Recent Progress on Transition Metal Catalyzed Macrocyclizations Based on C-H Bond Activation at Heterocyclic Scaffolds.

Macrocycles are essential in protein-protein interactions and the preferential intake of bioactive scaffolds. Macrocycles are commonly synthesized by late-stage macrolactonizations, macrolactamizations, transition metal-catalyzed ring-closing metathesis, S-S bond-forming reactions, and copper-catalyzed alkyne-azide cycloaddition. Recently, transition metal-catalyzed C-H activation strategies have gained significant interest among chemists to synthesize macrocycles. This article provides a comprehensive overview of the transition metal-catalyzed macrocyclization via C-H bond functionalization of heterocycle-containing peptides, annulations, and heterocycle-ring construction through direct C-H bond functionalization. In the first part, palladium salt catalyzed coupling with indolyl C(sp3)-H and C(sp2)-H bonds for macrocyclization is reported. The second part summarizes rhodium-catalyzed macrocyclizations via site-selective C-H bond functionalization. Earth-abundant, less toxic 3d metal salt Mn-catalyzed cyclizations are reported in the latter part. This summary is expected to spark interest in emerging methods of macrocycle production among organic synthesis and chemical biology practitioners, helping to develop the discipline. We hope that this mini-review will also inspire synthetic chemists to explore new and broadly applicable C-C bond-forming strategies for macrocyclization via intramolecular C-H activation.

Rh(II)-catalysed N2-selective arylation of benzotriazoles and indazoles using quinoid carbenes via 1,5-H shift.

An efficient Rh(II)-catalyzed highly selective N2-arylation of benzotriazole, indazole, and 1,2,3 triazole is developed using diazonaphthoquinone. The developed protocol is extended with a wide scope. In addition, late-stage arylation of these scaffolds tethered with bioactive molecules is explored. Control experiments and DFT calculations reveal that the reaction proceeds presumably via nucleophilic addition of the N2 (of the 1H tautomer) center to quinoid-carbene followed by a 1,5-H shift.

Role of mucin 2 gene for growth in Anas platyrhynchos: a novel report.

Introduction: The mucin gene is expressed in the mucous membrane of the inner layer of the internal organs. Intestinalmucin 2 (MUC2), amajor gel-formingmucin, represents a primary barrier component of mucus layers. Materials and methods: This is the first report on the role of mucin genes in growth traits in animals. In this study, we randomly studied Bengal ducks (Anas platyrhynchos) reared from day old to 10 weeks of age under an organized farm and studied the growth parameters as well as body weight and average daily body weight gain. Result and discussion: We characterized the mucin gene for Bengal ducks and observed glycosylation and EGF1 (EGF-like domain signature) as important domains for growth traits in ducks. We observed a better expression profile for the mucin gene in high-growing ducks in comparison to that of low-growing ducks with real-time PCR. Hence, the mucin gene may be employed as a marker for growth traits.

Weakly coordinating tert-amide assisted Rh(III)-catalyzed C4-cyanation of indoles: application in photophysical studies.

A rhodium(III)-catalyzed indole C4-selective cyanation is described using the bench-stable, user-friendly electrophilic cyanation agent N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as a coupling partner. A suitably positioned weakly coordinating tert-amide group was utilized for this site selectivity. The developed protocol proceeded with a broad scope. [Cp*Rh(MeCN)3][SbF6]2 was found to be an effective Rh(III) catalyst for this transformation. An initial study was carried out to know the photophysical properties of the C4-cyanated indole frameworks.

Rh(II)-Catalyzed Synthesis of N-Aryl 2-pyridone Using 2-Oxypyridine and Diazonaphthoquinone Via 1,6-Benzoyl Migratory Rearrangement.

A Rh(II)-catalyzed simple and efficient synthesis of N-arylated 2-pyridone derivatives is described using 2-oxypyridine and diazonaphthoquinone as coupling partners. The reaction proceeds through the insertion of the nitrogen atom of the 2-oxypyridine derivative into quinoid carbene and subsequent 1,6-benzoyl migratory rearrangement. The reaction is broadened with sufficient scope and has the potential to offer axially chiral N-arylated 2-pyridone derivatives under suitable asymmetric conditions.

Pd(II)-Catalyzed Oxidative Naphthylation of 2-Pyridone through N-H/C-H Activation Using Diarylacetylene as an Uncommon Arylating Agent.

A Pd(II)-catalyzed straightforward oxidative naphthylation of unmasked 2-pyridone derivatives is described using a twofold internal alkyne as a coupling partner. The reaction proceeds through N-H/C-H activation to provide polyarylated N-naphthyl 2-pyridones. An unusual oxidative annulation at the arene C-H bond of the diarylalkyne leads to the formation of polyarylated N-naphthyl 2-pyridones, where the 2-pyridone-attached phenyl ring of the naphthyl ring is polyaryl-substituted. Mechanistic studies and DFT calculations suggest a plausible mechanism based on N-H/C-H activation. The N-naphthyl 2-pyridone derivatives were studied to explore encouraging photophysical properties.

Biometric identification of Black Bengal goat: unique iris pattern matching system vs deep learning approach.

OBJECTIVE: Iris pattern recognition system is well developed and practiced in human, however, there is a scarcity of information on application of iris recognition system in animals at the field conditions where the major challenge is to capture a high-quality iris image from a constantly moving non-cooperative animal even when restrained properly. The aim of the study was to validate and identify Black Bengal goat biometrically to improve animal management in its traceability system. METHODS: Forty-nine healthy, disease free, 3 months±6 days old female Black Bengal goats were randomly selected at the farmer's field. Eye images were captured from the left eye of an individual goat at 3, 6, 9, and 12 months of age using a specialized camera made for human iris scanning. iGoat software was used for matching the same individual goats at 3, 6, 9, and 12 months of ages. Resnet152V2 deep learning algorithm was further applied on same image sets to predict matching percentages using only captured eye images without extracting their iris features. RESULTS: The matching threshold computed within and between goats was 55%. The accuracies of template matching of goats at 3, 6, 9, and 12 months of ages were recorded as 81.63%, 90.24%, 44.44%, and 16.66%, respectively. As the accuracies of matching the goats at 9 and 12 months of ages were low and below the minimum threshold matching percentage, this process of iris pattern matching was not acceptable. The validation accuracies of resnet152V2 deep learning model were found 82.49%, 92.68%, 77.17%, and 87.76% for identification of goat at 3, 6, 9, and 12 months of ages, respectively after training the model. CONCLUSION: This study strongly supported that deep learning method using eye images could be used as a signature for biometric identification of an individual goat.

Rh(III)-Catalyzed Weakly Coordinating 2-Pyridone-Directed Oxidative Annulation Using Internal Alkynes: A Reversal in Selectivity.

A rhodium(III)-catalyzed Satoh-Miura type oxidative annulation of N-aryl 2-pyridone derivatives is described using internal alkyne as a coupling partner. A weakly coordinating carbonyl group of the 2-pyridone ring is utilized for this transformation. The reaction proceeds with a broad scope and wide functional group tolerance. The solvent plays an important role in the developed method to furnish a different class of annulated product. A preliminary investigation was carried out to explore the photophysical properties of the obtained polyarylated N-naphthyl 2-pyridones.

Weakly Coordinating tert-Amide-Assisted Ru(II)-Catalyzed Synthesis of Azacoumestans via Migratory Insertion of Quinoid Carbene: Application in the Total Synthesis of Isolamellarins.

A weakly coordinating tert-amide-directed straightforward method was developed for the synthesis of azacoumestans using the corresponding azaheterocycle derivatives and diazonaphthoquinones under cheap Ru(II)-catalyzed conditions. The reaction proceeds via migratory insertion of quinoid carbene and subsequent Brønstead acid-mediated cyclization. The optimized C2-selective method offered a wide scope of important azaheterocycles. Bioactive natural products like isolamellarins A and B were synthesized via the developed protocol. Preliminary mechanistic studies highlighted the probable mechanistic pathway.

Cu(II)-Catalyzed Construction of Heterobiaryls using 1-Diazonaphthoquinones: A General Strategy for the Synthesis of QUINOX and Related P,N Ligands.

An efficient and straightforward method was developed for the synthesis of heterobiaryls using easily available N-oxides and diazonaphthoquinones under cheap Cu(II) catalysis. The developed method offered QUINOX and related congeners in a simple manner. A wide scope of important heterobiaryls was achieved with high site selectivity. The synthesized naphthols were transformed into the privileged related P,N ligands. Suitable resolution methods can directly afford the corresponding axially chiral heterobiaryls.

Rh(III)-Catalyzed mild straightforward synthesis of quinoline-braced cyclophane macrocycles via migratory insertion.

An efficient Rh(III)-catalyzed straightforward strategy is developed for the synthesis of quinoline braced cyclophane macrocycles via methyl (sp3) C-H functionalization. The method is mild, simple and regioselective with various ring sizes and has good functional group tolerance. The method proceeds via C8-methyl metalation, metal-carbene formation and a subsequent migratory insertion. High dilution is not necessary for this macrocyclization and the only byproduct is nitrogen. A preliminary investigation shows that the C-H metalation step is the rate-determining step.

Transition metal catalysed direct construction of 2-pyridone scaffolds through C-H bond functionalizations.

Substituted 2-pyridone is one of the most frequent scaffolds among nitrogen-containing bioactive natural products, pharmaceuticals and organic materials. Besides the classical syntheses to construct this class of molecules, retrosynthetically more straightforward approaches based on transition metal catalysed C-H bond functionalizations have been explored recently. In this review, we have summarized the recent progress in the direct transition metal catalysed construction of substituted 2-pyridone scaffolds via site-selective C-H bond functionalizations.

Straightforward Construction and Functionalizations of Nitrogen-Containing Heterocycles Through Migratory Insertion of Metal-Carbenes/Nitrenes.

Nitrogen-containing heterocycles are widely found in various biologically active substrates, pharmaceuticals, natural products and organic materials. Consequently, the continuous effort has been devoted towards the development of straightforward, economical, environmentally acceptable, efficient and ingenious methods for the synthesis of various N-containing heterocycles and their functionalizations. Arguably, one of the most prominent direct strategy is regioselective C-H bond functionalizations which provide the step and atom economical approaches in the presence of suitable coupling partners. In this context, site-selective migratory insertion of metal carbenes/nitrenes to the desired C-H bonds has proven as a useful tool to access various functionalized nitrogen heterocycles. In this personal account, we highlight some of our contemporary development toward constructing N-containing heterocycles and their direct functionalizations via transition metal catalysed C-H bond functionalizations based on migratory insertion of metal-carbenes and nitrenes.

A directing group free Pd(II)-catalysed desulfitative C6-arylation of 2-pyridone using an arylsulfonyl chloride.

A Pd(ii)-catalysed direct desulfitative arylation was realized at the C6-position of the 2-pyridone scaffold. Aryl sulfonyl chloride was used as an alternative arylating agent. The required site-selectivity occurred without the strategic installation of a heteroatom containing directing group. Preliminary mechanistic studies revealed that radical species were involved during this process.

Transition Metal-Catalysed Direct C-H Bond Functionalizations of 2-Pyridone Beyond C3-Selectivity.

2-Pyridone is a ubiquitous motif in natural products, drug molecules, ligands in catalysis and organic materials. There is a necessity of direct step-economic methods for the construction of 2-pyridone based molecules. Strategically, the primary developments have led to the C3-functionalizations due to the inherent reactivity of this center. Despite this, many elegant transition metal-catalysed methods have been established to introduce versatile functional groups at the C4, C5 and C6-position via direct C-H bond functionalizations. This minireview focuses on the categorized introduction of different functional groups at the 2-pyridone scaffolds beyond C3-selectivity and discusses substrate scope, limitations and plausible mechanistic details.

Rh(iii)-Catalyzed tandem indole C4-arylamination/annulation with anthranils: access to indoloquinolines and their application in photophysical studies.

An efficient Rh(iii)-catalyzed straightforward strategy was developed for the tandem C4 arylamination/annulation of indole derivatives with anthranil to provide indoloquinoline moieties. This method is simple and regioselective with a wide scope and functional group tolerance. Mechanistic studies revealed the important role of the newly installed azacycle in the conversion of O-protected aldoximes to their cyano derivatives. Studies were carried out to explore the promising photophysical properties of the obtained indoloquinoline derivatives.

RhIII -Catalyzed Synthesis of Highly Substituted 2-Pyridones using Fluorinated Diazomalonate.

A RhIII -catalyzed strategy was developed for the rapid construction of highly substituted 2-pyridone scaffolds using α,ß-unsaturated oximes and fluorinated diazomalonate. The reaction proceeds through direct, site-selective alkylation based on migratory insertion and subsequent cyclocondensation. A wide substrate scope with different functional groups was explored. The requirement of fluorinated diazomalonate was explored for this transformation. The developed methodology was further extended with the synthesis of the bioactive compound.

Rh(iii)-Catalyzed straightforward arylation of 8-methyl/formylquinolines using diazo compounds.

A straightforward Rh(iii)-catalyzed general strategy was developed for the introduction of naphthol/phenol moieties to the C(sp3)-H bond of 8-methylquinoline using diazonaphthalen-2(1H)-ones/quinone diazides. The developed method was further extended towards the arylation of 8-formylquinolines to accomplish diarylketone derivatives. The method is simple, relatively rapid, and chemo and regioselective with a wide scope and functional group tolerance. The synthetic utility was established through gram-scale synthesis and biologically active molecule construction.

Pd(II)-Catalyzed Direct Sulfonylation of Benzylamines Using Sodium Sulfinates.

A Pd(II)-catalyzed direct sulfonylation of benzylamines with sodium sulfinates using a removable bidentate directing group is illustrated. The transformation is highly regioselective and tolerates wide functional groups. The mechanistic study reveals that radical species are involved in this reaction. This method delivers a direct synthetic strategy to obtain highly functionalized sulfonylated benzylamines.

RhIII -Catalyzed Straightforward Synthesis of Benzophenanthroline and Benzophenanthrolinone Derivatives using Anthranils.

An efficient pot-economic and step-economic RhIII -catalyzed site-selective direct amination/annulation strategy was developed for the synthesis of benzophenanthroline derivatives using quinoline N-oxides and anthranils. The method was further extended to the synthesis of nitrogen-containing extended π-conjugated benzophenanthrolinone derivatives. Late-stage functionalizations of cinchonidine and cinchophen derivatives and synthesis of a bioactive quinolino-indole were achieved.