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.

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.

Nitroolefin is a common and versatile reagent. Its synthesis from olefin is generally limited by the formation of mixture of cis and trans compounds. Here we report that silver nitrite (AgNO2) along with TEMPO can promote the regio- and stereoselective nitration of a broad range of olefins. This work discloses a new and efficient approach wherein starting from olefin, nitroalkane radical formation and subsequent transformations lead to the desired nitroolefin in a stereoselective manner.

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Nitroolefins are essential elements for both synthetic chemistry and medicinal research. Despite significant improvements in nitration of olefin an efficient metal-free synthesis remains elusive so far. Herein, we disclose a new set of reagents to access nitroolefins in a single step under metal-free conditions. A wide range of olefins with diverse functionalities has been nitrated in synthetically useful yields. This transformation is operationally simple and exhibits excellent E-selectivity. Furthermore, site selective nitration in a complex setup makes this method advantageous.

A unique C–H allylation has been discovered with unbiased aliphatic olefins. An intimate M–L affiliation between a high-valent cobalt catalyst and amino-quinoline derived benzamides has been found to be crucial for this unprecedented selectivity. An exemplary set of aliphatic olefins, high yields coupled with excellent regio- and stereoselectivity, and wide functional group tolerances are noteworthy. In addition, a catalytically competent organometallic Co­(III) species has been identified through X-ray crystallography. This study is expected to facilitate new synthetic designs toward unconventional allylic selectivity with aliphatic olefins.

α-Branched amines are present in hundreds of pharmaceutical agents and clinical candidates and are important targets for synthesis. Here we show the convergent synthesis of α-branched amines from three readily accessible starting materials: aromatic C–H bond substrates, terminal alkenes, and aminating agents. This reaction proceeds by an intermolecular formation of C–C and C–N bonds at the sp 3 carbon branch site through an uncommon 1,1-alkene addition pathway. The reaction is carried out under mild conditions and has high functional group compatibility. Ethylene and propylene feedstock chemicals are effective alkene inputs with ethylene in particular providing for the one step synthesis of α-methyl branched amines, a motif prevalent in drug structures. The reaction is scalable, and 1% loading of an air stable dimeric rhodium precatalyst is effective for several different types of products. The use of chiral catalysts also enables the asymmetric synthesis of α-branched amines.

Regioselective functionalization of aromatic arenes has created a rapid insurgence in the modern era of organic chemistry. While the last few years have witnessed significant developments on site-selective ortho- and meta-C-H transformations, there existed very few reports on para-C-H functionalization. Recent advancements on template assisted protocols in para-C-H activation has emerged as a popular and convenient feat in this area. This review highlights the various protocols developed over the years for selective installation of suitable functional groups at the para-position of arenes thereby transforming them into value-added organic cores.