive environment.