Tunable Regioselective Allylic Alkylation/Iodination of Imidazoheterocycles in Water.

The switchable roles of allylic alcohol and molecular iodine as reagents and catalysts have been demonstrated in the regioselective allylic alkylation and iodination of imidazoheterocycles employing the mixture of allylic alcohol-I2. First, we have explored the catalytic activity of iodine for the allylation of imidazoheterocycles using allylic alcohol in an aqueous medium. The allylation of a library of imidazoheterocycles and other electron-rich heterocycles like indole, pyrazole, 4-hydroxy coumarin, and 6-amino uracil has been achieved by employing this methodology. The efficiency of the I2 catalyst for N-allylation of azoles has also been demonstrated. Next, we have shown that this mixture of allylic alcohol and I2 could be beneficial for the iodination of imidazoheterocycles under room temperature. Mechanistic studies indicate that the activation of allylic alcohol by molecular iodine took place probably through halogen bonding, and NMR studies show that the reaction did not proceed through allylic ether formation.

K2S2O8-Promoted Consecutive Tandem Cyclization/Oxidative Halogenation: Access to 3-Halo-Pyrazolo[1,5-a]pyrimidines.

A one-pot methodology has been developed to synthesize 3-halo-pyrazolo[1,5-a]pyrimidine derivatives through the three-component reaction of amino pyrazoles, enaminones (or chalcone), and sodium halides. The use of easily accessible 1,3-biselectrophilic reagents like enaminones and chalcone offers a straightforward approach for the synthesis of 3-halo-pyrazolo[1,5-a]pyrimidines. The reaction proceeded through a cyclocondensation reaction between amino pyrazoles with enaminones/chalcone in the presence of K2S2O8 followed by oxidative halogenations by NaX-K2S2O8. Mild and environmentally benign reaction conditions, wide functional group tolerance, and scalability of the reaction are the attractive facet of this protocol. The combination of NaX-K2S2O8 is also beneficial for the direct oxidative halogenations of pyrazolo[1,5-a]pyrimidines in water.

Visible-Light-Mediated Regioselective C3-H Selenylation of Pyrazolo[1,5-a]pyrimidines Using Erythrosine B as Photocatalyst.

A visible-light-induced efficient methodology has been developed for the C-H selenylation of pyrazolo[1,5-a]pyrimidine derivatives employing erythrosine B as the photocatalyst. This is the first report on the regioselective selenylation of pyrazolo[1,5-a]pyrimidines. The efficiency of this methodology for the selenylation of different electron-rich heterocycles like pyrazole, indole, imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, and 4-(phenylamino)-2H-chromen-2-one has been also demonstrated. The exploration of erythrosine B as a photocatalyst with a simple and mild procedure, wide substrate scope, and practical applicability and the employment of eco-friendly energy, oxidant, and solvent are the attractive characteristics of this methodology.

Visible-Light-Induced Regioselective C-H Sulfenylation of Pyrazolo[1,5-a]pyrimidines via Cross-Dehydrogenative Coupling.

A visible-light-induced cross-dehydrogenative methodology has been developed for the regioselective sulfenylation of pyrazolo[1,5-a]pyrimidine derivatives. Rose bengal, blue LEDs, KI, K2S2O8, and DMSO are all essential for this photocatalytic transformation. The protocol is applicable for the synthesis of a library of 3-(aryl/heteroaryl thio)pyrazolo[1,5-a]pyrimidine derivatives with broad functionalities. The selectivity and scalability of the methodology have been also demonstrated. Moreover, the efficiency of this strategy for sulfenylation of pyrazoles, indole, imidazoheterocycles, and 4-hydroxy coumarin has been proven. The mechanistic investigation revealed the radical-based mechanism and formation of diaryl disulfide as a key intermediate for this cross-dehydrogenative coupling reaction.

Visible light-promoted photocatalyst-free activation of persulfates: a promising strategy for C-H functionalization reactions.

The employment of renewable energy resources is highly desirable according to the twelve principles of green chemistry. In this context, visible light promoted organic transformations have gained much attention from synthetic chemists due to the employment of renewable energy. However, the inability of the majority of organic molecules to absorb visible light encouraged the use of photocatalysts in visible light-mediated organic transformations. As a result, different types of photocatalysts like transition-metal containing photoredox catalysts, organophotoredox catalysts, heterogeneous photocatalysts, etc. have emerged over the years. On the other hand, persulphates (K2S2O8, Na2S2O8, and (NH4)2S2O8) have been widely used as oxidants in various oxidative organic transformations under thermal and photochemical conditions. The initial formation of an active persulfate radical anion from a persulfate anion is the crucial step for these oxidative transformations and the conversions under visible light are generally carried out employing different photocatalysts. Although numerous methodologies have been successfully developed employing these photocatalysts, the development of new processes under photocatalyst-free conditions are more preferable from the viewpoint of sustainable development. Persulphates could be very useful for various organic transformations through C-H functionalizations under photocatalyst-free visible light irradiation. In this review, we will exemplify the efficiency of persulphates in various oxidative organic transformations under visible light irradiation without the employment of any photocatalysts. The utilities and mechanistic pathways of the methodologies will also be highlighted.

Recent advances in the synthesis of fluorinated compounds via an aryne intermediate.

The development of new methodologies for the synthesis of fluorinated organic molecules is in high demand due to their wide applications in agriculture and pharmaceutical sciences. Various strategies have been employed for this purpose for a long time. Arynes are well known synthetic intermediates and have gained the attention of synthetic chemists for the synthesis of various functionalized organic molecules. Consequently, these synthetic intermediates have been successfully employed in the synthesis of fluorinated organic moieties. Various useful fluorinated aromatic and heterocyclic molecules have been synthesized employing aryne intermediates. In this review, we will discuss all these methodologies developed in the last decade via aryne intermediates.

Visible light promoted C-H functionalization of imidazoheterocycles.

Direct C-H functionalization is very important in the late-stage functionalization of drug molecules. In this context, visible light promoted transformations have emerged as a green strategy for C-H functionalization compared to the conventional strategy. Various methodologies have been developed for the C-H functionalization of different bioactive heterocycles employing this visible light photocatalysis in the presence of either transition metal photocatalysts or organophotoredox catalysts and even in the absence of any photocatalyst. The focus of this review is the demonstration of the efficiency of visible light photocatalysis in the direct C-H functionalizations of pharmacologically active imidazo[1,2-a]pyridines and other related imidazoheterocycles.

Visible-Light-Promoted C(sp3)-C(sp2) Cross-Dehydrogenative Coupling of Tertiary Amine with Imidazopyridine.

A metal-free visible-light-promoted C(sp3)-C(sp2) cross-dehydrogenative coupling between tetrahydroisoquinoline and imidazo[1,2- a]pyridine has been developed to afford 3-substituted imidazopyridines using a catalytic amount of rose bengal as photosensitizer under aerobic conditions. The present methodology is also applicable to imidazo[1,2- a]pyrimidine, indolizine, indole, and pyrrole as well as N, N-dimethyl aniline. Wide substrates scope, use of organo photocatalyst, metal-free, and mild reaction conditions are the attractive features of this methodology.

C-Glycosidation of Unprotected Di- and Trisaccharide Aldopyranoses with Ketones Using Pyrrolidine-Boric Acid Catalysis.

C-Glycoside derivatives are found in pharmaceuticals, glycoconjugates, probes, and other functional molecules. Thus, C-glycosidation of unprotected carbohydrates is of interest. Here the development of C-glycosidation reactions of unprotected di- and trisaccharide aldopyranoses with various ketones is reported. The reactions were performed using catalyst systems composed of pyrrolidine and boric acid under mild conditions. Carbohydrates used for the C-glycosidation included lactose, maltose, cellobiose, 3'-sialyllactose, 6'-sialyllactose, and maltotriose. Using ketones with functional groups, C-glycosides ketones bearing the functional groups were obtained. The pyrolidine-boric acid catalysis conditions did not alter the stereochemistry of non-C-C bond formation positions of the carbohydrates and led to the formation of the C-glycosidation products with high diastereoselectivity. For the C-glycosidation of the carbohydrates under the pyrrolidine-boric acid-catalysis, the hydroxy group at the 6-position of the reacting aldopyranose was necessary to afford the product. Our analyses suggest that the carbohydrates form iminium ions with pyrrolidine and that boric acid forms B-O covalent bonds with the carbohydrates during the catalysis to forward the C-C bond formation.

Design, Synthesis, and Functionalization of Imidazoheterocycles.

Over the years, various strategies have been reported for the synthesis of imidazo[1,2-a]pyridines due to their importance in different fields. In this account, we represent the methods developed by our group for the synthesis and functionalization of imidazo[1,2-a]pyridines. Different synthetic strategies have been developed using easily accessible reactants for this purpose. We envisage that these newly developed protocols will be very useful for the synthesis of functionalized molecules bearing imidazo[1,2-a]pyridine scaffolds. These strategies will also be attractive for the construction of other pharmaceutically important heterocycles.

Iodine-catalyzed regioselective thiolation of imidazo[1,2-a]pyridines using sulfonyl hydrazides as a thiol surrogate.

Iodine-catalyzed regioselective sulfenylation of imidazo[1,2-a]pyridines via C(sp(2))-H bond functionalization has been achieved using sulfonyl hydrazides as a thiol surrogate. A library of 3-sulfanylimidazopyridines with broad functionalities was synthesized under metal and oxidant-free practical reaction conditions. This methodology is also applicable for the regioselective sulfenylation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole.

Regioselective oxidative trifluoromethylation of imidazoheterocycles via C(sp2)-H bond functionalization.

Catalytic oxidative trifluoromethylation of imidazopyridines has been carried out at room temperature through the functionalization of the sp(2) C-H bond employing Langlois reagent under ambient air. A library of 3-(trifluoromethyl)imidazo[1,2-a]pyridines with broad functionalities have been synthesized regioselectively. This methodology is also applicable to imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole.

Synthesis of imidazo[1,2-a]pyridines: a decade update.

Imidazopyridine is one of the important fused bicyclic 5-6 heterocycles and it is recognized as a "drug prejudice" scaffold due to its wide range of applications in medicinal chemistry. This moiety is also useful in material science because of its structural character. Synthesis of this moiety from the easily available chemicals is desirable due to its tremendous use in the various branches of chemistry. Here we report a review on the synthesis of this scaffold employing different strategies such as condensation, multicomponent reactions, oxidative coupling, tandem reactions, aminooxygenation, and hydroamination reactions.

Unprecedented catalytic activity of Fe(NO3)3·9H2O: regioselective synthesis of 2-nitroimidazopyridines via oxidative amination.

A unique iron-catalyzed oxidative diamination of nitroalkene with 2-aminopyridine for the synthesis of 2-nitro-3-arylimidazo[1,2-a]pyridines with complete regioselectivity has been achieved under mild and aerobic reaction conditions. This is the first method for the synthesis of 2-nitroimidazo[1,2-a]pyridines. These scaffolds were also synthesized directly from styrenes.

Functionalization of an sp(3) C-H bond via a redox-neutral domino reaction: diastereoselective synthesis of hexahydropyrrolo[2,1-b]oxazoles.

A diastereoselective synthesis of pyrrolidinooxazolidines was achieved by a metal-free, base-promoted reaction of pyrrolidine and aromatic aldehydes under microwave irradiation. The rare functionalization of an sp(3) C-H bond probably results from an in situ generated azomethine ylide that undergoes cycloaddition with aldehydes.