Aniruddha Dey

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.

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.

Reaching the south: metal-catalyzed transformation of the aromatic para-position

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.

Traceless directing group mediated branched selective alkenylation of unbiased arenes

Owing to the synthetic importance of branched olefinated products, we report palladium catalyzed formation of branched olefins facilitated by a C-H activation based protocol. This involves selective insertion of olefins and subsequent decarboxylation using a completely unbiased benzene ring as the starting precursor. The significance of the protocol has been further highlighted by exhibition of functionality tolerance along with a late-stage modification of the branched olefinated products leading to the formation of other functionalized molecules.

Mechanistic elucidation of C-H oxidation by electron rich non-heme iron(IV)-oxo at room temperature.

Non-heme iron(IV)-oxo species form iron(III) intermediates during hydrogen atom abstraction (HAA) from the C-H bond. While synthesizing a room temperature stable, electron rich, non-heme iron(IV)-oxo compound, we obtained iron(III)-hydroxide, iron(III)-alkoxide and hydroxylated-substrate-bound iron(II) as the detectable intermediates. The present study revealed that a radical rebound pathway was operative for benzylic C-H oxidation of ethylbenzene and cumene. A dissociative pathway for cyclohexane oxidation was established based on UV-vis and radical trap experiments. Interestingly, experimental evidence including O-18 labeling and mechanistic study suggested an electron transfer mechanism to be operative during C-H oxidation of alcohols (e.g. benzyl alcohol and cyclobutanol). The present report, therefore, unveils non-heme iron(IV)-oxo promoted substrate-dependent C-H oxidation pathways which are of synthetic as well as biological significance.

Chapter 9 – Recent Advances in Distal Aliphatic sp3 CH Functionalization

Abstract The growing importance of functionalities located at suitable positions within an organic moiety bestows it with specific properties. This renders value-added properties to these molecules, thereby augmenting their utilitarian characteristics. In regard to this, transformation of sp3 C H bonds becomes quite challenging owing to their low reactivity and relative inertness compared to their sp2 and sp congeners. Complexity is further amplified in the attempts for functionalization at remote positions with respect to the pre-installed functional groups. This chapter therefore highlights some recent advances made in the field of aliphatic distal C H functionalization which has been made possible through the employment of an assortment of strategies.

Chapter 12 - Recent Developments in Palladium-Catalyzed Natural Product Synthesis via C H Activation

Abstract Application of transition metal-catalyzed C H activation reactions to natural product synthesis is an emerging and exciting area of research that not only obviates the need for prefunctionalization of the substrates, but also bypasses multistep sequences providing opportunities for designing new retrosynthetic paradigms. The key challenges associated with this field are the compatibility and selectivity issues with polyfunctionalized substrates. Palladium-catalyzed directed functionalization of C H bonds is gaining a lot of attention as a new synthetic strategy maximizing the atom- and step-economy, and has found application in the planned synthesis of many natural products and biologically active compounds. In this chapter, we aim to highlight the recent applications of palladium-catalysis for the synthesis of complex molecular frameworks wherein C H activation was employed as a key step.

A Doubly Biomimetic Synthetic Transformation: Catalytic Decarbonylation and Halogenation at Room Temperature by Vanadium Pentoxide

The halogenation of the C−H bond by metal‐oxo‐peroxo species and the decarbonylation of aldehydes by metal‐peroxo species are performed routinely in biological systems. However, metal‐mediated decarbonylative halogenation is unknown in nature. In this work, we have shown that widely available V2O5 and VO(acac)2 (acac=acetylacetonate) can catalyze decarbonylative halogenation through the generation of an intermediate vanadium‐oxo‐peroxo species, which was characterized by using 51 V NMR, UV/Vis, and resonance Raman spectroscopy. Further detection of formic acid from the reaction mixture confirmed the biomimetic aspects of decarbonylative halogenation. A detailed experimental and DFT study indicated a concerted mechanism for this decarbonylative halogenation performed under simple and mild reaction conditions.