Palladium-Catalyzed Weak Chelation-Assisted Site-Selective C-H Arylation of N-Aryl Pyridones via 2-fold C-H Activation.

Palladium-catalyzed weak chelation-assisted oxidative cross-dehydrogenative coupling of arenes has been accomplished. The use of medicinally important pyridones as the intrinsic directing group, regioselectivity, 2-fold C-H activation, and late-stage modification of bioactive compounds are the important practical features.

Palladium-Catalyzed Annulative Coupling of Spirovinylcyclopropyl Oxindoles with p-Quinone Methides.

Pd-catalyzed annulative coupling of spirovinylcyclopropyl oxindoles with p-quinone methides has been accomplished via cascade carbon-carbon bond formation to afford bis-spirooxindole scaffolds. The mild reaction conditions, diastereoselectivity, functional group diversity, post-synthetic transformations, and mechanistic studies using DFT calculations are the important practical features.

Cobalt-Catalyzed Stereospecific C-N/C-O Bond Formation of Oxiranes with Diaziridines.

Co-catalyzed stereospecific C-N and C-O bond formation of oxiranes with diaziridines has been accomplished to furnish tetrahydro-[1,3,4]-oxadiazines at room temperature. Optically active oxiranes can be coupled with high optical purities (>96% ee). Stereoselectivity, functional group tolerance, mechanistic studies using DFT, and natural product modification are the important practical features.

Transition-Metal-Catalyzed Directing Group Assisted (Hetero)aryl C-H Functionalization: Construction of C-C/C-Heteroatom Bonds.

Transition-metal-catalyzed C-H functionalization is one of the fascinating scientific fronts in organic synthesis for the formation of conjugated arenes and has emerged as a benchmark to revolutionize the synthetic enterprise since past decades. In this realm, chelation-guided functionalization of C-H bonds using an exogenous directing group has received considerable attention recently for the expedient regioselective construction of C-C and C-heteroatom bonds as an efficient and sustainable alternative. This article outlines our contribution towards a wide variety of transformations that have been achieved by the directed C-H functionalization through the fine tuning of catalytic systems.

The transition-metal-catalyzed stereoselective ring-expansion of vinylaziridines and vinyloxiranes.

The transition-metal-aided stereoselective construction of sp3-carbon-rich heterocyclic scaffolds using strained-ring systems has received considerable attention in recent years due to the prominent presence of these scaffolds in myriad natural products, bioactive molecules, and pharmaceutical components. In this area, the catalytic ring-enlargement of vinylaziridines and vinyloxiranes plays a predominant role when synthesizing high sp3-content biorelevant heterocyclic compounds. This article aims to portray recent advancements in the ring-expansion of vinylaziridines and vinyloxiranes for accessing densely functionalized stereoselective heterocycles that have been developed over the past five years, with an emphasis on the substrate scopes and mechanistic insights into the key methodologies, and it is arranged based on the transition metals used and the ring sizes of the heterocyclic scaffolds.

Site-Selective Rh-Catalyzed C-7 and C-6 Dual C-H Functionalization of Indolines: Synthesis of Functionalized Pyrrolocarbazoles.

A site-selective dual C-7 and C-6 C-H functionalization of indolines with azabenzonorbornadienes has been accomplished using Rh-catalysis. The reaction affords a potential route toward pyrrolocarbazoles with broad scope and functional group tolerance.

Transition-Metal-Free Stereospecific Oxidative Annulative Coupling of Indolines with Aziridines.

Tandem C-N bond formation for the oxidative annulation of indolines with aziridines is accomplished employing the combination of DDQ and NaOCl at ambient conditions. Optically active aziridine can be coupled with high enantiomeric purity (>99% ee). The substrate scope, stereocontrol with the enantioenriched substrate, and scale-up are the important practical advantages.

Oxidative C-H/N-H Annulation of Aromatic Amides with Dialkyl Malonates: Access to Isoindolinones and Dihydrobenzoindoles.

A copper-mediated oxidative C-H/N-H annulation of aromatic amides with dialkyl malonates has been presented to afford synthetically valuable dihydrobenzoindoles and isoindolinones. The reaction proceeds through direct oxidative C(sp2)-H/C(sp3)-H coupling followed by an intramolecular N-H/C(sp3)-H dehydrogenative coupling to deliver the target motifs with broad scope and functional group tolerance.

Cp*Co(III)-Catalyzed C-7 C-C Coupling of Indolines with Aziridines: Merging C-H Activation and Ring Opening.

A Cp*Co(III)-catalyzed directing group-assisted C7 C-C coupling of indolines with aziridines has been developed by merging C-H activation and ring opening. The use of cobalt catalyst, detection of a Co(III) intermediate, and late-stage removal of the directing group are important practical features.

Stereospecific Copper(II)-Catalyzed Tandem Ring Opening/Oxidative Alkylation of Donor-Acceptor Cyclopropanes with Hydrazones: Synthesis of Tetrahydropyridazines.

Aerobic copper(II)-catalyzed tandem ring opening and oxidative C-H alkylation of donor-acceptor cyclopropanes with bisaryl hydrazones is accomplished to produce tetrahydropyridazines, in which copper(II) plays dual role as a Lewis acid as well as redox catalyst. The reaction is stereospecific, and optically active cyclopropanes can be reacted with high optical purities (89-98% enantiomeric excess). The substrate scope, functional group tolerance, dual role of the copper(II) catalyst, and the use of air as an oxidant are the important practical features. A product bearing a 3-bromoaryl group can be subjected to Pd-catalyzed Suzuki coupling with boronic acid in high yield.

Iron-Catalyzed Regioselective Remote C(sp2)-H Carboxylation of Naphthyl and Quinoline Amides.

Iron(III)-catalyzed regioselective direct remote C-H carboxylation of naphthyl and quinoline amides was developed using CBr4 and alcohol. The reaction involves a radical pathway using a coordination activation strategy and single electron transfer process. The use of sustainable iron catalysis, selectivity, and the substrate scope are the important practical features.

Cp*Co(III)-Catalyzed Regioselective C2 Amidation of Indoles Using Acyl Azides.

A cobalt-catalyzed C2-selective amidation of indoles using acyl azides has been accomplished. Isotope experiments suggest that C-H activation is reversible. The use of sustainable Co catalysis, functional group diversity, substrate scope, and regioselectivity are the important practical features.

Rh-Catalyzed tandem C-C/C-N bond formation of quinoxalines with alkynes leading to heterocyclic ammonium salts.

An efficient Rh-catalyzed oxidative C-H activation/annulation of 2-arylquinoxalines with internal alkynes is described using Cu(OAc)2·H2O and AgBF4 to afford a diverse variety of substituted quarternary ammonium salts at room temperature. The mechanism of the protocol is established on the basis of isolation of the 5-membered rhodacycle intermediate and kinetic isotope studies. The mild reaction conditions, substrate scope and functional group diversity are the salient practical features.

Ruthenium(II)-Catalyzed Positional Selective C-H Oxygenation of N-Aryl-2-pyrimidines.

Efficient Ru-catalyzed regioselective C-H oxygenation of N-aryl-2-pyrimidines is described with aryl carboxylic acids in the presence of AgSbF6 as an additive and Ag2CO3 as an oxidant. The reaction can be extended to alkyl, heteroaryl, and α,ß-unsaturated carboxylic acids. The regioselectivity, broad substrate scope, and functional group tolerance are the significant practical advantages.

Ru(ii)-Catalyzed C7-acyloxylation of indolines with carboxylic acids.

Ruthenium(ii)-catalyzed site-selective C7-acyloxylation of indolines with carboxylic acids is presented. The substrate scope and functional group tolerance are important practical features. The kinetic isotope studies suggest that C-H bond activation may be the rate-determining step.

Stereoselective Copper-Catalyzed Cross-Coupling of Aziridines with Benzimidazoles via Nucleophilic Ring Opening and C(sp2)-H Functionalization.

A copper-catalyzed cross-coupling of 2-alkyl-/2-arylaziridines with benzimidazoles is reported. The reactions involve a regiospecific ring opening of aziridines with benzimidazoles to give benzoimidazolylethylamine derivatives that lead to dehydrogenative cross-coupling between C(sp2)-H and N-H bonds to produce dihydroimidazobenzimidazoles. Optically active 2-arylaziridines can be stereoinvertivebly cross-coupled with high enantiomeric purities (77-97% ee). These aerobic catalytic systems comprise an inexpensive Cu(II) salt and PCy3 ligand at moderate temperature.

Copper(II)-Mediated Chelation-Assisted Regioselective N-Naphthylation of Indoles, Pyrazoles and Pyrrole through Dehydrogenative Cross-Coupling.

A copper-mediated picolinamide directed regioselective cross-coupling of naphthylamines with azoles is developed via C-H functionalization and C-N bond formation. The reaction of indoles leads to the formation of chiral C-N cross-coupled products with functional group tolerance. These reaction conditions can also be extended to the cross-coupling of pyrazole and pyrrole scaffolds.

Copper(II)-Catalyzed Nitroaldol (Henry) Reactions: Recent Developments.

Self-assembled copper(II) complexes are described as effective catalysts for nitroaldol (Henry) reactions on water. The protocol involves a heterogeneous process and the catalysts can be recovered and recycled without loss of activity. Further, C2-symmetric N,N'-substituted chiral copper(II) salan complexes are found to be more effective catalysts than chiral copper(II) salen complexes for reactions in homogeneous catalysis, with high enantioselectivities. The reactions involve bifunctional catalysis, bearing the properties of a Brønsted base, as well as a Lewis acid, to effect the reaction in the absence of external additives.

Copper(II)-Catalyzed Oxidative Cross-Coupling of Anilines, Primary Alkyl Amines, and Sodium Azide Using TBHP: A Route to 2-Substituted Benzimidazoles.

Copper(II)-catalyzed oxidative cross-coupling of anilines, primary alkyl amines, and sodium azide is described in the presence of TBHP at moderate temperature. This one-pot multicomponent protocol involves a domino C-H functionalization, transimination, ortho-selective amination, and a cyclization sequence. The broad substrate scope and functional group compatibility are the significant practical features. The protocol can be extended to the coupling of benzyl alcohols with moderate yields.

Domino Synthesis of Tetrasubstituted Thiophenes from 1,3-Enynes with Mercaptoacetaldehyde.

Domino synthesis of tetrasubstituted thiophenes is described from 1,3-enynes and mercaptoacetaldehyde using DABCO at room temperature via a Michael addition, 5-exo-dig carboannulation, and oxidation sequence under air. The broad substrate scope and mild reaction conditions are significant practical features.