Homogeneous Gold Catalysis for Regioselective Carbocyclization of Alkynyl Precursors.

π-Activation of alkynyl precursors possessing an endogenous carbon nucleophile is one of the imperative topics in homogeneous gold catalysis as it offers Csp3 -Csp2 and Csp2 -Csp2 linked carbocycles. However, the exo-dig and endo-dig cyclization modes unlocks the possibility of both small and large rings respectively, thereby losing regioselectivity. Nevertheless, several gold-catalyzed carbocyclizations which permits one isomer by controlling or avoiding the formation of other went largely unnoticed. Hence, this review is an attempt to summarize such approaches reported from early 2000's to till date along with our viewpoint on contributing parameters for regioselectivity. This review covers only unimolecular reactions with classifications primarily based on the type of endogenous nucleophiles such as silyloxyenols, enamides/enamines, benzenoids, heteroaromatics and alkyls/alkenyls. From an application perspective, these reactions are significant in total synthesis and materials science. Therefore, those reactions that finds application in natural product synthesis and π-functional materials are highlighted in appropriate places.

Step-Economical Mechanosynthesis of Hybrid Azoles: Deciphering Their π-Orbital and Pharmacological Characteristics.

A hybrid pharmacophore strategy for unifying 1,2,3-triazole with 1,2,4-triazole cores to prepare mixed triazoles was accomplished by a ball-milling approach. The developed chemistry works under the catalysis of cupric oxide nanoparticles with salient features like one-jar operation, lower number of synthetic steps, catalyst recyclability, time-dependent product control, and good overall yields. π-Orbital properties based on theoretical calculations supported the suitability of these molecules for pharmacological screening. Therefore, the biological potency of the synthesized molecules was evaluated for antioxidant, anti-inflammatory, and anti-diabetic activities. By virtue of their proton-donating tendency, all compounds showed promising radical-scavenging activity with the inhibition level reaching up to 90 %. These molecular hybrids also exhibited anti-inflammatory and anti-diabetic potencies similar to those of standard compounds, owing to their electron-rich nature. Finally, α-amylase inhibitory potential was demonstrated in silico; significant regions necessary for enzyme inhibition were identified by hydrogen bonding interactions.

Synthesis and Optoelectronic Features of Rhodamine-Triazole Dyads as Metallochromic Probes for Copper-Selective Chemosensing.

Rhodamine-based chromic materials have attracted significant interest owing to their cation recognition ability with high sensitivity. However, rhodamine chromophores with controllable sensing selectivity towards transition metal species are only at the advent. Herein, three triazole-conjugated rhodamine dyads with different peripheral substituents were synthesized. The key triazole precursors required for the desired chemistry were prepared by adopting our recently developed CTAB catalyzed mechano-click chemistry. Molecular properties derived from photophysics, electrochemistry and surface morphology of the synthesized dyads were analyzed. Furthermore, frontier molecular orbitals, electronic structure and secondary quantum chemical parameters of dyads were also compared. Screening of dyads for their sensing ability towards an array of alkali, alkaline and transition metal ions exhibited a noticeable naked-eye detection of Cu2+ ions and was confirmed by spectrophotometric titration. The specific binding mode of dyads as probable with Cu2+ over other metal ions attributes to the chemoselectivity.

Mechanosynthesis of Triazolyl-bis(indolyl)methane Pharmacophores via Gold Catalysis: A Prelude to Their Molecular Electronic Properties and Biological Potency.

Chemical structures possessing both 1,2,3-triazole and bis(indolyl)methane fragments gained considerable interest in drug synthesis owing to their established biological efficacies. However, 1,2,3-triazoles linked at the bridging position of bis(indolyl)methane is a logical and unexplored design approach. In this regard, nine new triazolyl-bis(indolyl)methane conjugates under AuCl catalyzed ball-milling conditions were accomplished. Comparative evaluation on absorptive and emissive properties of the synthesized dyads were also analyzed. To unravel the influence of different peripheral substituents on the electronic structure and π-orbital properties, theoretical investigations were performed. Screening of molecules for free radical scavenging, anti-inflammatory and antidiabetic showed comparable potency against reference drugs. In particular, compounds 7 h, 7 d and 7 a displayed good efficiency of α-amylase inhibition. The DNA gyrase inhibitory potential of all compounds were assessed in silico which revealed high binding affinity (ΔG=-8.99 Kcal/mol) for 7 i followed by 7 h (ΔG=-7.80 Kcal/mol) with the targeted protein.

Mechanochemical Access to Functional Clickates with Nitro-Retentive Selectivity via Organocatalyzed Oxidative Azide-Olefin Cycloaddition.

4-Nitro-1,2,3-triazoles are crucial precursors for high energy materials, and their practical synthesis is a long-standing problem. Herein, we communicate a mechanochemical route for the selective synthesis of 4-nitro-1,2,3-triazoles via organocatalyzed oxidative [3 + 2] cycloaddition between ß-nitrostyrenes and organic azides. Our conditions avoid divergent pathways and permit the retention of the valuable NO2 group on the product. Nontoxic catalyst, catalyst recyclability, no rigorous solvent-extraction, no toxic byproducts, atmospheric oxygen, and gram-scale synthesis are some of the salient features.

Azulene Bridged π-Distorted Chromophores: The Influence of Structural Symmetry on Optoelectrochemical and Photovoltaic Parameters.

Conjugated chromophores possessing π-twisted functionality such as tetracyanobutadiene (TCBD) have emerged as promising active layer materials for organic photovoltaics (OPVs). In this study, we disclose the synthesis of two azulenyl chromophores containing one and two TCBD groups. The symmetrical and unsymmetrical structural characteristics of these molecules inflict dissimilar optoelectronic and electrochemical properties. Based on molar absorptivity, aggregation behavior, HOMO-LUMO energies and other quantum chemical parameters, the symmetrical molecule (TATC2) appears to be a better non-fullerene acceptor (NFA) compared to its unsymmetrical counterpart (TATC1). For instance, higher absorptivity and deeper HOMO-LUMO levels for TATC2 (23950 M-1 cm-1 ; -6.01 eV/-3.86 eV) over TATC1 (12200 M1 cm-1 ; -5.46 eV/-3.64 eV) was observed. Validating this structure-property relationship on solar cell prototypes exhibited higher photovoltaic parameters (VOC =0.54 V, FF=0.48, JSC =6.42 mA/cm2 ) for TATC2 than TATC1 (VOC =0.47 V, FF=0.38, JSC =5.77 mA/cm2 ). Though the device parameters are not high, this work uncovers the intrinsic properties of azulene-tethered twisted chromophores as potential π-semiconductor choice for NFA solar cells. In particular, this report explores the utility of azulene-based π-twisted semiconductors as acceptor material for OPVs with cell efficiencies of 1.70 and 1.04 % for TATC2 and TATC1 respectively.

Cycloisomerization of π-Coupled Heteroatom Nucleophiles by Gold Catalysis: En Route to Regiochemically Defined Heterocycles.

Since the dawn of millennium, catalytic gold chemistry is at the forefront to set off diverse organic reactions via unique activation of π-bonded molecules. Within this purview, cycloisomerization of heteroatom nucleophiles linked to a π-system is one of the well recognized chemistry for the construction of numerous heterocyclic cores. Though the rudimentary aspects of this transformation are reviewed by several groups in different timeline, a holistic view on regiochemistry of such reactions went largely overlooked. Hence, this account emphasizes the gold catalyzed regioselective cycloisomerization of structurally distinctive π-connected hetero-nucleophiles leading to different heterocycles documented in the last two decades. From an application perspective, this account also highlights those methodologies which find a role in the total synthesis of natural products. Wherever appropriate, mechanistic details and contributing factors for selectivity are also discussed.

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C-H Bond Functionalization.

Gold coordinated to neutral phosphines (R3 P), N-heterocyclic carbenes (NHCs) or anionic ligands is catalytically active in functionalizing various C-H bonds with high selectivity. The sterics/electronic nature of the studied C-H bond, oxidation state of gold and stereoelectronic capacity of the coordinated auxiliary ligand are some of the associated selectivity factors in gold-catalyzed C-H bond functionalization reactions. Hence, in this review a comprehensive update about the action of different types of gold catalysts, from simple to sophisticated ones, on C-H bond reactions and their regiochemical outcome is disclosed. This review also highlights the catalytic applications of Au(I)- and Au(III)-species in creating new opportunities for the regio- and site-selective activation of challenging C-H bonds. Finally, it also intends to stress the potential applications in selective C-H bond activation associated with a variety of heterocycles recently described in the literature.

Harnessing the TEMPO-Catalyzed Aerobic Oxidation for Machetti-De Sarlo Reaction toward Sustainable Synthesis of Isoxazole Libraries.

A practical synthesis of isoxazole/isoxazoline derivatives via Machetti-De Sarlo reaction under sustainable conditions has been accomplished. This protocol involves the use of readily available 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) to catalyze the cyclocondensation of primary nitroalkanes with alkynes/alkenes to afford a library of isoxazole/isoxazoline products. From an eco-benign perspective, notable advantages of this method are as follows: (i) water as the solvent, (ii) air as the oxidant, (iii) transition metal-free, (iv) no base required, (v) no toxic byproduct, (vi) no need of solvent extraction, (vii) diverse substrate scope, (viii) high chemical yields, (ix) excellent chemo- and regioselectivity, (x) short reaction time, (xi) gram-scale synthesis, (xii) extension to heterogeneous version, and (xiii) catalyst recyclability. For these reasons, the developed method is appropriate for safe laboratory use and can be expected to inspire the progress of TEMPO-based organocatalysis for the preparation of isoxazole/isoxazoline moieties in an environmentally benign fashion.

Electropolymerization of thienyl tethered comonomers and application towards the electrocatalytic reduction of nitrobenzene.

The synthesis of different π-spacered thiophene comonomers via Suzuki cross-coupling in good synthetic yields was accomplished. Potentiodynamic electropolymerization of these precursors on ITO electrode by constant potential electrolysis results in the deposition of thin films of polymers between 0.05 and 0.2 µM. Interestingly, the as synthesized π-conjugated polymers exhibit electrochromic behaviour upon electrochemical oxidation. On the application side, the synthesized electropolymers showed catalytic activity better than glassy carbon towards electrochemical reduction of nitrobenzene.

Supercritical water assisted preparation of recyclable gold nanoparticles and their catalytic utility in cross-coupling reactions under sustainable conditions.

Preparation of gold nanoparticles (AuNPs) in environmentally friendly water without using any reducing agents under supercritical conditions is demonstrated. PXRD, XPS, FE-SEM and HR-TEM analysis confirmed the formation of phase-pure and crystalline AuNPs of the size of ∼10-30 nm. The catalytic potential of AuNPs was manifested through a generalized green procedure that could accommodate both Sonogashira as well as Suzuki coupling under aqueous conditions at low catalytic loading (0.1 mol%). The AuNP catalyst was found to be recuperated after the reaction and reused for up to six catalytic cycles with no leaching out of gold species as confirmed through ICP-OES analysis. With no confinement of AuNP catalysis to cross-coupling reaction, synthetic extension to one-flask preparation of π-conjugated semiconductors (4 examples) and their optoelectronic properties were also investigated. Other significant features of the present work include short reaction time, site-selectivity, wide substrate scope, high conversion, good chemical yields and applicability in gram-scale synthesis. Overall, the results of this paper signify an operationally sustainable supercritical fluid processing method for the synthesis of AuNPs and their catalytic application towards cross-coupling reactions in green media.

Gold catalyzed double condensation reaction: Synthesis, antimicrobial and cytotoxicity of spirooxindole derivatives.

Microwave assisted synthesis of spirooxindoles via tandem double condensation between isatins and 4-hydroxycoumarin under gold catalysis is reported. The reaction is practical to perform, since the products can be isolated by simple filtration without requiring tedious column chromatography. The scope of this chemistry is exemplified by preparing structurally diverse spirooxindoles (22 examples) in excellent yields. Antimicrobial evaluation of the synthesized compounds revealed that three compounds (3a, 3f and 3s) exhibited significant MIC values in comparison to the standard drugs. Molecular docking studies of these compounds with AmpC-ß-lactamase receptor revealed that 3a exhibited minimum binding energy (-117.819kcal/mol) indicating its strong affinity towards amino acid residues via strong hydrogen bond interaction. All compounds were also evaluated for their in vitro cytotoxicity against COLO320 cancer cells. Biological assay and molecular docking studies demonstrated that 3g is the most active compound in terms of its low IC50 value (50.0µM) and least free energy of binding (-8.99kcal/mol) towards CHK1 receptor, respectively.

Design, synthesis and cytotoxicity of pyrano[4,3-b]indol-1(5H)-ones: A hybrid pharmacophore approach via gold catalyzed cyclization.

Reported herein is the gold(III)-catalyzed 6-endo-dig cycloisomerization of 2-alkynyl-indole-3-carboxylic acids to form pyrano[4,3-b]indol-1(5H)-ones, which are pharmaceutically important structural motifs. The hitherto unknown substrates required for this methodology were conveniently synthesized in five steps with good overall yields. The utility of this new cycloisomerization is demonstrated by the excellent regioselectivity obtained using a range of substrates. The mildness of the method allowed functional group compatibility towards hydroxyl tether, displaying exquisite chemoselectivity. All the synthesized compounds were screened for their tumor cell growth inhibitory activity against human cervix adenocarcinoma (HeLa). Compound 7d emerged as the most active (IC50=0.69µM) among the tested series compared to the standard cis-platin (IC50=0.08µM).