Palladium-Catalyzed, Site-Selective C(sp2)8-H Halogenation and Nitration of 4-Quinolone Derivatives.

Selective installation of halo and nitro groups in heterocyclic backbone through a transition-metal-catalyzed C-H bond activation strategy is immensely alluring to access high-value scaffolds. Here in, we disclosed N-pyrimidyl-directed assisted palladium(II)-catalyzed C(sp2)8-H halogenation and nitration of substituted 4-quinolone derivatives in the presence of N-halosuccinimide and tert-butyl nitrite, respectively, offering structurally diversified 8-halo/nitro-embedded 4-quinolone frameworks in high yields. Mechanistic studies indicated that the reaction follows an organometallic pathway with a reversible C-H metalation step. This operationally simple protocol is scalable with a broad substrate scope and excellent functional group compatibility. Moreover, the postdiversifications of the synthesized derivatives are also showcased to ensure the synthetic versatility of the methodology.

Copper(II)-catalyzed, site-selective C(sp)2-H amination using 8-aminoimidazo[1,2-a]pyridine (8-AIP) as a directing group.

An efficient copper(II)-catalyzed regioselective ortho C(sp2)-H amination of arenes/heteroarenes has been developed with the assistance of 8-AIP (8-aminoimidazo[1,2-a]pyridine) as an efficacious 6,5-fused bicyclic removable chelating auxiliary. This operationally simple approach is scalable, has a broad substrate scope, and is highly compatible with functional groups. Furthermore, post-diversification of the synthesized derivatives demonstrates the methodology's synthetic adaptability.

Copper(II)-Mediated, Site-Selective C(sp2)-H Sulfonamidation of 1-Naphthylamines.

An operationally simple and efficient protocol for copper(II)-mediated, picolinamido-directed C8-H sulfonamidation of 1-naphthylamine derivatives with various sulfonamides has been developed. Remarkably, this cross-dehydrogenative C-H/H-N coupling reaction exhibits a broad substrate scope with excellent functional group tolerance, is scalable, and enables an expeditious route to a library of unsymmetrical N-arylated sulfonamides in good to excellent yields with exclusive site selectivity.

Transition Metal Catalyzed Free-Amine (-NH2 ) Directed C-H Bond Activation and Functionalization for Biaryl Frameworks.

Transition-metal-catalyzed direct transformation of inert C-H bond has revolutionized the arsenal of main-stream organic synthesis, providing a new upfront to forge structurally enriched and biologically relevant scaffolds in a step- and atom-economical way. Past decades have accounted for the major developments in this realm, proclaiming excellent site-selectivity by exploiting a variety of coordinating directing groups (DGs). Consideration of versatile, abundant, sp3 -hybridized free-amine (-NH2 ) functionality for the same purpose has always been a formidable task owing to its innate reactivity. In recent years, free-amine functionality has emerged as a potent DG for a wide range of C-C and C-heteroatom bonds formations and annulation cascades. In this review article, we have discussed the advancements of free-amine directed C-H activation/functionalization reactions towards biaryl frameworks made within a decade (2012 to 2021).

The C-H functionalization of N-alkoxycarbamoyl indoles by transition metal catalysis.

Indole and its congeners are ubiquitous nitrogen-containing organic scaffolds present in a plethora of natural products, marketed drugs, and other organic functional molecules. Recent years have witnessed tremendous advances in the diversification of this motif and its biological applications via transition-metal-catalyzed auxiliary assisted site-selective inert C-H functionalization. In this burgeoning field, N-methoxy/ethoxy/pivaloxy amide functionality has emerged as a most potent auxiliary/DG (directing group) for a wide range of C-C and C-heteroatom bond formations, providing a new advance for forging structurally fabricated polycyclic indole frameworks. This review aims to highlight evolved transformations, like arylation, alkylation, alkenylation, allylation, amidation, difluorovinylation, deuteration, hydroarylation, etc., and the applications of N-alkoxycarbamoyl indole derivatives made within the period of 2014-August 2021. Additionally, explicit mechanistic underpinnings have also been provided in the appropriate places.

NaI/KI/NH4I and TBHP as powerful oxidation systems: use in the formation of various chemical bonds.

In modern organic synthesis, the execution of reactions in the absence of expensive transition metals has received significant attention from the view-point of green chemistry and sustainable development. As a consequence, the combination of MI-TBHP as an oxidation system (M = Na, K, NH4) has opened a new avenue with significant impact for the succinct synthesis of complex heterocycle molecules via the construction of various chemical bonds [C-X (X = C, N, S, O), N-X (X = N, P) and S-N]. This comprehensive review article delineates the progress of recent developments in this emerging area, with an in-depth discussion on the substrate scope, limitations and proper mechanistic underpinnings. We hope this review will highlight the great potential of this MI-TBHP as a powerful oxidation system and inspire researchers to conduct further endeavors in this domain.

8-Aminoimidazo[1,2-a]pyridine (AIP) directed Pd(II) catalysis: site-selective ortho-C(sp2)-H arylation in aqueous medium.

We demonstrate herein the first example of a palladium(ii) catalyzed regioselective ortho-C(sp2)-H arylation in aqueous medium (a sustainable solvent) utilizing 8-AIP (8-aminoimidazo[1,2-a]pyridine) as a promising and removable bidentate directing group/auxilliary. This newly developed protocol features a broad substrate scope with excellent functional group tolerance and enables an expeditious route to a library of unsymmetrical amides in good to excellent yields with exclusive site-selectivity.

Organocatalytic synthesis of (Het)biaryl scaffolds via photoinduced intra/intermolecular C(sp2)-H arylation by 2-pyridone derivatives.

A unique N,O-bidentate ligand 6-oxo-1,6-dihydro-pyridone-2-carboxylic acid dimethylamide (L1) catalyzed direct C(sp2)-H (intra/intermolecular) arylation of unactivated arenes has been developed to expedite access to (Het)biaryl scaffolds under UV-irradiation at room temperature. The protocol tolerated diverse functional groups and substitution patterns, affording the target products in moderate to excellent yields. Mechanistic investigations were also carried out to better understand the reaction pathway. Furthermore, the synthetic applicability of this unified approach has been showcased via the construction of biologically relevant 4-quinolone, tricyclic lactam and sultam derivatives.

Palladium catalyzed 8-aminoimidazo[1,2-a]pyridine (AIP) directed selective ß-C(sp2)-H arylation.

Palladium catalyzed arylation of the inert ß-C(sp2)-H bond of carboxylic acid derivatives is reported herein for the first time utilizing 8-aminoimidazo[1,2-a]pyridine (AIP) as an efficacious and new inbuilt 6,5-fused bicyclic removable directing group. This protocol is scalable, exhibits high levels of ß-site selectivity and tolerates a broad spectrum of functional groups.

C-H functionalization of quinazolinones by transition metal catalysis.

Quinazolinone and its congeners are ubiquitous structural motifs found in numerous natural products due to their wide applications as anticancer, antiviral, anti-inflammatory, antifolate and antitumor agents etc. Previously, the synthetic community devoted their efforts towards synthetic approaches but recent years have also witnessed an upsurge in the diversification of this scaffold and its applications. Thus, this review (from 2011 to the beginning of 2020) comprehensively focuses on transition metal catalyzed C-H bond functionalization namely arylation, amination, acetoxylation, amidation, alkylation, alkenylation, alkynylation, halogenation, thiolation, trifluoroethylation etc. of quinazolin-4(3H)-one. Additionally, we also briefly elucidate the plausible mechanistic pathways, scope and limitations.

Generation of ArS- and ArSe-Substituted 4-Quinolone Derivatives Using Sodium Iodide As an Inducer.

An operationally simple sodium iodide-mediated C-S and C-Se bond formation protocol involving substituted 4-quinolone and thiols/diselenide to generate different ArS/ArSe-substituted 4-quinolone derivatives in excellent yields was developed. The versatility of this methodology has been successfully demonstrated by extension of the suitable reaction conditions to both substrates having different substituents. This regioselective C-H bond activation approach provides a direct access of structurally diverse 3-sulfenylated/selenylated 4-quinolone derivatives. Moreover, this new method proceeds without a transition-metal catalyst and prerequisite NH protection of 4-quinolone derivatives.

C(sp2)-H selenylation of substituted benzo[4,5]imidazo[2,1-b]thiazoles using phenyliodine(iii)bis(trifluoroacetate) as a mediator.

Herein, an expeditious metal-free regioselective C-H selenylation of substituted benzo[4,5]imidazo[2,1-b]thiazole derivatives was devised to synthesize structurally orchestrated selenoethers with good to excellent yields. This PIFA [bis(trifluoroacetoxy)iodobenzene]-mediated protocol operates under mild conditions and offers broad functional group tolerance. In-depth mechanistic investigation supports the involvement of radical pathways. Furthermore, the synthetic utility of this methodology is portrayed through gram-scale synthesis.

Metal free C-3 chalcogenation (sulfenylation and selenylation) of 4H-pyrido[1,2-a]pyrimidin-4-ones.

An expeditious metal free C-3 chalcogenation of 4H-pyrido[1,2-a]pyrimidin-4-one has been devised to synthesize diversely orchestrated 3-ArS/ArSe derivatives in high yields (up to 95%). This operationally simple reaction proceeds under mild reaction conditions, can be executed in gram scale, and also highlights broad functional group tolerance. Preliminary experimental investigation suggests a radical mechanistic pathway for these transformations.