Tandem Reactions of Electrophilic Indoles toward Indolizines and Their Subsequent Transformations through Pd(II)-Mediated C-H Functionalization to Access Polyring-Fused N-Heterocycles.

A simple and efficient synthetic approach for generating a library of structurally novel indolizines has been developed via sequential 1,3-dipolar cycloaddition-ring opening processes. Using this methodology, a series of indolizines bearing different substituents were made in moderate to good yields. The presence of two functionalizable C-H bonds in these indolizine motifs makes them attractive for accessing fused indolizine scaffolds. In this line, we have introduced palladium-mediated site-selective C-H functionalizations, where the N-center and the two C-H centers of the indolizine moiety can be readily functionalized to generate fused N-heterocycles. Utilizing a Pd-mediated dual C-H activation of 5-benzoyl-substituted indolizine afforded 6H-indeno-indolizine, and a tetracene, viz., indolizino[2,1-b]indoles, was produced in the same substrate by the Pd-catalyzed selective C-H amination in the presence of oxygen.

Annulation reactions of electrophilic benzannulated heterocycles towards heteroacenes.

The current review describes different annulation strategies reported with electrophilic benzannulated heterocycles for accessing heteroacenes. For the past two decades, the chemistry of electrophilic benzannulated heterocycles was extensively investigated, and several dipolar cycloadditions, metal and organo-catalyzed transformations were introduced for the generation of fused heterocycles. In this review, we have collected all the reports where the annulation of electrophilic benzannulated heterocycles results in a fully aromatic system, viz. heteroacenes with tri-, tetra-, and pentacyclic rings. We reviewed every paper on the synthesis of fused heterocycles that was accessible and categorized the review into several parts based on the electrophilic benzannulated heterocycle used in the heteroacene synthesis such as electrophilic indole, electrophilic benzothiophene, and so forth. The generality and mechanistic postulates of each methodology are highlighted. In addition, we have also tried to feature the advantages or shortcomings of each method and have mentioned the possible applications of these methodologies for accessing heteroacenes for material applications.

Copper-Catalyzed Annulation of Electrophilic Benzannulated Heterocycles with 2-Aminopyridine and 2-Aminoquinoline: Direct Access toward Polyring-Fused Imidazo[1,2-a]pyridines.

We have developed a direct method for the synthesis of polyring-fused imidazo[1,2-a]pyridines via a copper-catalyzed annulation of electrophilic benzannulated heterocycles with 2-aminopyridine and 2-aminoquinoline. From 3-nitroindoles and 2-aminopyridine, we could synthesize tetracenes, viz., indole-fused imidazo[1,2-a]pyridines, and by starting from 2-aminoquinoline, we could generate pentacenes, viz., indolo-imidazo[1,2-a]quinolines. In addition, we could also extend the methodology toward the synthesis of benzothieno-imidazo[1,2-a]pyridines starting from 3-nitrobenzothiophene. Furthermore, the basic photophysical properties of these synthesized heteroacenes were evaluated.

Discovery of Oxygen Induced Chemoselectivity in Pd-Catalyzed C-H Functionalization: Cross-Dehydrogenative Coupling vs C-H Amination.

We have come across a substrate namely, 5-benzoyl-pyrrolo[2,1-a]isoquinoline in which three different functionalizable C-H bonds were identified that could be judiciously transformed site selectively for the generation of complex polyring fused N-heterocycles. A Pd-catalyzed cross-dehydrogenative coupling of 5-benzoyl-pyrrolo[2,1-a]isoquinoline afforded 8H-indeno-pyrrolo[2,1-a]isoquinolinone and an oxygen induced palladium catalyzed selective C-H amination in the same substrate provided a pentacene viz., 9H-indolo-pyrrolo[2,1-a]isoquinoline. We also observed the formation of a multiring fused benzazepine scaffold by the site selective C-H amination in 5-(4-nitro benzoyl)-pyrrolo[2,1-a]isoquinoline.

Base-Mediated Annulation of Electrophilic Benzothiophene with Naphthols and Phenols: Accessing Benzothiophene-Fused Heteroacenes.

A base-mediated annulation of 2-nitrobenzothiophenes with naphthols was realized for the synthesis of hitherto unknown class of heteroacenes, namely benzothieno[2,3-b]naphthofurans. By using naphthols with a hydroxyl group positioned at 1st or 2nd position, we could synthesize two positional isomers, benzothieno[2,3-b]naphtho[2,1-d]furans or benzothieno[2,3-b]naphtho[2,3-d]furans. The annulation was found to be general with a range of substituted 2-nitrobenzothiophenes and naphthols. This heteroannulation of benzothiophene was extended using a range of phenols affording the corresponding benzothieno[2,3-b]benzofurans in moderate yields. The basic photophysical properties of these heteroacenes were evaluated, and we also demonstrated the applicability of this annulation on the gram scale.

Unprecedented access to functionalized pyrrolo[2,1-a]isoquinolines from the domino reaction of isoquinolinium ylides and electrophilic benzannulated heterocycles.

We have come across an unexpected reaction between electrophilic indoles and isoquinolinium methylides for accessing functionalized pyrrolo[2,1-a]isoquinolines. The reaction was found in general to yield the products in good yields. We also observed the formation of S-S-bridged bis-pyrrolo[2,1-a]isoquinolines from the reaction of 3-nitro benzothiophene and isoquinolinium methylides.

Synthesis of Benzothienobenzofurans via Annulation of Electrophilic Benzothiophenes with Phenols.

We have developed a metal-free, mild, and green synthetic route toward benzothieno[3,2-b]benzofurans by the annulation of 3-nitrobenzothiophene with phenols. The reaction was found to be general with a range of substituted phenols. In addition, we could extend the methodology for the synthesis of pentacenes and could demonstrate the synthesis in gram-scale. Moreover, we extended the strategy for the synthesis of benzothieno[2,3-b]benzofurans by starting from 2-nitrobenzothiophenes.

One-Pot MCR-Oxidation Approach toward Indole-Fused Heteroacenes.

A straightforward synthetic route toward indole-fused heteroacenes was developed. The strategy is composed of a one-pot process starting with a multicomponent reaction of cyclohexanone, primary amine and N-tosyl-3-nitroindole followed by an oxidation step. The one-pot approach was found to be general, affording both symmetric and nonsymmetric indolo[3,2-b]indoles in good yields. The strategy was also utilized for accessing 5-ring fused benzo[g]indolo[3,2-b]indole. We could extend the methodology for the synthesis of benzothieno[3,2-b]indoles starting from 3-nitrobenzothiophene. The importance of the developed method was exemplified by performing the reaction sequence on gram scale and also by the synthetic transformations of indolo[3,2-b]indoles. In addition, the change in photophysical properties with extension of conjugation of the synthesized heteroacenes was studied.

Heteroannulation of 3-Nitroindoles and 3-Nitrobenzo[b]thiophenes: A Multicomponent Approach toward Pyrrole-Fused Heterocycles.

A simple, efficient, and general multicomponent reaction involving an enolizable ketone, a primary amine, and an N-protected 3-nitroindole was developed for the synthesis of a range of functionalized pyrrolo[3,2-b]indoles. The methodology was efficaciously utilized for the "pyrroloindoliztion" of natural products, the pyrrolization of 3-nitrobenzo[b]thiophene, and the gram-scale synthesis of pyrroloindole. Furthermore, a "one-pot" approach for accessing indolo[3,2-b]indoles was realized.