C−C bond forming reactions incarnate the core of organic synthesis because of their fundamental applications to molecular diversity and complexity. In recent years, use of carboxylic acid as one of ...the coupling partners in place of conventional organometallic reagents has seen an upsurge due to its potency to generate similar organometallic intermediates after decarboxylation. This Review provides an overview on the most recent progress in the field of C−C bond formation involving decarboxylation as a key step. Different important developments, which are not included in earlier Reviews in this area, have been summarized with representative examples and discussions on their reaction mechanisms.
C here: This Review article covers the recent and important developments in the rapidly growing field of decarboxylative C−C bond formation.
Transition metal-catalyzed aryl C-H activation is a powerful synthetic tool as it offers step and atom-economical routes to site-selective functionalization. Compared with proximal
-C-H activation, ...distal (
- and/or
-) C-H activation remains more challenging due to the inaccessibility of these sites in the formation of energetically favorable organometallic pretransition states. Directing the catalyst toward the distal C-H bonds requires judicious template engineering and catalyst design, as well as prudent choice of ligands. This review aims to summarize the recent elegant discoveries exploiting directing group assistance, transient mediators or traceless directors, noncovalent interactions, and catalyst and/or ligand selection to control distal C-H activation.
Conspectus C–H activation has emerged as a powerful transformative synthetic tool to construct complex molecular frameworks, which are ubiquitous in natural products, medicines, dyes, polymers, and ...many more. However, reactivity and selectivity, arising from the inertness of C–H bonds and their overabundance in organic molecules, are the two major fundamental challenges in developing various carbon–carbon (C–C) and carbon–heteroatom (C–X) bond formation reactions via C–H activation technique. Functional groups with coordinating capacity to the transition metal catalysts, profoundly known as directing groups (DGs), have shown great promise in exerting selective C–H activation, often called site-selective or regioselective transformation of a target molecule. Advent of directing group (DG)-assisted strategies not only has resolved the selectivity issues but also offers a unique solution to the rapid synthesis of complex molecules in a convenient and predictable manner. Our laboratory, in this regard, is fascinated by the prospect of DG-assisted distal C–H functionalization of arenes, in which the target C–H bond is remotely located from the existing directing group. Notably, in opposition to proximal ortho-C–H activation, which proceeded via an energetically favorable five- to seven-membered metallacycle, distal C–H activation remained a formidable challenge as it required formation of a large macrocyclic metallacycle. Therefore, designing a suitable directing template that would maintain the required distance and geometric relationship between the target C–H bond and the appended directing auxiliary in order to ensure the prolific delivery of the metal catalyst to the closest proximity of targeted distal C–H bond was the key to success. In this regard, the Yu group devised an elegant “U-shaped” template for the first time to execute distal meta-C–H activation recruiting a cyano-based directing group. Our initial effort to diversify the scope of meta-C–H functionalization using a cyano-based template led us to realize that the “cyano-based DGs” are intrinsically limited with weak coordinating ability, competitive binding mode (end-on vs side-on), and incompatibility with acidic and basic reaction conditions. In search of a robust directing auxiliary, we were intrigued by the possibility of using the strongly coordinating ability of pyrimidine and quinoline-based DGs. In this Account, we describe our journey from the weakly coordinating cyano-based DG to the strongly coordinating pyrimidine-based DG to achieve diverse meta-C–H functionalization of electronically and sterically unbiased arenes. While some of the functionalizations were achieved by finding suitable reaction conditions, others were led by mechanistic understanding. Notably, initial development in this realm was constrained with short linkers, in which the DG was attached to the arene of interest through 2–4 atoms. In later studies, we demonstrated that the selective meta-C–H activation can be attained even though the DG is 10-atoms away from the targeted arene. More importantly, a transient DG was successfully utilized to deliver meta-C–H olefination of arenes via in situ imine formation, which provided a step-economic route to meta-C–H activation. We hope that this Account will stimulate further template design and will provide a guiding platform for the future development of distal meta-C–H functionalization.
Transition-metal-catalyzed C–H activation has developed a contemporary approach to the omnipresent area of retrosynthetic disconnection. Scientific researchers have been tempted to take the help of ...this methodology to plan their synthetic discourses. This paradigm shift has helped in the development of industrial units as well, making the synthesis of natural products and pharmaceutical drugs step-economical. In the vast zone of C–H bond activation, the functionalization of proximal C–H bonds has gained utmost popularity. Unlike the activation of proximal C–H bonds, the distal C–H functionalization is more strenuous and requires distinctly specialized techniques. In this review, we have compiled various methods adopted to functionalize distal C–H bonds, mechanistic insights within each of these procedures, and the scope of the methodology. With this review, we give a complete overview of the expeditious progress the distal C–H activation has made in the field of synthetic organic chemistry while also highlighting its pitfalls, thus leaving the field open for further synthetic modifications.
Among numerous solvents available for chemical transformations, 1,1,1,3,3,3-hexafluoro-2-propanol (popularly known as HFIP) has attracted enough attention of the scientific community in recent years. ...Several unique features of HFIP compared to its non-fluoro analogue isopropanol have helped this solvent to make a difference in various subdomains of organic chemistry. One such area is transition metal-catalyzed C-H bond functionalization reactions. While, on one side, HFIP is emerging as a green and sustainable deep eutectic solvent (DES), on the other side, a major proportion of Pd-catalyzed C-H functionalization is heavily relying on this solvent. In particular, for distal aromatic C-H functionalizations, the exceptional impact of HFIP to elevate the yield and selectivity has made this solvent irreplaceable. Recent research studies have also highlighted the H-bond-donating ability of HFIP to enhance the chiral induction in Pd-catalyzed atroposelective C-H activation. This perspective aims to portray different shades of HFIP as a magical solvent in Pd-catalyzed C-H functionalization reactions.
Among numerous solvents available for chemical transformations, 1,1,1,3,3,3-hexafluoro-2-propanol (popularly known as HFIP) has attracted enough attention of the scientific community in recent years.
Direct catalytic transformation of C–H bonds to new functionalities has provided a powerful strategy to synthesize complex molecular scaffolds in a straightforward way. Unstinting efforts of the ...synthetic community have helped to overcome the long-standing major challenge of regioselectivity by introducing the directing group concept. However, the full potential of the strategy cannot be realized unless the activated C–H bonds are stereochemically controlled. The enantioselective C–H bond functionalization could provide an imperative tool for a sustainable way of synthesizing chiral complex molecular scaffolds. Despite the intrinsic challenges in achieving stereocontrol, the synthetic community has developed different tools in order to achieve stereoselective C–H bond functionalization. In this review, we discuss the remarkable recent advances in the emerging area of enantioselective C(sp2)–H bond functionalization to highlight the challenges and opportunities, emphasizing the different techniques developed so far.
The study of carbon-based nanomaterials (CBNs) for biomedical applications has attracted great attention due to their unique chemical and physical properties including thermal, mechanical, ...electrical, optical and structural diversity. With the help of these intrinsic properties, CBNs, including carbon nanotubes (CNT), graphene oxide (GO), and graphene quantum dots (GQDs), have been extensively investigated in biomedical applications. This review summarizes the most recent studies in developing of CBNs for various biomedical applications including bio-sensing, drug delivery and cancer therapy.
Biaryl scaffolds are found in natural products and drug molecules and exhibit a wide range of biological activities. In past decade, the transition metal-catalyzed C-H arylation reaction came out as ...an effective tool for the construction of biaryl motifs. However, traditional transition metal-catalyzed C-H arylation reactions have limitations like harsh reaction conditions, narrow substrate scope, use of additives etc. and therefore encouraged synthetic chemists to look for alternate greener approaches. This review aims to draw a general overview on C-H bond arylation reactions for the formation of C-C bonds with the aid of different methodologies, majorly highlighting on greener and sustainable approaches.
Heterocyclic compounds are commonly found in the core structures of several pharmaceuticals, natural products, and agrochemicals, thus spurring intensive research for conducting their synthesis in a ...mild and simpler way. Over the years, a host of different strategies has been introduced in an effort to synthesize these heterocyles. In this context, significant attention has been gained by methodologies that ensure both step as well as atom efficiency. Synthesis of heterocyclic moieties
via
multiple C-H activations was found to fulfill these expectations besides guaranteeing the use of starting materials that are easily procurable. This review is focused on the current development in the field of benzofuran and indole synthesis using multiple C-H functionalization strategies.
Heterocyclic compounds are commonly found in the core structures of several pharmaceuticals, natural products, and agrochemicals, thus spurring intensive research for conducting their synthesis in a mild and simpler way.
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