C-CN bond formation: an overview of diverse strategies.

Nitrile or cyano compounds are an important part of structural motifs in dyes, agrochemicals, medicinal compounds, and electronic materials. Also, aryl nitrile is an important intermediate in the preparation of numerous compounds via transformations such as hydrolysis, hydration, reduction, cycloadditions, and nucleophilic additions. Such methods are beneficial for introducing sensitive functional groups in various positions in the multi-step synthesis of natural products and medicinal compounds. In the past decades, various cyanation methods have been reported in the vast arena of chemistry, which have made several building blocks accessible. Previously reported cyanation reviews, letters, and perspectives are written in parts. Thus, today a comprehensive review that will be able to guide readers through the vast pool of C-CN bond forming reactions via different approaches is obligatory. The present feature article depicts the various areas of cyanation methodologies that are based on the metal catalyst used, directed, non-directed, electrochemical, photochemical, asymmetric, and radical based approaches. This feature article will serve as a comprehensive tool to navigate the C-CN (cyanation) reactions across the vast area in synthetic chemistry.

para-Selective Arylation of Arenes: A Direct Route to Biaryls by Norbornene Relay Palladation.

Biaryl compounds are extremely important structural motifs in natural products, biologically active components and pharmaceuticals. Selective synthesis of biaryls by distinguishing the subtle reactivity difference of distal arene C-H bonds are significantly challenging. Herein, we describe para-selective C-H arylation, which is acheived by a unique combination of a meta-directing group and norbornene as a transient mediator. Upon direct meta-C-H palladation, one-bond relay palladation occurs in presence of norbornene and subsequently para-C-H arylation is achieved for sulfonates, phosphonates and phenols bearing 2,6-disubstitution patterns. The protocol is amenable to electron-deficient aryl iodides. Multisubstituted arenes and phenols are obtained by postsynthetic modification of the products. The protocol allows the synthesis of hexa-substituted benzene by sequential selective distal C-H functionalization.

Para-Selective Cyanation of Arenes by H-Bonded Template.

The significance of site selective functionalization stands upon the superior selectivity, easy synthesis and diverse product utility. In this work, we demonstrate the para-selective introduction of versatile nitrile moiety, enabled by a detachable and reusable H-bonded auxiliary. The methodology holds its efficiency irrespective of substrate electronic bias. The conspicuous shift in the step energetics was probed by both experimental and computational mechanistic tools, which heralds the inception of para-deuteration. The synthetic impact of the methodology was highlighted with reusability of directing group and post synthetic modifications.

Rhodium catalyzed template-assisted distal para-C-H olefination.

Rhodium catalysis has been extensively used for ortho-C-H functionalization reactions, and successfully extended to meta-C-H functionalization. Its application to para-C-H activation remains an unmet challenge. Herein we disclose the first example of such a reaction, with the Rh-catalyzed para-C-H olefination of arenes. The use of a Si-linked cyanobiphenyl unit as a traceless directing group leads to highly para-selective arene-olefin couplings.

Combining transition metals and transient directing groups for C-H functionalizations.

In the domain of synthetic chemistry, C-H bond activation has always remained in the spotlight for researchers over the last few decades. Although different strategies have been employed to chemically trigger unactivated C-H bonds, transition metal catalyzed directing group (DG) aided C-H bond activation is the most explored pathway of all because of its ability to perform diverse site selective functional metamorphosis. Despite its popularity, tedious synthetic methodology requiring additional steps for the installation and removal of DGs from the target substrate diminishes its efficacy. However, replacement of directing groups by transient directing groups (tDGs) reduces the hurdle to a greater extent without compromising the product yield and selectivity. In this report we have depicted the intense journey of transient directing groups with three (Rh, Ru, and Pd) prevalent second row transition metals.

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.

Palladium-catalyzed cyclization of benzamides with arynes: application to the synthesis of phenaglydon and N-methylcrinasiadine.

N-Methyl or methoxy benzamides reacted with benzynes in the presence of Pd(OAc)2, organic acid and K2S2O8 in CH3CN yielding tricyclic phenanthridinone derivatives in good yields.

A regioselective synthesis of 1-haloisoquinolines via ruthenium-catalyzed cyclization of O-methylbenzohydroximoyl halides with alkynes.

A ruthenium-catalyzed highly regioselective cyclization of substituted N-methoxy benzimidoyl halides with alkynes in the presence of CsOAc (25 mol%) to give substituted 1-halo and 1-alkoxy substituted isoquinolines in good to excellent yields is described.

Ruthenium-catalyzed intramolecular selective halogenation of O-methylbenzohydroximoyl halides: a new route to halogenated aromatic nitriles.

The intramolecular halogenation of O-methylbenzohydroximoyl halides in the presence of a Ru catalyst and the ligand diphenylacetylene afforded halo substituted aromatic nitriles in a highly regioselective manner. Further, substituted nitriles were converted into substituted tetrazole derivatives in the presence of NaN3 and I2.

Ruthenium-catalyzed regioselective oxidative coupling of aromatic and heteroaromatic esters with alkenes under an open atmosphere.

A ruthenium-catalyzed oxidative coupling of substituted aromatic and heteroaromatic esters with alkenes in the presence of catalytic amounts of AgSbF(6) and Cu(OAc)(2) to provide highly substituted alkene derivatives in good to excellent yields under an open atmosphere is described.

Ruthenium-catalyzed highly regioselective cyclization of ketoximes with alkynes by C-H bond activation: a practical route to synthesize substituted isoquinolines.

Aromatic and heteroaromatic ketoximes underwent cyclization with alkynes in the presence of a catalytic amount of [{RuCl(2)(p-cymene)}(2)] and NaOAc to give isoquinoline derivatives in good to excellent yields in a highly regioselective manner.