Cobalt(II)-catalyzed peri-C(sp2)-H selective hydroxylation of naphthalene monoimides.

Reported herein is an efficient and eco-friendly peri-selective monohydroxylation of naphthalene monoimides (NMIs) to access 4-hydroxy NMIs, which possess multidisciplinary applications. The key aspect of this method is the utilization of cobalt(II)-catalysis via a single electron transfer mechanism to achieve site-selective C(sp2)-hydroxylation. Transformation of the hydroxyl group into pseudohalides reveals its applications towards cross-coupling reactions.

A Sequential Transition Metal and Organocatalytic Approach to the Enantioselective Synthesis of C2-Spiroindoline Systems.

We report herein an organocatalyzed enantioselective spirocyclization strategy to access valuable C2-spiroindoline scaffolds bearing a quaternary stereocenter via an aza-Michael addition reaction, wherein the acid additive plays the role of dual functionality. The substrates for this key step were put together by an exo-selective, Pd-catalyzed γ-arylation of silyldienol ethers of the corresponding cyclohexenones. A close alliance between a low catalyst loading and a slow reaction rate yields C2-spiroindolines with good enantioselectivity.

Site-selective ring opening of bicyclo[n.1.0]alkanols: an Fe(II)-catalyzed 1,6-conjugate addition to p-quinone methides.

Herein, we report an efficient synthetic strategy for an Fe(ii)-catalyzed site-selective ring opening of bicyclo[n.1.0]alkanols and their concomitant 1,6-conjugate addition to p-quinone methides. Access to tertiary carbon centers with appendaged carbocycles of distinct sizes and functional groups are achieved, under a substrate-controlled bond scission of the fused cyclopropanols. Synthetic derivatizations further enhance the utility of the protocol.

Regiocontrol via Electronics: Insights into a Ru-Catalyzed, Cu-Mediated Site-Selective Alkylation of Isoquinolones via a C-C Bond Activation of Cyclopropanols.

A site-selective C(3)/C(4)-alkylation of N-pyridylisoquinolones is achieved by employing C-C bond activation of cyclopropanols under Ru(II)-catalyzed/Cu(II)-mediated conditions. The regioisomeric ratios of the products follow directly from the electronic nature of the cyclopropanols and isoquinolones used, with electron-withdrawing groups yielding predominantly the C(3)-alkylated products, whereas the electron-donating groups primarily generate the C(4)-alkylated isomers. Density functional theory calculations and detailed mechanistic investigations suggest the simultaneous existence of the singlet and triplet pathways for the C(3)- and C(4)-product formation. Further transformations of the products evolve the utility of the methodology thereby yielding scaffolds of synthetic relevance.

Synthesis of Ferrocene 1,3-Derivatives by Distal C-H Activation.

The third position of cyclopentadienyl ring of a monosubstituted ferrocene has remained as an inaccessible chemical space for direct functionalization. Until recently, functionalizing the C(3)-position while bypassing the predominantly active C(2)-position is the most challenging task. Herein, we report a distal C-H functionalization of monosubstituted ferrocenes using an easily removable directing group with precise site-selectivity, under a PdII / mono-N-protected amino-acid ligand catalytic system. The robust synthetic protocol leads to the synthesis of ferrocene 1,3-derivatives with broad scope in olefins while functionalizing ferrocenyl methylamine in moderate to good yields via a highly strained ferrocene appended 12-membered palladacycle intermediate.

Rh(III)-Catalyzed ortho-C-H Amidation of Naphthalene and Perylene Monoimides.

The direct formation of a C-N bond at the ortho-position of naphthalene monoimides (NMI) and perylene monoimides (PMI) is reported herein using dioxazolones as the amide source. This method affords direct access to ortho-amino NMI and PMI through an amidation and deprotection sequence. One-pot telescopic bay-bromination of ortho-amino PMIs was also achieved. The ortho-amidated NMIs and PMIs, accessed by the current methodology, show significant red shifts in their absorption and fluorescence spectra compared with the NMI and PMI alone. An improvement in the quantum yield and fluorescence lifetime was observed by the incorporation of pivalamide groups at the ortho-positions of NMI and PMI.

A three component 1,3-difunctionalization of vinyl diazo esters enabled by a cobalt catalyzed C-H activation/carbene migratory insertion.

We report herein, a modular, regioselective 1,3-oxyarylation of vinyl diazo esters via a Co-catalyzed C-H activation/carbene migratory insertion cascade. The transformation involves the formation of C-C and C-O bonds in a one-pot fashion and displays a broad substrate scope with respect to both, vinyl diazo esters as well as benzamides. The coupled products were subjected to hydrogenation to access elusive allyl alcohol scaffolds. Mechanistic investigations reveal interesting insights on the mode of transformation, involving C-H activation, carbene migratory insertion of the diazo compound followed by a radical addition as the key steps of the transformation.

Merging Rh-Catalyzed C-H Functionalization and Cascade Cyclization to Enable Propargylic Alcohols as Three-Carbon Synthons.

Reported herein is a reactivity of propargyl alcohols as "Three-Carbon Synthons" in a Rh(III)-catalyzed C-H functionalization of acetanilides, leading to the synthesis of core structures of isocryptolepine, γ-carbolines, dihydrochromeno[2,3-b]indoles, and diindolylmethanes (DIM) derivatives. The transformation involves a rhodium(III)-catalyzed C-H functionalization and heteroannulation to yield indoles followed by a cascade cyclization with both external and internal nucleophiles to afford diverse products. The role of the hydroxy group, the key function of the silver additive, the origin of the reverse regioselectivity and the rate-determining step, are rationalized in conformity with the combination of experimental, noncovalent interaction analysis and DFT studies. This protocol is endowed with several salient features, including one-pot multistep cascade approach, exclusive regioselectivity, good functional group tolerance and synthesis of variety of molecular frameworks.

A switch to vinylogous reactivity of vinyl diazo esters for the C-H allylation of benzamides by merging cobalt and photoredox catalysis.

Herein, a de novo vinylogous reactivity of vinyl diazo esters in the C-H bond allylation of benzamides has been developed by coalescing cobalt and photoredox catalysis via C-H activation/allyl carbene migratory insertion. A close relationship between the high valent cobalt catalyst and the photocatalyst has been found to be crucial for this reactivity. The reaction uses oxygen as the sole oxidant and produces benign nitrogen as the only by-product. The reaction shows a good substrate scope with respect to both vinyl diazo esters and benzamides. The utility of the protocol is demonstrated through the late-stage functionalization of several bioactive molecules.

Catalyst-Controlled Chemodivergent Reactivity of Vinyl Cyclopropanes: A Selective Approach toward Indoles and Aniline Derivatives.

Herein, we disclose a catalyst-controlled chemodivergent approach to access C2-substituted indoles and diverse aniline derivatives with good chemo- and stereoselectivity by employing vinylcyclopropanes (VCPs) as coupling partners via a tandem C-H/C-C activation/annulation strategy. The key feature of this work is the divergent reactivity profile showcased by VCPs, going beyond allylation under a high-valent Rh-/MPAA catalyst system.

Rh(III)-Catalyzed One-Step Synthesis of ortho-Alkynylated Perylene Imide Dyes: Optical and Electrochemical Properties of New Derivatives.

A one-step Rh-catalyzed site-selective ortho-C-H alkynylation of perylene as well as naphthalene mono- and diimides is reported. A single step regioselective access to ortho-C-H alkynylated derivatives of these ryleneimides not only increases the step economy of the ortho-functionalization on these dyes but also provides a quick access route towards highly functionalized dyes that have potential optoelectronic applications. Increased solubility of tetra(triisopropylsilyl)acetylenyl PDIs in organic solvents greatly enhances their utility for further derivatization.

Rh(III)-Catalyzed C(7)-H Alkylation of Quinolines in the Synthesis of Angular π-Extended Pyrroloquinolines for Single-Component White-Light Emission.

Reported herein is a sustainable approach for a regioselective, Rh(III)-catalyzed C(7)-H alkylation of 8-aminoquinolines via metal carbene migratory insertion. This transformation displays a high functional group tolerance and exquisite site selectivity to afford the C-7 alkylated products. These products are derivatized to afford π-extended angular pyrroloquinolines, one of which (4h) shows white-light emission (WLE) with CIE coordinates (0.26, 0.34). An excellent cell viability and in vivo cellular imaging substantiate the nontoxic nature of these compounds.

Ruthenium-catalyzed oxidative coupling of vinylene carbonate with isoxazoles: access to fused anthranils.

A ruthenium-catalyzed oxidative coupling of vinylene carbonate with isoxazoles has been developed to achieve the direct C-H formylmethylation of a diverse array of arylisoxazoles utilizing the isoxazole ring as the directing group. A simple manipulation of the established reaction conditions leads to the formation of fused-anthranils. Importantly, the vinylene carbonate functions as both a formylmethyl cation equivalent through a decarboxylation process and an acetylene equivalent. Control experiments were conducted to elucidate a plausible mechanism. This methodology is expected to provide a facile and expeditious approach for the synthesis of formylmethyl isoxazoles and fused-anthranils.

Iridium(III)-Catalyzed C(3)-H Alkylation of Isoquinolines via Metal Carbene Migratory Insertion.

An Ir(III)-catalyzed C(3)-H alkylation of N-acetyl-1,2-dihydroisoquinolines with diverse acceptor-acceptor diazo compounds has been achieved under a single catalytic system via metal carbene migratory insertion. Moreover, further synthetic transformations of the alkylated products such as aromatization, selective decarboxylation, and decarbonylation lead to the formation of several synthetically viable isoquinoline derivatives having immense potentials.

Transition-Metal-Catalyzed C-H Bond Functionalization of Arenes/Heteroarenes via Tandem C-H Activation and Subsequent Carbene Migratory Insertion Strategy.

The past decade has witnessed tremendous developments in transition-metal-catalyzed C-H bond activation and subsequent carbene migratory insertion reactions, thus assisting in the construction of diverse arene/heteroarene scaffolds. Various transition-metal catalysts serve this purpose and provide efficient pathways for an easy access to substituted heterocycles. A brief introduction to metal-carbenes has been provided along with key mechanistic pathways underlying the coupling reactions. The purpose of this review is to provide a concise knowledge about diverse directing group-assisted coupling of varied arenes/heteroarenes and acceptor-acceptor/donor-acceptor diazo compounds. The review also highlights the synthesis of various carbocycles and fused heterocycles through diazo insertion pathways, via C-C, C-N and C-O bond forming reactions. The mechanism usually involves a C-H activation process, followed by diazo insertion leading to subsequent coupling.

Ru(II)-Catalyzed, Cu(II)-mediated carbene migratory insertion in the synthesis of trisubstituted pyrroles from isoxazoles.

A convenient, "one-pot" synthesis of trisubstituted pyrroles via a Ru(ii)-catalyzed, Cu(ii)-mediated reaction of substituted isoxazoles with sulfonylhydrazones has been developed. A series of highly functionalized pyrroles are obtained via a synergistic formation of new C-C and C-N bonds. Mechanistic investigations were carried out to propose the plausible pathway. This protocol provides a facile and expeditious approach for the synthesis of various heterocyclic compounds bearing the pyrrole skeleton.

Palladium-catalyzed functionalizations of acidic and non-acidic C(sp3)-H bonds - recent advances.

A tremendous upsurge has been seen in the recent decade for the proximal and remote functionalization of activated and unactivated substrates via palladium redox pathways. This feature article discusses some of the recent reports on direct as well as indirect C(sp3)-H functionalization via cross-coupling reactions under palladium catalysis. Activated substrates (possessing acidic C(sp3)-H) including enones, ketones, aldehydes, silylenol ethers, esters, silyl ketene acetals, amides, cyano, α-amino esters, and O-carbamates, capable of undergoing cross-coupling reactions at the α-, ß-, γ-, δ- and ε-positions, will be discussed. To overcome the challenging task of achieving regioselectivity, a variety of innovative modifications have been reported. The reports of C-H activations based on directing group, and as native functionality have been illustrated at the ß-, γ- and δ-positions. Substrates such as α-amino esters, carbonyls, carboxylic acids and their derivatives, afford site-selective C(sp3)-H functionalization via varied-sized reactive metallacycles and are a unique class of substrates whose C(sp3)-H functionalizations were earlier considered as very difficult.

Unusual Reactivity of 4-Vinyl Isoxazoles in the Copper-Mediated Synthesis of Pyridines, Employing DMSO as a One-Carbon Surrogate.

An efficient protocol for the synthesis of nicotinate derivatives and tetrasubstituted pyridines through a copper-mediated cleavage of isoxazoles has been developed. The highlight of the work is the observation of an unusual reactivity of 4-vinyl isoxazoles under the reaction conditions. DMSO serves as a one-carbon surrogate generating an active methylene group during the reaction to form two C-C bonds. This protocol provides a facile and an expeditious approach for the assembly of densely substituted N-heterocyclic compounds.

Catalyst Control in Switching the Site Selectivity of C-H Olefinations of 1,2-Dihydroquinolines: An Approach to Positional-Selective Functionalization of Quinolines.

A unique approach to achieve site-selective C-H olefinations exclusively at the C-3- or C-8-positions in the quinoline framework has been developed by catalyst control. Distal C(3)-H functionalization is achieved by using palladium catalysis, whereas proximal C(8)-H functionalization is obtained by employing ruthenium catalysis. Switching the site selectivity within a single substrate directly indicates two diverse pathways, which are operating under the palladium- and ruthenium-catalyzed reaction conditions.

Palladium-Mediated Remote Functionalization in γ- and ε-Arylations and Alkenylations of Unblocked Cyclic Enones.

We report herein an extensive investigation of simple and regioselective endo- as well as exo-γ-arylations of silyl-dienol ethers of unblocked cyclic enones with the utilization of palladium-catalyzed, modified Kuwajima-Urabe conditions. We have also successfully explored a new exo-ε-arylation of silyl-trienol ethers of π-extended cyclic enones. In addition, we also report, herein, exclusive γ- and ε-alkenylation of silyl-dienol and silyl-trienol ethers of cyclic enones.