Fluorosulfonamide-Directed Heteroarylation of Aliphatic C(sp3)-H Bonds.

Herein, we describe a formal dehydrogenative cross coupling of heterocycles with unactivated aliphatic amines. The resulting transformation enables the direct alkylation of common heterocycles by merging N-F-directed 1,5-HAT with Minisci chemistry, leading to predictable site selectivity. The reaction provides a direct route for the transformation of simple alkyl amines to value-added products under mild reaction conditions, making this an attractive option for C(sp3)-H heteroarylation.

Dual-Catalytic Enantioselective Allylation of N-(Heteroaromatic-methyl)imine Derivatives.

We report the dual-catalytic enantioselective allylic alkylation of 2-(pyridylmethyl)amine-derived ketimines with allylic carbonates. The reaction proceeds under mild reaction conditions to generate α-amino heteroaryl benzylamine stereocenters in good yield and enantioselectivity. Enantioselectivity is achieved through the use of a copper catalyst modified with chiral bisphosphine ligand (2S,4S)-bis(diphenylphosphino)pentane.

Homologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C-C Bond Insertion.

The ability to manipulate C-C bonds for selective chemical transformations is challenging and represents a growing area of research. Here, we report a formal insertion of diazo compounds into the "unactivated" C-C bond of benzyl bromide derivatives catalyzed by a simple Lewis acid. The homologation reaction proceeds via the intermediacy of a phenonium ion, and the products contain benzylic quaternary centers and an alkyl bromide amenable to further derivatization. Computational analysis provides critical insight into the reaction mechanism, in particular the key selectivity-determining step.

Enabling the Facile Synthesis of Arenes by Transition Metal Catalyzed Decarbonylation Methodology.

Transition metal-catalyzed decarbonylation is an essential paradigm of synthetic organic chemistry. Decarbonylation offers a unique pathway to decoding the skeletal structure of arenes and enabling easy synthesis of structurally complicated molecules. Due to the omnipresence of carbonyl groups in a wide array of synthetically important complex molecules, the variety and scope of these transformations are enormous. As a result, the development of transition metal catalysts in such a simple decarbonylation reaction ranks among one of the most important topics in synthetic organic chemistry. Transition metals that have been employed range from 3d metals like V to second-row transition metals like Pd. The growing potential of this methodology has driven the pioneers of synthetic organic chemistry into delving into the details of this transition metal-catalyzed decarbonylation pathways. This review aims to take the readers through the employment of transition metals in various decarbonylation processes developed by our group, sticking not only to the scope and diversification of synthetically complex molecules, but also enabling the readers to understand the mechanistic insights, through computational and kinetic studies put forward in such reaction protocol, hoping to pave the way for future organic chemists to delve and hopefully solve the unique problems associated with this protocol.

Cu-Catalyzed C-N Coupling with Sterically Hindered Partners.

Copper, an earth-abundant metal, has reemerged as a viable alternative to the versatile Pd-catalyzed C-N coupling. Coupling sterically hindered reaction partners, however, remains challenging. Herein, we disclose the discovery and development of a pyrrole-ol ligand to facilitate the coupling of ortho-substituted aryl iodides with sterically hindered amines. The ligand was discovered through a library screening approach and highlights the value of mining heteroatom-rich pharmaceutical libraries for useful ligand motifs. Further evaluation revealed that this ligand is uniquely effective in these challenging transformations. The reaction enables the coupling of sterically hindered primary and secondary amines, anilines, and amides with broad functional group tolerance.

Copper-Catalyzed, N-Directed Csp3-H Trifluoromethylthiolation (-SCF3) and Trifluoromethylselenation (-SeCF3).

A direct and versatile copper-catalyzed trifluoromethylthiolation and trifluoromethylselenation of primary, secondary, and tertiary aliphatic C-H bonds was developed. The reaction provides direct access to molecules containing these emerging moieties in the presence of a wide range of common functional groups and in complex molecular environments.

Fenton-Inspired C-H Functionalization: Peroxide-Directed C-H Thioetherification.

Substoichiometric iron mediates the thioetherification of unactivated aliphatic C-H bonds directed by resident silylperoxides. Upon exposure to a catalytic amount of iron(II) triflate, TIPS-protected peroxides bearing primary, secondary, and tertiary C-H sites undergo chemoselective thioetherification of remote C-H bonds with diaryl disulfides. The reaction demonstrates a broad substrate scope and functional group tolerance without the use of any noble metal additives. Mechanistic experiments suggest that the reaction proceeds through 1,5-H atom abstraction by a hydroxyl radical generated with iron.

Correction: Remote meta C-H bond functionalization of 2-phenethylsulphonic acid and 3-phenylpropanoic acid derivatives.

Correction for 'Remote meta C-H bond functionalization of 2-phenethylsulphonic acid and 3-phenylpropanoic acid derivatives' by Atanu Modak et al., Chem. Commun., 2016, 52, 13916-13919.

Remote meta C-H bond functionalization of 2-phenethylsulphonic acid and 3-phenylpropanoic acid derivatives.

This discovery illustrates selective meta C-H bond activation from multiple non-equivalent C-H bonds present in medicinally relevant arylethanesulfonic acid and the 2-arylpropanoic acid moiety using weakly coordinating nitrile as a directing group. Transformation of the meta olefinated compounds to important organic molecules has been demonstrated. Efforts were made to obtain mechanistic detail of the meta C-H bond functionalization reaction.

Palladium-Catalyzed Directed para C-H Functionalization of Phenols.

Various practical methods for the selective C-H functionalization of the ortho and recently also of the meta position of an arene have already been developed. Following our recent development of the directing-group-assisted para C-H functionalization of toluene derivatives, we herein report the first remote para C-H functionalization of phenol derivatives by using a recyclable silicon-containing biphenyl-based template. The effectiveness of this strategy was illustrated with different synthetic elaborations and by the synthesis of various phenol-based natural products.

Metal catalyzed defunctionalization reactions.

Defunctionalization has a direct impact on the synthesis of value added products (e.g. biomass degradation). In synthetic chemistry it enables the functional group to act as a transient directing group. In this mini review, we have described the chronological development of metal assisted defunctionalization reactions from the stoichiometric to the catalytic stage with their application in synthetic organic chemistry. The proposed catalytic cycles of the transformations have been described to make this review comprehensible.

Palladium Nanoparticles Supported on Fibrous Silica (KCC-1-PEI/Pd): A Sustainable Nanocatalyst for Decarbonylation Reactions.

A practical and convenient decarbonylation of a variety of aromatic, heteroaromatic, and alkenyl aldehydes by using palladium nanoparticles supported on novel, fibrous nanosilica, named KCC-1-PEI/Pd, has been developed. Complete conversion of aldehyde functionalities into deformylated products was achieved in all cases and in nearly all cycles tested by reusing the catalyst systems. This method eliminates further purification of products after their isolation. Syntheses of at least three different deformylated products have been shown in sequence with the same catalyst system, which neither requires use of any additives, such as oxidants and bases, nor CO scavengers.

Remote para-C-H Functionalization of Arenes by a D-Shaped Biphenyl Template-Based Assembly.

Site-selective C-H functionalization has emerged as an efficient tool in simplifying the synthesis of complex molecules. Most often, directing group (DG)-assisted metallacycle formation serves as an efficient strategy to ensure promising regioselectivity. A wide variety of ortho- and meta-C-H functionalizations stand as examples in this regard. Yet despite this significant progress, DG-assisted selective para-C-H functionalization in arenes has remained unexplored, mainly because it involves the formation of a geometrically constrained metallacyclic transition state. Here we report an easily recyclable, novel Si-containing biphenyl-based template that directs efficient functionalization of the distal p-C-H bond of toluene by forming a D-shaped assembly. This DG allows the required flexibility to support the formation of an oversized pre-transition state. By overcoming electronic and steric bias, para-olefination and acetoxylation were successfully performed while undermining o- and m-C-H activation. The applicability of this D-shaped biphenyl template-based strategy is demonstrated by synthesizing various complex molecules.

Iron-Catalyzed Regioselective Direct Arylation at the C-3 Position of N-Alkyl-2-pyridone.

A number of pharmaceutical compounds possess an arylated 2-pyridone moiety. The existing reports using expensive starting materials and/or superstoichiometric metal salts have prompted us to explore a possible user-friendly method for their synthesis. In this report, we demonstrate an easy-to-handle reaction condition with an iron catalyst for the exclusive generation of C-3-arylated pyridone via C-H functionalization.

Meta-selective arene C-H bond olefination of arylacetic acid using a nitrile-based directing group.

A nitrile-based template attached with a phenylacetic acid framework promoted meta-selective C-H bond olefination. This palladium-catalyzed protocol is applicable to a wide range of substituted phenylacetic acids and tolerates a variety of functional groups. The versatility of this operationally simple method has been demonstrated through drug diversification.

Predictably selective (sp3)C-O bond formation through copper catalyzed dehydrogenative coupling: facile synthesis of dihydro-oxazinone derivatives.

An intramolecular dehydrogenative (sp(3))C-O bond formation in salicylamides can be initiated by an active Cu/O2 species to generate pharamaceutically relevant dihydro-oxazinones. Experimental findings suggest that stereoelectronic parameters in both coupling partners are controlling factors for site selectivity in bond formation. Mechanistic investigations including isotope labeling, kinetic studies helped to propose a catalytic cycle. The method provides a convenient synthesis of an investigational new medicine CX-614, which has potential in finding treatment for Parkinson's and Alzheimer's diseases.

Nickel-catalyzed hydrogenolysis of unactivated carbon-cyano bonds.

Selective hydrogenolysis of C-CN bonds can allow chemists to take advantage of ortho-directing ability, α-C-H acidity and electron withdrawing ability of the cyano group for synthetic manipulations. We have discovered hydrogenolysis of aryl and aliphatic cyanides under just 1 bar of hydrogen by using a nickel catalyst. This protocol was applied in the aryl cyanide directed functionalization reaction and α-substitution of benzyl cyanides.

An efficient dehydroxymethylation reaction by a palladium catalyst.

A general method for selective dehydroxymethylation has been discovered by using widely available Pd(OAc)(2). The present study offers a new synthetic strategy for the regioselective functionalization by employing the steric, electronic and coordinating nature of the hydroxymethyl (-CH(2)OH) group temporarily.

A general and efficient aldehyde decarbonylation reaction by using a palladium catalyst.

A facile decarbonylation reaction of aldehydes has been developed by employing Pd(OAc)(2). A wide variety of substrates are decarbonylated, without using any exogenous ligand for palladium as well as CO-scavenger.