Harnessing the benzyne insertion consequence to enable π-extended pyrido-acridine and quinazolino-phenanthridine.

Distinct protocols have been devised for the preparation of hybrid heterocyclic scaffolds like π-extended pyrido-acridines and quinazolino-phenanthridines duly materialized through Rh(III)- and Pd(II)-mediated catalytic courses commencing from acridine and quinazolimine scaffolds. Interestingly, the parent compounds (acridines and quinazolimines) are actualized from 2-aminobenzonitrile and anthranilic acid, where 2-aminobenzonitrile acts as the 1,4-dipolarophilic species and anthranilic acid as the benzyne precursor. The molecular assembly of acridine suggests the participation of two benzyne units. In addition, the structural motif of the quinazolimine ring features one benzyne unit. Further, indolizine ring containing the enaminonitrile skeleton upon exposure to benzyne forms an indolizine fused quinoline ring, decorated with three benzyne units.

Fused Furan Moieties from Enol-like Compounds and ß-Keto Sulfoxonium Ylides Involving sp2 C-H Activation and Concomitant Tandem C-O Annulation.

An efficient and fascinating protocol has been devised for the preparation of fused furan moieties involving a Rh(II) catalyzed one-pot C-H activation/concomitant tandem annulation process, employing an enolic compound and ß-keto sulfoxonium ylide as the reacting conjugates. The developed technique demands only Rh2(TFA)4 as the catalyst to proceed forward and is devoid of additional metallic or nonmetallic additives. The skeletal transformation of naphthoquinone fused furan to highly decorated naphthoquinone fused indolizines is a promising synthetic application.

Electrochemically Enabled C4-H and C3-H Functionalization of 2-Phenyl Quinazoline and Quinoxaline through Dehydrogenative C-H/C-H, C-H/P-H, and C-H/O-H Cross-Coupling.

Quinazoline moieties and particularly C4-substituted quinazoline scaffolds are widely distributed in biologically active molecules, and thus, direct C4-functionalization of quinazolines is the most convenient way to materialize new, straightforward, and sustainable strategies for the synthesis of useful medicinal targets. Retrospecting that, effort has been directed toward electrocatalytic C4-H bond diversification of quinazoline and related electron-deficient N-heterocycles (quinoxaline) offering C4 and C3 benzoyl-, acetyl-, phenol-, ether-, phosphonate-, and nitroalkane-incorporated N-heterocycles via a radical addition pathway under sacrificial oxidant- and additive-free conditions. Various coupling partners and quinazolines, as well as other structurally similar heterocyclic motifs, respond well, providing moderate to high yields of coupled products along with the gram-scale upgradation. Additionally, the performed control experiments and cyclic voltammetry investigations also nicely justified the proposed mechanism of the coupling process. Further, late-stage functionalization leading to the synthesis of indolo quinolines and vinyl-sulfonated products using the ruthenium-catalyzed skeletal transformation of benzoylated quinazoline 3b nicely appropriated the developed methodology. Finally, this reaction can be summarized as (a) anodic activation of the functionalized Hantzsch ester to furnish key radical species; (b) radical addition to an activated N-heterocycle; and (c) oxidation leading to the target product without the assistance of any metal chelation.

Access to π-Extended Heterocycles Containing Pyrrolo-Coumarin Cores Involving -COCH3 as a Traceless Directing Group and Materializing Two Successive sp2C-H/sp3N-H and sp2C-H/sp2N-H Activations.

An efficient protocol has been developed for the preparation of π-extended N-heterocycles involving a Rh(III)-catalyzed C-H activation reaction starting from 3-acetamidocoumarins and internal alkynes. The isolation of the intermediate pyrrolo-coumarin suggests that the -COCH3 group in acetamidocoumarins performs the role of a traceless directing group. Besides, the use of commercially available [Cp*RhCl2]2 adds more importance as no additional modification of the catalyst is required. A two-step protocol bearing intermediate pyrrolo-coumarin can be further functionalized to highly decorated heterocyclic moieties materializing sp2 C-H and sp2 N-H coupling. Moreover, one of the pyrrolo-coumarin compounds (3da) is capable of differentiating between Cr(III) and Cr(VI) ions as revealed via fluorescence spectroscopy. In addition, intermediate pyrrolo-coumarin is further functionalized to spirocyclic N-heterocycles.

"On water" palladium catalyzed diastereoselective boronic acid addition to structurally diverse cyclopropane nitriles.

An efficient palladium catalyzed diastereoselective addition of arylboronic acids to complex spirocyclopropyl dinitriles is developed in the presence of a catalytic amount of 4-dodecylbenzenesulphonic acid (DBSA) as a Brønsted acid surfactant in aqueous media. The protocol is also found to be highly effective when different types of nitrile compounds and organo-boron compounds are used. The overall reaction has been found to be very cost efficient since it requires low catalyst loading, mild thermal energy and short reaction time. Wide substrate scope, operational simplicity, good to excellent product yield, and use of green solvents make the reaction a practical route to transform nitrile into a keto functionality in biorelevant heterocyclic scaffolds. The scale-up synthesis of the target scaffolds can also be achieved with ease which also signifies the practicability of this protocol.